Search
Role of Snord123 in the translational regulation of gene expression in high endothelial venules – SNORD123-HEV
High endothelial venules (HEVs) are specialized blood vessels for lymphocyte trafficking found in lymph nodes and other lymphoid organs. HEVs play an essential role in the immune system because they are critical for immune surveillance and recirculation (homing) of lymphocytes throughout the differe
Investigating chromosome movements during meiotic prophase I – MeioMove
Meiosis is a key step in reproduction during which homologous recombination not only ensures genome stability (DNA repair, correct segregation of the homologous chromosomes in gametes) but also promotes genetic diversity (generation of new allelic combinations). Already many years ago, it was recogn
Genomic Distancing in yeast – GenoDist
Transcription by RNA polymerase II (RNAPII) is widespread in bacterial and eukaryotic genomes and leads to the production of myriads of non-coding RNAs derived from many non-annotated regions, a phenomenon known as pervasive transcription. The extensive presence of RNA polymerases is a constant chal
Linking nuclear pores to chromatin organization and senescence – NPCOS
In most somatic cells, the heterochromatin accumulates at the nuclear periphery and around the nucleoli. How this global chromatin organization is established and maintained and how it participates in the regulation of gene expression is not entirely clear. Using oncogene-induced senescence (OIS) as
NATURAL GENETIC VARIATION IN DROSOPHILA: AN ENTRYWAY TO INVESTIGATE THE DEVELOPMENT AND BEHAVIORAL FUNCTIONS OF THE VISUAL SYSTEM – WILD_EYES
Natural genetic variation affecting the nervous system is a major influence that shapes us as individuals. However, how small changes in our genomes cause dramatic changes in sensory perception and behaviour is poorly understood. This project is based on our preliminary observations of a surprisingl
Exploring chromatin functions in yeast spores – EpiSpores
SCIENTIFIC CONTEXT. Unicellular organisms need to adapt to rapid and unanticipated changes in their environment. Spores ensure their survival by encapsulating the genome in a protective configuration while awaiting optimal growth conditions. Indeed, yeast spores enter into a quiescent state with min
Exploring the link between chromatin organization and nucleoid dynamics in the compartmentalized Streptomyces chromosome – STREPTOMICS
Streptomyces are amongst the most prolific producers of specialized metabolites with applications in medicine, agriculture and the food. These bacteria possess a large linear chromosome partitioned into a central region harboring core genes, and two extremities enriched in specialized metabolite bio
Dynamic regulation of transcription and replication during quiescence and cell cycle re-entry – ExQui
Quiescence is a reversible, non-dividing state in which cells remain metabolically active and preserve the ability to resume proliferation. Quiescent, or G0, cells are found throughout the human body and play essential roles in development and differentiation as well as in tissue homeostasis and ren
Biophysical mechanism and functional consequences of TopBP1 condensation – BioTop
Signaling by the master checkpoint kinase ATR is necessary for cells to overcome DNA replication obstacles and for organismal survival. TopBP1 is the main activator of ATR. Our results indicate that the nucleation of non-stoichiometrically defined TopBP1 biomolecular condensates, visualized as foci
Birth and Activation of a piRNA cluster – BiopiC
Transposable elements (TEs) make up half of our genome and induce DNA damages when active. In recent years, an adaptive immune system against TE transposition has been uncovered. In the germline, a dedicated pathway based on small non-coding piRNAs targets TEs at the transcriptional and post-transcr
Programmed DNA elimination in a unicellular model: coordination between DNA cleavage and double-strand break repair – CURE
DNA double-strand breaks (DSB), a threat for genome integrity, are repaired through two alternative pathways: homologous recombination or non-homologous end joining (NHEJ). Although potentially harmful, programmed DSB (prDSB) contribute to essential physiological processes (e.g. meiotic recombinatio
Role of an orphan ribonuclease in Bacillus subtilis spore development – BSpoRNase
When facing severe nutritional stress, the Gram-positive model bacterium Bacillus subtilis forms highly resistant spores, one the best-studied developmental programs in bacteria. We have identified a new exoribonuclease called KapD that is expressed specifically in the mother cell during sporulation
Unraveling phosphate signaling by developing whole plant Live Transcriptional IMaging – ULTIM
Project abstract Transcriptional control is essential for plants to adapt to ambient fluctuations. By implementing the latest MS2 RNA imaging system combined with microfluidics, we achieved real-time quantitative measurements of the transcriptional activity of single loci, in all cells of entire or
Role of DNA methylation in reproductive success in plants – ReproMeth
DNA methylation is a key epigenetic mark involved in the control of genome stability and gene expression in many eukaryotes. In plants, substantial DNA demethylation takes place in the male and female gamete companion cells, a process that is critical for reproduction. We have recently shown that ac
Principles of mRNA regulation by piRNAs in stem cells: biological functions and molecular mechanisms – piRNAstem
PIWI-interacting RNAs (piRNAs), a specific class of small non-coding RNAs, have recently emerged as key regulators of mRNA surveillance in various stem cell lineages. This significantly expands their established role in the control of transposable elements in germ cells. In this project, we will add
