Table of Contents introduction 2 The CIG at a glance 2 The CIG Scientific Advisory Committee 3 Message from the Director 4 Highlights 5

Research 6 Richard Benton Chemosensory perception and in insects 8 Béatrice Desvergne Networking activity of nuclear receptors during development and in adult metabolic 10 Christian Fankhauser Light regulation of plant growth and development 12 Paul Franken Genetics and energetics of sleep homeostasis and circadian rhythms 14 David Gatfield Molecular mechanisms of circadian 16 Nouria Hernandez Synthesis of non-coding RNAs by RNA polymerases II and III: mechanisms of regulation 18 Winship Herr Molecular epigenetics 20 Henrik Kaessmann Functional evolutionary genomics in mammals 22 Liliane Michalik Molecular control of skin homeostasis 24 Alexandre Reymond Genome structure and expression 26 Andrzej Stasiak Functional transitions of DNA structure 28 Mehdi Tafti Genetics of sleep and sleep disorders 30 Bernard Thorens Physiological genomics of energy homeostasis 32 Walter Wahli The multifaceted roles of PPARs and micronutrients in health and disease 34 Other groups at the Génopode 36

Core facilities 40 Genomic Technologies Facility (GTF) 42 Protein Analysis Facility (PAF) 44 Core facilities associated with the CIG 46

Education 48 Courses and lectures given by CIG members 50 Doing a PhD or a Postdoc at the CIG 51 Symposia and seminars 52 The CIG and the public 56

PeoplE 58

1 Introduction

The Center for Integrative Genomics (CIG) at a glance

The Center for Integrative Genomics (CIG) is a department of the Faculty of and Medicine (FBM) of the University of Laus- anne (UNIL). Its main missions are to pursue cutting edge research, to deliver the highest quality teaching to students, and to inform the public at large. It encompasses 14 research groups working on genome structure and function using a large number of techniques and experimental systems, as well as two core facilities dedicated to providing the latest equipment and knowledge in genomics and proteomics to researchers at the UNIL and beyond (see chapter “core facilities”). The CIG research groups are involved in numer- ous collaborative research projects and programs both within Swit- zerland and at the international level (see chapter “research”). To train tomorrow’s scientists, CIG members are involved in the teaching program of the UNIL and contribute to developing new education programs. The Center proposes seminars, lectures, and scientific meetings for the scientists of the Lemanic region and beyond. Moreover, its members organize and actively participate in activities geared to the public at large (see chapter “education”). The CIG is currently composed of more than 200 members origi- nating from some 30 different countries, who together contribute to the development of its research, its core facilities and its educa- tional activities (see chapter "people").

2 Message from the SAC

Scientific Advisory Committee members From the perspective of the Scientific Advisory Committee (SAC) the CIG continues to be an increasingly dynamic presence within the Swiss and the international scientific communities. During the last Prof. Robert EISENMAN Prof. Ivan STAMENKOVIC several years the ties between the CIG, the UNIL and other scientific (President of the SAC) Director of Departement institutions in Switzerland have been strengthened as CIG faculty Fred Hutchinson Cancer of Experimental Pathology play teaching and administrative roles within the UNIL community Research Center University of Lausanne and as the CIG collaborates in numerous multi-institute initiatives. A University of Washington Lausanne, Switzerland noteworthy example is the new UNIL/CIG/Swiss Institute for Bioin- School of Medicine, formatics/Vital IT doctoral program in Integrative Experimental and Seattle, USA Prof. Markus STOFFEL Computational Biology (IECB) with its aim to train a new generation Institute of Molecular of biologists proficient in both laboratory benchwork and computa- Prof. Steve BROWN Health Sciences tional analysis. Director of MRC Harwell Swiss Federal Institute Mammalian Genetics Unit of Technology Zurich (ETHZ) The CIG continues to appoint and promote faculty of the highest Harwell, UK Zurich, Switzerland caliber and to recruit first-rate trainees to its laboratories. The SAC considers the diversity of the scientific programs within the CIG to Overall, the Advisory Committee Prof. Nicolas GALTIER Prof. Gisou VAN DER GOOT be one of its major strengths. Research in contemporary biology has Institut des Sciences Global Health Institute become increasingly multi-disciplinary and the diverse programs of views the CIG as a vibrant and de l’Evolution Ecole Polytechnique Fédérale de the CIG foster interactions between fields and unexpected synergies collegial institution that has Montpellier, France Lausanne (EPFL) between laboratories as well as providing a unique training environ- succeeded in attracting excellent Lausanne, Switzerland ment for graduate students and postdoctoral fellows. The shared- Prof. Ueli GROSSNIKLAUS use core facilities required to support these diverse research tech- scientists at every career level. Institute of Plant Biology Prof. Veronica nologies (e.g. Protein Analysis, Genome Technologies) appear to be University of Zurich VAN HEYNINGEN up-to-date, well-managed, and widely-used by the CIG and UNIL Robert N. Eisenman Zurich, Switzerland Medical Research Council (MRC) departments. President the Scientific Advisory Committee Human Genetics Unit During our last visit in June 2012 the SAC met with the CIG lead- Prof. Ueli SCHIBLER Western General Hospital ership, the Dean of the Faculty of Biology and Medicine, technical funding sources and the UNIL. In addition, it will be important for Department of Edinburgh, United Kingdom staff, administrators and assistants (graduate students and postdoc- the institute to become more proactive in identifying future employ- University of Geneva toral fellows). We noted that a number of issues raised during previ- ment opportunities for talented CIG postdoctoral fellows and gradu- Geneva, Switzerland ous visits, primarily concerning the desire for increased involvement ating students especially given the limited number of available aca- of assistants, administrators and technical staff in decision making demic positions. Increasing interactions with the biotechnology and processes at the CIG, are being satisfactorily addressed. In addition pharmaceutical industry may be useful in this regard and addition- avenues for more open communication have been established and ally provide avenues for translation of basic science discoveries. an ombudsman has been appointed to help resolve issues arising among assistants and faculty. Moreover, the director and faculty Overall, the Advisory Committee views the CIG as a vibrant and col- have approved implementation of a rigorous faculty review plan that legial institution that has succeeded in attracting excellent scientists will continue to ensure allocation of space and resources based pri- at every career level. Many of their recent discoveries are highlighted marily on scientific excellence. in this 2011-2012 Scientific Report. Under the leadership of the insti- tute’s director, Prof. Nouria Hernandez, and with the support of the While the CIG is clearly capable of building on its considerable UNIL, we expect that the CIG will continue to evolve and to make strengths, it nonetheless faces a number of challenges in the near important contributions to the scientific community. future. For example, hiring and promotion of CIG faculty and the launching and maintenance of new scientific initiatives will require Robert N. Eisenman increased, and relatively stable, financial support from both external President the Scientific Advisory Committee

