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Research news archive

 

December 2015

December 28, 2015

At the roots of mammals – specification of mammary cells

Mammary glands, or breasts, are the class defining features of mammals and successful development and function of the mammary glands is vital for the survival of offspring. Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia, 5 pairs in mice, on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin, but the molecular mechanisms of mammary cell fate specification are still poorly understood.

In a recent study, published in PLoS Genetics, Marja Mikkola’s research team at the Institute of Biotechnology, University of Helsinki, has addressed this question by analysing loss- and gain-of-function mice of the Ectodysplasin (Eda)/Edar/NF-κB pathway. Eda is a signaling molecule that regulates the formation of organs that develop as appendages of the skin (hair and several glands) in all vertebrates studied so far. In humans, mutations in the EDA pathway genes cause a congenital disorder characterized by sparse hair, missing teeth, and defects in exocrine glands including the breast. It was previously shown that even though Eda is dispensable for induction of mammary primordia, excess Eda induces formation of supernumerary mammary glands in mice.

The new study revealed that overexpression of Eda (in transgenic K14-Eda mice) led to formation of extra mammary glands also in the neck, a region previously not thought to harbor capacity to support mammary development. Further, the effects of Eda were shown to be mediated by transcription factor NF-κB. Genome-wide transcriptional profiling identified several downstream mediators of Eda/ NF-κB including many members of the Wnt signaling pathway.  With the aid of an ex vivo culture system, Maria Voutilainen, the first author of the study showed that suppression of canonical Wnt signaling dose-dependent inhibited  formation of supernumerary mammary primordia in K14-Eda tissue explants.

The presence of extra nipples is a fairly common developmental abnormality in humans, and it is tempting to speculate that misregulation of Eda or its effectors might account for some of these cases. Moreover, tinkering with the Eda pathway activity could provide an evolutionary means to modulate the number and location of mammary glands known to vary greatly between mammals, similar to its confirmed involvement in regulating the number of sweat glands in humans and armor plates in threespine sticklebacks.

Developing mammary glands in control and K14-Eda mouse embryos. Positions of mammary buds 1 to 5 are indicated; black arrows highlight the incipient supernumerary mammary primordia along the milk line and red arrow a supernumerary mammary bud in the neck.

Voutilainen M, Lindfors PH, Trela E, Lönnblad D, Shirokova V, Elo T, Rysti E, Schmidt-Ullrich R, Schneider P, Mikkola ML (2015). Ectodysplasin/NF-κB promotes mammary cell fate via Wnt/β-catenin pathway. PLoS Genet 11:e1005676.

Article in Plos Genetics

Picture: Maria Voutilainen

December 14, 2015

How do cells sense their mechanical environment?

Studies from the past few years have revealed that, in addition to guidance by biochemical signals such as growth factors, also the mechanical properties of extracellular matrix and neighboring cells have a fundamental role in cell morphogenesis, differentiation and migration.  Furthermore, it has become evident that defects in reading the mechanical properties of the extracellular environment are associated with cancer progression.

Contractile actin filament bundles, called stress fibers, are the major mechanosensitive structures in many animal cells. These actomyosin bundles form only in rigid environment, and their assembly and alignment can be controlled by external forces applied to the cell. However, the principles underlying the mechanosensitive formation of stress fibers have remained elusive.

In a new study, the laboratory of Pekka Lappalainen at Institute of Biotechnology, University of Helsinki, discovered that both assembly and disassembly of actin filaments in stress fibers are precisely regulated by tension. In this paper, published in eLife, they also identified a signaling pathway that controls mechanosensitive actin filament assembly in focal adhesions located at the tips of stress fibers.

-These findings uncover the principles by which mechanosensitive actin structures form in cells. Interestingly, many components in this pathway are de-regulated in various cancers. Thus, in the future it will be important to examine how disruption or re-activation of this newly identified mechanosensitive pathway affects cancer progression, says Sari Tojkander, the first author of this study.

'Actin stress fibers (left panel) can apply strong forces to their substrate as measured by traction force microscopy (right panel)

Tojkander S, Gateva G, Husain A, Krishnan R, Lappalainen P (2015): Generation of contractile actomyosin bundles depends on mechanosensitive actin filament assembly and disassembly. eLife

Picture: Lappalainen group

December 10, 2015

Pekka Katajisto receives 1,5M€ from ERC to investigate the mechanisms of asymmetric cell division in relation to aging

Our tissues are constantly renewed by stem cells. Over time, stem cells accumulate cellular damage that will compromise renewal and results in aging. As stem cells can divide asymmetrically, segregation of harmful factors to the differentiating daughter cell could be one possible mechanism for slowing damage accumulation in the stem cell. Earlier this year the laboratory of Pekka Katajisto discovered that some stem cells apportion chronologically old cellular components asymmetrically in cell division. Katajisto, a Group Leader at the Institute of Biotechnology, has now received ERC Starting Grant (1 500 000€) to investigate the mechanisms underlying this novel phenomenon and its relevance for aging.

- First we aim to identify how old and young cellular compartments differ, and how stem cells recognize them to facilitate the asymmetric segregation, says Katajisto.
The mechanistic studies will allow Katajisto’s lab to determine if age-selective segregation of organelles is necessary for stem cell maintenance and tissue regeneration. Results may also open new possibilities to target aging associated functional decline and the multitude of aging associated diseases.
- We are very excited for the ERC grant. The best results are yet to come, Katajisto continues.

Katajsto lab
European Research Council (ERC)

Picture: Veikko Somerpuro

November 23, 2015

Mart Saarma has been elected as a member of Academia Europaea

Professor Mart Saarma has been elected as a member of Academia Europaea - The Academy of Europe, which brings together leading scientists and scholars to collectively promote learning, education and research. Founded in 1988, with about 3000 members which includes leading experts from the physical sciences and technology, biological sciences and medicine, mathematics, the letters and humanities, social and cognitive sciences, economics and the law. Membership is by invitation.

Prof. Mart Saarma has studied the structure, biology and therapeutic potential neurotrophic factors and their receptors. His recent studies are focused on the role of neurotrophic factors in development and neurodegenerative diseases. He has received several domestic and international science prizes, including the Nordic Science Prize by Lundbeck Foundation in 2009. He is the member of several academies and EMBO. Currently Saarma is the member of EMBO Council and Vice President of the European Research Council.

Academia Europaea

Picture: Linda Tammisto

November 19, 2015

High-risk research, part 2:

Research in kidney development can provide solutions for many renal insufficiency patients

Supported by the Academy of Finland’s high-risk funding, Satu Kuure is studying the development of the kidneys and lower urinary tract.The research could help patients with congenital kidney disorders, cancer and diabetes.

Functional renal defects have a profound impact on our national economy. In addition to cleft lip/palate and heart disease, congenital kidney malformations are amongst the most common congenital defects. A reduced number of nephrons due to a developmental defect also renders the person susceptible to high blood pressure. As well, chemotherapy and diabetes can severely disrupt the function of the kidneys especially in the patients with already reduced nephron number.

“As many as one in three hundred children has a congenital kidney disorder, and there is currently no cure as such. Dialysis is extremely expensive and inconvenient, and approximately 60% of transplanted kidneys ultimately cease to function,” explains team leader Satu Kuure, who received high-risk funding from the Academy of Finland in September to support her research in the development of the kidneys and lower urinary tract.

The initial funding period is 16 months, and at the end of 2016 the Academy will evaluate the progress of the projects to select the ones eligible for extended funding.

Kuure, a biochemist who received her Master’s degree from the Faculty of Science at the University of Oulu and her doctorate from the Faculty of Medicine at the University of Helsinki, became interested in the development of the kidneys and cellular communication at an early stage. While working at Columbia University after completing her dissertation, she heard that there was a new mouse model with abnormally developing kidneys generated in Professor Mart Saarma’s lab at the Institute of Biotechnology.

“It turned out that overproduction of a protein that is instrumental in the proper growth and shape of kidneys, leads to smaller kidneys and problems with the differentiation of several other tissue types.”

Kuure team has since then worked with two other mouse models which are expected to be helpful in unlocking the secrets of kidney development. Research with these mouse models is not easy to carry out, as it involves simultaneous modification of three different genes.

“We are at the core of real medical problems: through basic research, we are ensuring the generation of new applications, which in turn may lead to new forms of treatment," remarks Kuure, who has worked as team leader for just over a year.

At the moment, Satu Kuure’s group employs four people.

November 19, 2015

Darshan Kumar represents University of Helsinki at international doctoral candidate meeting

Each capital university nominated just one representative for the UNICA and COIMBRA training in Dubrovnik in October

Darshan Kumar is a PhD student in the research group led by Eija Jokitalo at the Institute of Biotechnology, and an active member of the BiotechClub in the Integrative Life Science Doctoral Programme ILS. He was nominated by Vice Rector Keijo Hämäläinen to represent the University of Helsinki at the joint training for doctoral candidates in Dubrovnik, Croatia. The UNICA and COIMBRA training brought together students from each European capital university, one from each.

“The sole purpose of this training was to make all the PhD students from interdisciplinary fields realise the strengths of doing a PhD, and to learn to channel the skills acquired during a PhD to navigate your future career,” Kumar explains. “Not only did we get to understand various fields of disciplines where PhD holders could find jobs, we also got a feeling of what it is like being in those respective sectors. It was great to have made many connections and to have networked with junior to senior participants in the workshop representing various universities throughout Europe."

Darshan Kumar's participation was supported by the ILS doctoral programme.

"We encourage PhD students to open their eyes to international career options in both industry and academia," says ILS director, associate professor Ville Hietakangas from the Department of Biosciences and the Institute of Biotechnology.

Darshan Kumar brings back insight on the topics learned in the training and is sharing the knowledge with his fellow PhD students. The regular ILS networking events and the BiotechClub provide excellent platforms for such sharing.

"The group project work was challenging and made us realise not only how to execute various tasks under time constraints but also how to manage group dynamics,” continues Kumar. “Our sub-group of five doctoral students was awarded the best idea for a Horizon 2020 proposal on sciences-based business education. Overall it was an unforgettable event, with lots of fun and unmatched professional teaching.”

October 28, 2015

Plant regulatory network simulations reveal a mystery in cytokinin patterning

Researchers at the University of Helsinki have discovered that cytokinin patterning, an important process in plant development, cannot happen via diffusion alone. While investigating a regulatory network in plant roots, they identified unexpected physical constraints on how cytokinin patterns form.

Interactions between the hormones auxin and cytokinin are central in plant development. In the growing root, cytokinin activates molecular exporters which pump auxin out of cells and auxin activates a gene which blocks cytokinin activity. This mutual inhibition is believed to form an exclusive domain for each hormone. The cells where auxin accumulates become xylem cells, which make up wood.

Sedeer el-Showk, a PhD student at the Ari Pekka Mähönen’s group, Institute of Biotechnology, used computational simulations to test the auxin-cytokinin network in a root cross section. The simulations showed that the network is enough to form the observed patterns, but also identified unexpected limits on cytokinin movement and patterning.

Molecular transporters are known to regulate the movement of auxin, but similar transporters have not been found for cytokinin. Nevertheless, a gradient in the distribution of cytokinin is thought to be important in several plant developmental processes, from patterning in the early embryo to continuous growth of the shoot.

However, the simulations showed that cytokinin diffusion cannot form a pattern on a scale small enough for these tissues. “It's easy to propose a cytokinin gradient when you're doing an experiment, but it turns out that physical constraints make it very unlikely that diffusing cytokinin forms a pattern on these scales,” explains lead author Sedeer el-Showk. “The pattern has to be created in another way. It could be a pattern in the cytokinin receptors or it might be that there are cytokinin transporters waiting to be discovered. Either way, there's a mystery to solve.”

The work was carried out in collaboration with the groups of Verônica Grieneisen and Stan Marée at the John Innes Centre in the UK. “Our computational work started with experimental data. We've confirmed our simulations with new experiments, and then our computational model has also indicated new lines for experimental work,” says group leader Ari Pekka Mähönen. “The back-and-forth between experiments and computational work means the two approaches reinforce and double-check each other.”

Unrealistic physical parameters were used to simulate the cytokinin gradient shown here.

el-Showk S, Help-Rinta-Rahko H, Blomster T, Siligato R, Marée AFM, Mähönen AP, Grieneisen VA. Parsimonious Model of Vascular Patterning Links Transverse Hormone Fluxes to Lateral Root Initiation: Auxin Leads the Way, while Cytokinin Levels Out. PLOS Computational Biology

Article in PLOS Computational Biology

Image: Mähönen group

October 28, 2015

The BI SAB site visit 15-16 October, 2015

The BI Scientific Advisory Board visited the Institute on 15-16 October to evaluate the progress of nine BI Group Leaders, and also Institute as a whole. The Chair of the BI Board Jari Niemelä opened the evaluation and its first session on Thursday morning. Director Howy Jacobs give an overview of BI’s activities in 2013-2015, and presented a vision for coming years. Research Directors introduced the highlights, challenges and future plans of each research program. After the opening session the SAB site visit continued with closed meetings and group leader interviews.

On Friday afternoon SAB chair Joan Steitz chaired a Q&A session for the whole institute staff. Discussion was lively – e.g. position of team leaders, challenges in postdoctoral careers and many other issues were discussed. Program ended with the poster session where all evaluated groups presented their research. The visit will be followed by an evaluation report.

Picture: Elina Raukko

October 5, 2015

Genetic mechanisms of dietary sugar sensing revealed by Drosophila research

The conserved sugar-sensing transcription factor complex Mondo-Mlx controls the majority of sugar-activated genes.

Sugars are an important source of nutritional energy for many animals, but also contribute to metabolic diseases in human such as type 2 diabetes, metabolic syndrome and cancer.

Dietary sugars are sensed within the cell by Mondo-Mlx, a transcription factor that is functionally conserved among animals and controls expression of many key metabolic genes in response to sugar intake. The group of Ville Hietakangas has been studying the role of Mondo-Mlx in Drosophila and has earlier found that loss of Mondo-Mlx function results in Drosophila larvae that are unable to survive on a diet that contains sugar  (Havula et al. 2013 PLoS Genetics).

Most recently the Hietakangas group has adopted a genome-wide approach to study the function of Mondo-Mlx in sugar-induced gene transcription. “We wanted to identify the role of Mondo-Mlx in fast genetic response to dietary sugars in the whole organism. Drosophila is a great model to study nutritional responses, not only due to the ease of genetic manipulation and conserved metabolic pathways, but also because the larvae are eating continuously,” explains Essi Havula, co-first author of the study.

RNAseq analysis of sugar-fed mlx-mutant animals provided new insight into the control of sugar-regulated transcription. In an organism-wide setting, Mondo-Mlx controls the majority of sugar-regulated genes, implying that it has a much wider regulatory role than previously anticipated. In addition to the well-established roles in activating glycolysis and fatty acid synthesis, the study uncovered a number of new functions, such as regulation of digestive enzymes in the gut.

In addition to metabolic target genes, Mondo-Mlx also controls the expression of other regulatory genes, including transcription factors and secreted hormones.  One of the new targets of Mondo-Mlx, the GLI-similar transcription factor, Sugarbabe, was found to promote the activation of lipid and serine biosynthesis but also to repress gut amylase expression. The finding that Mondo-Mlx serves as a master-regulator of a sugar sensing regulatory network explains its ability to coordinate such a wide spectrum of metabolic genes.

A collaboration with Dr. Samuli Ripatti’s group (Institute for Molecular Medicine Finland, FIMM) revealed that the study may also help to understand the molecular mechanisms underlying human metabolic disorders and conditions. The ENCAGE Consortium has recently identified several gene variants associated with circulating triglyceride levels (Surakka et al. 2015 Nature). Interestingly human homologs of Mondo-Mlx targets were enriched among triglyceride-associated genes. Thus Mondo-Mlx targets can be used to predict putative causal genes related to the triglyceride-associated genomic variants in humans.

 

Above: Loss of mlx leads to developmental delay and lethality at larval stage when the animals fed with high sugar diet. Below: Most of the sugar upregulated processes, such as glycolysis and pentose phosphate pathway, are regulated by Mondo-Mlx.

Jaakko Mattila, Essi Havula, Erja Suominen, Mari Teesalu, Ida Surakka, Riikka Hynynen, Helena Kilpinen, Juho Väänänen, Iiris Hovatta, Reijo Käkelä, Samuli Ripatti, Thomas Sandmann and Ville Hietakangas: Mondo-Mlx mediates organismal sugar sensing through Gli-similar transcription factor Sugarbabe. Cell Reports 13, 1–15, October 13, 2015

Article in Cell Reports

Hietakangas group

Picture: Essi Havula and Erja Suominen

September 21, 2015

Risk-taking research, part 1: Growing whole teeth

Bad or missing teeth are not only an aesthetic matter, but they also contribute to the person's total health. MD and PhD Anamaria Balic aims at finding a way to grow tooth enamel and eventually whole teeth both in vitro and in vivo. She is one of the three recipients of the Academy of Finland special risk-taking funding in the Institute of Biotechnology for 2015–2016.

Anamaria Balic, MD, PhD, has been working in the Institute for two years in Professor Irma Thesleff's group. With a background of both dental development and cancer research, she has taken on the major task of discovering how whole teeth could be grown first in vitro and, eventually, in the mouth.

– The dentin part of the tooth, which is made by the stem cells within the dental pulp, the core of the tooth, has been grown in vitro before. No one has so far been able to grow enamel.

The enamel in humans thins out with age due to physical and chemical erosion. And once it is gone, it is gone for good, since we lose the stem cells that generate enamel already during childhood. Many rodents have a huge advantage over people as their dental stem cells keep on producing new dental tissues for their continuously growing teeth.

Accordingly, Anamaria Balic started with a mouse model to discover how tooth epithelial stem cells could be programmed into enamel-producing cells, ameloblasts. The road might be long, but if her efforts succeed, the results will be ground-breaking. At this stage she is very happy that the Academy of Finland has noticed the importance of her research.

– It is a good token that I am one of those who are considered to have a chance to succeed in what we are doing. This gives me a lot of self-confidence.

The Academy of Finland risk-taking funding system is transparent. The recipients need to report on their work by the end of the next year, and then it is estimated whether their funding will continue for the rest of the funding period.

– This absolutely motivates you - you work faster and more efficiently. Transparency means also transparency for the public, which is very important. You need to be close to the public and communicate!

Anamaria Balic in Tuhat

Thesleff group

Academy of Finland funding decision

Text and picture: Elina Raukko

__________

The other two recipients of the AoF risk-taking funding at the Institute of Biotechnology, Jaan-Olle Andressoo and Satu Kuure, will be presented later.

 

August 24, 2015

Hope for antivirals against parechoviruses

The Butcher and Wolthers labs as part of the AIROPico consortium have recently published an article providing an atomic model of human parechovirus 1. The atomic model was then used to define the epitopes and modes of neutralization for two potential therapeutic antibodies against human parechovirus 1.

Parechoviruses are medically-relevant human pathogens causing mild to severe infections. Currently there are no vaccines or antivirals against them. The Butcher and Wolthers labs as part of the AIROPico consortium in collaboration with the company AIMM Therapeutics, have recently published an article in the Journal of Virology providing an atomic model of human parechovirus 1.

The atomic model was then used to define the epitopes and modes of neutralization for two potential therapeutic antibodies against human parechovirus 1. These human monoclonal antibodies show cross-neutralization against other human parechoviruses as well.

The AM18 antibody recognizes arginine-glycine-aspartic acid motif present on viral capsid protein 1 and neutralizes the virus by competing with the cellular receptor which also recognizes the same motif. The AM28 antibody neutralizes by binding to a conformational epitope and blocking the viral RNA release site.

"This is a first step towards developing therapies against parechoviruses which is one of the long term goals of AIROPico," says Research Director Sarah Butcher.

The study was supported by the Seventh Framework Programme of the European Union AIPP under contract PIAPP-GA-2013-612308 (AIROPico), the Academy of Finland, the Sigrid Juselius Foundation, the Netherlands Organisation for Health Research and Development, The AMC Research Council, the European Molecular Biology Organization and the European Society of Clinical Virology.

Image: Pasi Laurinmäki (the model of antibody binding to human parechovirus 1.)

June 3, 2015

Cytoskeletons shaking hands

Cytoskeletal systems collaborate with each other in animal cells. Post-doctoral researcher Yaming Jiu has revealed that cytoplasmic intermediate filaments interact with arcs,  specific contractile actin filament structures which transport intermediate filaments from cell periphery toward the nucleus.

Animal cells harbor three types of cytoskeletal elements: actin filaments, intermediate filaments and microtubules. Despite their name, cytoskeletons are very dynamic structures, which undergo rapid reorganization in cells and thus contribute to numerous cellular processes, such as morphogenesis, motility, intracellular transport, and cell division. Consequently, defects in cytoskeletal structures lead to various diseases, including cancer and neurological disorders.

Different cytoskeletal systems do not function in isolation, but collaborate with each other in cells. Post-doctoral researcher Yaming Jiu working at the Institute of Biotechnology, University of Helsinki has now revealed that cytoplasmic intermediate filaments interact with specific contractile actin filament structures called arcs.

"Actin arcs transport intermediate filaments from cell periphery toward the nucleus. Consequently, disruption of actin arcs led to an abnormal spreading of the intermediate filament network toward the cell periphery and associated defects in cell morphogenesis. Intermediate filaments resist the movement of arcs, and their depletion led to abnormalities in the shape of the arc-rich leading edge of motile cells," describes research director Pekka Lappalainen.

This study provides the first example of specific actin filament structures functionally interacting with intermediate filaments, and proposes that interplay between different cytoskeletal systems is crucial for diverse cellular and physiological processes.

The work was carried out in collaboration between the groups of Pekka Lappalainen and Markku Varjosalo at the Institute of Biotechnology, and John Eriksson’s group at the Turku Centre for Biotechnology.

Jiu Y, Lehtimäki J, Tojkander S, Cheng F, Jäälinoja H, Liu X, Varjosalo M, Eriksson JE, Lappalainen P. Bidirectional Interplay between Vimentin Intermediate Filaments and Contractile Actin Stress Fibers. Cell Press 28 May 2015. (PubMed)

Pekka Lappalainen research group

May 13, 2015

New Academy Research Fellowships to BI

Andrii Domanskyi, Ville Paavilainen, Laura Ahtiainen, Markku Varjosalo and Sari Tojkander have been awarded the Academy Research Fellowships.

Anddrii Domanskyi works as a postdoctoral researcher in Mart Saarma’s group. In his research project “Neuroprotective microRNAs, trophic factors and stress in adult dopaminergic neurons: significance for Parkinson’s disease” Domanskyi aims to identify specific neurotrophic factor induced microRNAs that are essential for neuronal survival and are able to prevent the degeneration of dopaminergic neurons. The work may lead to the development of novel therapies to treat Parkinson's disease.

In project “Translocational regulation of protein biogenesis” Group Leader Ville Paavilainen proposes to reveal the mechanism by which a unique small-molecule Sec61 inhibitor achieves its substrate-selectivity. Additionally, the project aims to identify the cellular roles of a conserved translocon component whose inhibition can be utilized for therapeutic purposes.

Laura Ahtiainen is from Irma Thesleff’s group. Her project “Imaging cellular mechanisms of epithelial morphogenesis in development and disease” focuses on the cellular events that lie between the genetic signaling networks and observed phenotypes in transgenic mouse models.

In Group Leader Markku Varjosalo’s project “Human Kinome and Cancer” his team will identify the phosphorylation mediated informational flow and map the architecture and dynamics of molecular networks that have important clinical implications for cancer.

Sari Tojkander has been working in Pekka Lappalainen lab. She will start her own group in the Faculty of Veterinary Medicine and continue her research project “Cellular forces in breast cancer” there. In this project she is in understanding how tumor stroma influences the major force-producing actomyosin structures in breast cancer cells and how the consequent changes in intracellular force-production affects the ability of these cancer cells to scatter and invade.

The funding for Academy Research Fellows is granted for five years and the funding period is set to start in September.

Director Howy Jacobs congratulating Andrii Domanskyi

Photo: Tinde Päivärinta

April 28, 2015

Tommi Kajander’s team received 0.47M€ funding for structural studies of membrane proteins of the synapse

Grant from Jane and Aatos Erkko Foundation allows the group to expand on the studies of the synaptic integral membrane proteins.

Team leader Tommi Kajander received 470 k€ from Jane and Aatos Erkko foundation to study the structural biology of neuronal synaptic adhesion proteins and integral membrane proteins.

"The aim is to continue the structural and functional studies of synaptic adhesion molecules and their ligands. We have already recently crystallized some of them and solved some of their structures," Tommi Kajander says.

The most important goal of the Erkko funding according to Kajander is to expand on the studies of the synaptic integral membrane proteins. For most of these only structures of bacterial homologs are known.

"Our aim is to develop protein engineering and expression techniques towards solving structures of vertebrate synaptic proteins such as the voltage gated Ca2+ channel and other synaptic and neuronal membrane protein targets. "

The group also wishes to use imaging techniques of synaptic adhesion with fluorescence and electron microscopy to look at larger scale structures induced by the adhesion protein expression at the neuronal synapses.

All of the proteins studied are involved in neurological diseases and disorders, such cognitive disorders and epilepsy, stroke and pain and migraine. Therefore the structural and functional results will have important impact on understanding these diseases and the maintenance of synaptic functions overall.

Tommi Kajander team

April 24, 2015

Looking to fossils to predict tooth evolution in rodents

Fifty million years ago, all rodents had short, stubby molars – teeth similar to those found in the back of the human mouth, used for grinding food. Over time, rodent teeth progressively evolved to become taller, and some rodent species even evolved continuously growing molar teeth. A new study published in the journal Cell Reports predicts that most rodent species will have ever-growing molars in the far distant future

“Our analyses and simulations point towards a gradual evolution of taller teeth, and in our future studies we will explore whether tinkering with the genetic mechanisms of tooth formation in lab mice—which have short molar teeth—will replicate the evolution of taller teeth,” says co-senior author Ophir Klein, an associate professor at the University of California San Francisco School of Dentistry.

For their research, Dr. Klein and his colleagues used fossil data from thousands of extinct rodent species to study the evolution of dental stem cells, which are required for continuous tooth growth. They found evidence that most of the species possess the potential for acquiring dental stem cells, and that the final developmental step on the path toward continuously growing teeth may be quite small. "Just studying how molars become taller should tell us about the first steps in the arrival of stem cells," Klein says

The team’s computer simulations predict that rodents with continuously growing teeth and active stem cell reserves will eventually outcompete all other rodent species, whose teeth have a finite length. This won’t likely apply to people, however.

“As we humans have short teeth, evolutionarily speaking we would have to go through multiple steps that would take millions of years before we could acquire continuously growing teeth. Obviously, this is not something that would happen as long as we cook our food and don’t wear down our teeth,” says co-senior author Jukka Jernvall, an evolutionary biologist at the University of Helsinki, in Finland. “However, regarding rodents, it will be interesting to resolve the regional and taxonomic details of the 50 million year trend.”

Tapaltsyan V, EronenJT, Lawing AM,Sharir A, Janis C, Jernvall J, and Ophir, Klein OD. Continuously growing rodent molars result from a predictable quantitative evolutionary change over 50 million years. Cell Reports 2015; 11: 1–8.

