European Molecular Biology Laboratory Research at a Glance 2009 Contents 4 Foreword by EMBL’s Director General 5 EMBL Heidelberg, Germany 7 Cell Biology and Biophysics Unit 22 Developmental Biology Unit 31 Gene Expression Unit 41 Structural and Computational Biology Unit 52 Directors’ Research 55 Core Facilities 63 EMBL-EBI, Hinxton, UK European Bioinformatics Institute 87 EMBL Grenoble, France Structural Biology 97 EMBL Hamburg, Germany Structural Biology 108 EMBL Monterotondo, Italy Mouse Biology 118 Index of group leaders EMBL Research at a Glance 2009 Foreword by EMBL’s Director General EMBL – Europe’s flagship laboratory for basic research in molecular biology The vision of the nations which founded the European Molecular Biology Laboratory was to create a centre of excellence where Europe’s best brains would come together to conduct basic research in molecular biology. During the past three decades, EMBL has grown and developed substantially, and its member states now number twenty-one, including the first associate member state, Australia. Over the years, EMBL has become the flagship of European molecular biology and is ranked as one of the top research institutes worldwide. EMBL’s missions are to perform cutting-edge research in molecular biology, to offer services to Eu- ropean scientists, to provide advanced training to researchers at all levels, to develop new technolo- gies and instrumentation and to actively engage in technology transfer for the benefit of scientists and society. In research, the five EMBL sites (a central laboratory in Heidelberg, with outstations in Grenoble, Hamburg, Hinxton and Monterotondo) put strong emphasis on interdisciplinarity and collabora- tion, and when the researchers leave to assume key positions in the member states, they export their unique experience of working in a very energetic and international environment. Freedom, flexibil- ity and a regular turnover of staff allows EMBL to pursue the most exciting themes in molecular bi- ology as they arise. Our long-standing tradition of organising excellent courses, conferences and workshops and an extensive outreach programme ensure that know-how spreads further and in- forms the public about the impact modern biology has on our lives. In Research at a Glance you will find a concise overview of the work of our research groups and core facilities. Science at EMBL covers themes ranging from studies of single molecules to an under- standing of how they work together in complex systems to organise cells and organisms. Our re- search is loosely structured under thematic units, giving scientists the intellectual freedom to pursue the topics that most interest them. But what really distinguishes EMBL is the large number of inter-unit collaborations, bringing people with common interests but distinct expertise together to tackle ambitious projects. Cross-unit net- working and training further support scientists working on interdisciplinary projects. Increasingly, our young scientists come with physics, chemistry, mathematics and computer science backgrounds, bringing in expertise that helps us to move into the growing field of systems biology. EMBL combines a critical mass of expertise and resources with organisational flexibility, enabling us to keep pace with today’s biology. The impact of the laboratory’s scientific work, the quality of its services and its continued attractiveness to world-leading young scientists are testimony to EMBL’s success, and show that we are well-equipped for the future. Iain Mattaj EMBL Director General EMBL Heidelberg, Germany A city of about 140,000 inhabitants, Heidelberg is home to Germany’s oldest university, as well as leading biological and medical science institutes such as the Centre for Molecular Biology, the German Cancer Research Center (DKFZ) and the Max Planck Institute for Medical Research, making it an ideal site for EMBL’s main laboratory. Nestling in the wooded hills above the city, the complex is home to five of EMBL’s scientific units: Gene Expression, Cell Biology and Biophysics, Developmental Biology, Structural and Computational Biology and Directors’ Research, as well as the Core Facilities and the central administration, from which service functions are provided for the use of staff at all five EMBL sites. Heidelberg is also home to EMBLEM, the laboratory’s technology transfer company. Today more than 900 personnel are located at EMBL Heidelberg, and the close proximity of the other excellent institutes has led to numerous long-term collaborations. EMBL shares a campus with its sister organisation, the European Molecular Biology Organization. The two share strong historical ties and work together in many ways; for example, they combine to stage many highly-recognised