3 Introduction

Message from the Director

How to ensure that a department remains highly productive and It is incredibly important that young people joining a department competitive? In my last director’s report, I wrote about the CIG con- be assured that, if they deserve it, they can progress in their career, sidering implementing some form of faculty evaluation process. i.e. they can be tenured and then promoted. Promotions should be This is now set and done! The CIG faculty has voted favorably on based on performance, not on the number of years one has spent in a proposal for a review, every five years, of its tenured professors, a particular position, not on age (neither too old or… too young!), based on letters from external experts and a formal review by the and certainly not on departmental budgets. This is important not CIG Scientific Advisory Committee, with consequences on space and only to maintain the motivation of faculty already in the department, resources. This is an impressive illustration of the dedication of the but also to attract new young faculty, who want to know that they CIG faculty, who accepted to be regularly reviewed with the goal of are joining a meritocracy– that, if they do well, their accomplish- allowing the CIG to use its resources in the best possible way in the ments will be recognized. long term. The counterpart of endorsing faculty promotions when deserved is Evaluation of tenured faculty is an important tool in keeping a that retiring associate and full professors should not be replaced by department dynamic, but there is a second, at least as important associate or full professors, as is often the case in Swiss universities, and perhaps even more important, way to prevent stagnation, but, except in exceptional circumstances, by tenure-track assistant which has to do with hiring and promotions. A standard career path professors. Indeed, this is the only way to maintain a department It is incredibly important that young for a successful academic research scientist goes something along with faculty at all career stages and with the accompanying diversity people joining a department be these lines: as a student, one learns how to perform research, and as of skills, from a focus on outstanding research to broader academic assured that, if they deserve it, they a post-doctoral fellow, one learns how to develop and direct one’s service. Thus, this system avoids the sclerosis of a department where own research project, with which one can obtain an independent departing senior faculty are replaced by senior faculty, and where can progress in their career, i.e. they position. As a young assistant professor, one demonstrates the skills deserving junior faculty stay for too many years in the same position can be tenured and then promoted. required to build one’s own research group and thus to oversee sev- because of considerations external to their merit. eral research projects that, ideally, synergize with one another. As Nouria Hernandez, Nouria Hernandez, CIG Director an associate professor, one can continue developing one’s research group, often with more means than as an assistant professor. CIG Director Already however, one spends time contributing to the running of the institution, a tendency that increases as a full professor, with the price that one has less time to follow research projects on a day-to- day basis. The important concept here is that when one does well, there is a possibility to climb the ladder and to evolve in one’s career.

4 Walter Wahli becomes Highlights of 2011-2012 Professor emeritus

An important event was the retirement of the founding Director of the CIG, Professor Walter Wahli, which was marked by the 2012 CIG 2011 2012 symposium being held in his honor. For this occasion, we had the privilege to have Sir John B. Gurdon not only give a talk to his col- R. Benton is elected EMBO Young Investigator league biologists but also deliver the John Grace Lecture to a lay- A. Reymond receives a SNSF Sinergia grant January people audience, this a few months before winning the Nobel Prize (principal investigator) in Physiology or Medicine! Genomics Days at the Genopode R. Benton receives the 2012 Friedrich Miescher Award Professor Walter Wahli has had a remarkable scientific career, with February numerous achievements both in research and in the support of sci- A. Reymond receives a SNSF ProDoc grant Research Genomics Days at the Genopode ence, the CIG being perhaps the most remarkable example of the B. Desvergne is elected Dean of the Faculty of Biology latter. Fortunately for the advancement of research, Professor Wah- and Medicine li, although retiring from the University of Lausanne, is continuing R. Benton receives a HFSP young investigator grant March his activities as a Visiting Professor at the Lee Kong Chian Medical D. Gatfield is co-recipient of the Leenaards prize School, the joint medical school being developed by Imperial Col- R. Benton receives the 2012 AChemS Young Investigator Award lege London and Nanyang Technological University (NTU) in Sin- for research in olfaction gapore. There he will contribute to the development of one of the April three main topics of the school, metabolism and metabolic diseases. I. Xenarios presents his ”leçon inaugurale“ as full Professor ad We are excited that the first Honorary Professor of the CIG thus pro- personam at the CIG vides a “direct” link between the CIG and the Lee Kong Chain Medi- May M. Tafti receives the foundation NRJ award cal School, and we wish Professor Walter Wahli the very best for this W. Wahli becomes vice-president of the Swiss Science new endeavor. 5th CIG symposium ”Genetics of Behaviour“ and Technology Council 2nd Grace lecture, by Ralf Greenspan W. Wahli receives the FBM Lifetime Achievement Award Third visit of the CIG Scientific Advisory Committee June W. Herr receives the first FBM Jürg Tschopp Life Science Award 6th CIG symposium ”Transcription, from development to nutrigenomics“, in the honor of W. Wahli R. Benton receives the FBM Basic Life Science Research Award C. Fankhauser presents his ”leçon inaugurale“ as full Professor 3rd John Grace lecture by John Gurdon July August R. Benton becomes Associate Professor P. Franken receives a SNSF Sinergia grant (with B. Thorens and I. Xenarios (CIG), and J. Auwerx (EPFL)) D. Gatfield receives a Fondation Mercier pour la Science September CIG annual retreat award CIG annual retreat M. Tafti presents his ”leçon inaugurale“ as full Professor October November L. Michalik receives a UNIL Medical Teaching Award December