Article in Cell Reports

Image: Vagan Tapaltsyan and Ophir Klein

April 13, 2015

Connecting industry and academia

Dr Toomas Neuman spent two months in Finland creating wider networks and planning new business enterprises. This was made possible by AIROPico, a Marie Curie Industry – Academia Partnership and Pathways Grant within the EU’s Seventh Framework Programme, promoting staff exchanges between industry and academia in the picornavirus field.

CSO Toomas Neuman of an Estonian company Protobios has had a busy two month period in Finland. Since January, he has been taking part of all kinds of activities within AIROPico, a project generating more knowledge on infections caused by human picornaviruses. The project is also a part of another project creating contacts between enterprises and academia.

"Actually, this collaboration came in a good time. I am a molecular cell biologist and as such not familiar with analysing techniques for viruses," says Toomas Neuman, who has been doing business in the biotechnology field both in the U.S. and in Estonia since 1999.

Dr Neuman's time in Finland has been divided between contacts in Helsinki, Turku and Tampere. In the University of Helsinki he has been collaborating with Sarah Butcher's research group in the Institute of Biotechnology, attending seminars, giving lectures, taking part in workshops and generally getting to know people.

"Connections are important. My main target here is community building. That works better in Europe than in the U.S. as the grant system here forces you to find partners. In the U.S. you are more on your own."

In Helsinki Dr Neuman put together a group of students interested in starting a business of their own.

"We went through all the procedures step by step, so now the students know what it takes to build up a company. It is essential to realise that you need partners in creating a successful company. As a researcher, you can start one, but you cannot bring it much further without any money. And most researchers don't have all the business knowledge even if they have the best knowledge of their own field of science. So you will need connections."

Dr Neuman has for years had connections in Finland. He has collaborated with for example Professor Mart Saarma and Professor emeritus Antti Vaheri.

"Professor Vaheri and others have found out that a small number of vaccinated people – using one particular type of flu vaccine – develop narcolepsy. Collaborative research has identified that vaccinated people who develop narcolepsy developed antibodies that target sleep center in the brain and can be related to development of narcolepsy", Dr Neuman says.

Dr Neuman with his Finnish collaborators is planning to establish a new company in Finland to explore further the possibilities of this find. He also wants to encourage the researchers to start thinking about new possibilities. "Often the big things in science happen somewhere else than in small countries like Finland, Estonia and Sweden. We have to try to get those things happen here, too! But that needs work, and you can get nowhere without collaboration," Dr Neuman says.

Text and photo: Elina Raukko

April 7, 2015

Stem cells age-discriminate organelles to maintain stemness

Study suggests that asymmetric apportioning of old cellular components during cell division may represent an anti-aging mechanism by stem cells.

Tissue stem cells, that continuously renew our tissues, can divide asymmetrically to produce two types of daughter cells. One will be the new stem cell, where as the other will give rise to the differentiating cells of the tissue.

A study jointly lead by laboratories in the Institute of Biotechnology and Massachusetts Institute of Technology (MIT) investigated whether stem cells may also use asymmetric cell division to reduce accumulation of cellular damage. Damage buildup can cause stem cell exhaustion that results in reduced tissue renewal and aging.

Researchers developed a novel approach to follow cellular components, such as organelles, age-selectively during cell division.

“We found that stem cells segregate their old mitochondria to the daughter cell that will differentiate, whereas the new stem cell will receive only young mitochondria” says Pekka Katajisto, a Group leader and Academy research fellow at BI.

Mitochondria appear to be particularly important for stem cells, as other analyzed organelles were not similarly age-discriminated, and since inhibition of normal mitochondrial quality control pathways stopped their age-selective segregation.

“There is a fitness advantage to renewing your mitochondria,” says David Sabatini, Professor at MIT and Whitehead Institute. “Stem cells know this and have figured out a way to discard their older components.”

While the mechanism used by stem cells to recognize the age of their mitochondria remains unknown, forced symmetric apportioning of aged mitochondria resulted in loss of stemness in all of the daughter cells. “This suggests that the age-selective apportioning of old and potentially damaged organelles may be a way to fight stem cell exhaustion and aging,” says Katajisto.

Katajisto laboratory is now exploring how old mitochondria differ from old, and whether this phenomenon occurs in other cell types beyond the human mammary stem-like cells examined here as well as in in vivo.

Human mammary stem-like cell apportions aged mitochondria asymmetrically between daughter cells. Mitochondria were labeled age-selectively red 51 hours prior to imaging, leaving mitochondria that are younger unlabelled. The daughter cell that will become the new stem cell (bottom left) receives only few old mitochondria.

Katajisto P, Döhla J, Chaffer C, Pentinmikko N, Marjanovic N, Iqbal S, Zoncu R, Chen W, Weinberg RA, Sabatini DM. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. Science. 2015 Apr 2. pii: 1260384. [Epub ahead of print]

Article in Science

Katajisto lab

Picture: Julia Döhla

March 30, 2015

€ 0,9 M as grants from the Sigrid Juselius Foundation

According to the decision made on 18 March, Sigrid Juselius Foundation is financing 17 researchers in the Institute of Biotechnology with grants worth almost € 900,000. About € 200,000 of the total is directed to young research group leaders.

The researchers of the Institute of Biotechnology (BI) have been given almost € 0.7 M as established researchers' grants by the Sigrid Juselius Foundation. The established researchers' share in the BI is about 7.6 % of the total amount of the grants of their category.

The new and continued grants given by the SJF for new group leaders were worth € 1.16 M.  The Institute's share of those grants – almost € 0.2 M – was about 16.5 per cent of the total.

Grants for young research group leaders

Airavaara Mikko
Fagerholm Susanna 
Katajisto Pekka
Kuure Satu
Paavilainen Ville
total € 191 000

Grants for established researchers

Butcher Sarah
Hideo Iwai
Hietakangas Ville  
Jacobs Howard 
Lappalainen Pekka  
Mikkola Marja
Ojala Päivi   
Permi, Perttu  
Saarma Mart  
Shimmi Osamu  
Thesleff Irma  
Vartiainen Maria
total € 699 500

Sigrid Juselius Foundation grants 18 March 2015

March 23, 2015

SPPS Early Career Award to Ari Pekka Mähönen

SPPS Early Career Award is a monetary award to an early career scientist based in Scandinavia. The award is granted to a young, highly talented scientist, who has shown good progress and made significant, independent contributions to Scandinavian plant biology.

This time the Award was decided to give to two equally qualified young scientists, Dr. Ari Pekka Mähönen from the Institute of Biotechnology and Dr. Nathaniel Street, from Umeå University.

Societas Physiologiae Plantarum Scandinavica (SPPS) is an international society based in Scandinavia promoting experimental plant physiology from molecular biology to ecophysiology.

More information in the SPPS Newsletter

March 19, 2015

Recognition to several leading researchers and staff of the Institute

University rector Jukka Kola has recognized the outstanding contributions of 37 UH employees, including Group Leader Petri Auvinen, Research Technicians Merja Mäkinen, Riikka Santalahti, Technician Anna-Liisa Nyfors and Academician Irma Thesleff from BI, by the award of a special medal of honour.

In his speech Kola mentioned that the recipients have, as a members of the scientific community, met researchers, students and a wide range of customers for many years and made a significant contribution to University and society.

Golden scientific community medal may be granted at least 30 years in the service of the scientific community. It is granted by the Federation of Finnish Learned Societies.

More in Flamma

March 17, 2015

New collaborative effort among Nicolas Di-Poi’s Laboratory and Finnish herpetologists for researching craniofacial patterning and evolution in snakes

In collaboration with the tropical zoo “Tropicario” in Helsinki, Dr Nicolas Di-Poi’s Laboratory obtained about 25 large eggs of about 100 mm from African rock python (Python sebae), the Africa's largest snake and one of the five largest snake species in the world (specimens may approach or exceed 6 m). The female snake incubates them for about 3 months and aggressively defends her eggs.

Di-Poi’s Laboratory is using non-classical model organisms at key phylogenetic positions and showing high levels of morphological variation/innovation for studying the Evo-Devo of craniofacial tissues. Developing python embryos from those eggs will be used for understanding how the developmental genetic program has evolved to generate the impressive morphological diversity of skull bones in snakes.

Di-Poi Lab

Tropicario

Picture: Jarmo Lanki

March 5, 2015

New information on Parkinson’s disease: neural growth factor GDNF not needed by the midbrain dopamine system

Recent Finnish study overturns results from seven years ago.

A key factor in the motor symptoms associated with Parkinson’s disease is the gradual degeneration and death of dopamine neurons. The glial cell-derived neurotrophic factor, or GDNF, has been proven to protect dopamine neurons in test tube conditions and in animal models for Parkinson’s disease. GDNF and its close relative, neurturin, have also been used in experimental treatments of patients with severe Parkinson’s disease. The results have been promising, but vary widely in terms of efficacy. At the moment, two companies are conducting tests to determine the clinical effects of GDNF on Parkinson’s sufferers.

According to an article published in Nature Neuroscience in 2008, removing GDNF from adult mice through gene technology causes significant damage to the midbrain dopamine system as well as triggers motor disorders. The article concluded that GDNF is vital to the maintenance and function of dopamine neurons in adult animals.

At the same time, Academy of Finland Research Fellow Jaan-Olle Andressoo, from Professor Mart Saarma’s research group at the Institute of Biotechnology, had developed a mouse model that was equivalent to the model used in the other study, with minor technical differences. In Andressoo’s model, GDNF was removed from the central nervous system towards the end of the fetal period through gene deletion, and the mice remained healthy until high age. They studied the brains of the GDNF knockout mice together with the research group of University Lecturer Petteri Piepponen, based in the Faculty of Pharmacy.

“We decided to confirm the previous result using the mouse model Andressoo developed, and noticed that the complete absence of GDNF did not cause significant changes to the number or function of dopamine neurons. Since the result surprised us, we wanted to verify it using two alternative methods, one of which was identical to the method in the previously published article,” explains Dr Jaan-Olle Andressoo.

In addition, some of the experiments were conducted in parallel at Professor Anders Björklund’s laboratory at Lund University. The Lund tests similarly indicated no changes to the dopamine systems or the behaviour of the mice. This clearly established that GDNF is not a necessary component of the maintenance of midbrain dopamine system.

The manuscript including the new research results was approved for publication in the same series as the previous study – in a respected Nature Neuroscience journal. However, the study was subjected to even closer scrutiny than is associated with the normal publication procedure.

“The editors considered the manuscript to be a correction, so in addition to the normal peer review, they sent it to the researchers who published the previous results for comments. Ultimately, our results were deemed indisputable.”

Kopra J, Vilenius C, Grealish S, Härma MA, Varendi K, Lindholm J, Castrén E, Võikar V, Björklund A, Piepponen TP, Saarma M, Andressoo JO. GDNF is not required for catecholaminergic neuron survival in vivo. Nat Neurosci. 2015 Feb 24;18(3):319-22

Article in Nature Neuroscience

February 23, 2015

Mart Saarma has been appointed Vice President of the European Research Council

Professor Mart Saarma has been appointed Vice President of the European Research Council. He will take over the Life Sciences domain. He was already serving as ERC Scientific Council member since 2011.
The ERC Scientific Council represents the European scientific community, and decides the ERC strategy and distribution of funding.

Prof. Saarma has studied the structure, biology and therapeutic potential neurotrophic factors and their receptors. His recent studies are focused on the role of neurotrophic factors in development and neurodegenerative diseases. His group has characterised several new GDNF family receptors and demonstrated that RET receptor tyrosine kinase is the signalling receptor for GDNF. Recently his group has discovered a new neurotrophic factor CDNF and shown that it very efficiently protects and repairs dopamine neurons in animal models of Parkinson’s disease. He has received several domestic and international science prizes, including the Nordic Science Prize by Lundbeck Foundation in 2009. He is the member of several academies and EMBO. Currently he is the member of EMBO Council and Vice President of the European Research Council.

More information

ERC

January 14, 2015

A novel role for mRNA export factor Ddx19/Dbp5 in nuclear import of MKL1 identified

RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1

Controlled transport of macromolecules between the cytoplasm and nucleus is essential for homeostatic regulation of cellular functions. For instance, gene expression entails coordinated nuclear import of transcriptional regulators to activate transcription and nuclear export of the resulting mRNAs for cytoplasmic translation.

Kaisa Rajakylä from the research group of Dr. Maria Vartiainen has now linked these two processes by reporting a novel role for Ddx19/Dbp5, an established mRNA export factor and translation regulator, in nuclear import of MKL1, the signal-responsive transcriptional activator of SRF.

They show that Ddx19 is not a general nuclear import factor, and that its specific effect on MKL1 nuclear import is separate from its role in mRNA export. Mechanistically, Ddx19 operates by modulating the conformation of MKL1, which affects its interaction with Importin-b for efficient nuclear import. They thus propose that Ddx19 plays an important role in coordinating the key nucleo-cytoplasmic shuttling events in gene expression by linking transcriptional activation, mRNA export and translation.

In serum stimulated MCF7 cells MKL1-GFP (green) is nuclear (left), but becomes more cytoplasmic in cells depleted with Ddx19 (right). Nucleus is stained with dapi (blue).

Rajakylä EK, Viita T, Kyheröinen S, Huet G, Treisman R, Vartiainen MK. RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1. Nat. Commun. 6:5978 doi: 10.1038/ncomms6978 (2015).

Article in Nature Communications

Vartiainen lab

Text and picture: Maria Vartiainen and Kaisa Rajakylä

December 2014

December 17, 2014

Grant for Mart Saarma group for researching the regeneration of dopaminergic neurons in vivo

Parkinson's UK has granted Professor Mart Saarma, Yulia Sidorova and Merja Voutilainen a grant of £35,000 over 8 months. This is the first time the British organization has given a grant to Finnish researchers.

– We plan to develop orally administrable small molecules that act similarly to glial cell line-derived neurotrophic factor (GDNF). GDNF has earlier been recognized as a possible eliminator of the cause of Parkinson's disease. However, there are problems with the use of GDNF as such as it diffuses poorly, is expensive and does not penetrate blood-brain barrier. So we aim at molecules that could work better in this to support suffering neurons in the brains of Parkinson's disease patients, says Professor Mart Saarma.

The group has already identified several candidate molecules which activate GDNF receptors in immortalized cells and showed that one of them promoted survival of dopamineric neurons in vitro.

– In addition we have another candidate compound that has not yet been tested on dopaminergic neurons. It's ability was better that that of GDNF family member artemin to stimulate neurite outgrowth from sensory neurons.  We would like to test the activity of the the latter molecule towards survival of dopaminergic neurons and test both GDNF mimetics in animal model of PD.

Mart Saarma group

Parkinson's UK

December 15, 2014

Academy Professor Howard Jacobs will start as the Director of BI in March 2015

Howard Jacobs (b. 1955) is one of the world’s most distinguished and creative scientists in the field of mitochondria research, and one of only a handful of world-leading scientists based in Finland. Jacobs’ team uses both mammalian cell and fruit fly (Drosophila) models to analyse mitochondrial DNA replication and expression, to study the involvement of mitochondrial DNA in human disease and ageing, and to test strategies for therapy.

His research forms a critical link between basic and applied clinical research: the results coming out of his basic research can be put to immediate use both in the treatment of patients with mitochondrial diseases and in the treatment of many ageing-related diseases.

Professor Jacobs took his PhD at the University of Glasgow in 1981. In 1981–1983, he worked as a postdoctoral researcher in California, and then returned to Glasgow. Since 1996, he has served as Professor of Molecular Biology at the University of Tampere, and since 2006 as Academy Professor. He is Director of the Finnish Centre of Excellence in Research on Mitochondrial Disease and Ageing which includes groups both in Tampere and Helsinki.

Picture: Jacobs group

Jacobs group in University of Tampere

November 25, 2014

Ari Helenius Symposium

BI arranged a special mini symposium to celebrate the recent 70th Birthday of Professor Ari Helenius and to honor Ari's impact and efforts for our University and the Institute.

Ari Helenius served as the SAB chairman of the Institute of Biotechnology for several years, was a member of the Helsinki University board for the last 4 years, and is a highly appreciated scientist , mentor, colleague and friend for many here in Finland.

The symposium took place on Thursday November 20, 2014. The program started with the opening by Chancellor Thomas Wilhelmsson. After opening words the Chancellor gave Ari the University of Helsinki Silver Medal for his achievements.  The symposium program consisted of presentations by Ari himself as well as his former colleagues, collaborators, postdocs and PhD students.

November 14, 2014

New mechanism for growth control discovered

Research on Drosophila reveals that once activated during starvation, this regulatory system prevents the secretion of insulin like peptides, the counterparts of IGF and insulin in mammals.

Animal growth is closely regulated by environmental factors such as nutrition. If the nutrition of a growing animal is limited, growth slows down and the eventual size of the animal remains smaller. Insulin-like signaling plays a key role in coordinating growth in response to dietary status in multicellular animals.

Doctoral student Kiran Hasygar and Assistant Professor Ville Hietakangas from the Department of Biosciences and Institute of Biotechnology, have now uncovered a new regulatory mechanism coordinating animal growth in response to nutrition.

By genetic screening in the fruit fly Drosophila melanogaster, Hasygar and Hietakangas identified several new genes that are involved in the activation of insulin-like signaling.

The most important finding was a new regulatory system that senses nutrient deprivation and inhibits growth. Once activated during starvation, this regulatory system prevents secretion of insulin-like peptides, which are the Drosophila counterparts of IGF and insulin.

– A key component of the regulatory system is protein kinase ERK7. The physiological function of this atypical MAP kinase has previously been poorly understood, but now we are the first to have found an in vivo role for it, Assistant Professor Ville Hietakangas says.

Inhibition of insulin-like peptide secretion (right-hand side) leads to reduced body size in Drosophila.

Hasygar K, Hietakangas V. p53- and ERK7-Dependent Ribosome Surveillance Response Regulates Drosophila Insulin-Like Peptide Secretion. PLoS Genet. 2014 Nov 13;10(11):e1004764

Article on PLOS Genet

Hietakangas lab

Picture: Hietakangas lab

November 12, 2014

A new mechanism controlling proper organization of muscle sarcomeres indentified

Muscle-specific protein cofilin-2 controls the length of actin filaments in muscle cells.

Sliding of myosin and actin filaments past each other provides the force for muscle contraction. In contrast to most non-muscle cells, the actin filaments in muscle sarcomeres are of precise length and relatively stable. Defects in the organization of these actin filament arrays result in various heart and muscle disorders, such as myopathies.

The research group of professor Pekka Lappalainen has now revealed a new mechanism that is essential for the correct organization of sarcomeres.

"We discovered that a muscle-specific protein cofilin-2 ’trims’ the ends of sarcomeric actin filaments to control their precise length. To this end, cofilin-2 is specific in that it can also disassemble ATP-actin segments, which are expected to be present in the ends of sarcomeric actin filaments," Pekka Lappalainen explains.

These findings also explain why mutations in cofilin-2 gene result in nemaline myopathy.

Microscopy image of a cultured cardiomyocyte, where actin is visualized in red and alpha-actinin in green.

Article in Developmental Cell

Photo: Elena Kremneva

November 4, 2014

Professor Yrjö Helariutta’s research team recruited to University of Cambridge

Yrjö Helariutta, professor of developmental plant biology, has been recruited to the University of Cambridge to continue his work there in the same capacity. Some of the members of Professor Helariutta’s research group, approximately ten researchers in the Arabidopsis team, will move from Viikki to England.

Other members of the group, a handful of researchers focusing on vascular plants, will remain at the Institute of Biotechnology, with Helariutta serving as their telecommuting superior.

The work of the vascular plant team and the Arabidopsis team is closely interconnected. Arabidopsis is known as the “fruitfly of the plant world”, a model organism which enables researchers to study the functions of genes quickly and cost-effectively in a laboratory setting. Many of the plant’s basic biological functions are identical to those of large trees.

The Arabidopsis research in Cambridge can be characterised as typical basic research, and its publication profile is very prominent. Meanwhile, the wood research in Helsinki is more applied, and thus of more interest to industry.

Yrjö Helariutta's research group

Professor Yrjö Helariutta’s research team recruited to Cambridge

Photo: Veikko Somerpuro

October 30, 2014

Professor Irma Thesleff elected to Foreign Associate membership of the Institute of Medicine of the National Academies

The Institute of Medicine (IOM) announced the names of 70 new members and 10 foreign associates during its 44th annual meeting. Academician Irma Thesleff is one of the new associate members. Election to the IOM is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.

New members are elected by current active members through a selective process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care, and public health. The newly elected members raise IOM's total active membership to 1798 and the number of foreign associates to 128. With an additional 86 members holding emeritus status IOM's total membership is 2012.

Newly elected members of the Institute of Medicine

IOM

October 28, 2014

Integrins losing their grip drive reprogramming of dendritic cells and activate T cell immune responses

When integrins let go of their ligands and the actin cytoskeleton inside the dendritic cell, the activity of another cell surface receptor, the GM-CSF receptor, rises. This increased signaling induces the dendritic cells to head to lymph nodes to activate T cells.

Integrins are adhesion molecules expressed on the surface of cells. They play a crucial role in “integrating” the cell exterior and the interior cytoskeleton in cells.  The beta2-integrin family members are highly expressed in dendritic cells that are very important in immune responses. Dendritic cells pick up antigens in inflamed tissues and move to lymph nodes where they present the antigen to T cells and activate them to help fight infection.

Dr Susanna Fagerholm's groups at the Institute of Biotechnology in Helsinki and at the University of Dundee, UK, found out that one of the first steps in this activation chain is taken when the integrins lose their grip of their ligands in tissues and the actin cytoskeleton inside the dendritic cells.

– This leads to increased signaling through another cell surface receptor, the GM-CSF receptor, in dendritic cells. The increased signaling results in reprogramming of the dendritic cells to a mature, migratory phenotype and induces them to migrate to lymph nodes to activate T cells, says Susanna Fagerholm.

Susanna Fagerholm’s research teams in Helsinki and Dundee, and collaborators in Dundee, Glasgow and Manchester, used a novel knock-in mouse model of the beta2-integrin and in vivo immunological assays, combined with next generation RNA sequencing technology to investigate the roles of beta2-integrins in dendritic cells.

– Better understanding of this chain of events may help in the design of targeted therapies to block unwanted immune responses, such as those associated with autoimmunity. This type of research may also help to design more effective immune-based cancer therapies.

Morrison VL, James MJ, Grzes K, Cook P, Glass DG, Savinko T, Lek HS, Gawden-Bone C, Watts C, Millington OR, MacDonald AS, Fagerholm SC. Loss of beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype. Nat Commun. 2014 Oct 28;5:5359.

Article in Nature Communications

Fagerholm group

October 15, 2014

Novel mechanism affecting cell migration discovered

GMF protein controls the size and lifetime of protrusions in migrating cells.

Cell migration is important for development and physiology of multicellular organisms. During embryonic development individual cells and cell clusters can move over relatively long distances, and cell migration is also essential for wound healing and many immunological processes in adult animals. On the other hand, uncontrolled migration of malignant cells results in cancer invasion of metastasis.

Cell migration has mainly been studied in cell culture environment. However, in animal tissues cells predominantly migrate in a three-dimensional environment, where they have to push through adjacent cell-layers and extracellular matrix. Migrating cells are known to form dynamic protrusions at their leading edge, but the function of these actin-rich protrusions has remained elusive.

By using fruit fly as a model system, Minna Poukkula working at the Institute of Biotechnology, has now elucidated how actin-rich protrusions contribute to cell migration in animal tissues. She revealed that GMF, a protein that promotes the disassembly of branched actin filament networks, controls the size and lifetime of protrusions in border cell clusters migrating in fruit fly egg chambers. Importantly, diminished protrusion dynamics in GMF-deficient flies correlated with problems in border cell cluster migration.

- These findings demonstrate that efficient actin filament disassembly by GMF is essential for rapid dynamics of cell protrusions, and that this dynamics are important for cell migration in a three-dimensional tissue environment, says Minna Poukkula from the research group of Pekka Lappalainen

Fruit fly border cells form clusters of 6-8 cells, which display directional migration in egg chambers (from left to right in the image). Egg chamber is in red and border cells (their actin cytoskeletons) are in green. Please note that border cells display protrusions that are important for their migration in the tissue environment.

Poukkula M, Hakala M, Pentinmikko N, Sweeney MO, Jansen S, Mattila J, Hietakangas V, Goode BL, Lappalainen P. GMF Promotes Leading-Edge Dynamics and Collective Cell Migration In Vivo. Curr Biol. 2014 Oct 8. pii: S0960-9822(14)01130-0. doi: 10.1016/j.cub.2014.08.066. [Epub ahead of print] (PubMed)

Video
Fruit fly border cells form clusters of 6-8 cells, which display directional migration during oogenesis. Migration of border cells in egg chambers can be examined in detail by live-cell microscopy. Egg chamber is in red and border cells (their actin cytoskeletons) are in green. Please note that border cells display protrusions that are important for their migration in the tissue environment. The movie represents an approximately 2-hour time window of a fruit fly egg chamber.

October 10, 2014

PhD Kustaa Multamäki is the new Head of Administration of the Institute of Biotechnology

Kustaa Multamäki has started as the Head of Administration of the Institute of Biotechnology. He was born in Helsinki and did his doctoral thesis in 1999 on general history. Dr. Multamäki has from 2002 to 2014 worked as a Science Advisor in the Academy of Finland. He has also experience from University of Helsinki research institutes as he acted as Head of Development at the Helsinki Collegium for Advanced Study between 2009-2011.

October 1, 2014

Professor Irma Thesleff appointed a member of the Strategic Research Council of the Academy of Finland

The Finnish Government has appointed the Strategic Research Council of the Academy of Finland. The Council selects the projects to be funded in the strategic research programmes. The chair of the Council is Research Director Per Mickwitz from the Finnish Environment Institute. From the eight members of the council, two come from the University of Helsinki: Academician, Professor Irma Thesleff from the Institute of Biotechnology and Academy Professor Markku Kulmala from the Division of Atmospheric Sciences.

Other members (in Finnish)

September 8, 2014

Genome of the Glanville fritillary opens a window to chromosome evolution in Lepidoptera

Four  research groups from Genome biology program (Auvinen, Frilander, Holm, and Schulman) together with Academy professor Ilkka Hanski from biosciences department have sequenced the genome of Glanville fritillary butterly (Melitaea cinxia). The genome project, published in Nature Communications, represents the culmination of many years of collaborative work, not only among scientists on the Viikki campus, but also with researchers from the Kumpula campus (Esko Ukkonen and Veli Mäkinen), Turku University (Niklas Wahlberg), Karolinska Institutet in Stockholm (Minna Taipale), and the European bioinformatics Institute at Hinxton, UK (Daniel Lawson) as well as elsewhere.

The Glanville fritillary genome is the first eukaryotic genome sequenced, assembled, and annotated de novo in Finland. It is only the fifth published genome from the Lepidoptera and consists of 390 Mb of DNA. The majority of the genome (70%) could be localized to the mapped chromosomes. The structures and functions genome of the ca. 16000 genes found in the genome were predicted by using a suite of bioinformatic approaches. An integral part of the project was the construction of a high-resolution linkage map, which allowed precise placement of the genes and scaffolds onto the larger chromosomal framework. This in turn enabled chromosome level comparative analyses within Lepidoptera. These analyses revealed unique features of chromosome the Lepidopteran karyotype evolution, namely the original number of chromosomes, the extremely high level of synteny among different lepidopteran species and unexpectedly conserved chromosome fusion dynamics among the Lepidoptera.

