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Post-transcriptional regulation of the heat stress response in plants – HEAT-ADAPT
Global climate change is expected to result in a 1.5 to 5.8°C increases in temperature by 2100 and crop yields are predicted to decrease approximately 10% for every one-degree increase in temperature (USDA Release no. 501.09, 2009). Exceptionally high summer temperature is already leading to strong
Molecular mechanisms and impact of nonsense mediated mRNA decay on the RNA landscape in eukaryotes – CLEANMD
Extensive description of NMD associated factors in yeast. Functional assays to analyze mechanisms of NMD. A number of biochemical purification of the NMD complexes have been analysed by mass spectrometry. Nos results suggest that two disctinct complexes are involved, which might represent succesi
INDIVIDUAL CELL SELECTION TO MONITOR THE DYNAMICS OF EPIGENETIC MARKS DURING S-PHASE AND EARLY MAMMALIAN EMBRYOGENESIS. – CELLECTCHIP
In eukaryotic cells, how chromatin and epigenetic marks are imposed, inherited and/or changed is a central issue for cellular functions and cell fate maintenance. Understanding the logic behind their dynamics is of critical importance to determine the molecular mechanisms behind the maintenance of c
Molecular mechanisms of a novel Mediator function linking transcription and DNA repair in eukaryotes – MEDinREPAIR
The Mediator of transcription regulation is a large multiprotein complex (1.5 MDa) conserved in all eukaryotes. This complex is essential for activation of transcription by RNA polymerase II (Pol II) in response to transcription activators. In human, mutations that affect Mediator subunits lead to a
Genome duplication defects caused by homologous recombination deficiency. – StressHoR
Replication forks progression is routinely challenged by endogenous stress which jeopardizes the DNA replication completion and results in aneuploidy. Thus, intrinsic replication stress-induced genome instability represents essential and universal biological issues. Homologous recombination is a con
Specialized Polymerase involved in Unchallenged Replication: Requisite for duplication of heterochromatin regions during cellular differentiation and consequence on spontaneous mutagenesis – SPUR
Duplication of the genome prior to cell division occurs in a spatially and temporally organized manner. The temporal order of replication (replication timing) reflects the higher order organization of the genome. During the first half of the S-phase, euchromatic regions are replicated followed by fa
Genesis and maintenance of bacterial secondary chromosomes – MAGISBAC
Bacterial genomes are composed of two types of replicons: chromosomes and plasmids. Plasmids are mobile genetic elements acquired by horizontal transfer between strains or species. Their domestication by new hosts is of primary importance in the acquisition of complex traits, often determining the c
Transposase domestication and epigenetics: Impact on genome dynamics – PIGGYPACK
Transposases generally recognize the ends of their cognate transposon in a sequence-specific manner. In Paramecium, This project is focused on the role played by domesticated transposases in the programmed elimination of germline DNA from the differentiating somatic nucleus of the ciliate Paramecium
Unique features of bacterial small regulatory RNAs in transcriptional networks and translational control – UnifyRNA
Small regulatory RNAs (sRNAs) are now recognized as key regulators in bacteria and are involved in many biological processes. Previous work by many labs has unravelled fundamental aspects of sRNA biology, allowing for instance their identification, as well as that of many of their targets, and the e
Evolutionary variation of molecular mechanisms controlling epigenetic inheritance in C. elegans – EvolEpiElegans
Here we address these questions by characterizing natural genetic variation in epigenetic inheritance in the nematode Caenorhabditis elegans. We have established experimental paradigms to study multigenerational transmission of fertility defects induced by environmental stressors: (1) chronic exposu
Chromatin function in DNA Double Strand breaks repair: Prime, repair and restore DSB Inducible via AsiSI – DIvA
DSBs-induced chromatin modifications clearly contribute to adequate and efficient repair. However, a complete and detailed picture of the chromatin landscape set up at DSB is still awaited. More specifically the set of histone modifications associated with each repair pathway («repair histone code«)
A genetic survey on sudden cardiac death – GenSuD
We will explore familial forms of JWS and address the relative involvement of all known susceptibility genes for JWS in the population burden of SCD. At last, we will extend a recently published genome-wide association study on Brugada syndrome to stratify the risk of SCD in this highly exposed popu
Dicentric prevention and resolution – DICENs
We want to identify and dissect the pathways preventing dicentrics formation and decipher how dicentrics are broken upon mitotic exit and cytokinesis. Specifically, we will search for the determinants of dicentric occurrence in cycling versus quiescent cells and how they are impacted by nuclear org
Mecanism and regulation of DNA release from Cohesin – FineTuneCohesion
The general objective is to understand how Protein Phosphatase 4 regulates sister-chromatid cohesion, the identification of the relevant substrates of PP4 and understanding the underlying mechanisms. We identified two key serine residues within Rad21 which when phosphorylated shelter cohesin from Wp
Replication origins choice in the control of genomic stability and cell identity – ORICHOICE
At each cell division, DNA replication allows the faithful transmission to daughter cells of the genomic information contained in our chromosomes. It is an active process during embryonic development, that also permits the renewal of millions of cells each second in adult life. Errors in this proces
Systematic analysis of gene expression at the level of single RNA molecules – HI-FISH
Gene expression is of fundamental importance in all aspects of a cell’s life, and describing it at the highest level of precision and sensitivity is a major focus of the scientific community. This has led to key technological developments such as microarrays or massive parallel sequencing. With thes
Exploring the biological functions of the non-coding genome and its conservation in evolution using the X-chromosome inactivation paradigm – NoncodiX
We propose here the functional analysis of conserved as well as species-specific lncRNAs involved in XCI. These analyses will be performed for the most part in mouse and human embryonic stem cells, with which important XCI regulatory events can be investigated. We will also undertake the analysis of
Study of the association of microRNA and mitochondria and their role in regulation of neuronal cell death in Fragile X Tremor Ataxia Syndrome (FXTAS) – MITO-FXTAS
Fragile X-associated tremor/ ataxia syndrome (FXTAS) is an inherited neurodegenerative disease caused by 55 to 200 expanded CGG repeats in the FMR1 gene. Patients are characterized by progressive intention tremor, gait ataxia and cognitive decline. Importantly, FXTAS shares some common features with
Dynamics of DNA Repair within Chromatin and Transcription – DyReCT
Genome integrity is constantly threatened by a variety of toxic agents inducing lesions on the DNA molecule. Cells have set up systems to repair these lesions and restore the correct DNA sequence. Amongst all repair systems, the nucleotide excision repair (NER) has the task to remove lesions that di
Genomic and extragenomic roles of RTEL1 – GENEXGERTEL
RTEL1 is an essential helicase that has been linked to telomere replication and recombination in the mouse. In humans, RTEL1 mutations are associated with Hoyeraal-Hreidarsson syndrome but its precise role is still a matter of speculation. We have developed specific tools to study the role of human
Germline genome methylation guided by small RNAs – GuidedMethylation
Small RNAs serve as guides for post-transcriptional or transcriptional silencing machineries in most organisms including viruses, plants and animals. Animal germlines express a special class of small RNAs called the Piwi-interacting RNAs (piRNAs) that have come to be known as genome defenders becaus