5 6 research 7 Research

Richard Benton Chemosensory perception and evolution in insects Associate Professor For several hundred million years, animal brains have undergone Comparative analysis of chemosensory circuits remarkable diversification in their structure and function, as these We have completed a comprehensive neuroanatomical and physi- biological information processors are challenged and optimised ological analysis of the IR olfactory circuits, in which we have iden- (through natural selection of their organismal hosts) by the demands tified odour ligands and central circuit organization for the vast placed upon them in the ecological niche in which they operate. My majority of IR olfactory pathways. By comparing our findings with group is interested in defining the genetic mechanisms and environ- the properties of OR circuits, we can begin to explain how and why mental driving forces underlying neural evolution. two complementary olfactory subsystems have evolved in insects. We study the Drosophila olfactory system, a well-described and rap- Recently, we have shown that a large number of IRs are selectively idly evolving sensory system in a genetically accessible model organ- expressed not in the olfactory system, but in small subpopulations ism. Furthermore, genomic and genetic access to closely-related, but of neurons in peripheral and internal gustatory neurons, suggesting ecologically diverse, drosophilids and more distant insect species pro- roles for these receptors in taste detection and internal food assess- vides an unparalleled foundation for comparative genetic and func- ment. We are currently defining the ligands detected and behav- tional analysis of their olfactory circuits. We take an interdisciplinary iours controlled by these sensory pathways. approach to this problem, combining bioinformatics, molecular genet- ics and cell biology, neurophysiology and behavioural analysis. Under- Behavioural functions of IR circuits standing how and why particular olfactory molecules, circuits and We have used simple odour preference assays to define the innate behaviours have evolved in Drosophila will, we believe, yield general behaviours mediated by lR pathways. We have also analysed social insights into the mechanisms of, and constraints on, brain evolution. behavioural functions of IRs, prompted by our observation that one Our recent focus has been the Drosophila olfactory subsystem drosophilid-specific receptor, IR84a, is expressed in a population of expressing the Ionotropic Receptors (IRs), a divergent, chemosensory neurons implicated in control of sexual behaviours. We showed that subfamily of the synaptic ionotropic glutamate receptors. This model IR84a is essential to promote male courtship of females. Surprisingly, has proven to be fertile ground for illuminating the evolution of che- this receptor detects food-derived odours and not fly-derived phero- mosensory systems and stimulated diverse, new questions that start mones. Our results suggest a model in which IR84a has evolved in to address the mechanistic basis by which changes in these senso- drosophilids to co-ordinate feeding site selection and reproductive ry circuits have come about and the selective pressures that have behaviours. This model can explain the long-standing observation favoured these adaptations. that drosophilid fruit flies breed almost exclusively on their food sub- strates and highlights a direct sensory mechanism in which a species Comparative genomics of olfaction uses an environmental “aphrodisiac” to promote sexual behaviours. We have performed comprehensive bioinformatic analyses of the Current efforts are directed towards development of novel behav- IR repertoires in animal genomes to reveal the evolutionary ori- ioural assays in which we can precisely control the temporal pat- gin, expansion and diversification of this family of chemosensory tern of odour stimuli, and video-track single or groups of flies in a receptors, and how this relates to individual species’ chemosensory high-throughput manner. These technical advances are allowing us Richard Benton received his PhD in 2003 from the University of ecology. These analyses have provided an essential foundation for to describe previously unobservable olfactory-mediated behaviours. Cambridge for work on the molecular mechanisms of cell polarisation comparative functional studies of both the Drosophila olfactory sub- Olfactory circuit evolution with Daniel St Johnston at The Wellcome Trust/Cancer Research UK systems (expressing Odorant Receptor (OR) or IR repertoires) and Gurdon Institute. For his post-doctoral research, he joined Leslie Voss- individual IR olfactory pathways. Much of our current work focuses on obtaining mechanistic evolu- hall’s laboratory at The Rockefeller University, New York, studying the tionary explanations for the organisation and function of the extant molecular biology of odour detection in Drosophila, during which he Molecular biology of odour detection Drosophila olfactory system. Through comparative transcriptomics was supported by fellowships from the European Molecular Biology Through electrophysiological and cell biological approaches in vivo of OR and IR subsystems, as well as individual olfactory pathways Organisation and the Helen Hay Whitney Foundation. He joined the and heterologous cells, we have studied IR complex formation and within these subsystems, we aim in the future to identify and char- Center for Integrative Genomics in September 2007 as Assistant Pro- stoichiometry, and their trafficking, ion conduction and ligand-rec- acterise loci that have driven the developmental and functional fessor and was awarded a European Research Council Starting Inde- ognition properties. Our results provide insights into the conserved diversification of these olfactory circuits. In addition, we are expand- pendent Researcher Grant in 2008. He was the winner of the 2009 and distinct architecture of these chemosensory receptors and their ing our efforts to genetic, physiological and behavioural analysis of Eppendorf and Science Grand Prize for Neurobiology. In 2012, he was synaptic ancestors. In current work, we collaborate with structural drosophilid species that have distinct chemosensory preferences to promoted to Associate Professor and was elected to the EMBO Young biologists to visualise the three-dimensional organisation and dynam- D. melanogaster, to identify the genetic basis of their ecologically- Investigator program. He was also the recipient of the 2012 Fried- ics of the apo and odour-bound IR ligand-binding domain by X-ray important olfactory adaptations. rich Miescher Award and the Achens Young Investigator Award for crystallography and Nuclear Magnetic Resonance to understand the research in olfaction 2012. molecular basis and evolution of their odour recognition properties.