The basic number of Lepidopteran chromosomes was proposed, among others, by Academician Esko Suomalainen working at Genetics department at University of Helsinki  almost 50 years ago. Using the genome sequence, a group of selected annotated genes, and the linkage map, comparisons were made with similar data set from Bombyx mori (silkworm) and Heliconius Melpomene. The analysis revealed, gratifyingly, that 31 is the original number of chromosomes in Lepidoptera, as predicted by Suomalainen. This result was in this study further extended by Dr. Niklas Wahlberg from Turku University to cover large number of Lepidopteran species using comparative karyotype analysis.

Comparative analysis confirmed a high level of synteny, meaning that the genes stay on the same chromosomes, among the Lepidotera. This study extended the synteny analysis to cover at least 140 million years. This is a unique observation not seen in other groups of organisms such as mice and men. The truly surprising result came from the comparative analysis of so-called fusion chromosomes in other Lepidopteran species. In some species, such as in Bombyx and Heliconius a subset of chromosomes from the original n=31 set have been fused to yield smaller karyotypes. Unexpectedly, the present study revealed that the fusions are not random but seem to prefer those chromosomes that are the smallest in M. cinxia. More importantly, the chromosomes seem to maintain their unique identities even after the fusion, keeping a high level of synteny to the original pre-fusion chromosomes and resisting any rearrangements across the fusion boundary.  

Studying chromosomes of Lepidoptera has a long tradition in the University of Helsinki. The present study is a new chapter in a continuum of studies started by Professor Harry Federley, the founder of genetics in Finland, who in 1930’s determined the chromosome number in Melitaea cinxia. His successor, Academician Esko Suomalainen, performed pioneering work on the chromosomes of Lepidoptera and proposed that the original number of chromosomes would be the above-mentioned 31. The present study will open new avenues to investigate the evolution, ecology and molecular biology of Lepidoptera, a very abundant and diverse group of insects with more than 100 000 species. While some of these are used as model species in ecology (such as Glanville fritillary by Academy Professor Ilkka Hanski) and genetics, other are considered as pest causing significant losses of crop yields in agriculture worldwide.

Ahola V, Lehtonen R, Somervuo P, Salmela L, Koskinen P, Rastas P, Välimäki N, Paulin L, Kvist J, Wahlberg N, Tanskanen J, Hornett EA, Ferguson LC, Luo S, Cao Z, de Jong MA, Duplouy A, Smolander OP, Vogel H, McCoy RC, Qian K, Chong WS, Zhang Q, Ahmad F, Haukka JK, Joshi A, Salojärvi J, Wheat CW, Grosse-Wilde E, Hughes D, Katainen R, Pitkänen E, Ylinen J, Waterhouse RM, Turunen M, Vähärautio A, Ojanen SP, Schulman AH, Taipale M, Lawson D, Ukkonen E, Mäkinen V, Goldsmith MR, Holm L, Auvinen P, Frilander MJ, Hanski I. The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera. Nat Commun. 2014 Sep 5;5:4737. doi: 10.1038/ncomms5737.

Article in Nature Communications

August 25, 2014

Core mechanism of root growth identified

Academy Research Fellow Ari Pekka Mähönen and his colleagues have demonstrated how PLETHORA proteins and plant hormone auxin together orchestrate root growth.

During plant growth, dividing cells in meristems must coordinate transitions from division to expansion and differentiation. Three distinct developmental zones are generated: the meristem, where the cell division takes place, and elongation and differentiation zones. At the same time, plants can rapidly adjust their direction of growth to adapt to environmental conditions.

In Arabidopsis roots, many aspects of zonation are controlled by the plant hormone auxin and auxin-induced PLETHORA transcription factors. Both show a graded distribution with a maximum near the root tip. In addition, auxin is also pivotal for tropic responses of the roots.

Ari Pekka Mähönen with his group and Dutch colleagues has now found out with the help of experimentation and mathematical modelling how the two factors together regulate root growth. The results were published in Nature.

"Cell division in the meristem is maintained by PLETHORA transcription factors. These proteins are solely transcribed in the stem cells, in a narrow region within the meristematic cells located in the tip of the root. So PLETHORA proteins are most abundant in the stem cells," Ari Pekka Mähönen says (Figure 1.)

Outside the stem cells the amount of PLETHORA protein in the cells halves each time the cells divide. In the end there is so little PLETHORA left in the cells that they cannot stay in the dividing mode. This is when the cells start to elongate and differentiate (Figure 1.)

Auxin is the factor taking care of many aspects of root growth. If there is enough PLETHORA in the root cells, auxin affects the rate of root cell division. If there is little or no PLETHORA in the cells, auxin regulates cell differentiation and elongation. In addition to this direct, rapid regulation, auxin also regulates cell division, expansion and differentiation indirectly and slowly by promoting PLETHORA transcription. This dual action of auxin keeps the structure and growth of the root very stable.

When PLETHORA levels gradually diminish starting from the root tip upwards, the cell division, elongation and differentiation zones are created. And this inner organisation stays even if the growth direction of the root changes.

"The gravity and other environmental factors can change the auxin content of the cells, and quite rapidly. This all affects the growth direction of the root. And of course it is important for the plant to maintain the organization while directing their roots there where water and nutrients most likely are to be found."

 

Mähönen AP, Tusscher K, Siligato R, Smetana O, Diaz-Trivino S,Salojärvi J, Wachsman G, Prasad K, Heidstra R, Scheres B. PLETHORA gradient formation mechanism separates auxin responses. Nature doi:10.1038/nature13663

Mähönen lab

Figure: Mähönen group

August 11, 2014

The origin and loss of periodic patterning in the turtle shell

FiDiPro Professor Scott Gilbert’s group has examined the development and variation (normal and abnormal) of turtle scute formation. The team combined several approaches, integrating techniques from developmental biology, theoretical biology (computational modeling), and evolutionary biology (comparative morphology and phylogeny).

One can often recognize different species of turtles by the shape and pigmentation of their scutes (“Scutum” being the Latin word for shield), or modified scales, that cover the turtle shell in a tessellation. Scutes are interesting developmentally because they grow radially to cover the entire shell, and this growth must be coordinated with that of the underlying bones of the shell (though, the patterns of scutes and bones are different). Evolutionarily, scutes are interesting because few groups of turtles vary in the number of scutes on the carapace (dorsal part of the shell), and certain freshwater and marine taxa have lost these structures altogether.

Much progress has been made in the application of molecular genetic technologies to non-model organisms; however, the strict seasonal reproductive ecology of animals such as turtles can make the investigation of their developmental dynamics an odyssey. In the first season, the team discovered that an array of patterned placodes generates the scutes of the shell. The following summer, they added drugs to the culture media to look at candidate developmental signaling pathways, and found that the placodal pattern requires Shh, Bmp, and Fgf signaling to form properly. During the “off-season,” the team developed a computational model of scute formation, and hypothesized how both natural and abnormal variation is generated in turtle scutes. Finally, last summer, the hypotheses generated by the model were experimentally tested. The study was published in Development together with a cover image depicting the project.

Moustakas-Verho, J. E., Zimm, R., Cebra-Thomas, J., Seppälä, N. K.,Kallonen, A., Mitchell, K. L., Hämäläinen, K., Salazar-Ciudad, I.,Jernvall, J. & Gilbert, S. F. The origin and loss of periodic patterning in the turtle shell. Development 141: 3033-3039 (2014).

Article in Development

August 4, 2014

Evolutionary steps of teeth reproduced in the laboratory

Academy Professor Jukka Jernvall's group together with Isaac Salazar-Ciudad and Marja Mikkola at the Institute of Biotechnology and colleagues has fine-tuned mouse tooth morphology and produced step-wise transitions observable in the fossil record.

To reconstruct the tree of life of extinct animals, teeth are often the best, or even only evidence that paleontologists have at their disposal. Especially for mammals, the fine features of teeth are used to determine how fossil species are related to each other and modern animals.

In the past, biologists have studied mutant animals to discover how these fine features can help them reconstruct evolutionary history. However, the changes in the mutants are often too dramatic to be very informative.

Academy Professor Jukka Jernvall's group in the Institute of Biotechnology and colleagues have now discovered how to fine-tune the shape of a mouse tooth to produce the step-wise transitions observed in the fossil record. The results were published in the journal Nature.

In this evolutionary developmental biology (evo-devo) study, the researchers started from mutant mice in which the molar teeth are reduced to relatively simple cone shapes. Then, the researchers administered the protein of the mutant gene on cultured mouse molars in small, incremental steps.

The experiments revealed how cusps, the main features of teeth, reappeared in a step-wise fashion with increasing amounts of protein, and much in the same order that cusps have evolved in early mammal molars.

The researchers show how both rodents and carnivores follow the same rule of shape change suggested by the experiments. Finally, by adjusting another gene pathway in the mutant mice, teeth could be engineered to recapitulate some of the detailed cusp features present in the ancestors of rodents.

– This new research demonstrates that with advances in the study of the molecular regulation of development, it is now possible to produce intermediate morphologies that are relevant for studies of evolution. And for certain shapes appearing repeatedly in evolution, the answer may not be in the food but in the development, says Jukka Jernvall.

Harjunmaa, E., Seidel, K., Häkkinen, T., Renvoise, E., Corfe, I. J., Kallonen, A., Zhang, Z.-Q., Evans, A. R., Mikkola, M. L., Salazar-Ciudad, I., Klein, O. D. & Jernvall, J. Replaying evolutionary transitions from the dental fossil record.

Photos: Jukka Jernvall's group

August 4, 2014

Sieving for genes: developmental regulation of important plant phloem components discovered

Researchers at the Institute of Biotechnology have combined traditional genetic approaches with 3D reconstructions from scanning electron microscopy to discover and characterize genes regulating the development of plant sieve elements.

Sieve elements are a key component of phloem, the conductive tissue through which plants transport carbohydrates and a wide range of signalling molecules. Elongated cylindrical cells are capped at one end by a sieve plate and arranged end-to-end to form sieve tubes which in turn form a network throughout a plant's body.

“Sieve elements are very special cells which play an important role in carbon sequestration, yet so far very little has been known about their differentiation,” says Professor Yrjö "Ykä" Helariutta from the Institute of Biotechnology. “We've identified several genes regulating the process and characterized it with unprecedented precision.”

The results of the collaboration between the labs of Professor Ykä Helariutta and principal investigator Eija Jokitalo are published in a pair of papers appearing in Scienceand Nature Communications.

“Understanding how the phloem network develops is a significant aspect of plant development and could have important applications in biotechnology and synthetic biology,” describes Helariutta.

Programmed nuclear degradation during phloem development

Sieve elements lose their nucleus during the course of normal development. In the first paper, the team described how that happens and identified several genetic factors controlling the process. They used serial block-face scanning electron microscopy to reconstruct a 3D model of developing sieve elements from ultra-thin sections, enabling them to track enucleation of these cells.

The nucleus first deforms from a smooth sphere to a crumpled structure, before shrinking and loosing its contents into the cytoplasm, where they are degraded. This is coupled with the degradation of some organelles and shape changes of others.

The researchers identified two transcription factors, NAC045 and NAC086, which are expressed in sieve element cells before enucleation. Plants lacking both genes have defective sieve element formation and die at the seedling stage. Serial block-face scanning electron microscopy showed that sieve elements in the double mutant do not undergo enucleation.

Furthermore, by expressing NAC45 in cells where it isn't normally found, the researchers showed that it is sufficient to start the degradation of the nucleus and cytoplasm.
The researchers also identified a family of genes, dubbed NEN1-4, which act downstream of NAC045 and NAC086. Although the enucleation process starts in plants with mutations in these genes, it doesn't complete properly.

Control of choline transport is essential in phloem
A genetic screen identified the CHER1 gene, which encodes a choline transporter, as a crucial player in phloem development. In mutant plants, a fluorescent marker transported through the phloem failed to unload in the root tip, demonstrating defects in phloem transport. Further analysis revealed that the phloem strands are not continuous in the cher1 mutant, which also has short roots, abnormal roots hairs, and changes in the arrangement of the water-conducting xylem tissues.

CHER1 accumulates at one end of sieve element cells, collecting at the centre of the forming sieve plate. Examination with serial block-face scanning electron microscopy showed that mutant plants have smaller sieve plates with fewer, structurally-altered pores, inhibiting long-distance transport via the phloem.

“Control of choline transport is essential to form continuously connected phloem with proper sieve plates, but we still have to uncover the exact cellular processes involved,” says Helariutta.

Cell file undergoing sieve element differentiation in root as captured by msPI staining.

Photos: Helariutta group

June 11, 2014
Jukka Jernvall continues as an Academy Professor

The Board of the Academy of Finland has decided to fund seven new Academy Professors for the years 2014–2018. Jukka Jernvall is among the appointed Professors. The appointment is an extension to Jernvall's current Academy Professorship.

Academy Professor Jukka Jernvall is a recognised pioneer in the interdisciplinary field of evolutionary developmental biology. Using mammalian tooth development as a model, Jernvall has explored the biological principles that lie behind the individual’s three-dimensional phenotype. Jernvall’s current research focus is on sequencing the genome of the Saimaa ringed seal. Using mammalian tooth development as a model, Jukka Jernvall has explored the biological principles that lie behind the individual’s three-dimensional phenotype. Jernvall’s current research focus is on sequencing the genome of the Saimaa ringed seal.

Jernvall lab

May 14, 2014
L’Oréal-UNESCO “For Women in Science” award to Maria Vartiainen

Cosmetics company L’Oreal and UNESCO presents a grant of 15 000 € every second year for a young woman scientist working in the field of biosciences. The 2014 grant was awarded to Academy Research Fellow Maria Vartiainen for her innovative and pioneering research on nuclear actin, a protein belonging to the cytoskeleton.

Maria Vartiainen has worked as a Group Leader at the Institute of Biotechnology since 2007. Before that she did her post doctoral research at Cancer Research UK  in London. In 2012 she was awarded with a 1,5 million euro ERC starting grant.

The L’Oréal Foundation and UNESCO have rewarded scientific merit, encouraging young female researchers from all continents to join the program "For Women in Science" for the past 16 years.

Maria Vartiaiselle L'Orealin For Women in Science -apuraha

May 8, 2014
Researchers found a new protein supporting insulin-producing beta cells

Researchers in the Institute of Biotechnology have discovered that MANF protein promotes the proliferation and survival of insulin-producing beta cells in the pancreas. This finding may in the future help to treat and even to cure diabetes.

In diabetes, the number of beta cells in the pancreas diminishes and insulin production declines. Current medications can alleviate the symptoms of diabetes but their administration does not slow down or inhibit beta cell death and does not prevent the devastating micro- and macrovascular complications that follow with diabetes. Thus far, there is no effective treatment to promote the renewal of beta cells and thereby boost the secretion of insulin in the blood.

The research group led by Professor Mart Saarma of the Institute of Biotechnology, University of Helsinki, has previously shown that the MANF protein is important for the survival and protection of neurons in the rodent brain. The group has recently discovered that MANF is also fundamentally important for the proliferation and survival of beta cells in the mouse pancreas.

"We first developed and then studied mice which produce no MANF at all. These mice developed severe diabetes due to a progressive loss of beta cells. We then tested the effects of recombinant MANF protein on mouse beta cells in culture and discovered that the cells began to proliferate," says researcher Dr. Maria Lindahl of the Institute of Biotechnology.

Overexpression of the MANF protein in the pancreas of diabetic mice significantly protected the beta cells from diabetes-induced beta cell death compared to beta cells without excess MANF. In addition, overexpression of MANF promoted beta cell proliferation.

"This study brings new hope that, in the future, MANF may be able to regenerate the beta cells of diabetic patients to a normal level and thus restore blood sugar levels.  Therefore, we and our collaborators are now addressing many important questions concerning the mechanism of MANF action in beta cells. We need to know whether the MANF-induced novel beta cells are functional and whether MANF is a real player in the regeneration of the slowly dividing human beta cells."

The MANF diabetes research was carried out in tight collaboration with Jari Rossi, Academy Researcher of the Institute of Biomedicine in Biomedicum at the University of Helsinki, and Professor Timo Otonkoski and his group from the stem cell centre, also in Biomedicum.

The team has received a three-year grant from the Juvenile Diabetes Research Foundation (JDRF), USA for research connected with type 1 diabetes. The group recently received also a one-year grant from JDRF for studying the mechanisms of MANF action in beta cell regeneration.

Insulin- and glucagon immunohistochemistry of pancreas sections from pancreas-specific MANF knockout mice reveal beta cell loss and disturbed islet architecture.

Lindahl M, Danilova T, Palm E, Lindholm P, Võikar V, Hakonen E, Ustinov J, Andressoo JO, Harvey BK, Otonkoski T, Rossi J, Saarma M. MANF Is Indispensable for the Proliferation and Survival of Pancreatic β Cells. Cell Rep. 2014 Apr 24;7(2):366-75. (PubMed)

Picture: Maria Lindahl

May 8, 2014
EU funding to Professor Mart Saarma for Parkinson's disease research

A project focused on the development of a novel approach for the treatment of Parkinson’s disease coordinated by Professor Mart Saarma received almost € 900,000 funding from the EU. The plan is to design small molecules similar to neurotrophic factor GDNF.

Parkinson’s disease is caused by progressive degeneration and death of dopaminergic neurons in the brains of affected people. The existing therapies for the disease are based on dopamine replacement and neither prevents nor stops neuronal death and disease progression.

Prof essor Saarma and Dr. Yulia Sidorova from the Institute of Biotechnology together with Professor Raimo Tuominen and Professor Jari Yli-Kauhaluoma from University of Helsinki, Faculty of Pharmacy, and an Estonian small enterprise Molcode Ltd have recently launched a project, called GDNF mimetics, focused on the development of a novel disease–modifying treatment against Parkinson’s disease.

The consortium plans to design small molecules acting similarly to glial-cell derived neurotrophic factor, GDNF, which is a well-known survival factor for dopaminergic neurons. GDNF protein itself has poor pharmacological characteristics that hinder its clinical development. Orally administered small molecules with improved biodistribution and bioavailability will translate better to clinics.

To achieve the goal of the project, the team of scientists will use methods from different areas of science, including physical and computational chemistry, molecular and cellular biology, medicinal chemistry, biochemistry, neurosciences and behavioural sciences. This will provide broad possibilities to share knowledge and train participating researchers in adjacent fields via staff exchanges between the University of Helsinki and Molcode Ltd. Several scientists will also be recruited from outside the consortium to complement expertise of partners.

The project will last for 4 years and it is supported by the European Union’s Marie Curie IAPP initiative under the 7th Framework Programme.

Text: Yulia Sidorova ad Susanna Wiss
Picture: Susanna Wiss

Web page of the project

May 7, 2014
Jukka Jernvall one of the newly elected EMBO members

European Molecular Biology Organisation (EMBO) has elected 106 outstanding researchers in the life sciences to its membership. Academy Professor Jukka Jernvall from the Institute of Biotechnology is one of them. Another Finnish new EMBO member is Academy Professor Ilkka Hanski from the Department of Biosciences. The most recent scientists to join the EMBO membership come from 17 different countries and include 21 female scientists.  The EMBO Membership currently comprises more than 1600 life scientists.

EMBO has decided to strategically expand the scope of its membership on the occasion of its 50th anniversary to honour the progress that has been made in the fields of neuroscience and ecology & evolution. The 106 new members for 2014 include 50 scientists who have made exceptional contributions to these research areas.

EMBO Members make invaluable contributions to the organization by providing suggestions and feedback on the activities of EMBO. They serve on selection committees for EMBO programmes and mentor young scientists. Their input has helped to promote excellence in life sciences since 1964.

Newly elected members and associate members

Picture: Veikko Somerpuro

April 30, 2014
Occupational safety award to The Electron Microscopy Unit

The Electron Microscopy Unit of the Institute of Biotechnology received the Occupational safety award 2013 of the University of Helsinki for its personnel’s long-standing work to improve the work safety. The unit has been systematically developing good laboratory practices to reduce the chemical exposure and minimize the occupational hazards of its personnel and all its users.

The unit did their first Risk analysis assessment 12 years ago, and revised it few years later. After this, they prepared their own written plan of action containing separate instructions for fire, water leakage, electric shortcuts, and instrument malfunction as well as for handing of gases, liquid nitrogen, and chemical spills. Instructions were made as teamwork where the whole personnel participated actively into every step of the process. This way, the instructions are targeted and take into account the instrumentation and procedures special to the unit and the personnel are more aware of the instructions and committed to follow them. As a core facility, the laboratory space and instruments have ten times more outside users compared to its personnel, and the best way to keep them operational is to have well formulated laboratory practices that can be shared by everyone.

Text and photo: Eija Jokitalo

EM Unit

April 17, 2014
New form of treatment to reduce risk for surgery-related ischemic brain injury is?

A University of Helsinki study indicates that a simple pre-surgery diet could mitigate brain damage caused by blood clots associated with surgery.

Ischemic brain injury due to heart and vascular surgery cause more than 100,000 deaths annually in Europe and the United States. In addition, approximately 10–20% of patients undergoing heart and vascular surgery – at least 1.5 million people in Europe and the United States every year – suffer from ischemic brain injury as a side-effect of their surgery. Researchers from the Institute of Biotechnology at the University of Helsinki have found that water-only fasting or protein-free diet before stroke reduce the amount of damaged brain tissue in rats by nearly 40%.

Academy Research Fellow Jaan-Olle Andressoo notes that reducing brain damage caused by surgery, some of which results in what are known as “silent strokes”, would be extremely important. A silent stroke, often left undiagnosed, may disrupt the brain’s capacity to process information. Patients may experience cognitive difficulties after heart surgery, e.g. find that they can no longer complete everyday tasks as easily as before.

“Minimising brain damage is the main target of our research, and we are now seeking partners to enable us to test the pre-surgery diets on patient groups.”

Academy Research Fellow Kaisa Hartikainen, a neurologist at the Behavioural Neurology Research Unit at the Tampere University Hospital, considers the findings interesting.

“Despite an enormous amount of research in recent years into treatments and drugs that could protect neurons from irreversible damage caused by oxygen deprivation, neuroprotective treatments have largely proved ineffective in stroke patients. Results from short-term dietary restriction studies on rats, however, offer a promising new alternative for use in conjunction with surgical treatments associated with a significant risk for stroke

 

Protein free diet decreases lesion 48h after stroke

Normal diet (left) and Protein free diet (right)

Varendi K, Airavaara M, Anttila J, Vose S, Planken A, Saarma M, Mitchell JR, Andressoo JO. PLoS One. 2014 Apr 4;9(4):e93911.(PubMed)

Text and picture: Mikko Airavaara, Jaan-Olle Andressoo and Kaisa Hartikainen

April 14, 2014

New PI Ville Paavilainen digs deep into ER function

Ville Paavilainen started as a new Group Leader in the Institute of Biotechnology in February 2014. He is interested in the function of the endoplasmic reticulum (ER) protein homeostatic machinery and the possibility to perturb its function with small-molecule therapeutics.This approach could be used to selectively target cancer cells whose unregulated growth predisposes them to high proteotoxic stress.
 
Protein homeostasis networks in mammalian cells regulate the size and location of cellular proteomes. Failure to properly maintain these networks can result in protein accumulation, aggregation and cell death. Ville Paavilainen, a new PI at the Institute of Biotechnology, uses small molecule probes to study the complicated co-translational translocation pathway that cells use for creating secreted and membrane proteins.

“By revealing the cellular target and mechanism of action of these particular compounds, we can use them to gain insight into this intricate pathway”, Ville Paavilainen says.
At UC-San Francisco, he worked alongside synthetic organic chemists and used structure-guided drug design to develop covalent-reversible protein inhibitors for several proteins. This process taught him how to use small-molecule inhibitors to study complicated cellular processes.

“My main interest is in understanding how several components of the protein translocon promote the biogenesis of only a sub-set of secretory proteins. Also, we attempt to gain an atomic-level view on how a substrate-selective inhibitor of Sec61 prevents biogenesis of only a handful of the thousands of Sec61 substrate proteins. I envision that this information can enable rational development of substrate-selective inhibitors also for other protein homeostasis regulators”.

Ville Paavilainen's new lab uses methods of structural biology, biochemistry and cell biology in combination with chemical probes to gain insight into the cellular roles of several new ER homeostasis regulators.

Text and photo: Elina Raukko

April 14, 2014
Novel function for myosin 1c regulated actin filament arrays in endoplasmic reticulum sheet persistence.

The endoplasmic reticulum (ER) comprises a dynamic 3D network of sheets and tubules. To accommodate the vast range of functions, the ER network spreads throughout the cell, and its functions are distributed into structural subdomains according to their specific requirements. Proper ER operation requires an intricate balance within and in-between dynamics, morphology, and functions, but how these processes are coupled in cells in unknown.

The research group led by Eija Jokitalo have revealed the interplay between actin cytoskeleton and ER in mammalian cells. By using wide-field and confocal light microscopy and 3D-EM, the researchers showed that ER sheet-tubule ratio is counterbalanced by microtubules and actin cytoskeleton, and the loss of dynamic actin filament arrays leads to a structural conversion of ER towards tubular morphology. Based on 3D-models obtained from using serial block face scanning electron microscopy imaging (SB-EM), the authors demonstrated that the loss of the dynamic actin filaments resulted in reduced ER sheets and unevenly distributed ER network.

In order to identify proteins participating in the ER-actin interplay the researchers performed an shRNA-based screen (Genome Biology Unit, Institute of Biotechnology) where over 200 known functional actin-binding proteins were depleted one-by-one and analysed by light microscopy to identify those that would have a role on ER morphology and/or dynamics. Based on the screen, they identified the unconventional motor protein myosin 1c (myo1c), whose depletion led to a strong ER phenotype. Further studies revealed a novel role for the unconventional motor protein myosin 1c in regulating the ER-associated actin filament arrays.

Together their findings showed that in addition to tubular associations with MTs, interactions with the actin cytoskeleton are essential to create and maintain the ER sheet persistence and the characteristic architecture of the ER network in mammalian cells.

MTs and actin filaments can be found in close proximity to the ER. Two successive 250-nm sections from Huh-7 cells were prepared using high-pressure freezing and freeze substitution and subjected to electron tomography. From the resulting tomogram, microtubules, actin filaments, and the ER network comprising of tubules and highly fenestrated sheets were modelled (blue, red, and yellow, respectively).

This publication is part of Merja Joensuu’s Ph. D. thesis “Determinants of endoplasmic reticulum structure and dynamics”. The research was supported by the Academy of Finland, the Viikki Molecular Biosciences Graduate Programme and Biocenter Finland National imaging infrastructure network. During this project, services of four core facilities of the Institute of Biotechnology were utilized: Electron Microscopy Unit, Light Microscopy Unit, Genome Biology Unit and DNA Sequencing and Genomics Laboratory. The work has been published online in Molecular Biology of the Cell.

Joensuu, M., Belevich, I., Rämö, O., Nevzorov, I., Vihinen, H., Puhka, M., Witkos, T.M., Lowe, M., Vartiainen, M.K. and Jokitalo, E. (2014). ER sheet persistence is coupled to myosin 1c-regulated dynamic actin filament arrays. MBoC, 7:1111-26. (PubMed)

Text and picture: Eija Jokitalo

April 9, 2014
Sarah Butcher's team initiates a new picornavirus research consortium

Research Director Sarah Butcher’s structural biology team in the Institute of Biotechnology is a founding member of the FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP) AIROPico research consortium. In the consortium, scientists from 4 universities and 3 companies collaborate on human picornavirus research with a budget of €2,5M from 2014-2017.