international courses and conferences. Integrated in the EMBL campus the newly-built Advanced Training Centre (ATC) will host state-of-the-art training facilities for practical courses and computer labs together with a 450-seat auditorium, setting the scene for a new area of scientific conferences at EMBL promoting advanced scientific training and education in Europe. Cell Biology and Biophysics Unit The cell is the basic unit of life. Interestingly, living cells occupy the precise midpoint between the molecu- lar and macroscopic scales. Thus, in order to understand how organisms are built and how they function, we need to understand the molecular mechanisms and physical principles that give rise to cellular organi- sation and function. All cells (including prokaryotes) are divided into functional domains, each with different molecular com- positions. In addition, eukaryotes have compartments such as the nucleus, the cytoskeleton and the en- domembrane system. These compartments are permanently renewed by mechanisms that are still poorly understood. Research in the Cell Biology and Biophysics Unit focuses on the mechanisms and principles that underlie the organisation and function of these different compartments and the distribution of specific molecules to each cellular sub-system. Cell biologists and physicists at EMBL are therefore trying to define the role of targeting events, as well as that of more complex self-organisation processes in organising cellular space. These principles are best understood at transitions when the organisation of the cell undergoes dramatic changes to carry out new functions. This is the case when cells divide, or when they change their fate dur- ing the development of the organism to form specific tissues and organs. Both opportunities are exploited in the unit. As a cell prepares to divide, all the microtubules suddenly depolymerise to reassemble into the mitotic spindle. At the same time, the nucleus is disassembled, mitotic chromosomes are formed, the Golgi com- plex fragments and membrane traffic ceases. After segregation of the genome is achieved, cellular organisa- tion is re-established. Thus every cell cycle provides the opportunity to study the principles of the biogenesis of cellular compartments. Similarly, during development, when progenitor cells differentiate into new cell types, not only do the daughter cells receive a complement of chromosomes and organelles from the parent cell, but the genetic program is changed. A reorganisation of cellular architecture takes place, guided by rules that we begin to unravel. The elucidation of such rules and principles is a major chal- lenge to contemporary biology. The areas that we are presently concentrating on are membrane trafficking, cytoskeletal networks and chromosomes and the nucleus and their role in mitosis and meiosis as well as in develop- ment. New directions are therefore being explored at the interface between cell and developmental biology to under- stand how the cell organisation and collective cell behaviour leads to organ formation. Physicists and chemists working together with biologists are trying to elucidate the fundamental rules that gov- ern dynamic cell organisation and function while developing new instruments and tools. Novel developments in mi- croscopy and computer simula- tions are a particular strength of the unit. Jan Ellenberg and Eric Karsenti Joint Coordinators, Cell Biology and Biophysics Unit EMBL Research at a Glance 2009 Functional dynamics of nuclear structure during the cell cycle Previous and current research The genome of eukaryotic cells is compartmentalised inside the nucleus, delimited by the nuclear envelope (NE) whose double membranes are continuous with the endoplasmatic reticulum (ER) and stabilised by the nuclear lamina filament meshwork. The NE is perforated by nuclear pore Jan Ellenberg complexes (NPCs), which allow selective traffic between nucleus and cytoplasm. In M-phase, most metazoan cells reversibly dismantle the highly ordered structure of the NE. Nuclear membranes PhD 1998, Freie Universität that surround chromatin in interphase are ‘replaced’ by cytoplasmic spindle microtubules, which Berlin. segregate the condensed chromosomes in an ‘open’ division. After chromosome segregation the Postdoctoral research at the nucleus rapidly reassembles. Cell Biology and Metabolism Branch, NICHD, NIH, The overall aim of our research is to elucidate the mechanisms underlying cell cycle remodelling Bethesda. of the nucleus in live cells. Breakdown and reassembly of the nucleus and the formation and cor- Group leader at EMBL since rect movement of compact mitotic chromosomes are essential but poorly understood processes. 1999. To study them, we are assaying fluorescently-tagged structural