Ramlibacter tataouinensis, a new genus and species isolated a semi-arid region of South Tunisia, presents two different morphologies: cysts resistant to desiccation and highly motile rod-shaped cells. An unusual characteristic of its cell cycle is that it could make ‘rod-rod’ division but also ‘cysts-cysts’ division if water is available. Due to the strong correlation between light, heat and desiccation in desert environment, the effect of light on this cell cycle was studied. Blue light of low intensity strongly inhibits the cell division of Ramlibacter tataouinensis. Red light induces the ‘rod-rod’ division, while almost uniquely ‘cysts-cysts’ division occurs in the dark. Analysis of the genome reveals the presence of four blue light sensors and two red light sensors. The biochemical and biophysical properties of these two bacteriophytochromes are characterized. One of these bacteriophytochromes, RtaBphP2, absorbs maximally at 755 nm in the dark, typical to a Pfr form. The light-induced Pr form presents an absorption maximum…

The human Solute Carrier (SLC) transporters are important targets for drug development. Structure-based drug discovery for SLC transporters requires the description of their structure, dynamics, and mechanism of interaction with small molecule ligands and ions. The recent determination of atomic structures of human SLC transporters and their homologs, combined with improved computational power and prediction methods have led to an increased applicability of structure-based drug design methods for human SLC members. The utility of these methods will be illustrated by presenting case studies in which rational integration of computation and experiment was used to characterize SLC members that transport key nutrients and metabolites.

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.