AIROPico is the first EU consortium to join forces on human picornavirus research. Together, this consortium will develop fast, high quality diagnostic tools and therapies against picornaviruses based on a better understanding of the basic biology of infection.

“We are particularly focusing on difficult-to-work-with, clinically-relevant viruses like rhinoviruses linked to asthma and enteroviruses linked to cot death and diabetes. These viruses affect millions annually", says Sarah Butcher, leader of one of the three Finnish partners in the consortium.

The other Finnish partners are Petri Susi’s team in Turku University of Applied Sciences and University of Turku, and the industrial partner ArcDia International Ltd, located in Turku and specialized in rapid laboratory diagnostics of infectious diseases.

The AIROPico research project is based on the exchange of knowledge and ideas between academic institutions and the companies within the consortium. It will involve researchers visiting the companies taking part and employees from the companies spending time in research institutions. Research Director Butcher will be the first person to exchange into industry in the consortium. “I am looking forward to first-hand experience in industrial research and development in diagnostics with ArcDia.”

www.airopico.eu

Photo: Ari Aalto

 

March 18, 2014
New in vivo function for mitogen-activated protein kinase (MAPK) pathway

Organ development is largely guided by extracellular signals that are transmitted to the cells via receptor tyrosine kinases (RTK). While the functional requirements for several RTK pathways guiding development are well established, the cellular responses and intracellular cascades mediating such stimuli during the differentiation of distinct organs are poorly understood.

One of the major intracellular cascades induced by RTK signaling is mitogen-activated protein kinase (MAPK) pathway, which is probably best known for its function as a regulator of cell proliferation. In a recent study the research team led by Satu Kuure at the Institute of Biotechnology explored the activation and function of MAPK pathway in the branching epithelium of developing kidney (Ihermann-Hella et al., 2014).

The researchers found that MAPK activity co-localizes with Ret, a RTK activated by glial cell line–derived neurotrophic factor and crucial in kidney morphogenesis. Genetic deletion of the pathway activity specifically from the branching renal epithelium results in significantly reduced kidney size. Closer examination of the phenotype revealed that the epithelium lacking MAPK activity is able to grow by elongation but fails to change growth direction in the patter characteristic for normal kidney development thus demonstrating deficiency in secondary branch point formation. Surprisingly enough, the mitotic indices in the mutant epithelium remain comparable to control epithelium despite the greatly diminished cell numbers. The team identified defects in cellular adhesion primarily affecting dynamics of focal adhesion turnover with secondary effects on E-cadherin based adherens junctions.

Based on their results the researchers propose that MAPK activity promotes cell cycle progression and higher cellular motility through remodeling of cellular adhesions in guidance of renal branching morphogenesis. Upcoming studies will focus in revealing the details of how MAPK activity through phosphorylation of paxillin at focal adhesion sites then further regulates changes in E-cadherin mediated adherens junctions. Additional experimentation will also genetically address the dependence of MAPK activation on RET signaling to better understand the potential compensatory mechanisms covering renal differentiation.

Localization of pPaxillin in normal (left) and MAPK deficient ureteric bud epithelial cells.

While studying the function of MAPK pathway in branching epithelium, Ihermann-Hella et al. observed that the pathway is also activated in progenitor population of future nephrons as well in nephron precursors. The team is very interested in understanding the functional requirement for the pathway in nephron progenitor maintenance, propagation and/or differentiation.

  • Ihermann-Hella, A., Lume, M., Miinalainen, I.J., Pirttiniemi, A., Gui, Y., Peränen, J., Charron, J., Saarma, M., Costantini, F., Kuure, S. Mitogen-activated protein kinase (MAPK) pathway regulates branching by remodeling epithelial cell adhesion. http://www.plosgenetics.org/doi/pgen.1004193

Image of the day by The Scientist Magazine: Mitotic Mouse Cells

Text: Satu Kuure
Photos: Anneliis Ihermann-Hella

 

March 17, 2014
Passing of Dmitry Bloch

A longtime Institute of Biotechnology researcher docent Dmitry Bloch passed unexpectedly last Thursday at the age of 47. Dmitry defended his PhD at Moscow University in 1999. Already before this he visited the Helsinki Bioenergetics Group (HBG; then at the Department of Medical Chemistry) following an invitation by professor Michael Verkhovsky. Soon after this Verkhovsky recruited Bloch to Helsinki and he moved together with HBG to the Institute of Biotechnology.

Dmitry was a highly skilled experimentalist in biophysical chemistry and also theoretically very talented.  He made significant contributions to our understanding of how cells convert energy in the mitochondrial respiratory chain with over 30 publications to his name; a few selected publications are listed below. His scientific and teaching accomplishments also earned him a degree of a docent in physical biochemistry at the University of Helsinki. His passing is a big loss to the Institute of Biotechnology and to the field of biophysical chemistry as a whole.

Selected publications:

  • Bloch, D., et al.,  2004, The Catalytic cycle of cytochrome c oxidase is not the sum of its two halves, Proc. Natl. Acad. Sci. USA, 101, 529.
  • Bloch, D.A., Jasaitis, A. & Verkhovsky, M.I., 2009, Elevated proton leak of the intermediate OH in cytochrome c oxidase, Biophys. J. 96, 4733.
  • Verkhovskaya, M. & Bloch, D.A. 2013, Energy-converting respiratory Complex I: On the way to the molecular mechanism of the proton pump, Int. J. Biochem. Cell Biol., 45, 491.

 

February 27, 2014
Petri Auvinen and Filip Scheperjans receive funding for two years of further research on the microbiome in Parkinson’s Disease

Laboratory director Petri Auvinen (Institute of Biotechnology) and neurologist Dr. Filip Scheperjans (Helsinki University Central Hospital and the Department of Neurological Sciences of the University of Helsinki) were awarded $ 394,000 from The Michael J. Fox Foundation for Parkinson's Research to continue their research on the role of the microbiome in Parkinson’s Disease.

Parkinson’s Disease (PD) is a neurodegenerative movement-disorder that affects approximately 1% of the population above 60 years of age. The most overt symptoms are a slowing of movement, shaking of limbs and muscle stiffness. Recent research has revealed that patients also suffer from a broad spectrum of non-motor symptoms. Constipation, which affects up to 80% of PD-patients, is frequently present years before the onset of motor-symptoms and neuropathologic changes in the autonomic plexuses of the gut can be found sometimes even years before motor symptoms appear. Idiopathic constipation is one of the strongest risk-factors for PD and is associated with a twofold risk of developing the disease.

The cause of PD is essentially unknown, but mitochondrial dysfunction, dysregulation of calcium homeostasis and neuroinflammation are involved in PD related neurodegeneration. There is a considerable amount of evidence pointing towards an environmental factor playing a key role in PD pathogenesis probably against a background of genetic vulnerability. The early involvement of the gastrointestinal tract in PD lends support to the hypothesis that this environmental factor exerts its influences primarily via the gut. Recent research has suggested that changes of the complex equilibrium of the microbiome may be implicated in a multitude of human diseases. Knowledge about the interactions of the microbiome with the nervous system is still very scarce. However, there is accumulating evidence of an intense bidirectional interaction between gut microbiota and the brain influencing for example behaviour as well as levels of neurotransmitter receptors and neurotrophic factors.

Until recently it has not been possible to study the microbiome as a whole, but modern high-throughput DNA sequencing methods allow a relatively unbiased assessment of nearly all bacterial groups in a sample without the need for previously selecting specific groups of interest.

In their study Auvinen and Scheperjans are using 16S metagenome sequencing to investigate possible links between microbiota and PD that could improve our understanding of PD and may serve as a biomarker.

Petri Auvinen and Filip Scheperjans are co-PIs in this project.

Photo: Velma Aho

 

February 14, 2014
Irma Thesleff new Academician of Science

The letters of appointment will be presented to the new Academicians at a ceremony to be held at the House of the Estates in Helsinki on 18 February 2014. Based on nominations made by the Academy of Finland, the President of the Republic of Finland may confer the honorary title of Academician of Science to highly distinguished Finnish or foreign scientists and scholars. The title can be held by no more than twelve Finnish scientists and scholars at a time.

Irma is best known for her work on tooth development, but has also made significant contributions to the understanding of development of other ectodermal organs such as hairs and glands as well as cranial bones. A mammalian tooth model developd in her group has allowed for an in-depth examination of both embryonic and evolutionary development. The long-term goal is to unravel the complexities of intercellular communication during cell development. Finnish developmental biologists have studied these interactions ever since the 1930s, for example, leading figures such as Professor Sulo Toivonen and Irma's thesis supervisor Professor Lauri Saxén.

Irma obtained her PhD in Dental Science in 1975 at the University of Helsinki, and did postdoctoral studies at the National Institute of Dental Research in Bethesda, USA. She was recruited to the Institute of Biotechnology to head the new Developmental Biology Program. Within the program headed the Academy’s Centre of Excellence in Developmental Biology from 2002 to 2007 and the strong Finnish tradition continues within the new CoE in Experimental and Computational Developmental Biology headed by Jukka Jernvall. Irma considers the unique environment of the Institute of Biotechnology has been a critical element to the contnued success of developmental biology in Finland.

Irma is a recognized leader in the field globally demonstrated by the innumerable invitations to meetings and honorary professorships at universities in Europe and Canada.“I’m of course very humbled and honoured to receive this recognition. It’s a complete surprise. Though, I have to admit that it’s a bit terrifying to be among such esteemed company. I hope that the title of Academician will give me an opportunity to influence important issues in science and society,” Irma says. Congratulations on behalf of the Insitute of Biotechnology

Additional info:

In Finnish
In English

 

February 12, 2014
Members chosen to the BI Board and UH Collegiate

The BI Board comprises nine members, two of them must be chosen from amongst the Institute’s staff. BI staff meeting on 31.1.2014 decided to nominate Susanna Wiss and Tommi Kajander as personnel representatives to the BI Board for 2014-2018 and Annemari Narvanto and Sarah Butcher as their personal deputies.

A general meeting of UH research institutes on 5.2.2014 decided to nominate director Eero Castren from Neuroscience Center as a member to the 50-seat UH Collegiate. Director Juha Äystö from Helsinki Institute of Physics was nominated as deputy member. As there were no more candidates, there was no need to arrange elections.

 

February 5, 2014
Launch of the Institute of Biotechnology Seminar Series

The first seminar of the new Institute of Biotechnology Seminar Series (BISSE) on Friday 24th of January attracted an impressive crowd and at the same time celebrated the recent 50th birthday of the Institute’s director, Tomi Mäkelä, with prominent surprise speakers.

The lecture hall in the Viikki Infocenter was packed full for the launch of the seminar series. The renown visiting speakers for the first seminar were kept a secret from the Institute’s director, Tomi Mäkelä, as part of his surprise birthday party celebrations. Mäkelä was indeed surprised to see his former PhD student, Professor Derrick Rossi, kick off the seminar with the first talk of the afternoon.

Dr. Rossi is a well-known stem cell researcher at Harvard Medical School and Harvard University. Time magazine, for example, cited Dr Rossi’s discovery of modified-mRNA reprogramming as one of the top ten medical breakthroughs of 2010. Rossi’s talk concentrated on the work of his research group on hematopoietic stem cells (HSCs) and more specifically on the use of defined transcription regulators in cellular reprogramming.

“Despite the enormous clinical potential of HSCs, surprisingly little is known about the mechanisms that regulate their fundamental properties - our lab is working towards trying to understand these”, says Rossi.

Rossi’s talk was followed by a recap of the 15 years of research in Tomi Mäkelä’s lab on the LKB1 tumor suppressor by Yan Yan, currently a PhD student in the Mäkelä lab.

After Yan Yan, the final presentation of the day was by Professor Rene Medema, the director of the Netherlands Cancer Institute and a friend of Mäkelä from his post doc days in Boston. In his talk Dr. Medema focused on answering the following questions:  how do cells recover from DNA damaging insult and what mechanisms promote cell cycle re-entry. Medema’s group has identified several key transcription factors and protein kinases and phosphatases that control the cell recovery and repair from DNA damage.

The Institute of Biotechnology seminar series will continue on Fridays at 3pm.

Text : Ulla Tuomainen
Picture: Tea Vallenius

 

February 3, 2014
Professor Tomi Mäkelä Panel Chair of the ERC Starting Peer Review Grant Panel 2014

ERC Scientific Council has identified and invited panel chairs in the seventh ERC Starting Grants peer review process. Tomi Mäkelä will be the chair of the panel LS1: Molecular and structural biology and biochemistry.

There are in total 25 panels, divided between the 3 domains as follows: 9 panels in Life Sciences (LS), 10 panels in Physical Science and Engineering, and 6 panels in Social Sciences and Humanities (SH). The full list of ERC peer reviewers will be published by the European Commission after the conclusion of the current peer review process.

European Research Council (ERC)

 

December 2013

December 18, 2013
Golden angle in plants: two hormone-based fields needed for robustness of leaf orientation

A recent article in the Nature by a research consortium including Professor Yrjö "Ykä" Helariutta and a previous post doc in his group, Anthony Bishopp, sheds light to the phyllotactic golden angle mystery - why each new leaf emerges from the shoot apical meristem at an exact 137.5 degree angle from the previous one. It seems that plant hormone auxin together with a cytokinin signaling inhibitor AHP6 are both involved in regulating the arrangement of leaves on a plant stem.

Plant aerial organs are initiated at the shoot apical meristem. Their position and periodical initiation is highly controlled. As a result the leaves are arranged in a specific pattern on a plant stem. The golden angle - the angle separating two recently emerged plant organs such as leaves from each other - is 137.5 degrees, which has been known for long.

Plant hormone auxin triggers organ initiation but it is not enough in itself to create a well-organized apical meristem with new organs budding regularly. New research results recently published in the Nature show that two hormone-based fields are needed for the correct structure.

- The other hormone-based field is created by the intercellular movement of the cytokinin signaling inhibitor AHP6, in turn induced by auxin. AHP6-based fields establish patterns of cytokinin signalling in the meristem and they can create a temporal sequence on organ initiation, says Professor Yrjö "Ykä" Helariutta.

Besnard et al. Cytokinin signalling inhibitory fields provide robustness to phyllotaxis. Nature doi:10.1038/nature12791

Helariutta group

Photo: Wilma Hurskainen

December 5, 2013
Three-year research projects funding to Mikko Airavaara and Nicolas Di-Poi

Mikko Airavaara’s project "Novel primate-specific GDNFOS-3 gene in health and neurodegeneration" and Nicolas Di-Poi’s "Molecular developmental genetics of craniofacial tissue morphogenesis and regeneration in reptiles" were awarded University's funding to research projects for the years 2014-2016.

The University allocates yearly some of its funds to support research. The three-year research allocations are aimed to support promising researchers of the University of Helsinki, who have not yet received significant research funding from outside the University, and who are about to establish themselves as independent researchers and/or establishing their own research group.

The Rector decided to award funding to 20 research projects for the years 2014-2016. A total of 2.957.000 euros was awarded.

November 27, 2013
Stem cells and regeneration research fortified in the Institute of Biotechnology

Developmental and stem cell biology is a crucial field for understanding tissue regeneration and possibilities for creating regenerative medicine. Vertebrate tissues have a tremendous diversity in how they regenerate or how they are repaired. Two new group leaders in BI, Nicolas Di-Poi and Pekka Katajisto, have stem cells as a part of their research.

Nicolas Di-Poi combines both evolutionary and developmental (EvoDevo) biology with regenerative biology. He concentrates on non-classical model organisms such as reptiles.

"Adult mammals have limited regenerative capacities compared for example to amphibians and reptiles. The goal of our group is to provide an evolutionary context to the key signaling pathways of biological regeneration", Nicolas Di-Poi explains.
The Di-Poi research group has a special interest in craniofacial research.

"Craniofacial diseases and disorders account for a considerable portion of health problems worldwide. Also, the craniofacial organs are the best targets for evolutionary and ecological studies, because of their excellent fossil record. They also have a lot of morphological variation. That will be of crucial importance to discover key evolutionary changes in tissue development", Di-Poi says.

"No question is too big"

Research group leader Pekka Katajisto returned from the United States in July after an interesting four-year postdoctoral period at MIT’s Whitehead Institute for Biomedical Research to begin work as a group leader at the Institute of Biotechnology. Katajisto’s mentor at the Whitehead Institute was David Sabatini, who began their cooperation by encouraging the recent doctoral graduate to take about six months to decide what he wanted to research for the rest of his life.

As a result of this contemplation, Katajisto decided upon stem cell and geriatric research as his focus. Katajisto says that he has learned that no question is too big to ask.

“This is one attitude I want to import from the US, as well as the idea that every person should find the things that interest them most. That way researchers can maintain their interest, the research will not become routine, and any setbacks will seem like challenges.”

Ageing equals the accumulation of waste?

Pekka Katajisto uses intestines as the source material for his stem cell research. The intestine features the most dynamic tissue in the human system, since the cells in the bowel walls are completely renewed every five days. In addition, one 40-centimetre small intestine of a mouse can easily yield 100,000 stem cells, which are responsible for cell regeneration.
Stem cells exist in a microenvironment of other cells. If the right kind of environment is removed, the stem cell will not carry out its function. This means that the cells constituting the microenvironment constantly regulate the behaviour of the stem cells.

“We’ve found that as we age, the cells in the microenvironment can lose their ability to communicate the status of the tissue to the stem cells. The result is catastrophic, since organs become damaged as they get older, but are no longer repaired as necessary.”

On the other hand, when the stem cell divides, only one of the resulting daughter cells continues to function as a stem cell. The other cell specialises and ultimately dies.

“We have developed a completely new strategy which allows us to track the age of the cell components that are transferred to the daughter cells during cell division. Based on our research, the parts that go into the new stem cell are top notch. Older, potentially faulty elements are transferred to the differentiating cell,” Katajisto notes.

This may be the key to the ageing process. Young stem cells transfer their poorly functioning elements into the other daughter cell, but as the stem cell line ages, some of this waste can remain in a daughter cell intended to continue as a stem cell. As a result, the stem cells grow tired and lack vitality, and consequently no longer repair tissue damage.

Text and photos: Elina Raukko

November 20, 2013
Several BI research groups to be members of Biocentrum Helsinki in 2014-2016

Altogether 13 research groups in the Institute of Biotechnology have been chosen to join Biocentrum Helsinki, a large umbrella organization hosted by the University of Helsinki and Aalto University for the years 2014-2016. The total amount of research groups chosen from the University of Helsinki was 31.

Biocentrum Helsinki coordinates, establishes and supports research infrastructures on the campuses on which the member research groups are situated. It also coordinates research training by supporting weekly seminar series as well as relevant lectures and symposia in the University of Helsinki and Aalto University.

The groups lead by the following PI's were selected to be members of the BCH organization:

Dennis Bamford, Sarah Butcher, Mikko Frilander, Yrjö Helariutta, Ville Hietakangas, Jukka Jernvall, Pekka Katajisto, Pekka Lappalainen, Marja Mikkola, Tomi Mäkelä, Mart Saarma, Markku Varjosalo and Maria Vartiainen.

Biocentrum Helsinki

November 15, 2013
Genome of the silver birch (Betula pendula) mapped

University of Helsinki researchers including Professor Ykä Helariutta and Dr. Petri Auvinen from the Institute of Biotechnology have mapped the genome of the silver birch in cooperation with the Finnish Forestry Research Institute. Gained through state-of-the-art technology, this new information will be significantly useful in both the forestry industry and basic research.

The silver birch (Betula pendula) is the most important broad-leaved tree in Finnish forestry. With its many sub-varietals, the silver birch has adapted to a range of different climates, and is found all across Europe from the north to the south, and as far as northern Asia to the east.

For this project, the researchers gathered DNA samples from a single tree, using its leaves and the vascular cambium layer under the bark. First the DNA was chopped into millions of short fragments and analysed using next-generation sequencing equipment. The sequenced fragments were arranged into a full genome with the help of overlapping DNA regions.

Read more about the project

Helariutta group
Auvinen group

November 7, 2013
Alfred Kordelin Foundation Prize for Professor Mart Saarma

Academy professor Mart Saarma has been presented an Alfred Kordelin Foundation prize for promoting high-level research and university education in molecular biology.

Academy professor Mart Saarma is one of the leading researchers in molecular biology in Finland. His own research has for a long time concentrated on neurobiolology, especially on GDNF, a neurotrophic factor. He has scrutinized the role of the GDNF and the protein it produces, especially in relation with the Parkinson's Disease.

On 6th November, Professor Saarma was presented an Alfred Kordelin Foundation prize of € 30,000.

Professor Saarma did his PhD in Estonia in 1975 on molecular biology. From 1990 to 2008 he was the Director of the Institute of Biotechnology, from 2009 to 2010 the Director of Biocenter Finland and since 2008 the Director of the Centre of Excellence in Molecular and Integrated Neurosciences.

Professor Mart Saarma has been an Academy Professor (Academy of Finland) since 2009. His so-called H index in the Web of Science is extremely high, 48.

Professor Saarma in TUHAT research database
Professor Saarma's group
Alfred Kordelin Foundation (website in Finnish)

November 5, 2013
Scientific evaluation of the Institute of Biotechnology

The Scientific Advisory Board (SAB) visited the Institute on 5-6 September to evaluate 4 research programs, 11 Group Leaders and their associated Core Facilities, as well as to discuss future directions of the BI. The BI Board gave at the end of October its suggestions to the Director based on the SAB evaluation report.

General comments

According to the SAB report BI has continued to be very successful in its mission to generate significant new knowledge in biotechnology and integrative biology. Researchers continue to take innovative approaches to key scientific questions as demonstrated by their success in publishing in top journals such as Science and Nature, in achieving an outstanding 2011 UH research evaluation and in being awarded competitive grants like two ERC Starting Grants, one ERC Advanced Grant, and four new Academy of Finland Centers of Excellence starting 2014.

The Institute has continued to expand its contribution to teaching at the University of Helsinki. Its researchers are involved in major restructuring of molecular biosciences education at UH, and in developing new masters programs in collaboration with several faculties. BI has also been very active in PhD-level training.

Since 2011 BI has succeeded in recruiting 7 new Group Leaders from top universities and institutes such as MIT, EBI, University of Geneva, ETH Zürich, and UCSF. This reflects the important role of BI as a landing pad for successful scientists often at the beginning of their independent careers and with many options from which to choose.

Research programs, Future Director of the SBB and other specific issues

Research Programs at the BI are seen to fulfill several important functions like mentoring they serve for new Group Leaders, as well as for students and postdocs and organization of activities, such as seminars and literature review clubs for students and postdocs. In its report SAB encourages continuing flexibility in the nature and composition of the programs. Based on the SAB statement BI Board decided to continue the present programs until the next evaluation.

After Professor, Research Program Director Mårten Wikström retired in mid-2013, Professor Sarah Butcher has worked as an acting Director of the Structural Biology and Biophysics (SBB) program. In its report the SAB sees Professor Butcher as a highly productive and well-respected researcher especially in the field of virus structure and function, who attracts excellent research funding both within Finland and from international sources. She collaborates widely within the BI and also at national and international levels.  Based on SAB’s endorsement, the Board suggested to appoint Professor Butcher to the position of Director of the SBB Program.

One specific proposal that came out at the panel discussion organized during the SAB visit was to have all-BI symposia, which would foster interactions Institute-wide and provide feedback from PIs in different fields. The Board suggested that Director will start preparations for the weekly BI symposia.

Other specific issues that SAB took a stand were Biocenter Finland, doctoral training programs, the plans to develop the Viikki campus, recruitment, team leaders’ position and core facilities.

BI will continue its open recruitment policy. The Board has already earlier decided to open an international Group Leader Call in 2014.

Related news:
The BI SAB site visited the Institute 5-6 September, 2013

September 20, 2013
Freeze! A protein group affecting lipid dynamics at cell membranes discovered

BAR proteins can freeze the movement of certain lipid molecules in membranes almost completely. This finding provides an important step towards understanding the functions and dynamics of cellular membranes.

Eukaryotic cells are compartmentalized by membranes, whose shape and dynamics are precisely regulated to maintain their correct functions. Consequently, many cellular processes such as endocytosis, migration and morphogenesis rely on proteins that bind directly to membranes and sculpt them into desired shapes.

BAR domain proteins are among the central membrane-sculpting proteins in all eukaryote cells. Studies by Pekka Lappalainen laboratory at Institute of Biotechnology, University of Helsinki, Finland now reveal that BAR domain proteins not only bend membranes, but also generate extremely stable lipid microdomains by inhibiting the lateral diffusion of certain lipids nearly completely.

In a new study published in Cell Reports, Hongxia Zhao working in the Lappalainen laboratory discovered that all BAR domain proteins induce strong clustering of phosphoinositides, which are important lipids involved in regulating protein functions and cellular signalling.

Her studies also revealed that BAR domains assemble into extremely stable scaffolds on the membrane. Surprisingly, mobility of phosphoinositides was nearly completely frozen in these BAR domain induced lipid platforms. These extremely stable protein-lipid scaffolds may contribute to diverse cellular processes by generating lipid phase boundaries at the tips of the BAR domain scaffolds. Furthermore, the membrane microdomains induced by BAR domains are expected to function as diffusion barriers, which may for example trap membrane-associated receptor and cargo molecules at the endocytic bud.

Thus, distribution and mobility of specific lipid species at the plasma membrane appears to precisely regulated by membrane-associated proteins. Hongxia Zhao is now continuing studies on regulation of lipid dynamics as an Academy Research Fellow at University of Helsinki.

Article in Cell Reports

Lappalainen lab

Illustration: Hongxia Zhao

September 18, 2013
Docent Päivi Ojala appointed a K. Albin Johansson Research Professor and a part-time professor at the Imperial College London, UK

Focus on viral tumorigenesis and lymphatic reprorgamming

Docent Päivi Ojala from the University of Helsinki has been appointed K. Albin Johansson research professor for the Finnish Cancer Institute. The post is for five years and started September 1st, 2013. Päivi Ojala has also been appointed a part-time professor at the distinguished Imperial College London, UK.

The focus of Dr Päivi Ojala's research is on viral tumorigenesis and the role of dysregulation of lymphatic endothelial cells in the development and progression of cancer.

Ojala's work is internationally recognized as demonstrated by the interest of one of the esteemed universities, Imperial College London, to recruit her to join its ranks.

"I have accepted the Chair in Viral Tumorigenesis in the Section of Virology, Division of Infectious Diseases, at Imperial College as a part-time (25%) position. My appointment to the K. Albin Johansson research professor post gave a strong signal that my work is appreciated also here and that the Finnish Cancer Institute wants to see it continued in Finland", Ojala says.

Dr Päivi Ojala finds the research professorship very important for her career. It gives her the possibility to fully focus on the research for the next five years and promotes the integration to both the national and international cancer research communities.

Ojala's group has a long-term interest in understanding the origin and development of the cancers caused by viruses. One of the most important, recent findings of her group is that the Kaposi's Sarcoma herpesvirus can reprogram the infected cell identity: the virus induces lymphatic endothelial cells to transdifferentiate to so-called mesenchymal cells. This type of reprogramming can render cancer cells more aggressive and promote their spread by metastasis.

