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Chromatin dynamics and transcription in mitotic mESCs – ChroDynE
Cell mitosis has long been associated with an interruption of gene regulation: the nuclear envelope is disassembled, the chromatin condenses, many transcription factors (TFs) are inactivated, and transcription is globally down-regulated. The mechanisms by which gene expression programs are reactivat
CyclinA-Cdk1/2 Actors, from temporal control of DNA Replication to checkpoint adaptation and Mitotic Entry under stress – CARE-ME
Genome maintenance, cell identity and fate rely on the ordered execution of faithful DNA replication and accurate chromosome segregation across generations. Duplication of large genomes raises specific problems due to inherent limitations of several components of the replication machinery and relies
Initial events of large ribosomal subunit formation in eukaryotes – RIBOPRE60S
The ribosome catalyses peptide bond synthesis during the translation process. It is constituted by a large and a small subunit, each possessing an RNA scaffold bound by ribosomal proteins (RPs). The ribosome is a ribozyme since its catalytic center, carried by the large 60S ribosomal subunit, is mad
Tackling rRNA Methylation: Molecular Bases and Ribosome Translational Impact – MetRibo
Ribosome assembly and regulation of translation activity is crucial for cell growth and response to external cues or environmental conditions in all eukaryotic organisms. Ribosomal RNA (rRNA) are the linchpins of ribosome assembly and function. The rRNAs 25S, 5.8S, 5S and 18S form, respectively,
Role of G-quadruplexes in transcription regulation – G4Access
G-quadruplexes (G4s) are secondary DNA structures alternative to the Watson-Crick double helix, extremely stable and well characterized in vitro. Until recently, their role in transcription has remained obscure due to conflicting results. Based on a robust set of preliminary data and the development
Redox regulation in small RNA-mediated responses to biotic and abiotic stresses – RoxRNase
Environmental constraints like rising temperature and virus infections have major impacts on living organisms. Plants, as other species, develop various panels of mechanisms to cope with the effects of these stresses on growth and survival. Redox homeostasis is among the key players of cellular meta
Functions of condensin: from a structural role to the control of genomic stability – CONDENSin3R
The objective of the CONDENSin3R project is to characterize the role of the SMC-condensin complexes in the regulation of HR-associated processes. Three work packages are developed (WP). The WP1 aims at clarifying whether condensins associate with DNA during repair and what triggers this association.
Stress-induced phase separation in RNA expression control, organismal fitness and adaptive evolution – RNADAPT
Based on our preliminary data showing that RNA phase separation in the C. elegans germline displays extensive environmental and evolutionary variability, we will (1) test if RNA phase separation fine-tunes RNA expression in response to temperature stress; (2) test if natural genetic variation in C.
CrossOver interference phenomenon: regulating crossover number and spatial PATTerning during meiosis – CO-PATT
Homologous recombination is essential to maintain genome stability and to give access to the redundancy of genetic information that exists in the form of sister chromatids or homologous chromosomes when both strands of the DNA double helix are compromised and to generate genetic diversity in differe
Chromatin organization based mechanisms of TE silencing – COMETES
Transposable elements (TEs) constitute a large portion of eukaryotic genomes. Because of their mobility, they are potential threats for the host genome. One big challenge in biology is to determine how the chromatin silencing machinery establishes and maintains TE silencing. Based on preliminary dat
Evolutionary role of archaic genomic inheritance in the unique Melanesian human diversity – PapuaEvol
Part of our genome does not come from Homo sapiens but from extinct lineages, the archaic hominins. This project determines the function of this exceptional biological inheritance in the unique human diversity of New Guinea Island. Globally, these populations have the highest proportion of inherited
Tracking the evolution of human craniodental structures – GenoMorph
Comprehending the relationship between genotype and phenotype is the keystone in evolutionary biology and will allow us to shed new lights on the study of the paleoanthropological record. The GenoMorph project is based on a multidisciplinary approach mixing (paleo)genetics and morphological data bas
Phage-Bacteria Reciprocal Modulation of Mutation Rate and Its Consequences – MUMI
Our main objectives are - to characterize the occurrence of mutations in phage genomes during infection - to study the mechanisms explaining the high mutation rates of phages - determine how infection shapes the mutation rate of host cells and affects their ability to adapt We performed Dup Seq e
Evolution of the regulation of gene expression – VORTEX
The regulation of gene expression in response to environmental changes, a property known as expression plasticity, is critical for the adaptation of living organisms to a dynamically changing world. While decades of research uncovered the molecular mechanisms underlying gene expression regulation in
Staphylococcus aureus sRNA-mediated adaptation to metal-based host defense strategies – MetalAureus