8 Group members 2011-2012 Publications Funding Collaborations

Group leader MASTER student Grosjean Y, Rytz R, Farine JP, Ramdya P, Schaffter T, Floreano Swiss National Science D. Floreano Richard Benton Flavio Angei Abuin L, Cortot J, Jefferis GSXE, D, Benton R (2012) Fluorescence Foundation (SNSF) EPFL, Lausanne, Switzerland [email protected] Benton R (2011) An olfactory Behavioral Imaging (FBI) tracks Project grant G. Jefferis RESEARCH ASSISTANT receptor for food-derived odours identity in heterogeneous Sinergia grant (co-recipient) MRC Laboratory of Molecular Postdoctoral fellows Jaime Humberto Reina promotes male courtship in groups of Drosophila. PLOS ONE European Commission Biology, Cambridge, UK Drosophila. Nature 478:236-40 7:e48381 Benoîte Bargeton Copete European Research Council (ERC) R. Jin Carolina Gomez Diaz Silbering AF*, Rytz R*, Grosjean LeBoeuf A, Benton R** and starting independent researcher Sanford Burnham Medical Adria Le Boeuf TechnicianS Y*, Abuin L, Ramdya P, Keller L** (2012) The molecular grant Research Institute, La Jolla, USA Laura Lucia Prieto Godino Jefferis GSXE, Benton R (2011) basis of social behavior: models, Liliane Abuin European Molecular Biology L. Keller Pavan Ramdya Complementary function methods and advances. Curr Steeve Cruchet Organization (EMBO) UNIL, Lausanne, Switzerland Michael Saina and integrated wiring of the Opin Neurobiol 23:3-10 • Young investigator program F. Rentzsch Juan Antonio Sanchez Alcaniz APPRENTICE TECHNICIAN evolutionarily distinct Drosophila Benton R (2012) Sensing the • Long-term fellowship to Sars Centre for Marine Molecular Ana Florencia Silbering Jérôme Blanc olfactory subsystems. The long and the short of it. Nat J. Sànchez Alcañiz Journal of Neuroscience Biology, Bergen, Norway Neuro 15:501-3 Human Frontier Science PhD students 31:13357-75 C. Tang Secretary Silbering AF, Bell R, Galizia Program (HFSP) Wuhan Institute of Physics and Rati Bell Annick Crevoisier Benton R, Dahanukar A (2011) CG, Benton R (2012) Calcium • Young investigator grant Mathematics, Wuhan, China Vincent Croset [email protected] Electrophysiological recording imaging in the Drosophila • Long-term fellowship to Raphaël Rytz from Drosophila olfactory antennal lobe. Journal of P. Ramdya Anantha Sivasubramaniam sensilla. Cold Spring Harbor Visualized Experiments Novartis Foundation for Protocols 10.1101/pdb.prot5630 61:e2976 Biomedical Research Benton R, Dahanukar A (2011) Federation of European Electrophysiological recording Biochemical Societies (FEBS) from Drosophila taste sensilla. * equal contribution ** co-corresponding authors Long-term fellowships to Cold Spring Harbor Protocols L. Godino and to J. Sànchez 10.1101/pdb.prot5631 Alcañiz Benton R (2011) Decision Boehringer Ingelheim Fonds Making: Singin' in the Brain. • PhD fellowship to Vincent Neuron 69:399-401 Croset Smith CR et al. (including • PhD fellowship to Rati Bell Benton R) (2011) Draft genome Asturian Fellowship of the red harvester ant Foundation Pogonomyrmex barbatus. Proc Carolina Gomez-Diaz Natl Acad Sci USA 108:5667-72 Smith CD et al. (including Benton R) (2011) Draft genome of the globally widespread and invasive Argentine ant (Linepithema humile). Proc Natl Acad Sci USA 108:5673-8. Abuin L, Bargeton B, Ulbrich MH, Isacoff EY, Kellenberger S, Benton R (2011) Functional architecture of olfactory ionotropic glutamate receptors. Neuron 69:44-60

9 Research

Béatrice Desvergne Networking activity of nuclear receptors during development Professor and in adult metabolic homeostasis

As they mediate intracellular action, nuclear receptors play adipocytes in the bone marrow itself promotes myelopoiesis and de- a crucial multi-faceted role in coordinating growth during develop- represses osteoclastogenesis. Consequently, higher activity of osteo- ment, and homeostasis at adult stage. Among them, the peroxi- clast altered the stem cell niche and causes a severe cortical porosis some-proliferator activated receptors (PPARs) have an integrative in midshaft of long bones. Deletion of PPARgamma also activates role in controlling the expression of genes regulating the storage, LT-HSC differentiated into multi-potential progenitors and mobilizes mobilization, and/or utilization of lipids. progenitors into circulation.

Our activities have been centered on revealing and understanding Axis 2: Nuclear-receptor regulatory network in at the molecular levels the phenotypic expressions of PPAR muta- liver metabolism tions in mice, taking them as leads to explore the physiopathologi- cal signi-ficance and novel therapeutic advances that PPARs carry. In The study of the metabolic regulations has long been focused on the last two years, we have focused our efforts on two axes. First we mechanisms affecting the rate-limiting steps along a given pathway. used our newly obtained PPARgamma null mice to explore the mul- However, metabolic homeostasis relies on the cross talk between tifaceted consequences of lipodystrophy, revealing some key para- various regulatory pathways. We thus now shifted our exploration crine activity of the adipose tissue during development. Second we towards understanding the role of the nuclear receptors within reg- explore the liver network that drives metabolic ulatory networks focusing in the liver, which is the main metabolic homeostasis in the adult organism. organ with respect to energy homeostasis. In a first project, we explore a subset of nuclear receptors –LXR, Axe 1: A new model of PPARgamma null mice FXR, PPARalpha, HNF4 and PXR– in highly differentiated human liv- er cells. Global gene expression analyses in response to metabol- The effect of PPARgamma global deletion was not addressed so far ic signals surprisingly revealed that only a small set of differentially because of embryonic lethality due to a placenta defect. In our labo- expressed genes are shared by the different nuclear receptors stud- ratory, we recently created a new generalized PPARgamma-/- mouse ied, whereas GSEA analyses confirmed the important overlap at the model by preserving PPARgamma expression in the trophoblastic cells. pathway level. We are now working on modeling the results, inte- In accordance with the requirement of PPARgamma for adipocyte grating our experimental data into a rebuilt in-silico model of the differentiation, PPARgamma-/- mice are totally deprived of white known interactions between the investigated pathways (see Figure). and brown adipose tissue. This generalized lipodystrophy provoks in The second project along this axis is linked to the SystemsX pro- PPARgamma-/- mice an insulin resistance, starting at 4 to 5 weeks of ject CycliX, where we explore how the transcription factors interplay age followed by a severe type 2 diabetes (T2D) associated to metabol- coordinate cell, nutrition, and circadian cycles. Our group focused on ic inflexibility. In parallel, an advanced form of diabetic nephropathy exploring the sterol regulatory element binding protein 1 (SREBP1) develops, with a severe glomerular phenotype. Finally, the liver under- activity, which is both nutrient-responsive and influenced by the cir- go an important and spontaneous hepatic steatosis, accompanied by Béatrice Desvergne was trained as a MD. In 1984, she obtained cadian clock. We evaluated by ChIP-seq SREBP1 binding around the increased cell proliferation. Thus, PPARgamma null mice represent a both the MD degree and the specialization in Anesthesiology and clock, in the liver of wild type mice. The binding of SREBP1 to its tar- formidable tool for gaining insight into the mechanisms underlying Resuscitation. After practicing medicine for a few years, she decid- get regions showed an oscillatory profile, with a maximum around the pathogenesis of different metabolic disorders that accompanied ed to devote more time for fundamental research. She thus carried ZT18, which is consistent with the maximum of RNA expression and T2D, such as metabolic inflexibility, diabetic nephropathy and steato- out a post-doctoral stay from 1988 to 1992 at the National Institutes nuclear localization of the protein. However, one subgroup of tar- hepatitis, for which little “in vivo” models are satisfactory. of Health in Bethesda, first as visiting fellow and then visiting asso- get genes has an expression profile that is strictly following SREBP1 ciate in the National Institute of Diabetes and Digestive and Kidney PPARgamma null mice allowed us to demonstrate the crucial role binding, whereas two other subgroups have a temporal expression Diseases, in the field of Molecular Endocrinology. In 1992, she was of paracrine activities of the adipose tissue. First in the skin, where profile different from SREBP1 association. Thus other transcription appointed assistant professor at the University of Lausanne. She was we demonstrate that the lack of sub-cutaneous adipose tissue pro- factors –linked to circadian expression since in Bmal1KO mice the then recruited as associate professor at the same university, joined the vokes a delay in hair morphogenesis and we are now searching the expression of all SREBP1 target genes are synchronized and fol- Center for Integrative Genomics in 2003, and was promoted full pro- adipocyte-generated paracrine signal that acts onto hair follicle ini- low SREBP1 binding– participate in the regulation of these genes. fessor in 2008. In addition to her teaching and research activities, she tial development. Around 5 weeks, a phenotype of cicatricial alo- Thus, our results define SREBP1 binding pattern in the physiologi- was President of the Section of Fundamental Sciences and Vice-Dean pecia developped, but this is now due to the lack of PPARgamma cal context of both rhythmic food absorption and of the Faculty of Biology and Medicine from 2009 to 2012. In August in the hair follicle cells, and more particularly in sebocytes. Second and they give the first tools to comprehensively explore how SREBP1 2012, she was elected Dean of the Faculty of Biology and Medicine. in the bone marrow niche, where we show that the absence of activity is connected to circadian-driven regulatory events.