"Now our goal is to understand the detailed mechanisms of virus-induced lymphatic endothelial reprogramming and assess its contribution to Kaposi's sarcomagenesis as well as to explore its role also in other cancers involving the lymphatic system. During the five years we aim to produce more detailed information about the molecular mechanisms of cancer development. We also intend to identify new, effective targets for therapeutic approaches", Ojala says.

The image displays the cell-cell contacts and cytoskeleton of the lymphatic endothelial cells.

Päivi Ojala is a group leader at the Institute of Biotechnology, University of Helsinki since 2011. From 2002 to 2011 she was leading a research group in the Research Programs Unit, at the Faculty of Medicine, University of Helsinki.

The Ojala group belongs to the new Centre of Excellence in Translational Cancer Biology (2014-2019) of the Academy of Finland. The Centre of Excellence is led by Academy Professor Kari Alitalo. From 2008-2013 Päivi Ojala has held a research professor post of the Finnish Cancer Institute.

Päivi Ojala lab

Text: Päivi Lehtinen / Elina Raukko

September 9, 2013
The BI SAB site visited the Institute 5-6 September, 2013

The BI SAB site visited the institute 5-6 September, 2013 as a part of the scientific evaluation. On Thursday, the program started with opening words by Professor Marja Makarow from the Academy of Finland. After that Director Tomi Mäkelä gave a presentation about BI at 2011-2013 and the Research Directors presented their research programs by introducing the highlights, challenges and future plans of their research. After the presentations SAB started to evaluate the Group Leaders.

On Friday after the evaluation of Group Leaders there was a poster session where all groups presented their research. The program ended with the panel discussion on the future of the Institute of Biotechnology. The panel was chaired by Professor Marja Jäättelä and the members were Professors Pernille Rorth and Urban Lendahl from the SAB and Ying Yang , Henri Blomster, Jaan-Olle Andressoo and Sarah Butcher from BI. The panel discussed about the role of research programs, meaning of mentoring at all levels, international staff support and finally importance of changing environment and research subject after PhD and postdoc period. The visit will be followed by an evaluation report.

August 29, 2013
The protein version of alternative splicing discovered

cis- and alternative trans- splicing by inteins produces combinatorial proteins.

Dr Hideo Iwai's group has discovered that proteins can be spliced in an alternative way. This discovery might open a way to develop new inhibitors of any enzyme.

Protein splicing is similar to RNA splicing that cuts out the non-coding intervening genes before translation. In proteins the splicing is catalyzed by intervening protein sequences, inteins, which excise themselves from the host proteins. The end products are the final polypeptide sequences (the joined host protein and excised intein).

Protein splicing has become increasingly important in biotechnological and biomedical applications. It has been applied for protein purification, production of biofuel, in vivo protein engineering, genetically modified plants, specific labeling, chemical modifications, improving protein stabilities, and so on. The biological roles of protein splicing are still not wholly understood.

Biochemical and structural analysis of multiple inteins shows that inteins can swap domains before protein splicing. This leads to unexpected alternatively spliced products. This phenomenon is termed intein-mediated protein alternative splicing (iPAS). The iPAS can possibly be used as a protein-conformation driven switch for functions in highly specific manner, for example protein interference.

"This discovery now allows us to develop new inhibitors of any enzyme by applying the same principle", says Hideo Iwai, group leader in the Institute of Biotechnology.

The study was published online on 25 th August in Nature Chemical Biology

Figure: Hideo Iwai

August 7, 2013
Professor Mart Saarma receives $ 495 000 for diabetes research

The Juvenile Diabetes Research Foundation (JDRF) has awarded a research grant of $ 495 000 for three years for supporting a collaborative team headed by Professor Mart Saarma at the Institute of Biotechnology, University of Helsinki and Professor Timo Otonkoski at Biomedicum Stem Cell Center. The aim of the project is to study therapeutic potential of neurotrophic factor MANF (Mesencephalic Astrocyte-derived Neurotrophic Factor) in preclinical research for type 1 diabetes. The therapeutic effect of MANF will be studied using rodent and human pancreatic islets, b -cell lines and in rodent models of diabetes.

Professor Mart Saarma's team is currently studying the structure, biology and therapeutic potential of neurotrophic factors GDNF, CDNF and MANF for neurodegenerative diseases. The indication for neurotrophic factor MANF to be a candidate therapeutic factor for diabetes came from Dr. Maria Lindahl´s work (Saarma group, Institute of Biotechnology). These studies showed that Manf-deficient mice were diabetic due to progressive loss of insulin-producing pancreatic b -cells. The team in the collaborative project includes top experts in the fields of endocrinology, neurosciences and genetic engineering of mice.

Prof. Timo Otonkoski is a pediatrics endocrinologist whose research topic for many years has been in the development and renewal of insulin-producing pancreatic b -cells. Dr. Maria Lindahl´s research has focused on the role of neurotrophic factors in the endocrine system by developing and analysing several genetically modified mice models. Dr. Jari Rossi (Institute of Biomedicine) has extensive experience in genetically engineered mice, and studying energy balance and metabolism. Doctoral students M.Sc. Tatiana Danilova and MD Erik Palm will be tightly involved in the project by working on cell lines, rodent islets and mouse models. MD Elina Hakonen will focus on human islets and cell lines.

 JDRF is the leading global organization funding type 1 diabetes (T1D) research. JDRF's goal is to progressively remove the impact of T1D from people's lives until we achieve a world without T1D.

One of the main goals in type 1 diabetes therapy is to define a method for functional b -cell proliferation and regeneration.

" We have found that MANF can protect and stimulate proliferation of b -cells in a mouse model of type 1 diabetes. In addition, we generated mice which lack MANF protein, resulting in development of T1D. Since MANF has direct effects of mouse b -cells and is expressed and regulated in human b - cells we hope that MANF has therapeutic potential for the treatment of T1D, where b -cell protecting and regenerating therapies are not available" says Professor Mart Saarma. 

Text: Maria Lindahl

June 18, 2013
One step closer to a vaccine for a common respiratory disease (June 18, 2013)

Young children and the elderly are especially susceptible to respiratory syncytial virus (RSV). The three-dimensional structure of respiratory syncytial virus has been solved by an international team from Finland and Switzerland.

RSV is a common cause of respiratory infection, but there is no vaccine available. It causes flu-like symptoms in healthy adults, but becomes life-threatening in young children and the elderly. It is estimated to cause over 100 000 deaths yearly worldwide.

The teams of Research Director Sarah Butcher (Institute of Biotechnology, University of Helsinki) and Professor Ari Helenius (ETH Zurich) have now solved the three-dimensional structure of RSV.

“The structural model helps us to understand how infectious viruses are formed. This information can be useful in the intelligent design of vaccines” said the researcher Lassi Liljeroos.

“RSV is related to measles and mumps viruses. All three viruses parasitize human cells, stealing parts of the cell membrane to use as their own. In RSV the resulting virus membranes look likes tubes and spheres. We could show that the virus’ matrix protein controls this shape”.

“In addition, we observed that the fusion protein on the surface is in two different forms. The fusion protein is responsible for attaching the virus to human cells and invading them. This is an important finding because the fusion protein is the key molecule in developing therapeutic antibodies to the virus. “

This publication is part of Lassi Liljeroos’ Ph. D. thesis where he has earlier studied measles virus. The research was supported by the Academy of Finland, the Sigrid Juselius Foundation, the Viikki Molecular Biosciences Graduate Programme, the European Research Council, and the European Molecular Biology Organisation. The work has been published online in the Proceedings of the National Academy of Sciences (U.S.A.)

Article in PNAS

Illustration: Pasi Laurinmäki and Lassi Liljeroos

June 7, 2013
Funding for the genome of the Saimaa ringed seal from Jane and Aatos Erkko Foundation

Academy Professor Jukka Jernvall and Dr Petri Auvinen received 1,32 million euros from the Jane and Aatos Erkko Foundation to sequence the genome of the Saimaa ringed seal, the first mammalian species to be sequenced in Finland. The Saimaa ringed seal ( Pusa hispida saimensis ) is the world's most endangered seal, with around 300 individuals left, thus offering an excellent opportunity to study an extreme genetic bottleneck in great detail. The combination of reduced genetic variation with derived morphological traits, such as large eye orbits and unique tooth shapes, makes the Saimaa ringed seal a valuable model to uncover the genetic underpinnings of phenotypic traits in natural populations. In collaboration with researchers from the University of Eastern Finland Joensuu, the teams will sequence different seal populations. Thorough knowledge of the genomic structure of seal populations should help in future conservation biology efforts . The grant provides ample opportunities to develop both sequencing pipelines and analytical tools in genomics research.

Text and photo: Jukka Jernvall

June 5, 2013
The Maikki Friberg Equality Prize to Sarah Butcher

"The modern university should offer everyone equally the best possible opportunity to succeed," says Sarah Butcher, who on 5 June 2013 received the University of Helsinki Maikki Friberg award for work promoting equality.

Sarah Butcher, principal investigator and group leader at the Institute of Biotechnology, believes that promoting equality at the University benefits everyone. Solving the problems of one group improves things for all others.

"I want everyone at the University to enjoy the best possible opportunities, irrespective of their gender, language, home country or other background factors," Butcher explains.

This attitude of responsibility traces back to her childhood days as a Girl Scout and has gradually spread into all spheres of her activities.

"What I want to do is first identify problems and then try to solve them. You can really make a difference in committees, even though I'm not particularly fond of meetings," says Butcher, who is a member of many decision-making bodies.

More attention to diverse backgrounds

Many of those working at the Viikki Campus speak a language other than Finnish or Swedish as their mother tongue. In some units, non-Finns account for as much as half the staff.

Although the amount of English-language communication has continued to increase at the University, Finnish language skills are the only guarantee for equal treatment at work and in studies.

"Many forms, salary-related details and legal texts are all Greek even to people who speak Finnish reasonably well," Butcher declares. "To date, many courses have been offered only in Finnish or Swedish. The first English-language course in management is supposed to begin this autumn," says Butcher, who for years has urged non-Finns to attend Finnish language courses in Viikki.

Recruitment ensures a more equal future

Butcher would like to see double hiring, popular in the USA, gain a foothold in Finland. Recruiting both partners of researcher couples reduces situations in which a researcher's spouse follows along to a foreign country without a promise of work.

The employment opportunities of parents with small children are in a class of their own in the Nordic countries.

"Parental leave and widely available daycare services are huge advantages, which make it a lot easier for researchers with families to organise their work. Far too often, however, duties are distributed unevenly, and many at the University end up shouldering too many administrative responsibilities," Butcher concludes.

Sarah Butcher's research group

Text: Elina Raukko
Photo: Ari Aalto

June 5, 2013
The long arm of virus evolution

The viruses that cause human disease are connected to ones found in some of the most extreme environments on Earth

An international team led by Sarah Butcher in the Institute of Biotechnology, University of Helsinki, Finland, and including scientists from the University of Pittsburgh, USA have found a key ancient molecular fossil (protein) in a virus from a salt pan that is evolutionarily related to the virus causing human herpes.

This common protein structure has for the first time been found in organisms from all domains of life.

"This supports the idea that these viral capsids - the container that viruses use to shuttle between different hosts - are ancient and have been shared between different organisms very early in evolution. That is why we have now found them in an archaeal virus (Haloarcula sinaiiensis tailed virus 1), a bacterial virus and a virus infecting humans", says research director Sarah Butcher.

Maija K. Pietilä, Pasi Laurinmäki, Daniel A. Russell, Ching-Chung Ko, Deborah Jacobs-Sera, Roger W. Hendrix, Dennis H. Bamford, Sarah J. Butcher. Structure of the archaeal head-tailed virus HSTV-1 completes the HK97-fold story. PNAS Early Edition 3.6.2013

Article in PNAS

Butcher lab

Text: Sarah Butcher
Ilustration: Pasi Laurinmäki

June 4, 2013
Success in Center of Excellence call at BI

The Academy of Finland selected 6 new Centers of Excellence (CoE) in life sciences, and BI researchers participate in four of these. Jukka Jernvall leads the CoE in Experimental and Computational Developmental Biology with a strong team from BI: Marja Mikkola (vice director); Irma Thesleff; Osamu Shimmi, and Isaac Salazar-Ciudad. Ykä Helariutta and Ari-Pekka Mähönen are in the CoE of Primary Energy Production lead by Eva-Mari Aro (Univ. Turku). Pekka Lappalainen is member in a focused Coe in Membrane Research looking at lipid-protein interactions lead by Elina Ikonen. Päivi Ojala and Tomi Mäkelä are in a CoE in Translational Cancer Biology lead by Kari Alitalo where Mäkelä acts as vice director. Participation in the majority of Finnish life science CoE's indicates maintenance of top quality and reflects the integrative role of BI research programs. The CoE's start in 2014 with funding level to be determined in the fall.

More funding for Mart Saarma's CDNF research from The Michael J. Fox Foundation for Parkinson's Research

Academy Professor Mart Saarma gets almost $ 180,000 from The Michael J. Fox Foundation for Parkinson's Research for his additional CDNF research for one year. MJFF has also funded Saarma's CDNF work with over a million US dollars in 2010-2012.

CDNF is a neurotrophic factor found by professor Mart Saarma group in 2003. CDNF has a unique mode of action, but its receptors and signaling pathways remain elusive. CDNF has neuroprotective effects that might be used in curing Parkinson's disease. Two neurotrophic factors GDNF and it homologue neurturin are in clinical trials but their clinical benefits have so far been very modest.

"One reason for this is that we don't know all that much about the optimal routes for neurotrophic factor delivery. CDNF has so far been delivered only to the striatum. The information about its efficacy after delivery to the substantia nigra and comparison with the efficacy of simultaneous infusion to striatum is critically important" Mart Saarma describes.

Now the MJFF has promised additional funding for Dr. Saarma's CDNF research. Mart Saarma will compare CDNF efficacy in rat 6-OHDA model of PD after CDNF delivery to the striatum, substantia nigra, or with simultaneous delivery to both substantia nigra and striatum.

Mart Saarma is the principal investigator of the project. The co-investigators are Dr. Mikko Airavaara, team leader at the Institute of Biotechnology and Professor Raimo K. Tuominen from the Faculty of Pharmacy.

The Michael J. Fox Foundation for Parkinson's Research

Saarma lab

Text: Elina Raukko
Photo: Kert Mätlik

Laminopathies: key components in the disease mechanism identified

A collaborative study between American and Finnish scientists shows that abnormal structure of the nuclear lamina, caused by laminopathy mutations, leads to changes in gene expression by disturbing the function of a specific transcription regulating protein.

Laminopathies are hereditary diseases that affect mainly the muscle tissue. These diseases include for example Emery-Dreifuss Muscular dystrophy, dilated cardiomyopathy, limb-girdle muscular dystrophy and Hutchison-Gilford progeria syndrome.

The underlying defect in these diseases is mutation in the genes encoding lamins or lamin-associated proteins. For example, many mutations in the lamin gene LMNA have been associated with different diseases.

Lamins are crucial components of the nuclear lamina that underlies the inner side of nuclear envelope, and provides mechanical stability to the nucleus. Lamina also participates in many different nuclear processes.

Two theories exist, why mutations in the lamina components cause disease. According to the first theory, mutations cause changes in the nuclear structure, which can lead to cell death in tissues that undergo harsh mechanical strain, such as the muscle. The second theory postulates that disturbed lamina causes changes in the gene expression patterns that are then deleterious for the cell.

A collaborative study between American and Finnish scientists bridge these two theories in a paper that was published Online Publication (AOP) of Nature

The study shows that abnormal structure of the nuclear lamina, caused by laminopathy mutations, lead to changes in gene expression by disturbing the function of a specific transcription regulating protein.

The researchers found out that in laminopathy cells, the regulation of SRF (serum response factor), which controls the expression of many important genes, is disturbed. The molecular basis for this is that LMNA mutations that cause laminopathy alter the cellular localization of emerin, which is an important constituent of the nuclear envelope. Emerin regulates actin in the cell nucleus, and actin in turn is a critical regulator of SRF activator MKL1. Therefore, mis-localized emerin in laminopathies results in reduced activation of SRF by MKL1, and reduced expression of SRF target genes. Because many SRF target genes are critical for muscle function, this finding explains, why laminopathies affect mainly this tissue type. It also gives a mechanistic link between altered nuclear envelope structure and gene expression.

This study will give a glimmer of hope to the patients suffering from laminopathies, by identifying key components that underlie the disease mechanism. Restoring MKL1 activity in laminopathies might be a productive intervention mechanism for these devastating diseases.

This study was done in collaboration between scientists from Cornell and Helsinki Universities, In Finland, the corresponding author is Maria Vartiainen from the Institute of Biotechnology, who is studying how the regulation of nuclear actin affects gene expression. In Finland, the study was funded by the Academy of Finland and Sigrid Juselius foundation.

In normal cells (upper panel), MKL1 (green) accumulates into the nucleus (red, blue) upon growth factor stimulation to activate SRF-mediated transcription. However, in cells with LMNA-mutations (lower panel), this accumulation is disturbed.

Article in Nature
Vartiainen lab

Text: Maria Vartiainen
Photo: Kaisa Rajakylä

3D simulation shows how form of complex organs evolves by natural selection

Researchers at the Institute of Biotechnology of the University of Helsinki have developed the first three-dimensional simulation of the evolution of morphology by integrating the mechanisms of genetic regulation that take place during embryo development. The study, published in Nature , highlights the real complexity of the genetic interactions that lead to adult organisms' phenotypes (physical forms), helps to explain how natural selection influences body form and leads towards much more realistic virtual experiments on evolution.

"Right now we have a lot of information on what changes in what genes cause what changes in form. But all this is merely descriptive. The issue is to understand the biological logic that determines which changes in form come from which changes in genes and how this can change the body", explains Isaac Salazar, a researcher at the University of Helsinki and lead author of the article. In nature this is determined by embryo development, during the life of each organism, and by evolution through natural selection, for each population and species.

But in the field of evolution of organisms it is practically impossible to set up experiments, given the long timescale these phenomena operate on. This means that there are still open debates, with hypotheses that are hard to prove experimentally. This difficulty is compensated for by the use of theoretical models to integrate in detail the existing experimental data, thus creating a virtual simulation of evolution.

The researchers used a theoretical model based on experiments on embryo development, on a previous study, also published in Nature (Salazar-Ciudad and Jernvall, 2010), and on three different mathematical models of virtual evolution by natural selection of form. Evolution takes place virtually on the computer in populations of individuals in which each individual can mutate its genes, just as this works in nature. Through the development model, these produce new morphologies and natural selection decides which ones pass on to the next generation. By repeating the process in each generation, we can see evolution in action on the computer.

This simulation enables a comparison of the different hypotheses in the field of evolution regarding which aspects of morphology evolve most easily. The first vision is that all metric aspects of form contribute to adaptation and that, consequently, all are fine-tuned by evolution over time. The second vision is that some aspects of form have greater adaptive value and that the remainder evolve collaterally from changes in these. The third is that no aspect of form is intrinsically more important, but what is important adaptively is a complex measurement of the form's roughness.

"What we have found is that the first hypothesis is not possible and that the second is possible in some cases. Even if ecology favoured this type of selection (the first vision), embryo development and the relationship between genetic and morphological variation imposed by this is too complex for every aspect of morphology to have been fine-tuned. In one way, what we are seeing is that natural selection is constantly modelling body forms, but these are still a long way from perfection in many ways", points out Salazar.

The study was led by Isaac Salazar-Ciudad and involved a PhD researcher, Miquel Marín Riera, from the Autonomous University of Barcelona. Isaac Salazar-Ciudad is part of the Helsinki "evo-devo" community (embryonic evolution and development) at the Institute of Biotechnology.

Real-time graph of virtual evolution process. The horizontal axis corresponds to evolution time and the vertical axis to the population's degree of evolutionary adaptation. In this case the form of the tooth adapts by increasing the number of tips, moving from a simple tooth to a more complex one.

Salazar-Ciudad I , Marín-Riera M. Adaptative dynamics under development-based genotype-Phenotype maps. Nature . 2013 May 1. doi: 10.1038/nature12142. [Epub ahead of print]

Article in Nature

Text and photo: Isaac Salazar

March 2013

Research

BI Annual report 2012

BI Annual Report 2012 has been published as an online version

BI Annual Report 2012

 

The best doctoral thesis award to Enni Harjunmaa

Dr. Enni Harjunmaa from the Jernvall group received the award of the best doctoral thesis in year 2012 at the University of Helsinki for her PhD Thesis " Tinkering with cusp patterning : Developmental Genetic Mechanisms in Mouse Molar Development" .

"Our results provide new information on the developmental genetic mechanisms of tooth crown patterning, on how these mechanisms provide developmental stability, and on the kind of evolutionary constraints they cause. We also found that in the case of tooth crowns, increase in morphological complexity correlates positively with the number of signalling pathways tuned simultaneously" Harjunmaa describes.

The award of the best doctoral thesis will be granted to especial distinguished PhD thesis.

Photo: Elina Raukko

Tinkering with cusp patterning : Developmental Genetic Mechanisms in Mouse Molar Development" .

February 2013

Hair follicle regeneration - one step closer?

The induction and morphogenesis of many organs including hair follicles is regulated by reciprocal interactions between epithelial and mesenchymal tissues. The initiation of hair follicle development is marked by reorganization of epithelial cells into a local thickening called a placode. Concomitant with placode formation, the underlying mesenchymal cells cluster into a condensate, the precursor of hair-specific fibroblasts known as dermal papilla cells. It is well established that the dermal condensate/papilla (but not the hair producing epithelial follicular cells) bears the hair-inducing capacity and can provoke hair follicle development even when combined with non-hair-forming epithelium. However, therapeutic efforts to use dermal papilla cells to induce hair neogenesis have been hampered by their low abundance and loss of hair follicle-inducing properties in culture. Therefore, how the dermal condensate is induced and maintained is a focus of intensive regenerative medicine research. Until now, relatively little has been known about how dermal condensate cells gain hair-inductive potential, and the signal(s) governing dermal condensate formation has remained elusive.

In a recent study published in Genes & Development , teams headed by Marja Mikkola from the Institute of Biotechnology and David Ornitz from Washington University School of Medicine in St. Louis, present progress in dissecting the early inductive events in hair follicle formation. This study identifies Fgf20, a member of the fibroblast growth factor family, as a placode-derived signal essential for dermal condensate formation. Using mouse models, it is shown that Fgf20 functions downstream of ectodysplasin/NF-?B and Wnt/ß-catenin, two key pathways necessary for hair placode formation in all mammals, to initiate formation of the underlying dermal condensate. Perhaps in the future this knowledge can be harnessed to generate dermal papilla cells for the treatment of hair loss.

A hair placode is marked by expression of P-cadherin (green) and the dermal condensate by Sox2 (red).

Huh SH*, Närhi K*, Lindfors PH, Häärä O, Yang L, Ornitz DM, Mikkola ML. Fgf20 governs formation of primary and secondary dermal condensations in developing hair follicles. Genes Dev. 2013;27:450-458. *) equal contribution (PubMed)

Text: Team Mikkola
Photo: Otso Häärä

January 2013

Yrjö Helariutta gets a grant of about 2,4 million euros from the ERC

Academy professor Yrjö Helariutta receives a 2,4 million euros Advanced grant from the European Research Council ERC. The grant is for five years.

 Academy professor Yrjö "Ykä" Helariutta has been researching matters related to wood formation for years. Now he has received a much sought-after European Research Council (ERC) Advanced grant. The five-year grant is worth about 2,4 million euros.

Helariutta researches now the role of symplastic communication during root development. That area is still very much uncharted.

This time the European Research Council ERC gave out Advanced grants worth of 680 million euros. There were 302 senior research leaders in 24 different countries across Europe that were given the grant for five years. The grant can be up to 2,5 million euros per project. 15 per cent of the selected scientists are women, and the average age of the researchers funded is 51 years.

Helariutta lab

Text: Elina Raukko
Picture: Veikko Somerpuro

 

December 2012

Research Director in Structural Biology/Biophysics and Tenure-track Group Leaders

For its call in 2012  BI received a record number  (112) of applications  for Research Director in Structural Biology and Biophysics (16) and Tenure-track Group Leader (96) positions. 80% of the applications were from abroad (top countries USA, Germany, UK, Switzerland, Spain) and 20% of applicants were female.

A Search Committee consisting of  Sarah Butcher,  Yrjö Helariutta,  Jukka Jernvall,  Pekka Lappalainen, and  Tomi Mäkelä arranged for 17 interviews combined with seminars and visits in the Helsinki area. Based on a statement on 2 Research Director, 7 Group Leader, and 1 Joint Group Leader applicants from the Scientific advisory board, the Board of BI recommended the director to initiate detailed discussions with the listed applicants (in rank order)  with a recommendation to recruit 2-3 tenure-track Group Leaders : 

1) Christoph Bieniossek;   EMBL Grenoble (Berger lab); transcription machinery complexes; crystallography
2) Nicolas Di-Poi;  Univ Geneva (Milinkovitch lab); regeneration of dentitions and brain; molecular and developmental genetics
3) Pekka Katajisto;  Whitehead Inst./MIT (Sabatini lab); stem cells & asymmetric cell division in aging; cell biology and mouse models
4) Marja Mikkola; Institute of Biotechnology;  e pithelial morphogenesis; developmental biology and mouse models.

Furthermore, one of the recruited Group Leaders should be  from a field of structural biology/biophysics.  The inability to recruit at the Research Director level was due to the  decision of the University of Helsinki to not provide strategic funding for the Research Director startup packages. The Board also supported the possible recruitment of professor Marikki Laiho  (Johns Hopkins University) to a Joint Group Leader Position if the Faculty of Pharmacy decide to invite Laiho. 

Mart Saarma group gets funding from Michael J. Fox Foundation

Researchers of the Mart Saarma group at BI got a 125 000 dollar grant from Michael J. Fox Foundation for Parkinson's Research.  The group strives to prevent the death of dopaminergic brain cells with the help of the CDNF nerve growth factor.

Parkinson's disease is connected with the distruction of dopaminergic nerve cells. The cells get clogged with a protein called alpha-synuclein. The gene coding alpha-synuclein is also mutated in the hereditary forms of Parkinson's disease.
CDNF, a nerve growth factor that might prevent the alpha-synuclein-induced nerve cell death, has been found in the Institute of Biotechnology.  Michael J. Fox Foundation for Parkinson's Research has given a 125.000 dollar grant for Mart Saarma group to test the effects of CDNF.

“Earlier our group has studied another nerve growth factor, GDNF. It hasn't, however, functioned in dopaminergic brain cells with alpha-synuclein protein clumps. CDNF is predicted to have different effects, because its mechanism differs from the GDNF completely”, research team leader Mikko Airavaara says.

CDNF is part of a nerve growth factor family whose mechanism seems to be connected with the stress of the endoplasmic reticulum (ER) and protein folding.

 “We think that this might be significant for two reasons from Parkinson's point of view. The dopaminergic pathway is sensitive to ER stress, and alpha-synuclein is also known to induce that stress”, Airavaara says.

About The Michael J. Fox Foundation for Parkinson's Research
As the world's largest private funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers.  In addition to funding over $270 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure.

Michael J. Fox Foundation for Parkinson’s Research 

Saarma lab

Text: Mikko Airavaara and Elina Raukko

Research Director in Structural Biology/Biophysics and Tenure-track Group Leaders

The Institute of Biotechnology received a total of 112 applications for the Research Director in Structural Biology and Biophysics and Tenure-track Group Leader positions.

