Gruber Lab

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. Follow us @Gruber_Lausanne.

• How are genomes organized in the cell ?
• How are chromosomes segregated during cell division ?
• How is DNA damage repaired ?

‘In science, truth always wins.‘ Max Perutz

‘The two most powerful warriors are patience and time.‘ Leo Tolstoy

‘There is no substitute for being first‘ John F Marko

DNA Organization, Dynamics & Repair

Cells organize and compact the long and flexible DNA molecules within chromosomes to precisely control gene expression patterns, to support 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.

SMC proteins & DNA loop extrusion

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 & cellular regulation

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.

Our approach

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.

New focus

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.

	Hammam Antar hammam.antar[a]unil.ch +41-21-692-5611 2017-2019 – M. Sc. Immunology, Microbiology & Infectious Diseases (IMD) – University of Grenoble Alpes, France
	Florian Bock florianpatrick.bock[a]unil.ch +41-21-692-5611 2013-2016 – M. Sc. Biochemistry – Ludwig Maximilians University, Munich
	Ophélie Gosselin ophélie.gosselin[a]unil.ch +41-21-692-5611 2017-2019 – M. Sc. Biochemistry, Molecular and Cellular Biology – UC Louvain, Belgium
	Stephan Gruber Short CV stephan gruber unil ch +41-21-692-5601 OrcID, ResearchGate, Google Scholar
	Maya Houmel maya.houmel[a]unil.ch +41-21-692-5611 2018-2020 – M. Sc. Genetics, Magistère Européen de Génétique, University of Paris, France
	Franziska Kemter – DFG Postdoc franziska.kemter[a]unil.ch +41-21-692-5611 2014-2019 – Ph. D. and Postdoc, Chromosome Biology – Waldminghaus lab, SYNMICRO, Philipps-University Marburg, Germany 2012-2014 – M. Sc. Molecular and Cellular Biology – Philipps-University Marburg, Germany
	Yan Li yan.li[a]unil.ch +41-21-692-5611 2015-2019 – Ph. D. , Panne lab, EMBL Grenoble, France 2010-2013 – M. Sc. Structural Biology – University of the Chinese Academy of Sciences, Shanghai, China
	Hon-Wing Liu – EMBO Postdoc hon-wing.liu[a]unil.ch +41-21-692-5611 2015-2020 – Ph. D. , Uhlmann lab, The Francis Crick Institute, London, UK 2011-2015 – MA M. Sc. Biochemistry – University of Cambridge, UK
	Nicolas Pellaton nicolas.pellaton[a]unil.ch +41-21-692-5611 2020- M. Sc. student, University of Lausanne 2017-2020 – B. Sc. Biology, University of Lausanne, Switzerland
	Florian Roisné-Hamelin florian.roisne-hamelin[a]unil.ch +41-21-692-5611 2016-2021 – Ph. D., Marcand lab, Institut de Biologie François Jacob, CEA, Paris, France 2014-2016 – M. Sc. Genetics & Cell Biology- University of Lyon 1, France
	Michael Taschner – Research scientist michael.taschner[a]unil.ch +41-21-692-5611 2010-2017 – Postdoc – Lorentzen lab, Max Planck Institute of Biochemistry, Munich, Germany 2005-2009 – Ph. D. Biochemistry – Svejstrup lab, UCL, UK 2000-2004 – Diploma Biology – University of Vienna, Austria

