Chromosome Organization & Dynamics
The Gruber lab at the Department of Fundamental Microbiology (DMF) in Lausanne studies elementary processes in the cell using microbial model organisms. Our main focus is on chromosome organization and genome maintenance. Find out what we do and who we are.
Cells organize and compact long and flexible chromosomal DNA molecules to precisely control gene expression patterns, DNA repair processes and DNA recombination events, and to faithfully segregate chromosomes during cell division. What determines chromosome superstructure and how it impacts upon genome expression and genome maintenance are major open questions in biology. We aim to elucidate fundamental principles of chromosome folding by studying microbial model organisms including the Gram-positive bacterium Bacillus subtilis and budding yeast Saccharomyces cerevisiae.
Our work focuses on two widely distributed factors in chromosome organization: SMC protein complexes and ParABS systems. SMC complexes form multi-subunit ATPases with a characteristic ring topology. They organize DNA as genome linkers by clamping together pairs of chromosomal DNA segments. To uncover how they bring together the “right” pairs of DNA double helices, we investigate how SMC complexes interact with DNA and chromosomes. The emerging view is that DNA loop extrusion by SMC DNA motors plays the key role in the remarkable process of chromosome organization. In bacteria, SMC complexes load onto chromosomes at defined entry sites — parS sites — and then translocate onto flanking DNA helping to shape entire bacterial chromosomes. We want to understand how local SMC loading and subsequent DNA translocation brings about global chromosome folding.
ParABS systems promote chromosome segregation and plasmid maintenance in many bacteria and some archaea. It also supports additional regulatory functions in the cell. ParABS systems work by ParB protein binding to centromeric parS sequences to form large nucleoprotein complexes that act in concert with specific ATPases, ParA and Smc, to partition plasmid and chromosome copies. We have recently discovered that ParB proteins are enzymes — the first known CTP hydrolases — which form DNA sliding clamps that self-load onto parS DNA. We are particularly interested how ParB CTP binding and hydrolysis act together with ParA and Smc ATPases to promote chromosome organization and segregation in bacteria.
Knowledge of the architecture and structure of macromolecular assemblies is often a prerequisite for a basic mechanistic understanding. We integrate genetics, molecular & cell biology and biochemistry with structural biology approaches to reveal the molecular basis for protein function and cellular activity.
We investigate protein-DNA complexes and DNA organization in vitro using an array of biophysical techniques and structural biology and in vivo for example by ChIP-Seq, Hi-C, directed or random mutagenesis and site-specific cross-linking. Bacillus subtilis develops natural competence under starvation and can readily be genetically manipulated, supporting easy and high-throughput allelic replacements.
In relatively new lines of investigation, we are focusing on the roles of SMC and SMC-like proteins (Rad50, RecN and the Smc5/6 complex) in the maintenance of DNA integrity in bacteria and eukaryotes.
 | Anna Anchimiuk anna.anchimiuk[a]unil.ch 2012-2014 – M. Sc. Biotechnology – University of Gdansk and Medical University of Gdansk |
 | Hammam Antar hammam.antar[a]unil.ch 2017-2019 – M. Sc. Immunology, Microbiology & Infections Diseases – University of Grenoble Alpes, France |
 | Florian Bock florianpatrick.bock[a]unil.ch 2013-2016 – M. Sc. Biochemistry – Ludwig Maximilians University, Munich |
 | Eryk Dunski eryk.dunski[a]unil.ch 2016-2018 – M. Sc. Biology-Biotechnology – University of Copenhagen, Denmark |
 | Stephan Gruber stephan gruber unil ch |
 | Young-Min Soh youngmin.soh[a]unil.ch 2010-2015 – Ph. D. Structural Biology – Oh lab, KAIST, Daejeon, Korea |
 | Michael Taschner michael.taschner[a]unil.ch 2010-2017 – Postdoc – Lorentzen lab, Max Planck Institute of Biochemistry, Munich, Germany |
 | Roberto Vazquez Nunez robertojareth.vazqueznunez[a]unil.ch 2013-2015 – M. Sc. Biochemical Sciences – National Autonomous University, Mexico |
Alrun Basfeld, Intern, now @ Lohmann & Rauscher, Cologne, Germany
Mélanie Beraud, Postdoctoral fellow, now senior technician @ Université de Mons, Mons, Belgium
Martin Blettinger, Technician, now @ Hexal Sandoz, Munich, Germany
Frank Bürmann, PhD student, now Postdoc @ MRC-LMB Cambridge, UK
Marie-Laure Diebold-Durand, Postdoctoral fellow, now @IGBMC Strasbourg, France
Alexandre Durand, Postdoctoral fellow, now EM Facility Manager – Inserm @IGBMC Strasbourg, France
Victor Gimenez -Oya, Postdoctoral fellow, now @ LMU Munich, Germany
Daniel Meyer, Technician, now @ Max Planck Institute for Quantum Optics, Munich, Germany
Anita Minnen, PhD student, now Postdoc @ Max Planck Institute of Biochemistry, Munich, Germany
Laura Ruiz Avila, Postdoctoral fellow, currently on parental leave, Munich, Germany
Chris Toseland, Postdoctoral fellow, now group leader @ University of Kent, UK
Larissa Wilhelm, PhD student, now @ Bristol-Meyers Squibb, Munich, Germany