The Search Committee has made a decision on initial applicants to interview. The call was highly competitive and there were applications from several top Universities like Cambridge, Oxford, Chicago, Yale, Princeton , Johns Hopkins and Columbia . The initial interviews will take place in August-September and the aim is to make final selections after statements by the Scientific Advisory Board by the end of the year.

Research Director in Structural Biology:

16 applications
- 7 Germany, 3 USA, 2 Spain, 4 other countries
- no female applicants
- 3 applicants for interview

Tenure-track group leader positions:

96 applications
- 19 Finland, 16 USA, 15 Germany, 8 UK, 7 Switzerland, 6 Spain, 25 other countries
- 22 female (32%)
- 13 applicants for interviews (2 female)

Search Committee:
Sarah Butcher
Yrjö Helariutta
Jukka Jernvall
Pekka Lappalainen
Tomi P. Mäkelä

November 2012

Research teams to the Second stage in Centre of Excellence call have been selected

The Board of the Academy of Finland has selected 34 research teams that will proceed to the second stage of the Centre of Excellence (CoE) call. At the first stage of the two-stage call for funding, the Academy received a total of 128 plans of intent covering a wide range of disciplines and research fields. The plans of intent were reviewed by international experts.

Among the teams that will proceed to the second state BI researchers are involved in:

Ihmisen ja taudinaiheuttajien rajapinnan huippuyksikkö, Director: Adrian Goldman ( PIs: Sarah Butcher , Markku Varjosalo )

Kalvotutkimuksen huippuyksikkö: lipidi-proteiinien-vuorovaikutuksista biologisiin toimintoihin, Director: Elina Ikonen (PI: Pekka Lappalainen )

Kokeellisen ja laskennallisen kehitysbiologian huippuyksikkö, Director: Jukka Jernvall ( PIs: Marja Mikkola, Isaac Salazar-Ciudad , Osamu Shimmi, Irma Thesleff )

Centre of Excellence in Translational Cancer Biology, Director: Kari Alitalo (PIs: Tomi Mäkelä , Päivi Ojala )

Primaarienergian tuoton kansallinen huippuyksikkö, Director Eva-Mari Aro (PI: Ykä Helariutta)

Mikrobien, virusten ja bioaktiivisten aineiden huippuyksikkö, Director: Kaarina Sivonen (PI: Dennis Bamford)

List of projects invited to the second stage

Photo: Eeva Anandi

A new future for an old crop: barley enters the genomics age

Higher yields, improved pest and disease resistance and enhanced nutritional value are among potential benefits of an international scientific research effort that has resulted in a high-resolution sequence resource of the barley genome, as described in a paper published in the prestigious journal Nature.

The new resource, produced by the International Barley Sequencing Consortium (IBSC), a worldwide group, will facilitate the development of new and better barley varieties able to cope with the demands of climate change. It should also help in the fight against cereal crop diseases, which cause millions in losses every year.

The Finnish team was led by researchers in MTT/BI Plant Genomics Laboratory, a joint facility of MTT Agrifood Research Finland and the Institute of Biotechnology, University of Helsinki.

First cultivated more than 15,000 years ago, barley belongs to the Triticea e family - which includes wheat and rye - and that together provides around 30% of the calories consumed worldwide. It is the world's fourth most important cereal crop both in terms of area of cultivation and in quantity of grain produced, and it is also Finland's most important grain crop, accounting for 41% of the total yield and also 41% of the total hectares of grain in 2011, worth € 310 million.

The barley genome is almost twice the size of that of humans and determining the sequence of its DNA has presented a major challenge. This is mainly because its genome contains a large proportion of closely related sequences, which are difficult to piece together. By developing and applying a series of innovative strategies that allowed them to circumvent these difficulties, the IBSC has succeeded in producing a high resolution assembly of the majority of barley genes in linear order. This is an important milestone towards eventually unravelling a full barley genome sequence.

Their publication in Nature provides a detailed overview of the functional portions of the barley genome, revealing the order and structure of most of its 32,000 genes and a detailed analysis of where and when genes are switched on in different tissues and at different stages of development. They describe the location of dynamic regions of the genome that carry genes conferring resistance to diseases. This will provide a far better understanding of the crop's immune system. The achievement will also highlight with unprecedented detail the differences among a range of different barley cultivars.

The leader of the Finnish group was Professor Alan Schulman of MTT and the University of Helsinki. He commented: "Access to the genes of barley will speed efforts to improve barley production through breeding. We will better able to find solutions for diseases and the effects of climate change and to produce more sustainable barley needing less chemical inputs. It will accelerate research in barley, and its close relatives, wheat and rye. Breeders and scientists will be to deal with the worldwide issue of food security. This opens the door to getting the full genome sequence, which now will be a straightforward, if major undertaking."

The article in Nature

Schulman lab

Text: Alan Schulman
Photo: Tapio Tuomela / MTT archive

Pekka Lappalainen started as the professor of quantitative cell biology at the Institute of Biotechnology

Pekka Lappalainen has been a familiar face at BI since 1998. Now he starts as the professor of quantitative cell biology.

From the beginning of September Pekka Lappalainen became the first ever permanently employed professor in any of the independent research institutes in the University of Helsinki. So far this kind of employment arrangement has been possible only in the departments within the faculties.

Mart Saarma the future professor of biotechnology likewise employed in the BI, starts his work in January 2014. His Academy of Finland professorship lasts till the end of 2013.

No major changes yet

Pekka Lappalainen, also the deputy director of the BI, predicts that his work as a professor does not change that much from the one of a group leader. At least not right now.

"I believe my job and its contents will build up with time. I for example don't suppose I'll give more lectures, at least not right away. On the other hand, I have been running the GPBM doctoral programme which is one of the biggest and most visible doctoral programs in the University of Helsinki, but I'm trying to end my part in it gradually before the end of the year".

Researcher right from the start

Pekka Lappalainen wanted to be a researcher from early on and he first planned to go to a medical school. However, when it dawned on him that in order to be a MD carrying out research one must also work as a medical doctor in a hospital for a while, he decided to choose biology instead.

Pekka Lappalainen's laboratory now studies the mechanisms of actin and plasma membrane dynamics. Although these research topics have significant importance in medicine - for example in cancer biology - his main interests are, at least currently, on understanding the fundamental biochemical and biological principles of these processes.

In addition to research, teaching and administration, Pekka Lappalainen serves as an executive editor of the journal Cytoskeleton and as an editorial board member of Cell Reports

How to get the best researchers?

During his PhD-work at EMBL, Heidelberg and post-doctoral years in Berkeley, U.S.A. Pekka Lappalainen became aware how important it is to choose the most talented people to the research group and make sure that they work well together. For this purpose, his post-doctoral supervisor had a brilliant way to choose people to the research group.

"All the people in the group had a discussion with the applicant, each and every one individually. Finally the group leader gave the group his credit card and told them to go and grab a bite and have some beer. This wasn't only a time for relaxing, as the applicant might imagine. The group members observed the applicant's behaviour and if something annoying turned up, the applicant could be turned down. And sometimes really was."

Pekka Lappalainen uses the same system - without the restaurant part - when he's getting new people to his group. All the members of the group have to feel that the newcomer fits in.

Evaluation promotes high quality

The group leaders in the Institute of Biotechnology are evaluated every four years. Depending on the results they can either continue or must leave.

"Even if you have to leave it doesn't mean that your research has been second-rate. Our aims just are so high. Evaluation guarantees that we stay alert. If the only way to get new people in is to wait for the currently employed to retire, it might not improve the quality of the research. And the new permanently employed professors still get evaluated", Pekka Lappalainen points out.

Pekka Lappalainen also praises the BI for its flexibility. Sometimes during a researcher's career it can happen that funding periods fail to follow each other closely. Short term funding crises can be helped within the BI.

"Also recruiting is easier when the structure is less rigid", Pekka Lappalainen agrees.

Text and photo: Elina Raukko

The findings of the ENCODE project were published

As Dr. Ewan Birney promised in his lecture at the Institute, the findings of the ENCODE project studying the human genome, were published on 5 September, in more than 30 peer-reviewed publications in Nature, Genome Research and Genome Biology. The ENCODE project is not only one of the most significant accomplishments in genome biology since the human genome sequence, but the way that the results and findings are published is revolutionary. The publication home page allows the reader to follow "threads" through many different publications across multiple journals; many of the images in the web-versions of the articles are interactive and allow manipulating the data shown; and, in addition to being all open access, computational analyses forming the basis of the findings can be reproduced using a downloadable virtual machine.

ENCODE Home page

Text: Ari Löytynoja

The role of the actin in the nucleus: getting solved

"The nucleus is the command centre of the cell. It is highly organized, and the actin filaments belonging to the cytoskeleton most likely play an important role in its compartmentalization", says Maria Vartiainen from the Institute of Biotechnology. She has been awarded with a 1,5 million euro ERC starting grant for her nuclear actin research.

The nucleus of the cell is in many drawings depicted like a ball full of holes. The nucleolus floats inside it in what seems like porridge made of DNA and proteins: chromatin. Despite its disarranged looks the nucleus is the command centre of the cell. It couldn't function without a high level of organization.

"The nucleus is actually very highly compartmentalized. The inner order varies, and for example some diseases and cell differentiation have effect in the compartmentalization", explains Maria Vartiainen, a researcher in the Institute of Biotechnology

New ways, new information

Researching the nucleus has been problematic so far. The inner structures are hard to make visible and when the structures can be seen, their function is difficult to find out. New techniques offer better views to the events inside the nucleus.

"With this microscope we can look for example at living cells in a cell culture. We can also research interactions between proteins. The most powerful microscopes of this kind can reach almost as deep as one millimetre inside the sample", Maria Vartiainen says presenting a multiphoton microscope standing on a vibration-resistant table.

Answers to big questions

Maria Vartiainen focuses on actin, a protein belonging to the cytoskeleton. Actin was found also in the nucleus some 40 years ago. Its precise nuclear functions are, however, still unclear.

" Actin is an excellent candidate in mediating cell compartmentalization. There are still two big, open questions: What is the biological meaning of nuclear actin? And furthermore: what is the molecular system that actin uses for functioning in the nucleus?" Vartiainen wonders.

Maria Vartiainen and her research group have recently identified a mechanism that imports actin to the nucleus. By modifying this transport mechanism it is possible to manipulate both nuclear actin levels and its polymerization properties.

"This way we can for the first time identify genes whose expression is dependent on actin. Also the role of the nuclear actin in the compartmentalization will get clearer", Maria Vartiainen says.

Microscopy intrigues

Maria Vartiainen will soon receive a 1,5 million euro European Research Council starting grant for her nuclear actin research. The grant is one of the three dealt for life sciences this year in Finland. The grant spans five years.

"The now existing research group probably will get a member or two more. We can also plan bigger and more expensive experiments now - something that we have earlier on just dreamed of" Vartiainen explains.

Maria Vartiainen is the scientific leader of the light microscopy unit in the Institute of Biotechnology. She readily admits that she now has her dream job. The equipment is one of the best in Finland and microscopy is as interesting as ever. "During my postdoctoral years in London I spent a lot of time in the cellar with a microscope. I just love it. The cells do all kinds of funny things under the microscope. And it still is the highlight of the week when I get to look at the samples", Maria Vartiainen laughs.

Vartiainen Group

Beyond the Visible: Actins (YuoTube)

Text and photo: Elina Raukko

Dr. Ewan Birney will visit the Institute on 31 August

Dr. Ewan Birney, the Associate Director of the EMBL-EBI and a highly successful bioinformatician will be visiting BI on 31 August. Ewan Birney has a central role in most of the big genome projects of the past 10 years.

He will give a lecture on the ENCODE project studying the human genome that he directs. In the afternoon there will be a panel discussion. The topics will include the role of computational analysis in molecular biology research and the need of bioinformatic skills by biologists. The event is open for everybody.

More information about the event can be found on the blog page.

July 2012

The first integral membrane protein structure solved in Finland

The first integral membrane protein structure solved in Finland provides a basis for the development of drugs against malaria and the development of biological batteries.

Professor Adrian Goldman's group in the Institute of Biotechnology at the University of Helsinki is the first one in Finland to solve the structure of a membrane-integral protein. This sodium-ion pumping pyrophosphatase may in the future be part of a biological battery. The structure may also lead to the development of new drugs against malaria and other diseases caused by protozoan parasites.

Though 60 percent of all drugs bind such proteins, they are extremely difficult to solve and represent less than 2 percent of all solved structures. The work is thus a breakthrough in Finnish science. The structure just solved is a sodium-ion pumping pyrophosphatase: a molecular machine that transfers ions from one side of a membrane to the other. The protein pump gets the energy needed for pumping the ions from pyrophosphate, which could be produced reasonably cheaply by industry. Professor Adrian Goldman predicts that membrane-integral pyrophosphatases might thus in the future produce electricity for biological batteries.

Membrane-integral pyrophosphatases do not occur in humans but are important in plant development and in the growth of protozoan parasites, like the malaria parasite. Now that the structure has been solved, drugs can be rationally designed to prevent it working.

The membrane-integral protein the research group has solved comes from Thermotoga maritima, a bacterium that grows in deep sea vents. The structure has been solved by x-ray crystallography. In this method, the protein is produced and crystallised, and the crystals studied at very bright x-ray sources. In this way, each atom in the protein can be seen.

The structure of the sodium-pumping pyrophosphatase and a description of its mechanism was published on July 27, in Science , one of the most important scientific journals in the world.

The authors from Goldman Group: Tommi Kajander (left), Adrian Goldman, Konstantin Kogan and Juho Kellosalo.

Kellosalo J, Kajander T, Kogan K, Pokharel K, Goldman A . The structure and catalytic cycle of a sodium-pumping pyrophosphatase. Science . 2012 Jul 27;337(6093):473- 6.

Article in Science

The Goldman Group

Text: Elina Raukko and Adrian Goldman
Photo: Elina Raukko

Molecular regulation of dental stem cells: a step closer to tooth bioengineering

The loss of teeth affects oral health, quality of life as well as one's appearance. Despite progress in bioengineering protocols, building a tooth from stem cells remains a long-term goal. To develop such protocol, studies are performed on mouse front teeth (incisor) where the stem cells are already localized. They are responsible of the life-long incisor growth.

In this new study, published in Developmental Cell, Frederic Michon and Emma Juuri in the group of Professor Irma Thesleff from the Institute of Biotechnology analyzed in details the molecular signals at work for the dental stem cell maintenance and differentiation. The transcription factor Sox2 was found to be expressed by a specific subset of cells in the incisor stem cell niche. The use of transgenic mouse tools revealed that the Sox2 -expressing cells are a self-renewing population, which gives rise to all the dental epithelial lineages during the tooth renewal. These two features are specific for adult stem cells. The study describes as well the tight molecular regulation of Sox2 expression by Fgf8 and micro-RNAs. These results increase the knowledge related to dental stem cell maintenance. Moreover, the discovery of Sfrp5 as marker of the early Sox2 + cell progeny gives proper tools to study further the biology of dental epithelial stem cells.

Fine-tuning of the molecular network involved in adult stem cell maintenance is the key to life-long renewal activity. Understanding how stem cells are segregated in embryonic organs, maintained, and then progressively lost in aging process is a long-term goal. Achieving it should lead to organ bioengineering protocols and clinical applications.

Figure: (A) Sox2+ SCs (green) in the distal tip of the labial CL give rise to progeny that move in four main directions (blue arrows), all going through the Sfrp5+ area (red): the ameloblast lineage along the labial surface of the incisor, the IEE/OEE ridge on both sides, and the OEE in the posterior part of the labial CL.(B) The progeny from Sox2+ SCs (blue) form ameloblasts and SI, SR, and OEE cells and take part in the renewal of the ERM (yellow). CL, cervical loop; ERM, epithelial rests of Malassez.

Juuri E, Saito K, Ahtiainen L, Tummers M, Seidel K, Klein OD, Hochedlinger K, Thesleff I, Michon F. Sox2+ stem cells contribute to all epithelial lineages of the tooth via Sfrp5+progenitors. Dev Cell 2012 Jul 19.

Article in PubMed

Thesleff Group

Text and photo: Thesleff Group

May 2012

Professor Yrjö Helariutta selected as new Academy Professor

The Board of the Academy of Finland has selected professor Yrjö Helariutta as new Academy Professor for the years 2013-2017. Seven other new Academy Professors are Professors Lauri Aaltonen, Jaakko Kaprio, Antti Kupiainen, Juha Merilä, Uskali Mäki and  Adjunct Professor Elina Vuola from the University of Helsinki, and Professor Kari Rissanen from the University of Jyväskylä. Their five-year term will start 1 January 2013.

The new Academy Professors represent a wide range of research fields: genetic epidemiology and cancer genetics, ecology, plant biology, mathematical physics, supramolecular chemistry, philosophy of science, and theology. According to the international reviewers, the selected Academy Professors are world-class researchers in their own fields. They all have great potential to achieve major scientific breakthroughs.

Professor Yrjö Helariutta works as a Group Leader and Research Director at the Institute of Biotechnology. Helariutta and his team are investigating the molecular basis of wood development and its diversity. Wood is derived from stem cells that occur as a cylindrical sheet in the trunk of a tree. They investigate how genes regulate these stem cells in tree systems and in the more amenable Arabidopsis . The group has shown that cytokinins promote stem cell identity during root development in Arabidopsis . In addition to specifying vascular cell identity, cytokinins have a second role in controlling the rate of proliferation of vascular cell files. Together, their results show that cytokinins are major hormonal regulators required for cambial development.

Wood Development Group

Photo: Veikko Somerpuro

BI Research communities succeeded in UH research and doctoral training evaluation

Report of the international evaluation of research and doctoral training at the University of Helsinki 2005-2010 was published 7th May. According to the report all major disciplines at the University of Helsinki perform leading research at the international level.

The report shows that in international publications, research results of the University of Helsinki are referred to more frequently than the average. In 2005, the number of references obtained by the University was 50% higher than the international average, and the figure had increased to 59% by 2010. The impact of the University of Helsinki was exceptionally high particularly in bio science publications

BI Research communities were evaluated in The Biological, Agricultural and Veterinary Sciences and The Medicine, Biomedicine and Health science panels. In their feedback the panels stated that the BIO sector at UH is in a healthy position, and includes several world class research groups as well as nationally significant training centres feeding into industry and the wider community. The Panel was generally impressed with the training programs outlined in the RC documents and the quality of individual researchers: There are excellent publication track records and some very outstanding RCs. The doctoral training programs seems running very well.

Between 2013 and 2016, the University of Helsinki will be allocated a total of €10.5 million in research allowance for researcher communities that were among the most successful 30% in the five assessment categories. Five of the awarded RCs were from BI : Prof. Yrjö Helariutta: ViiGen, Prof. Jukka Jernvall: EvoDevo, Prof. Pekka Lappalainen: Cell MolBiol, Prof Irma Thesleff: HelDevBio and Mart Saarma: Neurointroph.

The Evaluation Report of Research and Doctoral Training at the University of Helsinki 2005-2010

Photo: Ida Pimenoff

April 2012

EMBO Laboratory Management Course " The Art of Leadership" for Group Leaders

Päivi Ojala, a group leader from the Institute participated in the four-day EMBO Laboratory Management Course " The Art of Leadership" for Group Leaders, on April 15-19, 2012, in Leimen, Germany. The training program included topics on personnel recruitment/selection, leadership and team development, communication skills and provided tools and solutions for effective conflict and problem solving. These courses have been highly rated since they began in 2004 .

The format of the course comprised of compact introduction(s) to the theoretical background followed by immediate practical exercises, in the form of interactive role-play and discussion groups. This setup provided very useful hands-on experience/practice on the topics and practical tools to give feedback and constructive criticism, help group members to learn how to solve many of their problems themselves, and delegate tasks efficiently.

"I feel that I am more tuned to understand the dynamics in the lab, the needs of my lab members, and how to improve the lab's performance level. It was indeed very helpful to realize that it is normal to have management problems, and that understanding and accepting it is already a huge step forward to solve them. This course totally exceeded my expectations and I think it will have a major impact on my future leadership as I learned that there are tools and processes to help me lead my group rather than just to rely on intuition. The teachers/trainers of hfp consulting were extremely professional with excellent perception and knowledge what it takes to lead a successful research group in the field of life sciences", Ojala said.

Text & Photo: Päivi Ojala

Viral replication program impedes the efficacy of a targeted therapy against virus-induced lymphomas

Kaposi's sarcoma herpesvirus (KSHV) is a human tumor virus and an etiological agent for Kaposi?s sarcoma and primary effusion lymphoma (PEL). PELs are aggressive lymphomas with reported median survival time shorter than six months after diagnosis. Researchers at the University of Helsinki discovered that spontaneous induction of KSHV lytic replication in tumors drastically attenuated the p53-dependent apoptotic response not only to a targeted therapy (Nutlin-3) but also to genotoxic anti-cancer agents

The findings by the research groups of Päivi Ojala  (Institute of Biotechnology & Research Programs Unit, Univ. of Helsinki) and Pirjo Laakkonen  (Research Programs Unit, Univ. of Helsinki) provide valuable in-depth knowledge on the use of reactivation of p53 as a highly selective treatment modality for the virally-induced lymphoma. The project involves scientists from the Genome-Scale Biology and Molecular Cancer Biology Research Programs. The study was published 2.4.2012 in the Oncogene.

TP53 gene encodes a transcription factor (p53) that plays a central role in protecting cells from tumor development by inducing cell-cycle arrest or apoptosis via a complex signal transduction network referred to as the p53 pathway. TP53 gene is mutated or deleted in 50% of all malignant tumors. A potent strategy for restoration of p53 function is based on the inhibition of the interaction of p53 with its negative regulator MDM2 via a selective small-molecule inhibitor of the p53 MDM2 interaction, the Nutlin-3.

PEL is a non-Hodgkin type lymphoma latently infected with KSHV, and it manifests as an effusion malignancy in Kaposi?s sarcoma patients. There are no current therapies effective against the aggressive KSHV-induced PEL. KSHV displays two patterns of infection: latent and lytic phase. During latency, only a restricted set of viral genes is expressed. The KSHV genome encodes several homologues of cellular proteins, which engage cellular signaling pathways, govern cell proliferation and modulate apoptosis.

Majority of the PELs appear to have an intact TP53 gene suggesting that genetic alterations are not selected for during PEL tumorigenesis. Earlier report from the same researchers showed that Nutlin-3 selectively induces massive apoptosis in PEL cells leading to efficient anti-tumor activity in a subcutaneous xenograft model for PEL (Sarek et al. 2007).

Here they report viral lytic replication as a factor, which can hamper the otherwise efficient apoptotic response of p53 restoration in vivo. Spontaneous induction of viral lytic replication in the tumors drastically attenuated the Nutlin-3-induced p53-dependent apoptotic response. Attenuation of the cell death response in the lytic PEL cells was not restricted to p53 reactivation by the MDM2 inhibitor Nutlin-3, but was also observed upon induction of apoptosis by genotoxic agents. Importantly, the undesired resistance was overcome and the sensitivity of cells to Nutlin-3-induced apoptosis was restored by inhibition of viral replication.

Sarek S, Ma L, Enbäck J, Järviluoma A, Moreau P, Haas J, Gessain A, Koskinen PJ, Laakkonen P, Ojala, PM. Kaposi's sarcoma herpesvirus lytic replication compromises apoptotic response to p53 reactivation in virus-induced lymphomas. Oncogene, April 2012, Advanced online publication. (PubMed)

Sarek G, Kurki S, Enbäck J, Iotzova G, Haas J, Laakkonen P, Laiho M, Ojala PM. Reactivation of the p53 Pathway as a Novel Treatment Modality for KSHV-induced Lymphomas. J Clin Invest. 2007; 117(4): 1019-1028. (PubMed)

Text: Paivi.M.Lehtinen
Photo: Ojala group

UH Reform Committee's report on Instute of Biotechnology

The Institute of Biotechnology (BI) on the Viikki campus operates in a good collaboration with faculties especially in the areas of doctoral training and core facilities. The collaboration is widely considered as a win-win situation on campus where all operators benefit from each other. Institute of Biotechnology researchers participate to a variable degree also in education provided by faculties at all educational levels, although focus is understandably at the doctoral stage. Separately the Reform Committee proposed that UH Animal Facility operations should be rearranged in a way where Viikki operations would become administratively part of the Institute of Biotechnology. The indicated motivation was to  improve cost efficiency. 

March 2012

A novel pathway regulating mammary gland branching morphogenesis identified

Mammals are unique as their survival depends on the ability of the mother to feed the young by producing milk from a specialized gland, the mammary gland. To this end, mammary gland ductal epithelia undergo extensive branching morphogenesis, which is initiated during embryogenesis but is only completed upon pregnancy to support lactation. It has been long recognized that mammary glands, like many other organs, are formed by an exchange of paracrine factors between epithelia and the stroma (mesenchyme), but signals regulating onset of branching morphogenesis during embryogenesis have remained elusive.

In this new study, published in PNAS , a team headed by Academy Research fellow Marja Mikkola from the Institute of Biotechnology used mouse models to identify ectodysplasin (Eda), a tumor necrosis factor-like signaling molecule, as an important mesenchymal regulator of mammary ductal growth and branching. The functions of Eda were shown to be mediated by transcription factor NF- k B, more famous for its role in immunity, inflammation, and cancer. Loss of Eda, or inhibition of NF- k B, led to smaller ductal trees with fewer branches. On the other hand, overexpression of Eda caused a striking, NF- k B -dependent phenotype characterized by precocious and highly increased ductal growth and branching that correlated with enhanced cell proliferation. Several signaling molecules were identified as transcriptional targets of Eda. An in-house developed unique mammary bud culture system was used to manipulate mammary development ex vivo. It was shown that Eda-induced molecules stimulate embryonic branching morphogenesis ex vivo suggesting that they may cooperatively mediate the effects of Eda in vivo.

The ectodysplasin signaling pathway has a conserved function in all vertebrates. In humans, inactivating mutations in Eda cause a congenital condition known as ectodermal dysplasia, characterized by missing teeth, sparse hair, and inability to sweat. Reports on breast defects in ectodermal dysplasia patients are scanty, but together with this study, they suggest that Eda is an important regulator of human breast development as well. On the other hand, elevated levels of NF-?B activity have been associated with hormone-independent breast tumors with poor prognosis raising the possibility that Eda signaling, if deregulated, may contribute to tumorigenesis.

Mammary buds of wild-type (left) and Eda-overexpressing (right) embryos were cultured for 5 days ex vivo.

Voutilainen M, Lindfors P, Lefebvre S, Ahtiainen L, Fliniaux I, Rysti E, Murtoniemi M, Schneider P, Schmidt-Ullrich R, Mikkola ML. Ectodysplasin regulates hormone-independent mammary ductal morphogenesis via NF- ? B. Proc Natl Acad Sci USA 2012 Mar 26. [Epub ahead of print]

Article in PNAS

Text: Team Mikkola
Photo: Maria Voutilainen

Adaptive radiation of multituberculate mammals before the extinction of dinosaurs

Conventional wisdom holds that during the Mesozoic Era, mammals were small creatures that held on at life's edges. But at least one mammal group, rodent-like creatures called multituberculates, actually flourished during the last 20 million years of the dinosaurs' reign and survived their extinction 66 million years ago.

New Finnish - USA - Australian research suggests that the multituberculates did so well in part because they developed numerous tubercles (bumps, or cusps) on their back teeth that allowed them to feed largely on angiosperms, flowering plants that were just becoming commonplace.