Staphylococcus aureus is an opportunistic human pathogen responsible for a wide range of superficial and severe systemic infections. Even more alarming is the emergence and worldwide spread of hypervirulent multidrug-resistant isolates such as methicillin-resistant S. aureus (MRSA), which is include
Revisiting the Budding Yeast Life Cycle – BuddY
Saccharomyces cerevisiae has served as a model for nearly a century to understand the principles of the eukaryotic life cycle. The classical budding yeast life cycle describes an alternation between diploid and haploid phases. Diploid cells proliferate mitotically under nutrient rich conditions and
Congenital microcoria a rare disease model to study ocular development and glaucoma – MCORGLAUC
Congenital microcoria (MCOR) is a rare autosomal dominant disease characterized by unreactive pinhole pupils lacking iris dilator muscle (DM). Open angle glaucoma (OAG) and high myopia (HM) are frequently associated with this condition. Our work disclosed unanticipated complex mechanisms linked wit
Functioning and dysfunctioning of the transcription/repair factor TFIIH – TFIIH
Complex gene regulatory networks govern organism development and homeostasis. Dysfunction of these networks impacts fundamental cellular functions, leading to many human diseases. The characterization of complexes involved in these fundamental cellular pathways, the study of their cellular dynamics
Determinants of transcription regulation by co-activator complexes – COACTIVATOR
Transcription involves the coordinated activities of a multitude of regulatory factors. An important class of regulators has chromatin-modifying or –remodeling activities and function as co-activators during transcription initiation. Co-activators are typically multifunctional complexes that integra
CHROMAtin and GeNome evolutiON – CHROMAGNON
The essential role of chromatin in genome functional organization and expression has been largely ignored in evolutionary studies, since chromatin structure is much less traceable than coding sequences over evolutionary time. Recently, we developed a simple physical model of nucleosome occupancy bas
Functions of the Replication Protein A (RPA) in telomere maintenance and genome stability, implication in pulmonary fibrosis and telomere diseases – TeloRPA
Telomeres are short tandemly repeated DNA sequences at the end of chromosomes that preserve genome stability. Abnormal telomere shortening causes telomere syndrome, a rare monogenic disease characterized by bone marrow failure Dyskeratosis Congenita, aplastic anemia and idiopathic pulmonary fibrosis
Deciphering the role of the N-terminal extension of POLRMT in the regulation of mammalian mitochondrial gene expression – MitoPoNT
Mitochondrial dysfunction is associated to a broad spectrum of human diseases ranging from severe inherited metabolic disorders to common neurodegenerative diseases like Parkinson’s or Alzheimer’s disease, to heart disease, obesity, type 2 diabetes and cancer, and is also linked with common age- rel
Deciphering silencing establishment at newly inserted DNA copies: interest for transposable element-based plant breeding – NeoDNAcontrol
Transposable elements (TEs) constitute the vast majority of most eukaryotes. Because of their propensity to multiply and move, TEs represent both a motor for the evolution of genomes and a threat to their integrity. Therefore, understanding TE silencing and reactivation mechanisms is a major challen
Role of the lysine methyltransferase PR-Set7/SET8 in gene regulation through non-histone signaling – LysMeth
Histone methylation by lysine methyltransferases (KMTs) is known to fundamentally regulate chromatin structure and functions. However, these enzymes have also non-histone substrates, which extend their functions beyond the histone code. Yet, despite the fundamental roles of these enzymes and their c
CHApiTRE : CHAracterization of piRNA cluster expression throughout development and their capacity to tame a sudden TRansposable Element activity – CHApiTRE
Eukaryotic genomes are mainly composed of repeated sequences including transposable elements (TEs), highly mutagenic mobile DNA sequences which constitute a serious threat for the genome integrity. These TEs reside in the genome of all species and represent almost half of the human genome. A fine co
Learning from conflict: widespread inhibition of natural transformation by mobile genetic elements – TransfoConflict
The key objectives of the TransfoConflict project are to make a large-scale quantification of the frequency of transformation across the genetic diversity of two bacterial species and use this data to characterize, for the first time, the causes and consequences of variation in natural transformatio
MBNL loss of function and motor unit dysfunction in Myotonic dystrophy – Motor-DM
Myotonic dystrophy type 1 (DM1) is a RNA gain of function disorder due to the abnormal expansion of CTG repeats in the 3’UTR of the DMPK gene. Toxic mutated RNA aggregates in the nucleus and sequester MBNL RNA binding proteins leading to RNA metabolism abnormalities. The principal aim of this resear
m6A RNA methylation: a new pathway controlling endogenous retroviruses – MARMER
Endogenous retroviruses (ERVs) form a large and heterogenous group of retrotransposons that sum up 10% of the mouse and human genomes. Over the course of evolution, ERVs acted as an important and beneficial source of genetic innovations. However, on the short term, ERVs can compromise genomic integr