10 Group members Publications Funding Collaborations 2011-2012

Group leader Yamamoto H, Williams EG, Canella D, Bernasconi D, Brunner JM, Plattet P, Swiss National Science J. Auwerx Béatrice Desvergne Mouchiroud L, Canto C, Gilardi F, LeMartelot G, Doucey MA, Rosso L, Foundation (SNSF) EPFL, Lausanne, Switzerland [email protected] Fan W, Downes M, Heligon C, Migliavacca E, Praz V, Cousin Curie T, Montagner A, Wittek Project grant S. Ferrari Barish GD, Desvergne B, Evans P, Delorenzi M, Hernandez N, R, Vandelvelde M, Zurbriggen European Commission University of Geneva, Switzerland RM, Schoonjans K, Auwerx J Cyclix Consortium*, (2012) A A, Hirling H, Desvergne B MAÎTRE-ASSISTANTE Project EuMODIC R. Gruetter SUPPLEANTE (2011) NCoR1 is a conserved multiplicity of factors contributes (2012) Morbillivirus glycoprotein Federation of European CIBM, Lausanne, Switzerland physiological modulator of to selective RNA polymerase III expression induces ER stress, Federica Gilardi Biochemical Societies (FEBS) muscle mass and oxidative occupancy of a subset of RNA alters Ca homeostasis and results L. Hirt Postdoctoral fellowship function. Cell 147:827-39 polymerase III genes in mouse in the release of vasostatin. CHUV, Lausanne, Switzerland Postdoctoral fellows to L. Quignodon Casals-Casas C, Desvergne B liver. Genome Res 22:666-80 PLoS One 7:e32803 P. Karnik Cristina Casals Casas Novartis Foundation (2011) Endocrine disruptors: Case Western Reserve University, Greta Giordano Attianese Postdoctoral fellowship from endocrine to metabolic *B. Desvergne is a member of the Cyclix Cleveland, USA Aurélien Naldi to C. Casals-Casas Barbara Toffoli disruption. Annu Rev Physiol Consortium S. Kersten Laure Quignodon 73:135-62 Faculty of Biology University of Wageningen, and Medicine (FBM), UNIL Le Martelot G, Canella D, The Netherlands Interdisciplinary research grant PhD students Symul L, Migliavacca E, Gilardi F, G. Krönke (co-recipient) He Fu Liechti R, Martin O, Harshman University of Erlangen-Nuremberg, Sajit Thottathil Oommen K, Delorenzi M, Desvergne B, SystemsX.ch Germany RTD project CycliX (co-recipient) Mariagiovana Parente Herr W, Deplancke B, Schibler D. Moulin Chiara Sardella U, Rougemont J, Guex N, CNRS UHP Nancy, France Mariano Schiffrin Hernandez N, Naef F (2012) Genome-wide RNA polymerase L. Nagy MASTERs STUDENTS II profiles and RNA accumulation University of Debrecen, Hungary Marianna Di Chiara reveal kinetics of transcription R. Paus Jean-Gaël Diserens and associated epigenetic University of Lübeck, Germany Linda Müller changes during diurnal cycles. Nicoletta Corti PLoS Biol 10:e1001442 Nadra K, Medard JJ, Quignodon Technicians L, Verheijen MH, Desvergne Michaël Baruchet B, Chrast R (2012) Epineurial Maude Delacombaz adipocytes are dispensable for Carine Winkler Schwann cell myelination. J Neurochem 123:662-7 ADMINISTRATIVE ASSISTANT Nadra K, Medard JJ, Mul JD, Han GS, Gres S, Pende M, Metzger Loyse Rebord D, Chambon P, Cuppen E, The model of the hepatic nuclear Saulnier-Blache JS, Carman GM, receptor network was built based on SECRETARY data available in the literature. Green Desvergne, B Chrast, R (2012) rectangles represent different stimuli Marlène Petit Cell autonomous lipin 1 function that can influence the activity of distinct [email protected] is essential for development nuclear receptors (violet rectangles), and maintenance of white and which in turn regulate the transcription of a number of target genes (ellipsis of arbi- brown adipose tissue. trary colors). The behavior of the network Mol Cell Biol 32:4794-810 is then compared with experimental data, obtained from microarray analysis of gene expression in human hepatic cells, treated with the same stimuli.

