Establishment of gene expression patterns requires the regulated transcription of mRNAs, a process which will expose the genetic material to potentially harmful agents and come into conflict with genome duplication. Nonetheless, genome integrity has to be maintained over generations without accumulation of deleterious mutations. Coordination of these distinct DNA-dependent transactions is therefore required to ensure genome homeostasis. In this respect, mRNAs packaging into mRNPs (messenger ribonucleoparticles) involves the recruitment of a battery of proteins controlling mRNA fate, but also counteracting the formation of genotoxic mRNA::DNA hybrids (or R-loops) between the nascent mRNA and its DNA template. We are investigating the cis- and trans-acting regulations that target mRNP biogenesis and their impact on gene expression and genetic stability in budding yeast. In this frame, we have more particularly explored (i) the rôle of SUMOylation events in the regulation of mRNP assembly and (ii) the importance of intronic sequences in the maintenance of genomic…

Monod et le phénomène de diauxie Jacques Monod, François Jacob et André Lwoff obtiennent en 1965 le Prix Nobel de physiologie ou médecine pour leurs travaux sur les mécanismes de régulation des gènes. La diauxie, un phénomène de croissance bactérienne qualifié d’aberrant par Monod est à l’origine de ces recherches. Selon les récits des historiens, Monod en 1940 pendant sa thèse aurait observé ce phénomène découvert avant lui par le pasteurien Frederic Dienert en 1900. Lwoff aurait interprété la diauxie comme un cas d’adaptation enzymatique, ce qui aurait conduit Monod a consacré la totalité de son activité scientifique à ce problème jusqu’au Nobel. Pourtant, la lecture de la thèse de Monod, nous apprend qu’il est le premier à caractériser la diauxie, et que, pour lui, il s’agissait d’un phénomène d’inhibition d’enzymes. Ses publications montrent que l’inhibition diauxique était au centre de son travail après sa thèse et qu’il a continué de s’intéresser à cette…

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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