Among the signals that control the epigenetic landscape, non-coding (nc)RNAs have been identified to play a major role but the generalization and the mechanisms of their activity are still poorly apprehended. Recent data using high-throughput technologies have profoundly changed our view on how the genomes are organized. Indeed transcriptome analyses have shown that large genomic regions are pervasively transcribed producing a broad variety of ncRNA which functions on the epigenome remain to be deciphered. Our recent works show that S. cerevisiae’s genome also supports production of non-coding protein large transcripts, which are strongly controlled by RNA decay pathways. Of specific interest are the lncRNA XUT that we described recently, mostly antisense to class II genes and associated with a consistent regulatory potential through epigenetic modifications. Interestingly, histone methyl transferase and histone deacetylase show strong interplays with large antisense ncRNA. Mechanistic insights of their regulatory activities will be presented and generalization of their…

Vibrios are bacteria responsible for a significant proportion of infections affecting marine invertebrates and represent the major cause of mortality in farmed marine species. They are able to colonize many habitats, exist in free-living planktonic seawater, adhered to surfaces within biofilms or associated with various marine hosts. This high adaptability is linked to their capacity to generate high-levels of genetic diversity, a significant proportion via lateral gene transfer (LGT). LGT is being increasingly recognized as a major driving force in the evolution of virulence traits in vibrio. In contrast to species that are pathogenic to humans little data is available regarding invertebrate pathogens. Recent advances in genomics alongside the domestication of marine invertebrates has provided an opportunity to close the gap in our understanding of vibrio pathogens infecting invertebrates, leading to new and original scientific questions.

The Nakaseomyces clade includes Candida glabrata, a major fungal pathogen of immuno-compromised patients, and five other species, two of which have recently also been identified as human opportunistic pathogens. The genome of C. glabrata was published in 2004, and we have recently sequenced the genomes of all other known species of the Nakaseomyces genus. This clade is much closer to Saccharomyces cerevisiae than to the major Candida clade that includes C. albicans. Indeed, the Nakaseomyces derive from the same ancestor as S. cerevisiae that underwent a whole-genome duplication event, and their genomes contain the elements needed for mating-type switching in S. cerevisiae. These consist of mating-type cassettes of both types in haploid genomes, and the HO gene, that encodes the endonuclease initiating the switching event. Nonetheless, the four “Candida” species within the clade have been described as asexual, and no mating-type switching has been directly observed in any species. All Nakaseomyces seem…

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…