Detailed and mechanistic characterization of Topologically Associating Domain (TAD) boundaries using complementary single-molecule sequencing and super-resolution imaging approaches – TADwalker
Topologically Associated Domains (TADs) compartmentalize vertebrate genomes into functional neighbourhoods for gene regulation, DNA replication, recombination and repair. Both structural variation in the genome and perturbed protein function can cause the reorganization of TAD structure. In the cont
Exploring dynamic regulation by RNAs – Kinebiotics
Rapid adaptation to environmental changes is a key requirement for all living organisms. In the last decades, regulatory RNAs have emerged as tremendous players in such adaptative responses by controlling gene expression. In Escherichia coli and other bacteria, small regulatory RNAs (sRNAs) were sho
EJC impact on mRNA localization and packaging – Eat_local
mRNA intracellular localization is widespread. It favors local expression of specific proteins contributing to cell polarity and differentiation. Recently, we described the first vertebrate mRNA whose localization depends on the exon-junction complex (EJC). Loaded onto spliced exon junctions, EJCs a
Single Molecule Analyses of homologous Recombination Tracts – SMART
DNA double-strand breaks (DSBs) occur accidentally or are self-inflicted, such as during meiosis, where they produce chiasmata, ensuring accurate homolog segregation. DSB are a threat to genome integrity and therefore must be faithfully repaired, in order to avoid aneuploidy, genetic diseases or can
Pairing and pairing release of bacterial sister chromatids – SISTERS
Chromosome segregation is a fundamental yet poorly understood cell cycle process allowing cells to transmit genetic material to their progeny. In all organisms it is tightly regulated and highly accurate to avoid the loss of genetic information (aneuploidy, chromosome breaks). In spite of an apparen
Cellular Regeneration Articulated with Chromatin Kinetics – CRACK
Context: Regenerative healing allows reconstruction of an identical body part following wound or loss. Whereas mammals do have a limited ability to accomplish such processes naturally, this pales in comparison to spectacular cases of full body plan reconstruction following decapitation in planaria
Deciphering the biogenesis of the Signal Recognition Particle, and its connections with ribosome biogenesis and nucleolar structure. – BioRiboSRP
Many cellular functions are achieved by a family of molecular machines made of RNA-protein complexes, called non-coding ribonucleoprotein particles (ncRNP). Understanding how these complexes are faithfully produced in cells and how the amount produced is controlled are essential issues. Many factors
Architecture of algae mItochondria translation system and its interplay with mRNA maturation – ARAMIS
Around two billion years ago, the acquisition of mitochondrion, a double membrane-bound endosymbiotic organelle, has dramatically influenced eukaryotic cells evolution. Indeed, mitochondria are central to eukaryotic bioenergetics, with their primary role in ATP generation by oxidative phosphorylatio
Nuclear mobilities of cis-regulatory hubs in transcriptional control – HUBDYN
Eukaryotic genes are frequently controlled at a distance by cis-regulatory modules (CRMs) such as enhancers. Until very recently, it was assumed that CRMs formed close physical contacts with target genes to confer regulation, but this now been brought into doubt by new microscopy studies. The findin
Uncovering the rules and mechanism of target-directed microRNA degradation – SCOuBiDou
MicroRNAs ("miRNAs") are important gene regulators: they recognize specific target mRNAs through sequence complementarity. Their expression level depends on their transcription and maturation (which are well known), as well as on their stability. Several observations suggest that miRNA stability is
RNA modifications in Staphylococcus aureus during stress responses, antibiotic treatments and virulence: impact on translation and its regulation – SaRNAmod
RNA modifications are involved in numerous biological processes and are present in all classes of RNA. These modifications are constitutive or modulated in response to adaptive processes and can impact RNA base pairing formation, protein recognition, RNA structure and stability. However, their roles
Long non-coding RNAs in cell fate decisions – RNAFATE
Since their discovery, long non-coding RNAs (lncRNAs) have been shown to contribute to cell identity in normal and pathological situations by modulating genome expression and integrity. However, our mechanistic knowledge of their role in cell fate decisions remains largely elusive. Conserved through
Fundamental mechanisms of translation of Tau mRNA in Alzheimer Disease – RiboTAUxic
Protein translation is a complex and highly regulated multi-step process that requires numerous factors and relies on mRNAs sequence and structure. Dysfunctions in translation initiation often occur under stress conditions and are associated with human diseases. In the case of Alzheimer's disease, s
Physiological and pathological mechanisms of wobble adenosine to inosine modification in tRNAs – InotRNA
In the last decades, our understanding of the RNA world and its complexity has drastically enlarged with the characterization of numerous non-coding RNA species that participate together with mRNAs and tRNAs to the regulated development of cells and organisms. Notably, many RNA posttranscriptional m