Some 170 million years ago, multituberculates were about the size of a mouse. Angiosperms started to appear about 140 million years ago and after that the small mammals' body sizes increased, eventually ranging from mouse-sized to the size of a beaver. Following the dinosaur extinction, multituberculates continued to flourish until other mammals , mostly primates, ungulates and rodents, gained a competitive advantage. That ultimately led to multituberculate extinction about 34 million years ago.

In multituberculates, sharper bladelike teeth were situated toward the front of the mouth. But the new analysis shows that in some multituberculates these teeth became less prominent over time and the teeth in the back became very complex, with as many as 348 patches per tooth row, ideal for crushing plant material.

The scientists examined teeth from 41 multituberculate species kept in fossil collections worldwide. They used laser and computed tomography (or CT) scanning to create 3-D images of the teeth in very high resolution, less than than 30 microns (smaller than one-third the diameter of a human hair).

Using geographic information system software, they analyzed the tooth shape much as a geographer might in examining a mountain range when charting topography. This method, which was developed in the Institute of Biotechnology, has been previously used to analyze teeth of living species and experimentally manipulated mouse teeth.

The paper's authors are Gregory P. Wilson from University of Washington, USA, Alistair Evans of Monash University in Australia, Ian Corfe , Jukka Jernvall (Institute of Biotechnology), and Mikael Fortelius ( Department of Geosciences and Geography) from the University of Helsinki, Finland and Peter Smits from the UW and Monash University.

Artist's reconstruction of a multituberculate mammal shown atop its teeth, with a complexity map of the teeth at right. The analysis of tooth complexity shows that multituberculates began diversifying millions of years before dinosaurs died out. In addition to extinct species, the method can be used to analyze mutant mouse teeth. Image: Jude Swales (mammal reconstruction); Alastair Evans (teeth).

Wilson GP, Evans AR, Corfe IJ, Smits PD, Fortelius M, Jernvall J. Adaptive radiation of multituberculate mammals before the extinction of dinosaurs. Nature. 2012 Mar 14. doi: 10.1038/nature10880. [Epub ahead of print]

Article in Nature

Text & photo: Jernvall group

Where are complex mutants?

Mammalian cheek teeth are a good example of things becoming complex in evolution. Teeth of many groups of mammals have evolved new features called cusps through time. For example, in mammalian groups evolved to eat fibrous plants, such as in horses and pandas, cheek teeth have a high number of cusps. Yet, when one examines molars of laboratory mice in which scientists have changed the ways genes function, cusps or entire teeth can be missing. The same applies to human teeth where a loss of cusps and teeth is much more common than a gain.

In the new study, published in Nature, University of Helsinki researchers from the Institute of Biotechnology ( Jernvall group) and Department of Physics ( Hämäläinen group), look into producing new cusps by chemically adjusting gene function. Experiments on cultured mouse cheek teeth revealed that adjusting function of three different gene pathways individually, produced only moderate increases in cusps number. A cocktail of three chemicals, however, doubled the number of cusps. By using new high-resolution tomography methods to examine the treated teeth, researchers discovered that they had turned mouse teeth into small versions of panda teeth.

According to an 'economics of signalling' model proposed in the study, the lack of complex mutants may be due to the requirement of multiple gene pathways to increase structures such as tooth cusps. One implication of the study is that an increase in complexity would require stronger natural selection than a decrease in complexity. Future studies are needed to test whether the model applies to other organs and whether there may still be uncovered 'complexity genes' hiding in the genomes that could individually increase number of cusps.

IIn cultured ShhGFP reporter mouse teeth, adjusting multiple signaling pathways simultaneously produces an increase in cusp number (control on the left, treatment on the right).

Harjunmaa E, Kallonen A, Voutilainen M, Hämäläinen K, Mikkola ML, Jernvall J. On the difficulty of increasing dental complexity. Nature. 2012; doi:10.1038/nature10876.

The article in Nature

Jernvall lab at the Institute of Biotechnology

Text & photo: Jernvall group

February 2012

Active nuclear transport of actin is required for transcription

The protein actin has a well-established role in the cell cytoplasm as a crucial component of the cytoskeleton, responsible for cell morphogenesis and movement. However, the past decades of cell biological research has pointed numerous tasks for actin also in the cell nucleus. These tasks vary but a common theme is the connection of actin to many nuclear machines that regulate or directly facilitate transcription. Despite these findings, the direct involvement of actin in these functions has been difficult to prove and it has not been known how actin enters the nucleus in the first place to participate in these essential processes. A team led by Academy Research fellow Maria Vartiainen from the Institute of Biotechnology has unraveled this mystery in the article published in PNAS.

Through the application of live cell imaging techniques, the researchers first discovered that in living cells actin enters and exits the nucleus very rapidly. This reveals that cytoplasmic and nuclear actin pools are very intimately connected, with actin constantly exchanging between the two. The fast transport rates demonstrate that actin uses an active transport mechanism to enter and exit the nucleus. They then performed an RNA interference screen to identify proteins that would regulate nuclear transport of actin. Importantly, the screen highlighted a single candidate, importin 9, as the karyopherin protein responsible for carrying actin into the nucleus through the nuclear pore complexes, through which all traffic in and out of the nucleus takes place. The team then employed RNAi vs. importin 9 to investigate what happens in the nucleus almost completely devoid of actin. Measurements on transcriptional activity showed that lowered actin levels in the nucleus decrease global transcription of the cell, which could be rescued by delivering actin into the nucleus via another import route not dependent on importin 9.

This work thus pinpoints the regulatory points at which nuclear actin levels can be controlled and identifies the key proteins responsible for carrying actin in and out of the nucleus. Importantly, it depicts the first direct evidence for actin in the gene expression process and suggests a nuclear role of extreme importance for this once solely cytoplasmic protein. The tools developed in this study also enable further studies on the relevance of nuclear actin during other essential nuclear processes.

Cultured mouse cells depleted of importin 9 depicting ongoing levels of transcription (white, red) together with actin (green) microinjected into the nucleus. Cells resupplied with actin show restored transcription.

Dopie J, Skarp KP, Kaisa Rajakylä E, Tanhuanpää K, Vartiainen MK. Active maintenance of nuclear actin by importin 9 supports transcription. Proc Natl Acad Sci U S A . 2012 Feb 9. [Epub ahead of print] (PubMed)

Text & photo: Vartiainen group

 

December 2011

Viral miRNAs as key players in inhibition of apoptosis

A recent finding by the groups of Päivi Ojala (University of Helsinki) , Sebastien Pfeffer (University of Strasbourg) and Jürgen Haas (University of Edinburgh) show that KSHV miRNAs are involved in the control of apoptosis both when expressed in stable cell lines and in the context of viral infection. Using a microarray based approach the researchers identified putative cellular targets, among which the effector caspase 3 is targeted by three of the viral miRNAs. Finally, they show that blocking these miRNAs in infected cells results both in increased Casp3 levels and a higher apoptosis rate. These findings indicate that miRNAs of viral origin are key players in cell death inhibition by KSHV. The results were published online in PLoS Pathogens on December 8, 2011.

 Guillaume Suffert ¶ , Georg Malterer ¶ , Jean Hausser ‡ , Johanna Viiliäinen ‡ , Aurélie Fender, Maud Contrant, Tomi Ivacevic, Vladimir Benes, Frédéric Gros 6 , Olivier Voinnet, Mihaela Zavolan, Päivi M. Ojala*, Juergen G. Haas*, Sébastien Pfeffer*.Kaposi's Sarcoma Herpesvirus microRNAs Target Caspase 3 and Regulate Apoptosis. PLoS Pathogens 2011. Epub 2011 Dec 8.

¶ These authors contributed equally and are joint first authors on this work.
‡ These authors are joint second authors on this work.
* Shared correspondence

Article in PLoS Pathogens

Text & Photo: Päivi Ojala

Size matters: Sugars regulate communication between plant cells

Multicellular organisms must have a means for cells to communicate with one another. Past research has shown that plants possess the ability to directly transfer materials between adjacent cells, through holes in their cell walls called plasmodesmata (PD). Now, a study published by Cell Press in the December issue of the journal Developmental Cell reveals one way to control the size of these PD channels, to prevent or allow the passage of important signals between cells, during plant development.

Although evidence suggests that plant cells have the ability to control the size of their PDs, and therefore regulate intercellular trafficking, it is not clear how this size control is orchestrated. “Previous research has suggested an important role for the plant sugar polymer callose in regulating the PD aperture or size exclusion limit,” explains the senior author of the study, Professor Ykä Helariutta, from the University of Helsinki in Finland. “For example, callose degradation enhances cell-to-cell movement and increased callose accumulation at the PD has been linked with impaired trafficking.”

In their study, Professor Helariutta and colleagues developed genetic tools to control the amount of callose at the PD, so that they could manipulate the flow through PD in specific tissues of the plant. The researchers went on to show that these changes affected the intercellular movement of key plant development signaling molecules and therefore strongly influenced root formation. “Our results indicate that spatial and temporal control of callose production regulates the passage of signaling molecules through the PD during plant development,” concludes Professor Helariutta.

A transmission electron micrograph (By York-Dieter Stierhof ) shows altered structure of the plasmodesmata (PD) caused by callose deposition at the PD. Trafficking of transcription factor SHORT-ROOT (shown in blue-purple) and microRNA165 (shown in green-yellow) is prevented by spatiotemporally controlled callose synthesis .

Vaten A, Dettmer J, Wu S, Stierhof Y-D, Miyashima S, Yadav SR, Christina Y, Roberts C.J., Campilho A, Bulone V , Lichtenberger R, Lehesranta S, Mähönen A P, Kim J-Y, Jokitalo E, Norbert Sauer S, Scheres B, Nakajima K, Carlsbecker A, Kimberly L. Gallagher K. L. and Helariutta Y.Callose Biosynthesis Regulates Symplastic Trafficking during Root Development. Developmental Cell, 2011; 21: , 1144-1155.

Article in Developmental Cell

Text & Photo: Helariutta Group

Kaposi's sarcoma herpesvirus induces reprogramming of lymphatic endothelial cells to invasive mesenchymal cells

Human tumor viruses contribute to 15-20% of human cancers worldwide. Kaposi's sarcoma herpesvirus (KSHV) is an etiological agent for Kaposi's sarcoma (KS) and two other rare lymphoproliferative malignancies . KS is the most common cancer in HIV-infected untreated individuals and remains a primary cause of cancer deaths in many subequatorial African countries as a result of the AIDS pandemic . Researchers at the Institute of Biotechnology and Research Programs Unit (Genome-Scale Biology) at the University of Helsinki have discovered a novel viral oncogenesis mechanism in which KSHV oncogenes co-opt cellular signaling pathways and modify the cellular microenvironment more permissive for viral replication.

The findings by the group of Research Professor Päivi Ojala (Institute of Biotechnology, University of Helsinki) demonstrates the first lymphatic-specific endothelial-to-mesenchymal transition (EndMT) induced by a human tumor virus. The virus-induced EndMT can contribute to development of KS by giving rise to infected, invasive cells, and providing the virus a permissive cellular microenvironment for efficient spread of the virus. This information can be used for developing targeted therapies to prevent or at least slow down the progression of KS in immunosuppressed patients. The study was be published in the Cell Host & Microbe .

By developing a novel three-dimensional (3D) cell model to better mimic the in vivo microenvironment, the researchers show that KSHV induces transcriptional reprogramming of primary lymphatic endothelial cells (LEC) to mesenchymal cells via EndMT, a process implicated in promoting tumor growth and cell invasiveness. Mesenchymal markers were found co-distributed in the same cells with KSHV in primary KS tumor samples, suggesting that the 3D culture in this work succeeds in recapitulating the known heterogeneity of the cell types in KS tumors.

The results also reveal a key enzyme in cancer cell invasion, MT1-MMP, as a previously unrecognized signaling molecule downstream of Notch to induce EndMT. Moreover, the 3D KSHV-LEC transcriptome showed significant up-regulation of invasion related genes, that were found co-regulated in 3D KSHV-LECs and KS biopsies and suggesting that virus-induced EndMT may contribute to development of KS. The results further demonstrate that the 3D culture provides a permissive microenvironment for continuous viral replication and persistence, indicating the importance of virus-cell interactions for viral spread and thereby for oncogenesis. The unraveled molecular mechanisms can lead to identification of novel cellular targets for pharmacological control in virus-associated cancers.

This work is a collaboration between the research teams headed by Kaisa Lehti, Kari Alitalo, Lauri Aaltonen, and Sampsa Hautaniemi (all from University of Helsinki), Chris Boshoff (UCL Cancer Institute, University College London) and Adam Grundhoff (Heinrich Pette Institute-Leibniz Institute for Experimental Virology). The project involves scientists from two Academy of Finland National Centre of Excelle nce Programs, the Translational Genome-Scale Biology and Cancer Biology.

The image depicts a sprouting spheroid of KSHV-infected LECs in 3D that has undergone EndMT. The mesenchymal sprouts are stained with an antibody for  alfa smooth muscle actin  (in red) and the nuclei with DAPI (in blue). Image by P. Pekkonen and P. M. Ojala.

Cheng F*, Pekkonen P*, Laurinavicius L,* Sugiyama N, Henderson S, Günther T,Rantanen V, Kaivanto E, Aavikko M, Sarek G, Hautaniemi S, Biberfeld P, Aaltonen L, Grundhoff A, Boshoff C, Alitalo K, Lehti K**, and Ojala PM**. KSHV-initiated Notch activation leads to membrane-type-1 matrix metalloproteinase-dependent lymphatic endothelial-to-mesenchymal transition. Cell Host & Microbe, December 15, 2011. * equal contribution; ** equal contribution.

Preview of the article

Article in Cell Host & Microbe

Ojala lab

Text & photo: Ojala Group

Mart Saarma appointed as a visiting professor of Wuhan University

Professor Mart Saarma visited Wuhan University's School of Basic Medical Science in December 2011. During the visit, he accepted an appointment to be a WHU visiting professor. The Deputy Secretary of WHU's Party Committee, Luo Yuyan, presented an appointment letter to Professor Saarma. Luo noted that this would help to enhance the friendship between China and Finland and would contribute to cooperative research between WHU and medical research institutions in Finland.

"Along with rapid social development in China, many Chinese scientists are becoming renowned for their research capabilities", Saarma said.   He also wanted to take advantage of the opportunity to strengthen the cooperation between WHU and Finland. After the ceremony, Professor Saarma delivered a lecture and carried out discussion with WHU students.

The period of the visiting professor is from December 2011 to December 2014.

Photo: Mart Saarma

November 2011

The Michael J. Fox Foundation awards Professor Mart Saarma nearly $ 200 000 to develop novel drugs for Parkinson's disease

The Michael J. Fox Foundation for Parkinson's Research (MJFF) has awarded a grant to Academy Professor Mart Saarma, PhD, and his team at the Institute of Biotechnology of the University of Helsinki. The funding will be used in conjunction with HermoPharma Company for the therapeutic development of the neurotrophic factor cerebral dopamine neurotrophic factor (CDNF) as a potential treatment for Parkinson's disease (PD) .

Saarma's major breakthrough in this field was the discovery of CDNF, and he has performed subsequent demonstrations that it has potential to both protect and repair injured neurons in pre-clinical models of PD. MJFF has been funding Saarma's team to investigate CDNF since 2006, including a $500,000 award in 2010 to study the therapeutic potential of CDNF in pre-clinical models of PD. The newly-awarded grant will be used to further complete these studies.

PD is a disorder of the central nervous system that results from the loss of dopamine-producing brain cells. Neurotrophic factors are are proteins that promote the survival, growth and function of neurons in the brain, and therefore, are of major interest to PD researchers.

Saarma's team and a team headed by Professor Raimo K. Tuominen, MD, PhD, of the Faculty of Pharmacy, have in the past compared the neuroprotective and neurorestorative properties of CDNF with those of other neurotrophic factors like g lial cell line-derived neurotrophic factor, or GDNF . The results were promising in terms of developing CDNF as a novel treatment for PD.

Future pre-clinical studies on the efficacy of CDNF on PD are being carried out in collaboration with Judy L. Cameron, PhD, of the University of Pittsburgh and with Zhiming Zhang, MD, of the University.

About MJFF

As the world's largest private funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $264 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure.

Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world. Now through December 31, 2012, all new and increased giving to The Michael J. Fox Foundation, as well as gifts from donors who have not given since 2009 or earlier, will be matched on a dollar-for-dollar basis with the $50-million Brin Wojcicki Challenge, launched by Sergey Brin and Anne Wojcicki.

Text: Kirsikka Mattila and Mart Saarma
Photo: Ari Aalto

Laboratory of Molecular Neuroscience at the Institute of Biotechnology:

Michael J Fox Foundation

Michael J Fox Foundation at Facebook

The Michael J. Fox Foundation Rapid Response Innovation Award to Dr. Urmas Arumäe

The Michael J Fox Foundation supports Dr. Urmas Arumäe and his team at the Institute of Biotechnology with USD 74,580 grant to develop new drugs for Parkinson's disease.

The funding will be used to study the therapeutic potential of the neuroprotective peptide derived from the novel neurotrophic factor MANF (short for Mesencephalic Astrocyte-Derived Neurotrophic Factor) in pre-clinical models of Parkinson's disease (PD). MANF and the related neurotrophic factor CDNF have shown to be potent treatment factors in pre-clinical models of PD. both expressing neuroprotective and neurorestorative potential. CDNF was discovered in 2003 by Academy Professor Mart Saarma 's group at the Institute of Biotechnology. Saarma is a co-principal investigator on Dr. Arumäe's study, and has been funded by MJFF to investigate CDNF since 2007.

Arumäe's group is studying the mechanisms behind how MANF prevents the death of neurons in the brain. These studies led to the discovery of a MANF-derived peptide that potently protects the cultured neurons against toxic stimuli, including the dopaminergic neurons that degenerate in PD.

The grant was awarded to test the peptide on pre-clinical models of PD. The small size and cell-penetrating properties of this peptide make it an attractive candidate for a therapy for PD . A small peptide has several advantages over the larger parental protein as it is likely to spread better in the brain, and could be easier to apply to patients. The experiments will be carried out in collaboration with Professor Raimo K. Tuominen from the Faculty of Pharmacy, University of Helsinki.

Dr. Urmas Arumäe is a member of the Centre of Excellence in Molecular and Integrated Neuroscience Research of the Academy of Finland.

About The Michael J. Fox Foundation for Parkinson's Research

As the world's largest private funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers.  In addition to funding over $270 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure.

Arumäe lab at the Institute of Biotechnology

Finnish Centre of Excellence in Molecular and Integrated Neuroscience Research

The Michael J. Fox Foundation

October 2011

Surprises of the measles virus structure

Professor Sarah Butcher's research group from the Institute of Biotechnology report in the 24 th October issue of the journal Proceedings of the National Academy of Sciences (U.S.A.) a three-dimensional model of measles virus. The new model helps to explain many previous, unaccounted for observations in the life cycle of the virus.

Measles is an important disease worldwide that is highly infectious, causing the deaths of over 100000 people annually. According to the latest figures from the World Health Organisation, 33 countries in Europe have reported cases in 2011. As there is an effective vaccine against measles given to children, most of the infections detected in Finland are the result of exposure abroad.

Measles virus belongs to a family of viruses whose members are all pleomorphic enveloped viruses. All the members of this family contain a so called "matrix" protein which has previously been thought to line the inside of the envelope and play a major role in the budding of the virus from the cell.

The group's research shows that matrix actually forms helical tubes inside the virus that are wrapped around the viral genome and nucleocapsid. So matrix helps to compact the genome to fit it into the virus. Thus the researchers believe that matrix will regulate both the start of virus replication in the cell, and also the movement of the genome within the cell as the virus assembles. The research used modern electron cryo-tomography and image processing to solve the structure, a method analogous to X-ray tomography of the human body.

Lassi Liljeroos , M.Sc. a Ph.D. student in the Butcher group will now follow up on these results by looking at related viruses to see if they are similar. Structurally, measles virus may be similar to other viruses causing respiratory tract infections like influenssa and RS-virus.

The understanding of virus structure at the molecular level can help in the design and development of new antiviral drugs. The measles virus research was carried out as a collaboration with researchers from Oxford and Turku Universities. The research was funded by the Academy of Finland, the Sigrid Juselius Foundation, the European Molecular Biology Organisation and the Viikki Doctoral Programme in Molecular Biosciences. The Butcher group belongs to the Academy of Finland's Centre of Excellence in Virus Research (2006-2011).

Text: Sarah Butcher, Lassi Liljeroos and Kirsikka Mattila

Picture: Juha Huiskonen

Article in PNAS

The Butcher Group at the Institute of Biotechnology

Centre of Excellence in Virus Research

September 2011

A coveted ERC Starting Independent Researcher Grant to Ville Hietakangas

The European Research Council has awarded an ERC Starting Independent Researcher Grant to Academy Research Fellow Ville Hietakangas, who works as a group leader at the Institute of Biotechnology. The five-year grant totals approximately EUR 1.5 million.

Ville Hietakangas is delighted as the grant allows for goal-orientated work in the long term.

- This type of funding is extremely important to a recently established team of researchers. It enables us to fully focus on the issues that I think are essential in our field, he says.

With his team, Hietakangas studies the messages that the organism of a fruit fly sends about its nutritional status. Among other things, the team has discovered a genetic mutation in a fly that severely disturbs glucose metabolism. The reason for the metabolic imbalance remains partly unclear, which makes this mutation and its exceptional glucose metabolism an interesting discovery in terms of further research.

The team is interested in communication within organisms: how does an organism use the information it collects to control metabolism?

The project that was awarded the funding focuses on detecting glucose and the related gene regulation. The goal is to find new gene regulators that contribute to glucose metabolism.

Metabolic diseases are increasing

Fruit flies have been used for research in experimental biology for more than a hundred years. They are also suitable for metabolism research. The fruit fly is an excellent model system, because its genes can be switched on and off in any specific tissue. It also enables broad genetic screens as raising flies is relatively inexpensive and fast.

Although people and fruit flies differ in appearance, their metabolic systems and many other cell-level functions have remained quite similar throughout evolution.

- Our work involves basic research in biology, but the results may benefit the development of treatments for diabetes and other metabolic diseases in the long run, says Hietakangas.

Metabolism research is growing in significance, because morbid obesity and related metabolic diseases are becoming more common around the world.

Through its Starting Independent Researcher Grants, the European Research Council supports young researchers who are in the process of establishing a research team or finding stability for a project that has been running for a few years. Hietakangas is the third recipient of an ERC Starting Independent Researcher Grant at the University of Helsinki this autumn.

Text: Kirsikka Mattila
Photo: Linda Tammisto

Hietakangas lab

Publications by Ville Hietakangas

Scientific evaluation of the Institute of Biotechnology

The new BI SAB site visited the institute 6-7 September, 2011 as a part of the scientific evaluation. On Tuesday, the program started with opening words by Rector Thomas Wilhelmsson . He welcomed the new SAB to Helsinki to continue the valuable tradition of continous evaluations at BI. The Rector also presented a surprised Jonathan Knowles with the UH medal for his astonishing 21-year stint in the BI SAB as a member and a Chairman. After that Director Tomi Mäkelä gave a presentation about BI at 2009-2011 and the Research Directors presented their research programs by introducing the highlights, challenges and future plans of their research. The SAB also visited the facilities at Biocenter 1 & 3 and Cultivaotr 2 prior to starting evaluations of the Group Leaders.

On Wednesday after the evaluation of Group leaders there was a poster session where all groups presented their research. The program ended with the panel discussion on new initiatives chaired by Professor Joan Steitz . Panellists included Professors Marja Jäättelä , Annalisa Pastore and Kai Simons from the SAB and Yajing Gao , Jukka Kallijärvi , Tommi Kajander and Ari-Pekka Mähönen from BI. Initiatives included improvement of BI Internet image, scientific computing strategy, availability of an equipment list , whether post docs should be encouraged to go abroad for a while, and whether getting BI under one roof would provide added value. On the whole the SAB appeared very pleased with the visit, and also there was very active participation from our staff. The visit will be followed by a report expected in November.

Photo: Kimmo Tanhuanpää

August 2011

New mechanism of sculpting the plasma membrane in intestinal cells indentified

The research group of Professor Pekka Lappalainen at the Institute of Biotechnology, University of Helsinki, has identified a previously unknown mechanism which modifies the structure of plasma membrane in intestinal epithelial cells. Unlike other proteins with a similar function, the new protein - named 'Pinkbar' by the researchers - creates planar membrane sheets. Further research investigates the potential connection of this protein with various intestinal disorders. The study was published in the August issue of Nature Structural & Molecular Biology journal.

A dynamic plasma membrane surrounds all eukaryotic cells. Membrane plasticity is essential for a number of cellular processes; changes in the structure of the plasma membrane enable cell migration, cell division, intake of nutrients and many neurobiological and immunological events.

Earlier research has shown that certain membrane-binding proteins can "bend" the membrane to generate tubular structures with positive or negative curvature, and consequently induce the formation of protrusions or invaginations on the surface of the cell. These membrane-sculpting proteins are involved in various vital cellular processes and can control the shape of the plasma membrane with surprising precision. Many of them have also been linked to severe diseases such as cancer and neurological syndromes.

Identified by Anette Pykäläinen, a member of Professor Lappalainen's group who is currently finalising her dissertation, the new membrane sculpting protein has a different mechanism than other proteins studied previously. Instead of generating positive and negative curvature, the Pinkbar protein is able to produce planar membrane sheets. Lappalainen's group determined the membrane-sculpting mechanism of Pinkbar in collaboration with prof. Roberto Dominguez laboratory at USA . In humans, Pinkbar is only found in intestinal epithelial cells where it may be involved in the regulation of intestinal permeability. In the future, it will be important to identify the exact physiological function of Pinkbar in intestinal epithelial cells and to study the possible links of this protein to various intestinal disorders.

Pykäläinen A , Boczkowska M, Zhao H , Saarikangas J , Rebowski G, Jansen M, Hakanen J, Koskela EV , Peränen J , Vihinen H, Jokitalo E , Salminen M, Ikonen E, Dominguez R, Lappalainen P . Pinkbar is an epithelial-specific BAR domain protein that generates planar membrane structures. Nat Struct Mol Biol . 2011 Jul 10;18(8):902-7.

Article in Nature

Text: Kirsikka Mattila
Photo: Lappalainen group

June 2011

Institute's Biocenter 3 Lab day

Institute of Biotechnology groups working in Biocenter 3 arranged an internal one-day scientific meeting on June 15, in "Telkänpönttö" to stimulate interactions and increase knowledge on the technologies and instruments available and find common interests in different expertise and have some new ideas. The program consisted of scientific talks from all floors and posters from each group in which the work going on in the labs were presented.

