.

Dynamic chromosome organization is not random and plays a role in genome expression and integrity. Our discoveries have collectively contributed to the current understanding of the principles of yeast chromosome organization and their functional role towards the repair of a double stranded DNA break (DSB) (Berger et al., NM 2008; Therizols et al., PNAS 2010; Zimmer and Fabre ,JCB 2011; Brickner et al., GD 2012; Agmon et al., NCB 2013).  Further, chromosome motion is required for Homologous recombination to occur. I will present recent work on the role of actin and cytoskeleton connections with the nucleopore in subtelomeres movement and DSB repair (Spichal et al. JCS 2016). In addition to motion induced by actin, I will present recent discoveries on the role of chromatin physical properties in chromosome mobility upon random DNA damage. 

Bacteria adapt raidly to changing conditions that they encounter in their environments. Changes in in gene expression according to the environment are well documented. For exemple stress reponses allowing bacteria to cope with genotoxic, acid or oxidative stresses are well charcaterized. However the consequences that such stresses have on the cell cycle of multiplying bacteria are less characterized. We focus our work on understanding cell cycle response of a pathogenic E. coli bacteria that invades macrophages were it encounters many different stresses. We unraveled that medium acidification and genotoxic stresses are promoting dramatic chromosome  replication and cell division alterations that can ultimatly produce dormant cells that fully tolerate environmental stresses.

The greatest challenge facing our global future today is ‘Health’. To have a better living standard, a growing world population will need easily available and cheaper medicament, especially in metabolic disorder diseases (Cancer, Type-2 diabetes & etc.) and infectious diseases. To combat this impending situation, discovering of novel molecules with unmet physiochemical properties are needed especially in the area of endemic metabolic disorder and infectious diseases. Novel bioactive molecules can be developed by combining basic research with applied science keeping in mind that chemistry is central to everything. This talk will place the scale of the global medical issue in perspective and then discuss some of the issues related to basic science that is needed to emulate drug discovery. With this basic science in place, the design and synthesis of desired compounds and their application to cure diseases through controlling the cell fate in vitro and in vivo will be presented.

Genome interspecific introgressions drive evolution across the animal, plant and fungal kingdoms. We use the model system S. cerevisiae to investigate the birth, evolution and function of interspecies introgressions. Sequencing 1011 S. cerevisiae genomes revealed a ubiquitous gene flow with S. paradoxus. Intorgressions are rare in the highly diverged Asian lineages, consistent with secondary contacts with S. paradoxus occurring mainly after the out-of-China dispersal and promoted by human driven environments.Introgressions initiate from archaic interspecific admixtures, but near-universal hybrid sterility has made their evolution a mystery. We recently discovered a “living fossil” S. cerevisae / S. pardoxus hybrid that reveals a new role for genomic instability at the onset of introgressions. Finally, we use quantitative genetics to measure the fitness landscape of interspecies introgressions across multiple environments

Genomic diversity and composition evolve under diverse and complex constraints such as demography, selection, mutations, or genomic rearrangements. However, the influence of these evolutionary forces and their interactions remain to be fully understood. In that prospect, I will present two projects based on the human genome. First, I will use a population genomics approach and show that purifying selection at linked sites (i.e. background selection) and GC-biased gene conversion (gBGC) together affect as much as 95% of the variants of our genome. Their magnitude are largely determined by variation in recombination rate and base composition and previous reconstruction of human demography based on synonymous sites for instance are thus likely biased by these two mechanisms. However, when focusing on genomic regions with recombination rates above 1.5 cM/Mb and mutation types (C↔G, A↔T), the effects of background selection and gBGC are minimal. I will advocate to use these neutral regions to reconstruct demographies.…

Temporal control over protein phosphorylation and dephosphorylation is crucial for accurate chromosome segregation and forcompletion of the cell division cycle during exit from mitosis.Degradation of mitotic cyclins and activation of Cdk‐counteracting phosphatases lead to protein dephosphorylation. In budding yeast, theCdc14 phosphatase is thought to be a major regulator at this time, while in higher eukaryotes PP2A phosphatases take a dominant role. We usetime-resolved phosphoproteome analysis in budding yeast to evaluate the respective contributions of the kinases and phosphatase input. Thisreveals that successive inactivation of Cdks and of the mitotic kinase Polo contributes to order mitotic exit dephosphorylation events. Cdc14instructs the sequential pattern of phosphorylation changes, in part through its preferential recognition of serine-based cyclin-dependentkinase (Cdk) substrates. PP2ACdc55  in turn exhibit a broad substrate spectrum with some selectivity for phospho-threonines. Our resultsillustrate synergy and coordination between kinases and phosphatases to orchestrate the phosphoproteome by recognising some specific dockingmotifs, phosphoresidus and amino acid regions surrounding the phosphosite.