Bacterial Cell Biology

Currently, our lab is mainly focusing on four connected research topics:

  1. Chromosome replication and maintenance in Caulobacter crescentus

Over the last decade, we demonstrated that the regulated inactivation of the highly conserved DnaA initiator of chromosome replication (the RIDA process) is the main mechanism controlling the frequency of chromosome replication in the model Alphaproteobacterium Caulobacter, so that it happens only once per cell cycle. We also showed that two master regulators of the cell cycle, DnaA and CtrA, are strongly influenced by the (p)ppGpp alarmone, which is produced when bacterial cells need to adapt to nutrient-poor environments.

We are now characterizing novel regulators of chromosome replication and exploring the connections between DNA replication, DNA repair and DNA methylation in Caulobacter.

Schematic highlighting the impact of DNA methylation on genome evolution/maintenance and on gene expression.

(MTase: methyltransferase; RM: Restriction/Modification; MM: DNA mismatch; VSP: Very Small Patch; MMR: DNA Mismatch Repair; HGT: Horizontal Gene Transfer; 5mC: 5-methyl-cytosine)

  1. Epigenetic control of the cell cycles of Caulobacter crescentus and Agrobacterium tumefaciens

Our past work uncovered a strong connection between DNA methylation by the orphan adenine methyltransferase CcrM and cell cycle control in the environmental Caulobacter bacterium. We are now investigating how DNA methylation can coordinate gene expression with the progression of chromosome replication and we wish to identify novel and conserved epigenetic regulators of the cell cycle in Caulobacter and in the Agrobacterium tumefaciens plant pathogen.

  1. Temporal and spatial control of cell division in Caulobacter crescentus

Over the last years, we characterized several mechanisms controlling when and where the conserved FtsZ-ring assembles to mediate cell division in Caulobacter: (i) we discovered that its expression requires the methylation of the promoter of its gene, explaining why DNA methylation by CcrM is an essential process in Caulobacter; and (ii) we uncovered an interesting connection between ftsZ expression and the metabolic status of the cell. In addition, we observed the 3D-organization of the FtsZ-ring at the nanoscale by PALM, as part of a collaboration with the Manley lab at the EPFL.

3D-architecture of the Caulobacter Z-ring visualized by PALM. From Holden et al., PNAS, 2014.

  1. Discovery and characterization of chromosomal toxin-antitoxin systems in Caulobacter crescentus and Mycobacterium tuberculosis

As part of a novel project, we wish to identify novel toxin-antitoxin systems encoded by bacterial chromosomes and to characterize them to uncover their mechanism of action, their regulation and their physiological role. We anticipate that many of these play a key role in reducing growth or in blocking the cell cycle when bacteria are facing adverse environmental conditions such as exposure to antibiotics. Our collaborators for this SNSF Sinergia project are members of the Viollier lab at the University of Geneva (CH), of the Falquet lab at the University of Fribourg (CH) and of the Genevaux lab at the University of Toulouse III (FR).