11 Research

Christian Fankhauser Light regulation of plant growth and development Professor

Almost all our food, feed, fuel and fiber ultimately derive from plants. Phototropism is a directional growth response enabling plants to Plant growth depends on photosynthesis, the process in which light optimally position their photosynthetic organs (leaves). Phototropin energy is harnessed for the synthesis of high-energy carbon com- photoreceptors (phot1 and phot2 in Arabidopsis) sense light direc- pounds. In order to capture light, plants have evolved unique ways tion to initiate phototropism. These light sensors also control leaf of building cells, tissues and organs, a highly diverse metabolism, and flattening, chloroplast movements and opening of stomata (pores a life-long continuation of versatile growth and development. Plants on leaves regulating gas exchange) and thereby contribute to the possess numerous photoreceptors enabling them to sense changes optimization of photosynthesis. Phototropins are blue-light activated in the amount, spectral composition, photoperiod and direction of protein kinases composed of two light-sensing LOV (Light Oxygen light. The main goal of our research is to understand how light mod- Voltage) domains and a carboxy-terminal protein kinase domain. We ulates plant growth and development allowing these sessile organ- study signal transduction mechanism leading from photoreceptor isms to optimize their growth habit depending on the environmental activation to phototropin-mediated growth responses (phototropism conditions. We use the model plant Arabidopsis thaliana and concen- and leaf positioning). These two processes require the PKS (Phyto- trate on two specific light responses: the shade avoidance syndrome chrome Kinase Substrate) proteins that act early in this signaling cas- and phototropism. cade and are one focus of our studies. In crowded environments light becomes a limiting resource. Plants sense foliar shade from competitors primarily using phytochrome (phy) photoreceptors to initiate the shade avoidance syndrome. Phy- tochromes are synthesized as Pr (red-light absorbing). Upon light excitation they are photo-transformed into Pfr (far-red-light absorb- ing), which is the active conformer that is converted back into the inactive Pr by far-red light. In direct sunlight phytochrome phyB is mostly in its active conformation and inhibits the shade avoidance response. Foliar shade is poor in red light and rich in far-red light leading to inactivation of phyB, which triggers the shade avoidance syndrome. phyB activity is partly mediated by the conformation-spe- cific interaction between Pfr and a family of bHLH class transcrip- tion factors known as PIFs (Phytochrome Interacting Factor). We are studying this signaling cascade to understand how a change in the light environment leads to PIF-regulated growth and development.

Christian Fankhauser received his PhD from the UNIL in 1994 after carrying out his thesis at Swiss Institute for Experimental Can- cer Research (ISREC) in the laboratory of Dr. Viesturs Simanis. He performed postdoctoral studies with Dr. Marty Yanofsky at UCSD then with Dr. Joanne Chory at The Salk Institute for Biological Stud- ies in San Diego. He became a Swiss National Science Foundation Professor at the Department of Molecular Biology of the University of Geneva in 2000. He joined the Center for Integrative Genom- ics in January 2005, where he was appointed Associate Professor. Christian Fankhauser was promoted Full Professor in 2011.

12 Group members 2011-2012 Publications Funding Collaborations

Group leader VISITING STUDENTS Fankhauser C, Ulm R (2011) Kami C, Hersch M, Trevisan Swiss National Science S. Bergmann Christian Fankhauser Marçal Gallemi Light-regulated interactions M, Genoud T, Hiltbrunner A, Foundation (SNSF) UNIL and SIB, Lausanne, [email protected] Kirsty McInnes with SPA proteins underlie Bergmann S, Fankhauser C • Project grant and bonus of Switzerland -mediated (2012) Nuclear phytochrome a excellence M. Blazquez Postdoctoral fellows RESEARCH ASSISTANTS gene expression. Genes Dev signaling promotes phototropism • National Center of University of Valencia, Spain 25:1004-9 in Arabidopsis. Plant Cell Competence in Research Emilie Demarsy Séverine Lorrain J. Christie 24:566-76 (NCCR) “Plant Survival” Tino Dornbusch Patricia Hornitschek Foreman J, Johansson H, University of Glasgow, UK Mieke de Wit Hornitschek P, Josse EM, Lorrain S, Fankhauser C (2012) SystemsX.ch J. Friml Anupama Goyal TECHNICIANS Fankhauser C, Halliday KJ (2011) Plant development: should I • RTD project “Plant Growth in University of Gent, Belgium Chitose Kami Laure Allenbach Light receptor action is critical stop or should I grow? Curr Biol Changing Environment” Tobias Preuten Martine Trevisan for maintaining plant biomass 22:R645-7 • iPhD project (co-principal M. Geisler & E. Martinoia University of Zürich, Switzerland Bogna Szarsynzka Bérangère Philippon at warm ambient temperatures. Radotic K, Roduit C, Simonovic investigator) Plant J 65:441-52 J, Hornitschek P, Fankhauser European Commission K. Halliday PhD students APPRENTICE TECHNICIAN Gallego-Bartolome J, Kami C, Mutavdzic D, Steinbach Marie Curie post-doctoral University of Edinburgh, UK Patricia Hornitschek Jerôme Blanc C, Fankhauser C, Alabadi D, G, Dietler G, Kasas S (2012) fellowship to T. Dornbusch A. Hiltbrunner Markus Kohnen Blazquez MA (2011) A hormonal Atomic force microscopy University of Tuebingen, Paolo Schumacher SECRETARY regulatory module that provides stiffness tomography on living Germany Nathalie Clerc flexibility to tropic responses. Arabidopsis thaliana cells reveals Master students S. Kasas [email protected] Plant Physiol 156:1819-25 the mechanical properties of EPFL, Lausanne, Switzerland Gaelle Berthoud Ding Z, Galvan-Ampudia CS, surface and deep cell-wall Olivier Michaud layers during growth. Biophys J L. Lopez-Molina Demarsy E, Langowski L, Kleine- University of Geneva, Switzerland Clément Quan Vehn J, Fan Y, Morita MT, Tasaka 103:386-94 Samuel Rappo M, Fankhauser C, Offringa R, Hornitschek P, Kohnen MV, R. Solano Paolo Schumacher Friml J (2011) Light-mediated Lorrain S, Rougemont J, Centro National de polarization of the PIN3 auxin Ljung K, Lopez-Vidriero I, Biotechnologia, Madrid, Spain transporter for the phototropic Franco-Zorrilla JM, Solano K. Shimazaki response in Arabidopsis. Nat R, Trevisan M, Pradervand S, Kyushu University, Fukuoka, Cell Biol 13:447-52 Xenarios I, Fankhauser C (2012) Japan Lee KP, Piskurewicz U, Tureckova Phytochrome interacting factors R. Smith V, Carat S, Chappuis R, Strnad 4 and 5 control seedling growth University of Bern, Switzerland in changing light conditions M, Fankhauser C, Lopez-Molina S. Tolutomi by directly controlling auxin L (2012) Spatially and genetically Osaka Prefecture University, signaling. Plant J 71:699-711 distinct control of seed Osaka, Japan germination by phytochromes A Dornbusch T, Lorrain S, I. Xenarios and B. Genes Dev 26:1984-96 Kuznetsov D, Fortier A, Liechti UNIL and SIB, Lausanne, R, Xenarios I, Fankhauser C Demarsy E, Schepens I, Okajima Switzerland K, Hersch M, Bergmann (2012) Measuring the diurnal S, Christie J, Shimazaki KI, pattern of leaf hyponasty and Tokutomi S, Fankhauser C (2012) growth in Arabidopsis – a novel Phytochrome Kinase Substrate phenotyping approach using 4 is phosphorylated by the laser scanning. Functional phototropin 1 photoreceptor. Plant Biology 39:860-9 EMBO J 31:3457-67