Former lab members

Ania Anchimiuk

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

Jae Shin, Postdoc, now Senior Researcher @ NanoLund, Sweden

Young-Min Soh, Postdoctoral fellow, now fellow @ NIH, US

Chris Toseland, Postdoctoral fellow, now group leader @ University of Kent, UK

Roberto Vazquez Nunez, PhD student, now Postdoctoral fellow @ NIH, US

Larissa Wilhelm, PhD student, now @ Bristol-Meyers Squibb, Munich, Germany

Preprints

• Roberts D. M., Anchimiuk A., Kloosterman T. G., Murray H., Wu L. J, Gruber S., Errington J.*, 2021. Chromosome remodelling by SMC/Condensin in B. subtilis is regulated by Soj/ParA during growth and sporulation.
  preprint [BioRxiv]
• Bock F. P., Anchimiuk A., Diebold-Durand M.-L., Gruber S.*, 2021. The ParB clamp docks onto Smc for DNA loading via a joint-ParB interface.
  preprint [BioRxiv]
• Tisma M., Panoukidou M., Antar H., Soh Y.-M., Barth R., Pradhan B., van der Torre J., Michieletto D., Gruber S., Dekker C.*, 2021. ParS-independent recruitment of the bacterial chromosome-partitioning protein ParB.
  preprint [BioRxiv]
• Nomidis S.S., Carlon E., Gruber S., Marko J. F.*, 2021. DNA tension-modulated translocation and loop extrusion by SMC complexes revealed by molecular dynamics simulations.
  preprint [BioRxiv]

2021

• Antar H.°, Soh Y.-M.°, Zamuner S., Bock F. P., Anchimiuk A., De Los Rios P., Gruber S.*, 2021. Relief of ParB autoinhibition by parS DNA catalysis and ParB recycling by CTP hydrolysis promote bacterial centromere assembly.
  Science Advances
  Vol 7, Issue 41 [Pubmed] [DOI]
  preprint [BioRxiv]
• Taschner M., Basquin J., Steigenberger B., Schaefer I., Soh Y.-M., Basquin C., Lorentzen E., Räschle M., Scheltema R. A., Gruber S.*, 2021. Nse5/6 inhibits the Smc5/6 ATPase and modulates DNA substrate binding.
  EMBO Journal
  e107807 [Pubmed] [DOI]
  preprint [BioRxiv]
• Anchimiuk A., Lioy V. S., Minnen A., Boccard F., Gruber S.*, 2021. A low Smc flux avoids collisions and facilitates chromosome organization in B. subtilis.
  eLife
  65467 [Pubmed] [DOI]
  preprint [BioRxiv]
• Gallay C.°, Sanselicio S.°, Anderson M. E., Soh Y.-M., Liu X., Stamsas G. A., Pelliciari S., van Raaphorst R., Dénéréaz J., Kjos M., Murray H., Gruber S., Grossman A. D., Veening J.-W.*, 2021. CcrZ is a pneumococcal spatiotemporal cell cycle regulator that interacts with FtsZ and controls DNA replication.
  Nature Microbiology
  021-00949-1 [Pubmed] [DOI]
  preprint [BioRxiv]
• Vazquez Nunez R. J.°, Polyhach Y.°, Soh Y.-M., Jeschke G., Gruber S.*, 2021. Gradual opening of Smc arms in prokaryotic condensin.
  Cell Reports
  35(4) 109051 [Pubmed] [DOI]
  preprint [BioRxiv]

2020

• Soh Y.-M., Basquin J., Gruber S.*, 2020. A rod conformation of the Pyrococcus furiosus Rad50 coiled coil.
  Proteins
  prot.26005 [Pubmed] [DOI] [PDB: 6ZFF]
  preprint [BioRxiv]
• Metwaly G., Wu Y., Peplowska K., Röhrl J., Soh Y.-M., Bürmann F., Gruber S., Storchova Z.*, 2019. Phospho-regulation of the Shugoshin-Condensin interaction at the centromere in budding yeast.
  PLOS Genetics
  16(8) [Pubmed] [DOI]
  preprint [BioRxiv]
• Jeon J.-H., Lee H.-S., Shin H.-C., Kwak M.-J., Kim Y.-G., Gruber S. and Oh B.-H.*, 2020. Evidence for binary Smc complexes lacking kite subunits in archaea.
  IUCrJ
  7(2) [Pubmed] [DOI]
• Prassler J., Simon F., Ecke M., Gruber S. and Gerisch G.* 2020. Decision making in phagocytosis.
  AEMB
  1246:71-81 [Pubmed] [DOI] [PDF]