In his opening words the chair of the organizing committee   Osamu Shimmi noted that today groups in Biocenter 3 are from all BI research programs with expertise in structural biology, biophysics, cell biology, developmental biology and genome biology. This has brought new people and equipment in and potential for new ideas. Osamu also gave an overview of 2nd floor "fly-equipment" and his groups progress in understanding how fly wings develop through intracellular and spatial regulation of BMP (Dpp) signaling. Ari-Pekka Mähönen   introduced plant development activities on the 6th floor and demonstrated the power of in vivo imaging in understanding plant development and stem cells; the plant groups have become the largest users of the Light Microscopy Unit (LMU). Anthony Bishopp's presentaion was on how the Helariutta lab had discovered  the genetic process which determines how xylem (transporting cells) are specified in plant roots. Hannu Maaheimo from the shared VTT/BI NMR facility demonstrated the power of NMR in biotechnological applications such as improving processes to use plant pectin to generate compunds for e.g. new plastic-type materials. Alan Schulman revealed how retrotransposons - at one time considered "junk DNA" - are active elements of the genome apparently  making packaged RNA/DNA particles moving from one cell to another and likely contributing to stress responses. Katariina Hattula  presented experiments trying to resolve how the peroxins Pex3 and Pex19 build the peroxisome membrane through structural studies using hydrogen-exchange mass spectrometry. 

During lunch break, poster session took place. All the groups presented the posters and had discussion with participants.

In the afternoon session, Jesper Oeemig introduced X-ray Crystallography group on the 4 th floor and presented DnaE Intein from Nostoc punctiforme and its potential application. Niina Lietzen from the protein chemistry research group introduced a technical application of mass spectrometry-based proteomics and presented her PhD study, proteomics of influenza virus infected macrophages.

In the closing discussion chaired by Sarah Butcher the participants agreed that the BI lab day should take place at regular bases, and next time all the groups in the BI should
be included. Also, the audience supported the idea of arranging group leader lecture series.

Text: Ari Pekka Mähönen, Tomi Mäkelä and Osamu Shimmi
Photo: Satu Sankkila

May 2011

The genetic process which determines how xylem are specified in roots has been discovered

An international effort led by Professor Yrjö Helariutta has discovered the genetic process which determines how xylem (transporting cells) are specified in roots.

All multicellular organisms start life as a single cell. As this and consequent cells divide the daughters need take on new identities. Understanding the genetic messages which control these processes means that scientists can generate new ways to direct development in ways which benefit mankind (for example by producing more or less of a certain cell/organ type). The research team investigated the factors controlling the formation of xylem cells in plant roots and discovered that the interaction between two hormones controls the extent to which xylem forms in the root. When the activity of genes which affect the movement or perception of these hormones is altered, plants with more or less xylem can be generated. The results were published as two back-to-back publications in the journal Current Biology.

This work enhances our understanding of how plants develop. Anthony Bishopp explains "When an egg cell is fertilized, there is one cell which contains all the genetic information for the whole organism. As this organism grows subsequent cells take on new identities and new structures appear. It doesn't matter if it is a plant or a person, the processes which co-ordinate the formation of just one structure such as an eye or a leaf are amazing, but the generation of a whole organism is awe-inspiring". In reality the process is anything but simple, but in this research the team make a significant contribution towards understanding this. "In plants the formation of water transporting tissues has been paramount to their colonization of the land. We are now reporting a mechanism through which the identity of water conducting xylem cells can be assigned. This is exciting stuff".

The second importance of this work involves its potential to direct future crop and forest tree improvements. Biofuels can be generated by the fermentation of sugars in plant tissue. The majority of the sugars in the plant come from cellulose and this is locked in the xylem. By engineering plants with increased xylem, we can deliver plants with more cellulose to the biofuel industry. Forest industry could also benefit from trees that have modified wood properties to meet the demands of process technology. At the moment this research has all been carried out in using a small weed, the model plant Arabidopsis thaliana , but the group has plans to start investigating this in commercially relevant species.

The research was carried out as part of a European Research Network aimed at bringing together European Research institutions to stimulate economic growth, competitiveness and sustainability. This concerted effort was lead by Professor Yrjö Helariutta and the majority of the work was carried out in the Institute of Biotechnology, by Anthony Bishopp and Hanna Help .

Bishopp A, Lehesranta S, Vatén A, Help H, El-Showk S, Scheres B, Helariutta K, Mähönen AP, Sakakibara H, Helariutta Y. Phloem-Transported Cytokinin Regulates Polar Auxin Transport and Maintains Vascular Pattern in the Root Meristem. Curr Biol . 2011 May 25. [Epub ahead of print] (Current Biology)

Bishopp A, Help H, El-Showk S, Weijers D, Scheres B, Friml J, Benková E, Mähönen AP, Helariutta Y. A Mutually Inhibitory Interaction between Auxin and Cytokinin Specifies Vascular Pattern in Roots. Curr Biol . 2011 May 25. [Epub ahead of print] (Current Biology)

Text: Anthony Bishopp
Photo: Helariutta's team

Dennis Bamford appointed as Academy Professor

ResearchThe Board of the Academy of Finland has selected Dennis Bamford as Academy Professor together with eight other professors for the period January 1 2012-December 31 2016. They all are leading-edge researchers in their own fields, both in Finland and internationally and have great potential to achieve major scientific breakthroughs. In their research, they will be tackling questions that are significant for society in a wider perspective. The new Academy Professors besides Bamford are Professors Ilkka Hanski (University of Helsinki), Olli Ikkala (Aalto University), Risto Ilmoniemi (Aalto University) Howard Jacobs (University of Tampere), Martti Koskenniemi (University of Helsinki), Olli Raitakari (University of Turku), Riitta Salmelin (Aalto University) and Juha Sihvola (University of Jyväskylä).

Professor Bamford is a group leader at the Institute of Biotechnology and head of the Finnish Centre of Excellence in Virus Research at the universities of Helsinki and Jyväskylä.

Bamford's research interests are in the structure and evolution of viruses. He hasdiscovered previously unknown structural similarities between very different types of viruses.Current evidence suggests that viruses infecting bacteria and archaea share structural features in common with viruses that infect higher organisms, including humans. Based on these similarities, it seems that all current viruses have evolved from the same origins. If this theory proves to be true, the systematics of viruses will need considerable rewriting. It might even change our understanding of the early evolution of life on Earth.

Apart from his work in the field of virus evolution, he is currently interested in developing methods for the structural analysis of viruses as well as technologies for the detection of individual molecules. This work has already found commercial applications. Viral proteins are used to produce RNA molecules that are capable of targeted gene silencing.

Bamford has published extensively: to date, he has more than 280 scientific publications to his name. He is also actively engaged in training young scientists and has been supervisor of more than 30 PhD theses. Seven PhD graduates from Bamford's team have been appointed to a professorship and six currently have their own research teams.

Bamford has served as a member of several scientific committees and program committees for international conferences and has been invited speaker at numerous meetings worldwide. He is a member of several international science communities. He has chaired the EU's ESFRI INSTRUCT Working Group and is currently head of the virus production and purification centre under the ESFRI BMS INSTRUCT project at the University of Helsinki.

Publications by Dennis Bamford

Finnish Centre of Excellence in Virus Research

E.J. Nyström Prize to Professor Irma Thesleff

Research

The Finnish Society of Sciences and Letters awarded Professor Irma Thesleff with the Nyström Prize, 25 000 €. The prize is awarded for her academic merits and it was presented at the annual celebration of the Society on April 29.

Professor Thesleff is the Research Director of the Developmental Biology Research Program at the Institute of Biotechnology. The prize was awarded on her research on the development of teeth and other craniofacial structures.

The Finnish Society of Sciences and Letters is an independent society for researchers from all fields of research to which researchers are invited because of their academic merits. It works to promote science and the humanities.

Societas Scientiarum Fennica - The Finnish Society of Sciences and Letters

New Method To Determine Protein Structure

The structures of many protein molecules remain unsolved even after extensive work. An international collaboration including Hideo Iwai's group of the Institute of Biotechnology has led to a new, high-performance method that rapidly determined the structure of protein molecules in several cases where previous methods had failed. The results were published in Nature.

To determine high-resolution protein structures for drug design or understanding protein functions, there are two widely used methods, i.e. X-ray and NMR spectroscopy. For X-ray crystallography, even after obtaining high quality crystals, it is still necessary to obtain the phase information of X-ray diffraction intensities for determining protein structures. Molecular replacement is a method of solving the phase problem in X-ray crystallography, which search for placements of a starting model based on a previously determined structures by X-ray or NMR within the crystallographic unit cell that best account for the measured diffraction amplitudes, followed by automatic chain tracing methods have allowed the rapid solution of large numbers of protein crystal structures. Despite extensive work, molecular replacement or the subsequent rebuilding usually fail with more divergent starting models based on remote homologues with less than 30% sequence identity.

The researchers found that even very poor electron density maps from molecular replacement solutions could be useful. These maps could guide Rosetta structural prediction searches that are based on energy optimization. By taking these energy-optimized predicted models, and looking for consistency with the electron density data contained in the X-ray crystallography, new maps are generated. The new maps are then subjected to automatic chain tracing to produce 3-D models of the protein molecular structure. The models are checked with a sophisticated monitoring technique to see if any are successful. To test the performance of their new integrated method, the researchers looked at 13 sets of X-ray crystallography data on molecules whose structures could not be solved by expert crystallographers. These structures remained unsolved even after the application of an extensive array of other approaches. The new integrated method was able to yield high resolution structures for 8 of these 13 highly challenging models. 

Dimaio F, Terwilliger TC, Read RJ, Wlodawer A, Oberdorfer G, Wagner U, Valkov E, Alon A, Fass D, Axelrod HL, Das D, Vorobiev SM, Iwaï H, Pokkuluri PR, Baker D. Improved molecular replacement by density- and energy-guided protein structure optimization. Nature . 2011; 473(7348): 540-3.

Article in Nature

April 2011

Dr. Ari Löytynoja will start as a new Group Leader at the Institute of Biotechnology

ResearchDr. Ari Löytynoja comes from the European Bioinformatics Institute, where he has made seminal discoveries in  improving evolutionary modelling in sequence alignments as a senior postdoctoral fellow in the group of Nick Goldman. Dr. Löytynoja was trained as a Population Geneticist at the University of Oulu, and turned to bioinformatics and multiple sequence alignment studies for his PhD with Michel Milinkovitch at the Free University of Brussels (ULB).  His work on alignment methods, published in high-profile journals such as Science and PNAS, has been highly influential in the field of molecular evolution and systematics.  Sequence alignment is of fundamental important to all sequence-based analysis in molecular evolution and phylogenetics, and poses considerable statistical and computational challenges also for next-gen sequencing data.  Dr. Löytynoja hopes to join the large genomics and RNA-seq projects on campus and together improve methods to analyze next-gen DNA sequencing data.

Publications by Ari Löytynoja

Welcoming lecture by a visiting developmental and evolutionary biologist

Research

Professor Scott F. Gilbert, who is joining the Institute of Biotechnology at the University of Helsinki through the FiDiPro programme, held his official opening lecture to a full house on 11 April.

Professor Gilbert , from Swarthmore College in the United States, is one of the leading experts in issues related to bioethics and to the mechanisms by which animals change their anatomies during evolution.

To students of development and evolutionary biology, he is known as the author of several key textbooks in the discipline, including Developmental Biology , Ecological Developmental Biology , and Bioethics and the New Embryology . He is a popular lecturer who has talked about stem cell research at meetings in the Vatican and at Planned Parenthood.

According to Academy Professor Jukka Jernvall , the chair of the event, Gilbert was talking about evolutionary developmental biology even before the whole research field had been invented.

- At the University of Helsinki, he will teach, lecture and lead his own research group studying the development and evolution of tortoises. Do not hesitate to approach him!

Evolution favours partnerships

The key message of Gilbert's lecture was that instead of favouring strong individuals, nature favours working partnerships. We like to think we are individuals but in reality there is a vast network of microbes working for us.

- You can even kill a host by destroying the symbiont. We need bacteria probably more than they need us. Even now it is the Team Scott Gilbert speaking here.

Traditionally, developmental biologists have only studied organisms in laboratory conditions. This overlooks the fact that organisms do not develop independently since symbionts are often necessary for normal development. According to Gilbert, this perspective should be more emphasized in the research of evolutionary development biology.

Gilbert uses many delicious examples to describe how modest symbionts support their hosts. The eggs of the yellow-spotted salamander do not develop without the cooperation of an alga that oxygenates them. The Large Blue butterfly is fed by ants that its caterpillars also eat. A land-dwelling frog species would not survive if it were not for the pools provided by deep elephant tracks.

The Finland Distinguished Professor Programme is a programme jointly financed by the Academy of Finland and Tekes, which provides an opportunity to invite the best foreign or expat Finnish researchers to Finland for a fixed period.

FiDiPro - the Finland Distinguished Professor Programme » »

Text: Kirsikka Mattila
Photo: Scott Gilbert

February 2011

Dr. Markku Varjosalo was nominated for the Head of Protein Chemistry and Proteomics Core Facility

After the Institute´s recruit committee´s evaluation of the applicants, the SAB´s statement and recommendation of the Board, Dr. Markku Varjosalo was nominated for the Head of Protein Chemistry and Proteomics Core Facility. He will start in September, 2011.

Dr. Varjosalo´s background is in molecular biology, biochemistry, and systems biology. He has a continuing interest in understanding how the cellular information flow is altered in cancer.

His current research uses quantitative mass spectrometry to identify the molecular context in which cancer linked proteins such as kinases and phosphatases function.

Varjosalo works currently as a postdoctoral fellow with Professor Ruedi Aebersold at the Institute of Molecular Systems Biology, ETH Zürich.

Publications by Markku Varjosalo

January 2011

Host or foreign - the body's frontline defence mechanism understood

The highly-respected US Academy of Sciences journal (PNAS) has published an article describing how the first line of defence of the human immune system distinguishes between microbes and the body's own structures. The basis of this recognition mechanism has been unclear since the key protein components were discovered over 30 years ago - and has now finally been cracked by a collaboration between high-level research groups at the University of Helsinki. When a microbe has infected us, the first defence mechanism that attacks it is a protein-based marking and destruction system called complement. It usually suffices that foreign targets are marked as enemy while our own targets are left untouched, so that white blood cells attack only foreign targets like bacteria, viruses and parasites.

Researchers at the Haartman institute and the Institute of Biotechnology at the University of Helsinki have, as a result of years of dedicated work, been able to show how complement distinguishes foreign structures from our own structures - all days before antibodies have a chance to develop. The key to unlocking the problem was when the groups of Sakari Jokiranta and Adrian Goldman in Helsinki, along with David Isenman 's group in Canada, were able to solve the structure of two components of the system at atomic resolution. The structure revealed a stunning unexpected arrangement: factor H bound two of the C3bs, which mark foreign targets, in two different ways. Laboratory tests showed that this actually happened: to recognise our own cells, factor H binds not only C3b but also the cell surface at the same. Thus, the system mark only foreign structures for destruction by the white blood cells.

This new understanding of how host and foreign structures are distinguished by the front-line defence mechanism also explains how the severe and often fatal form of disease "Hemolytic Uremic Syndrome" (HUS) starts. This rare disease often occurs in children and can be caused by genetic defects in factor H or in C3b, or else by the disruption of factor H activity by antibodies. In Finland, too, some of these patients have had to have complete liver-kidney transplants because of the severity of the disease. Consequently, the research's surprising and wide-reaching result will be important not only in terms of advancing basic immunological research but also in the diagnosis and treatment of very sick children.

Complement factor H binds and inhibits C3b of complement alternative pathway on host surfaces, protecting them from complement attack. The structure and binding studies by Kajander et al., published in PNAS, describes how the C-terminus of factor H (blue) recognises host surfaces. It binds the C3d domain (sand and green) of C3b (gray) in two ways. This enables the N-terminus of factor H to bind and help inactivate C3b. Pathogenic bacteria mimic the interaction shown here to protect themselves; and mutations in the C-terminus of factor H lead to haemolytic uremic syndrome.

Image courtesy of Tommi Kajander and Adrian Goldman.

Tommi Kajander, Markus J. Lehtinen, Satu Hyvärinen, Arnab Bhattacharjee, Elisa Leung, David E. Isenman, Seppo Meri, Adrian Goldman, and T. Sakari Jokiranta: Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement. PNAS Early Edition, 2Feb, 2011. Article »»

Text: Adrian Goldman, Sakari Jokiranta, and Tommi Kajander

 

December 2010

Group Leader and Principal Investigator winter meeting

Group Leader and Principal Investigator seminar was held on December 10 th , in the snowy environment of Kokoushotelli Rantapuisto in Vuosaari. The program started with Director Tomi Mäkelä´ s glance forward to 2011 and beyond including proposed members for a new SAB followed by looking at next steps in the 2005-2010 University evaluation by Planning Officer Minna Oja. Two of the new Group Leaders starting in 2011 - Päivi Ojala and Ari Pekka Mähönen - also introduced their research projects.

The main program for the day was a workshop on what Integrative Biology is today and tomorrow at BI facilitated by Sampsa Hautaniemi heading a systems biology and bioinformatics group on the Meilahti campus. Participants were divided into five groups that competed against each other in trying to generate competitive programs in Integrative Biology leveraging on current and future expertise at BI. Highly innovative proposals were subsequently evaluated and ranked. The proposal "OxyFly" (Andressoo, JO; Nyman, T; Shimmo O; Wikström, M) applying for 500 000 € was rewarded with 1000 "Repe dollars" by a (biased) review panel , where the audience was free to take part to panel discussion and give feedback. Tomi Mäkelä and Administration Director Arto Halinen were given a task to present a project to decrease administrative burden of researchers. The poster presentations can be viewed on the announcement board.

Professor Mart Saarma as a new member of the ERC's Scientific Council

The European Commission has appointed seven new members of the Scientific Council, the covering body of ERC

The term of office of the new members runs from 2 February this year till the end of 2013.

The new members have been identified by the independent ERC Identification Committee, composed of six high level scientists and appointed by the European Commission in September last year.

The Scientific Council , the ERC's governing body, defines the scientific funding strategy and methodologies, and acts on behalf of the scientific community in Europe to promote creativity and innovative research. It is presently chaired by Prof. Helga Nowotny and is composed of 22 eminent scientists and scholars, including some Nobel Prize winners.

The European Research Council (ERC) is the first pan-European funding organisation for frontier research. It aims to stimulate scientific excellence in Europe by encouraging competition for funding between the very best, creative researchers of any nationality and age.

Dr. Saarma is the Academy Professor and Director of the Centre of Excellence in Molecular and Integrated Neuroscience Research of the Academy of Finland at the Institute of Biotechnology, University of Helsinki. He has studied neurotrophic factors and their receptors in neurodegenerative diseases. Currently his group is investigating the mechanism of action and therapeutic potential of CDNF and also the biology of GDNF. Dr. Saarma is the member of several academies and EMBO. He has received several domestic and international scientific prizes and awards including the prestigious Nordic Science Prize.

November 2010

The Publication Forum Quality Assessment Project

Research

Professor Irma Thesleff nominated as chair of Biosciences II Panel of the Publication Forum Quality Assessment Project . The publication forum quality assessment project has been established from Finnish Universities - Unifi`s initiative in order to assess the quality of publications. The project aims to create a system where the scientific publishing can be assessed quantitatively but also qualitatively. The system is based on the quality assessment of publication channels, namely the scientific journals, series and publishers. Assessment will take place in 23 discipline-specific expert panels.

Mart Saarma co-opted as a member of EMBO Council

EMBO Council co-opted Professor Mart Saarma as a member of the Council. Saarma has been EMBO member since 2005. The Council membership is for a three-year period starting in January 2011, with the possibility of one renewal. EMBO Council is the governing body of EMBO, responsible for ensuring the development of the organization. It consists of 15 members. The current Chair of EMBO Council is Carl-Henrik Heldin and the Vice-Chair is David M. Shore .

The European Molecular Biology Organization (EMBO) is an international, science-academy-type organisation, established in 1964. EMBO promotes excellence in molecular life sciences in Europe by recognizing and fostering talented scientists. Leading scientists are elected annually to become EMBO members based on proven excellence in research. Today, the number of members is more than 1400, 53 scientists with the EMBO membership have received the Nobel Prize. EMBO members are involved in guiding the execution of the many EMBO initiatives offered to life scientists and can have a significant impact on the direction of European life sciences. EMBO funding, training and networking activities help many young scientists annually to advance their research and develop international reputations. The EMBO Executive Director is Professor Maria Leptin .

EMBO

October 2010

Genome Biology Research Program retreat

The first annual Genome Biology Research Program retreat was organized at Hyytiälä Forestry Field Station

The first annual Genome Biology Research Program retreat was organized on 18 to 19 October, 2010, at Hyytiälä Forestry Field Station, with the aim of introducing the member groups of the recently established research program to each other and to find out ways for the members to benefit from the program. 34 participants from Auvinen, Frilander, Helariutta, Holm, Mäkelä and Schulman groups were present. The first afternoon was dedicated to the group leaders' presentations on their group's research. After sitting in the lecture hall for the whole afternoon it was time for outdoor exercise in the form of football and a game of mölkky. After dinner, the participants enjoyed the sauna and a refreshing dip into the lake. Later in the evening, everyone gathered in the old dining hall, where discussions on all aspects of a scientist's life went on well into the night over drinks and snacks.

The second day of the retreat was reserved for what turned out to be the most fruitful part of the meeting: group discussions on how the research program can benefit its members. Participants were divided into groups that brainstormed on new ideas on education, meetings, information flow between the groups and promoting the science within the program. Many new courses were suggested to be organized by the member groups. Lots of ideas came up concerning the sharing of expertise between groups. At least a mailing list and the program's own web pages should soon be up and running, perhaps also more interactive forms of communication such as an online discussion forum. The Genome Biology retreat was decided to be organized annually. In addition, less formal ways of interaction were suggested, such as scientific afternoons over coffee and pulla or beer. With enthusiastic people, the new Genome Biology Research Program will certainly prove useful to its members in both scientific and social exchange.

Text: Heli Pessa
Photo: Sedeer El-Showk

September 2010

New Group Leaders

ResearchDr. Thomas Sandmann was trained as a biochemist, but has since mostly studied regulation of gene expression using genome-wide and computational strategies using the fruitfly as a model system. His current interest is focused on posttransciptional regulation by RNA-binding proteins and miRNAs. The goal is to understand how the surprisingly small number of genes can generate the tantalizing complexity and diversity of organisms. Dr. Sandmann works currently as a postdoctoral researcher with Michael Boutros at the German Cancer Research Centre (DKFZ) in Heidelberg.
Publications by Thomas Sandmann

Research

Dr. Päivi Ojala has a background in molecular genetics, cell biology, and virology. Ojala aims to decipher molecular mechanisms underlying cellular reprogramming, and transformation by viruses causing cancer such as the Kaposi's Sarcoma herpes virus. Dr. Ojala is currently a Research Professor of the Finnish Cancer Institute in the Genome-Scale Biology Program at Biomedicum Helsinki. Publications by Päivi Ojala

Research

Dr. Ari Pekka Mähönen works in the area of plant biology studying stem cell regulation and growth dynamics in root vascular cambium. The work addresses highly significant questions relating to wood formation and production of renewable energy. Dr. Mähönen has recently completed a post-doctoral period in the group of Ben Scheres at Utrecht University, following a highly awarded PhD at the Institute of Biotechnology.
Publications by Ari Pekka Mähönen

April 2010

Ontogenesis is regulated by moving microRNA molecules

The genes in humans and many other species have been surveyed but their operating principles remain rather unknown. Researchers do not know precisely how genes guide development of various human tissues, or what causes developmental disorders. MicroRNA molecules, are recently identified regulatory factors, whose on-going analysis, provide more insight into the matter.

A team from the Institute of Biotechnology and the Department of Biosciences of the University of Helsinki, Duke University, Uppsala University and Boyce Thompson Institute will publish the latest results of their research in the journal Nature. The article introduces new information about this gene group, which is essential for the formation of structure of plants and animals.

MicroRNAs are small molecules that regulate the activity of other genes. They affect development and differentiation of tissues. MicroRNAs are negative regulators, which means they are also capable of stopping the operations of certain genes. Negative regulation is often important because if it is prevented, tumours, cancer and other developmental disorders may occur.

In a new study, Professor Yrjö Helariutta's team and colleagues show the key role of these molecules in chemical communication between plant cells. They showed that microRNAs are capable of moving from cell to cell, and conveying information between them. However, the research findings are universal, since besides plants, these molecules also appear in animal and human tissues, such as in brains.

Mutual communication between plant cells

The researchers described, in its entirety, a model where plants' different cells 'discuss' with each other. One cell layer sends a signal to another layer which replies to the first. In this way, cells know their place in the three-dimensional structure of the plant.

The researchers showed that microRNAs are synthesised in the cell's endodermic layer from where they move to the surrounding cells. This movement regulates how the cells within and outside the microRNA field will develop.

The findings can be applied generally to plant biology but also other fields, perhaps even medicine, and plant biology. It is possible that the microRNA molecules found in animals also move from cell to cell, establishing regulatory fields during development of human tissues, for example in the brain.

This work is a collaboration between the research teams headed by Yrjö Helariutta (University of Helsinki), Philip Benfey (Duke University), Annelie Carlsbecker (Uppsala University) and Ji-Young Lee (Boyce Thompson Institute).

Carlsbecker A, Lee J-Y, Roberts CJ, Dettmer J, Lehesranta S, Zhou J, Lindgren O, Moreno-Risueno M-A, Vatén A, Thitamadee S, Campilho A, Sebastian J, Bowman J L, Helariutta Y & Benfey PN. Cell signalling by microRNA165/6 directs gene dose-dependent root cell fate. Nature 2010; advance online publication 21 April 2010. (doi :10.1038/nature08977)

The article in Nature >>

Text: Kirsikka Mattila
Photo: Helariutta's team

March 2010

The formula for making teeth will soon be found

Academy Professor Jukka Jernvall and his team investigate the evolutionary development of mammal teeth. After over 15 years of work, the team has compiled so much data that the main aspects of a formula for making teeth are beginning to be clear. The results were published in Nature, the esteemed science journal.

Salazar-Ciudad I, Jernvall J. A computational model of teeth and the developmental origins of morphological variation. Nature. 2010 Mar 25;464(7288):583-6. Article >>

See also University of Helsinki research news: The formula for making teeth will soon be found >>

February 2010

Brachypodium: A small grass with a big role to play

Researchers at the Institute of Biotechnology have reported (Nature 463: 763-768, 11 February 2010) the sequence of Brachypodium distachyon, purple brome grass. This is the first wild grass to be sequenced.

Photo: courtesy of the John Innes Centre

The work represents a breakthrough because the Brachypodium genome, which is small like the plant, is organized in much the same way regarding gene content and order as are the large, unsequenced genomes of key crops including wheat, barley, rye, oat, and fodder grasses. Brachypodium this serves as an excellent model for identification of candidate genes in the cereal crops for such traits as stress and disease resistance, sustainability, and quality.

Sequencing and analysis of the Brachypodium genome was carried out by a team of 60 researchers. One of the teams, led by Alan Schulman of the Institute of Biotechnology and MTT and by Thomas Wicker of the University of Zurich, characterized the transposable elements of the genome. The team was especially interested in understanding why the Brachypodium genome is small, because normally transposable elements, particularly retrotransposons, expand the genome and comprise most of the DNA. Schulman, together with Jaakko Tanskanen of the Institute of Biotechnology and MTT, found that rapid turnover of retrotransposons, rather than lack of activity, is the answer. The Schulman group is currently using the Brachypodium genome as a guide for positional cloning of a disease resistance gene in wheat, as well as examining the genome dynamics of wild Brachypodium populations.

The International Brachypodium Initiative. Genome sequencing and analysis of the model grass Brachypodium distachyon. Nature. 2010; 463: 763-768. (doi: 10.1038/nature08747) Abstract >> Article >>

See also University of Helsinki research news Genome of useful plants is being revealed >>