13 Research

Paul Franken Genetics and energetics of sleep homeostasis Associate Professor and circadian rhythms

In the study of sleep two main regulatory processes have to be con- Clock genes & sleep homeostasis sidered: a homeostatic process that is activated by and counters the effects of sleep loss and a circadian process that determines the time– Although the circadian and homeostatic processes are thought to of–day sleep preferably occurs. The fine–tuned interaction between operate independently, using reverse (knock out) and molecular the two permits us to stay awake and alert throughout the day and genetic (qPCR, micro-array, miRNA arrays) approaches, we found to remain asleep at night. To gain inside into the molecular corre- that the genes known to set circadian time (referred to as clock lates of the homeostatic process and its interaction with the circadian genes) are also involved in the homeostatic regulation of sleep. process we apply a combination of forward, molecular, and reverse Thus, in mice lacking one or a combination of two of the core genetic approaches in the mouse. Moreover, we have implemented clock components (e.g. Clock, Npas2, Bmal1, Cry1, and Cry2) sleep a variety of novel tools and techniques that, e.g., allow us to follow homeostasis is altered. We also showed that the expression of the metabolic state over the circadian cycle in individual cells, to image clock genes Per1 and Per2 in the forebrain is tightly linked to the clock gene expression in the mouse in vivo, and to mathematically prior sleep–wake history. Thus contrary to the prevailing notion that predict the impact of sleep, waking, and stress on gene expression. circadian and homeostatic processes are separate, at a cellular level, the same molecular circuitry seems to be implicated in both circa- Genetics of sleep dian rhythms and sleep homeostasis. We now focus on the mech- anisms that link clock gene expression to time–spent–awake. The We use Quantitative Trait Loci (QTL) analysis as a forward genetics observation that the transcriptional activity of CLOCK and NPAS2 tool to map genomic regions that regulate sleep or brain activity depends on and affects intracellular energy charge is an exciting first as quantified by the electroencephalogram (EEG). The first mouse clue because this would represent a direct molecular link between genetic reference population (GRP) we phenotyped was a panel of cellular metabolism and the need for sleep. We are currently inves- recombinant inbred (RI) lines derived from the two strains C57BL/6J tigating this issue at the cellular level using redox–sensitive GFP and DBA/2J (referred to as the BXD panel). The analyses revealed probes. We have previously established that the sleep-wake depen- several genomic regions affecting sleep and EEG traits. Especial- dent changes in Per1 and Per2 are, in part, mediated by their tran- ly EEG traits were found to be under strong genetic control. Thus scriptional regulator NPAS2. Using chromatin immunoprecipitation far, we successfully identified the genes modifying two such traits (ChIP) analyses we now could demonstrate that sleep loss reduces thereby implicating novel signaling pathways involved in rhythmic the binding of NPAS2 to the E-boxes of specific target genes. More- brain activity. We now have initiated two more large scale (and lon- over, we discovered that corticosterone importantly contributes to ger term) projects to phenotype and QTL map sleep traits in mice. the transcriptome changes in the brain after sleep loss and that of In a first project we use the genetically diverse CFW-outbred mice the genes in particular. Using mathematical modeling we Paul Franken received his PhD from the University of Groningen, The in an approach similar to a genome wide association study (GWAS) were able to quantify the complex relationship between changes in Netherlands, in 1993 for his work on sleep homeostasis and thermo- in humans. Of the planned total of 3’000 CFW mice to be pheno- clock gene expression in the forebrain, the sleep-wake distribution, regulation at the University of Zurich under the direction of Alexan- typed and genotyped, an approximate 700 have meanwhile passed and circulation corticosterone levels. Model predictions are useful in der A. Borbély. He was a postdoctoral fellow with H. Craig Heller at through the phenotyping pipeline. We employ a novel, non-invasive, helping to design relevant experiments to unravel these non-linear Stanford University, USA, where he studied the cellular mechanisms and high throughput method to measure sleep, which we helped relationships. underlying resetting. In 1996 he joined Mehdi Tafti at develop. In a second project, we will further exploit the BXD pan- the University of Geneva where he used QTL analysis to map sleep el, which has been extended by some 70 new lines, with empha- and EEG traits in mice. He then moved back to Stanford in 2000 as a sis on sleep and metabolic phenotypes. Finally, at a European level senior research scientist to establish an independent lab. He continued we recently launched a COST action (“SYSGENET”) to establish a to work on the genetics of sleep homeostasis and further focused on systems genetics network for the study of complex genetic human the molecular interactions between circadian rhythms, sleep homeo- diseases using mouse GRPs. A specific aim is to house and make stasis, and brain metabolism. In 2005, he joined the CIG as a Maî- available the ‘Collaborative Cross’ GRP in Europe. The Collaborative tre d’Enseignement et de Recherche. In 2009 he received the Sleep Cross is a panel of several hundred RI lines derived from eight inbred Science Award from the American Academy of Neurology. In 2013, lines, which will be a particularly powerful community resource to he was promoted to Associate Professor. map complex traits.