Identification and characterization of mosquito factors interacting with the untranslated terminal regions (UTRs) of the RNA genome of Dengue and Zika viruses – DeZincRNA
Dengue (DENV) and Zika (ZIKV) flaviviruses infect millions of people worldwide. Circulating between both human and mosquito hosts, their RNA genomes harbor multifunctional untranslated regions (UTRs) that are essential for pathogenesis. While some functions of flaviviral UTRs have been described in
Apollo at the nexus of DNA repair, telomere protection, and aging. – APOthesis
Aging is a complex process that involves cellular and organismal pathways and deciphering its determinants has become an important topic in modern science. Research on aging in Biology goes through the study of diseases characterized by premature aging, analysing physiological aging in multiple spec
Molecular Etiology and Epigenetic Landscape of Rahman Syndrome – RAHMAN
Germline frameshift mutations in one of the alleles of the linker histone H1E were causally linked to an as-yet poorly defined syndrome, called Rahman syndrome. Affected individuals exhibit characteristic craniofacial features, hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, s
Regulation of Mammalian Enhancers by DNA methylation – REMEDY
Cellular function depends on a precise pattern of gene expression, and alterations of this process are linked to human diseases. This pattern is determined by interactions between transcriptional regulators, regulatory elements (promoters and enhancers), and the cell’s epigenetic landscape. Three ke
ADAR1 and RNA editing in development and maintenance of peripheral nervous system – RNAediting-inPNS
Our consortium combines the expertise of 3 partners in developmental and cellular biology, mouse and human genetics. We aim to decipher the role of the ADAR1 enzyme and Adenosine to Inosine (A-to-I) RNA editing in the development of Schwann cells and in the maintenance of myelin of the peripheral ne
Life-Saving Toxins – LST
Escherichia coli SOS response is an archetype of the DNA damage response regulon, which hugely contributed to the understanding of how different DNA damage repair and tolerance functions are coordinated as a function of the nature, quantity and persistence of DNA damages. Because SOS regulon was fir
Breaking into the secret conversation between cholesterol and genome stability – GenomeSterolity
The nucleus of the cell, defined by the nuclear membrane, encloses the genetic material, whose maintenance is essential to ensure the homeostasis of cells and organisms. A dedicated surveillance and repair network, believed to be mostly composed by proteins, accomplishes this task in the nucleus. Re
Gametes and RNA Decay – GaRDe
Regulation of the different steps of the gene expression pathway in mammalian organisms contributes to development and cell differentiation. Hence, it has been shown that regulation of mRNA stability, mainly achieved by modulating the rate of poly(A) tail trimming, participates to the control of pro
Impact of chromosomal integrons on bacterial life and evolution – Chromintevol
Bacteria exchange and recombine DNA to accelerate their evolution and adapt to new stress. Their evolvability is illustrated by the rapid emergence of multi resistant bacteria after the introduction of antibiotics. The most powerful driver of antibioresistance is the integron system. Integrons are a
Activities and diversity of natural L1 retrotransposon copies in human genomes – ActiveLINE
L1 retrotransposon sequences form 20% of the human genome, and L1 mobilization drives germline and somatic genome mutations in health, aging and disease. Only one L1 subfamily, L1HS, is functional in humans, and only a few L1HS loci are active in each cell-type. Two hypotheses can explain locus- and
Facultative Heterochromatin Silencing (H3K27me3) Through RNA Decay – Epigenetic-State_RNA-Fate
We have recently discovered that in animals facultative heterochromatin can be silenced by specific RNA decay, and not only by transcriptional repression. Notably, we found that the RNA-binding LSM2-8 complex and the ribonuclease XRN-2 mediate the degradation of transcripts exclusively arising from
Investigating protein-rDNA interactions and their link to DNA damage and replicative aging – rDNAproxi
The ribosomal DNA (rDNA) is a highly repetitive genomic region which is essential to initiate ribosome biogenesis. In budding yeast, frequent DNA damages within the rDNA (rDNA damages) triggers the formation of extra-chromosomal rDNA circles (ERCs), which are implicated in replicative aging through
Ribosome biogenesis: The yin and yang of protein homeostasis – RASTR
Protein homeostasis or proteostasis is the concept that integrated biological pathways within cells maintain proteins in the correct concentration, folding, and subcellular location. A key feature of protein homeostasis in all organisms is involvement of proteasome components and the expression of u
Paleogenomic study of human populations from the Neolithic to the 17th century in the Paris Basin – ParisAncientDNA
The recent development of paleogenetics, the analysis of ancient DNA, has significantly contributed to a better understanding of the origins and evolutionary history of modern human populations, in Eurasia in particular. From this perspective, the territory of present-day France, notably the Paris B
Régulation de l'épissage alternatif par citrullination à l'arginine. – ACT
Arginine citrullination is the post-translational modification of arginine to the citrulline catalyzed by a family of enzymes called peptidyl arginine deiminases (PADIs). Among the five PADI family members, PADI2 is the most conserved and widely expressed. An elevated level of PADI2 is known to asso