The folding of chromosomes is a carefully regulated process, essential to the function and propagation of DNA molecule(s) over generations. Past and recent work have revealed its importance in bacteria or eukaryotes, where regulatory mechanisms have evolved to coordinate chromosome organization with other DNA-related metabolic processes such as segregation. Our research is focusing on the interplay between chromosome dynamics, cell cycle, and consequences on chromosome stability, that we study principally on microorganisms. To do so, we use a combination of genome-wide and single-cell technologies (3C, Hi-C, imaging), synthetic methods (neo-chromosome assembly), as well as in vitro and in vivo approaches.
Among our recent results, we are reaching at a better understanding of the organizational changes experienced by yeast and bacterial genomes during replication and cell cycle, and how it is being influenced by metabolism (e.g. Lazar-Stefanita et al., 2017; Marbouty et al., 2015; Guidi et al., 2015). We pursue our investigation of yeast synthetic chromosomes in collaboration with the Sc2.0 project coordinated by Jef Boeke (NYU) (Mercy et al., 2017), while developing our own synthetic chromosomes in yeast to address questions related to homolog pairing (Muller et al., biorxiv). We also have concomitantly developed computational techniques aiming at improving genome assembly and metagenomic/pan-genomic analysis through the exploitation of chromosome physical 3D signatures (Marbouty et al., 2014, 2017; Marie-Nelly et al., 2014a, 2014b). These “proximity ligation” approaches have opened up new areas of research, which holds potential for both fundamental discoveries and biomedical applications (Flot et al., 2015; Marbouty and Koszul, 2015) .
Our ongoing research projects include yeast chromosome dynamics during the cell cycle (Lazar-Stefanita et al., 2017); broadening our understanding of the regulation of chromosome organization and segregation in bacteria; influence of chromatin organization of meiotic double-strand break repair and mitotic genome stability. We also pursue our development of contact genomic applications, that we are now applying to a broad variety of questions, including metagenomic analysis, gene flow, and comparative genomics of complex genomes. Our projects usually involve collaborative efforts between geneticists, biophysicists and mathematicians, some in the lab and some through collaborations.
Check out our Github space for code and programs