14 Group members Publications Funding Collaborations 2011-2012

Group leader Technician Astori S, Wimmer RD, Prosser Vienne J, Lecciso G, Swiss National Science U. Albrecht Paul Franken Yann Emmenegger HM, Corti C, Corsi M, Liaudet N, Constantinescu I, Schwartz S, Foundation (SNSF) University of Fribourg, [email protected] Volterra A, Franken P, Adelman Franken P, Heinzer R, Tafti M • Project grant Switzerland Secretary JP, Luthi A (2011) The CaV3.3 (2012) Differential effects of • Project grant to A. Vassalli P. Bourgin Postdoctoral fellows Annick Crevoisier calcium channel is the major sodium oxybate and baclofen (co-applicant) Université de Strasbourg, France sleep spindle pacemaker in on EEG, sleep, neurobehavioral • Sinergia collaborative project Thomas Curie [email protected] J. Flint & J. Nicod thalamus. Proc Natl Acad Sci U performance, and memory. (principal investigator) University of Oxford, UK PhD studentS S A, 108:13823-8. Sleep, 35:1071-83. • Agora (co-principal investigator) N. Guex & I. Xenarios Mongrain V, La Spada F, Curie European Commission Shanaz Diessler UNIL and SIB, Lausanne, T, Franken P (2011) Sleep loss • Project EuMODIC Francesco La Spada Switzerland Géraldine Mang reduces the DNA-binding of • Marie Curie Intra-European Ralf Wimmer BMAL1, CLOCK, and NPAS2 fellowship to T. Curie H.C. Heller to specific clock genes in the • ESRS - EU Marie Curie project Stanford University, USA mouse cerebral cortex. • European Cooperation in A. Lüthi PLoS One 6:e26622. Science and Technology (COST): UNIL, Lausanne, Switzerland Hinard V, Mikhail C, Pradervand Project “Sysgenet” B.F. O’Hara S, Curie T, Houtkooper RH, National Sciences & University of Kentucky, Auwerx J, Franken P, Tafti M Engineering Research Lexington, USA (2012) Key electrophysiological, Council (Canada) M. Tafti molecular, and metabolic Research fellowship UNIL, Lausanne, Switzerland signatures of sleep and to V. Mongrain wakefulness revealed in primary Novartis Foundation cortical cultures. J Neurosci Research Fellowship to T. Curie 32:12506 -17. Wimmer RD, Astori S, Bond CT, Rovo Z, Chatton JY, Adelman JP, Franken P, Luthi A (2012) Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold. J Neurosci 32:13917-28. Hasan S, Dauvilliers Y, Mongrain V, Franken P, Tafti M (2012) Age-related changes in sleep in inbred mice are genotype dependent. Neurobiol Aging, 33:195 e13-26.

15 Research

David Gatfield Molecular mechanisms of circadian gene expression SNSF Professor

Virtually all organisms on earth have developed endogenous time- elucidate their roles in regulating circadian physiology and metabo- keeping systems, known as circadian clocks, that allow anticipat- lism by molecular loss- and gain-of-functions studies in mice. ing daily changes in the environment. In mammals, circadian clocks By combining molecular genetics, genome-wide studies and bio- coordinate the daily timing of vital processes such as sleep-wake chemistry in mice and cultured cells we are currently addressing the cycles, locomotor activity, heartbeat, blood pressure, renal plas- following specific aims: ma flow, body temperature, and the secretion of many . Most of these physiological parameters remain rhythmic even when • Identify the transcripts whose parameters of rhythmic accu- organisms are exposed to constant environmental conditions, indi- mulation (e.g. amplitude, phase) are dependent on miRNAs. cating that their timing is indeed controlled by an endogenous circa- To this end, we are assembling a transcriptome-wide, time- dian pacemaker. resolved atlas of miRNA activity in liver by RNA high-throughput The overall goal of the projects in our lab is to understand the sequencing (RNA-Seq). For these experiments, we make use of molecular mechanisms underlying circadian rhythmicity and rhyth- a mouse model in which miRNA production in hepatocytes can mic gene expression. Over the last two decades, impressive prog- be inactivated. For the most interesting and physiologically rel- ress has been made in identifying genes and proteins that func- evant miRNA targets identified in the study, we use tion within the mammalian rhythm-generating core clock circuitry. systems and reporter assays for follow-up experiments. Even- Genetic and biochemical studies have thus led to a molecular mod- tually, we wish to address the physiological importance of the el according to which transcriptional activators and repressors are identified regulatory mechanisms by loss-of-function studies of organized in loops that constitute the clock’s individual miRNAs in mice. basic rhythm-generating architecture. Core clock transcription fac- • Identify RBPs whose loss- and/or gain-of-function affects the tors such as CLOCK:BMAL1 or REV-ERB/ROR are also responsible for activity of the circadian clock in cultured cells. Through such driving rhythms in clock output gene transcription, thus relaying the RBPs, we aim to uncover novel molecular mechanisms by which clock’s timing information to downstream rhythmic gene expression rhythmic gene expression is regulated, occurring potentially on and physiology. Microarray studies dedicated to the genome-wide detection of oscillating mRNAs have indicated that (depending on all post-transcriptional levels, from transcription to mRNA splic- the algorithms used for the detection of rhythmic transcripts) around ing, translation, localisation and degradation. 2-15% of an organ’s transcriptome is under circadian control. • Develop novel methodology to facilitate the identification of the Interestingly, with the exception of post-translational protein modi- “client RNAs” that are bound by our RBPs of interest. Our aim fications that represent a long-standing research focus in the circa- is to establish standardized experimental protocols to facilitate dian field, the potential contribution of post-transcriptional mecha- the UV-crosslinking and immunoprecipitation (CLIP) of protein- nisms to circadian clock functions has been barely addressed. Most bound RNAs, followed by their identification by high-through- projects in our lab are thus dedicated to uncover how mechanisms put sequencing. The approaches we are currently testing rely A biochemist by training, David Gatfield performed his PhD work acting on the RNA level are implicated in regulating rhythmic gene on the in vivo biotinylation of RBPs that are expressed from at the European Molecular Biology Laboratory (EMBL) in Heidelberg, expression. To this end, we are currently pursuing two main direc- BAC transgenes, followed by the purification of protein-RNA Germany. Under the direction of Elisa Izaurralde, he studied the cellu- tions: first, we wish to define the role that microRNAs play as regu- complexes using the biotin-streptavidin interaction. In collabo- lar mechanisms underlying the nuclear export and the degradation of lators of circadian gene expression, and second, we aim to identify ration with other groups, we aim to establish similar biotin- mRNAs. He then joined the group of Ueli Schibler at the University of RNA binding proteins (RBPs) that carry novel functions in the circa- tagging tools also to facilitate chromatin immunoprecipitation Geneva, Switzerland, as a postdoctoral fellow, where h