2019

• Soh Y.-M., Davidson I. F., Zamuner S., Basquin J., Taschner M., Bock F. P., Veening J.-W., De Los Rios P., Peters J.-M., Gruber S.*, 2019. Self-organization of parS centromeres by the ParB CTP hydrolase.
  Science
  360(6469) p. 1129-1133 [Pubmed] [DOI] [Free] [PDB: 6SDK] [PDF] [F1000_recommendations] [Perspective by Barbara Funnell]
• Vazquez Nunez R.°, Ruiz Avila L. B.°, Gruber S.*, 2019. Transient DNA occupancy of the SMC interarm space in prokaryotic condensin.
  Molecular Cell
  75(5) p. 1-15 [Pubmed] [DOI] [Free full-text] [Preview by Tomoko Nishiyama]
  preprint [BioRxiv]
• Marko J. F.*, De Los Rios P., Barducci A., Gruber S., 2019. DNA-segment-capture model for loop extrusion by structural maintenance of chromosome (SMC) protein complexes.
  Nucleic Acids Research
  gkz497 [Pubmed] [DOI]
  preprint [BioRxiv]
• Diebold-Durand M.-L., Bürmann F., Gruber S.*, 2019. High-throughput allelic replacement screening in Bacillus subtilis.
  Methods in Molecular Biology
  2004 p. 49-61 [Pubmed] [DOI] [PDF]

2018

• Pfeiffer F., Zamora-Lagos M.-A., Blettinger M., Yeroslavic A., Dahl A., Gruber S.*, Habermann B. H.*, 2018. The complete and fully assembled genome sequence of Aeromonas salmonicida subsp. pectinolytica and its comparative analysis with other Aeromonas species: investigation of the mobilome in environmental and pathogenic strains.
  BMC Genomics
  19(1):20 [Pubmed] [DOI]
• Gruber S., 2018. SMC complexes sweeping through the chromosome: Going with the flow and against the tide.
  Current Opinion in Microbiology
  42:96-103 [Pubmed] [DOI] [PDF]
• Stockmar I., Feddersen H., Cramer K., Gruber S., Jung K., Bramkamp M.*, Shin J. Y.* 2018. Optimization of sample preparation and green color imaging using the mNeonGreen fluorescent protein in bacterial cells for photoactivated localization microscopy.
  Scientific Reports
  8(1): 10137 [Pubmed] [DOI]

2017

• Diebold-Durand M.-L.°, Lee H.°, Ruiz Avila L.°, Noh H., Shin H.-C., Im H., Bock F. P., Bürmann F., Durand A., Basfeld A., Ham S., Basquin J., Oh B.-H.*, Gruber S.*, 2017. Structure of full-length SMC and rearrangements required for chromosome organization.
  Molecular Cell
  67(2) p. 334-347 [DOI] [Web of Science] [Pubmed] [PDB: 5NMO, 5NNV]
• Bürmann F., Basfeld A., Vazquez Nunez R., Diebold-Durand M.-L., Wilhelm L., Gruber S.*, 2017. Tuned SMC arms drive chromosomal loading of prokaryotic condensin.
  Molecular Cell
  65(5) p. 861-872 [DOI] [Web of Science] [Pubmed] [F1000 recommendation]
• Gruber S., 2017. Shaping Chromosomes by DNA Capture and Release: Gating the SMC Rings.
  Current Opinion in Cell Biology
  46:87-93 [DOI] [Web of Science] [Pubmed] [PDF]
• Wilhelm L., Gruber S.*, 2017. A Chromosome Co-Entrapment Assay to Study Topological Protein–DNA Interactions.
  Methods in Molecular Biology
  1624 p. 117-126 [DOI] [Web of Science] [Pubmed] [PDF]. An updated version of the protocol (using agarose microbeads instead of agarose plugs) is available here: [DOI].

2016