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Deciphering the roles of Insulators and co-factors in Nucleosome-Positioning and Nuclear Bodies – INSULa
Cell fate and cell division are processes tightly controlled by the functional and structural organization of the genome intochromatin. Two emerging concepts in chromatin biology are a) nucleosome-positioning, i.e. how the accessibility of the genetic information is controlled through the specific p
Retinal stem cells activity in neural tissue growth and repair – EYE-STEM
While retinal stem cells are active in amphibians, there are quiescent in mammals. What are the molecular cues governing such different behaviour of retinal stem cells ? As a first step, our objective is to shed light on the molecular mechanisms underlying retinal stem cell proliferation in a fro
Muscle and tendon interactions during development: Growth factors, transcription factors and collagens – Muscolten
All the genes responsible for muscular dystrophies in human are not identified. We have identified a number of candidate genes, which display muscular phenotypes in animal models which could be candidate genes for the muscular dystrophies. The tendon/ligament repair is a major clinical challenge
The architecture of elongation, a basic developmental process – DEV-PROCESS
The project starts from the trivial remark that genomes are not just combination of genes and of intergenic sequences but elements of systems. Other components of these systems are the genes products and the external factors. This conclusion was first reach more than fifty years ago with bacteria. I
Molecular and biological roles of the imprinted miR-379-miR-410 cluster – ImpMir
miRNAs are endogenously expressed short non-coding RNAs that silence gene expression mostly at the post-transcriptional level. In animals, most miRNAs bind to mRNAs via short, imperfect base-pairing interactions that occur preferentially within the 3’ untranslated regions (UTRs) of target mRNAs. Thr
Molecular and evolutive bases for the cell adhesion properties of some non-catalytic alpha/beta-hydrolases – MOLADCEL
Our previous works have led to (i) define the properties of the alpha/beta hydrolase fold superfamily of proteins and the evolutionary relationships of these proteins with the ESTHER database, (ii) characterize structurally and functionally two distinct family members, the enzyme acetylcholinesteras
Tenascin-C and Fibronectin during tumor angiogenesis and ex vivo angiogenesis in engineered biomaterials – ANGIOMATRIX
This project aims at the understanding of the function of two prominent components with an unequivocal role in tumor angiogenesis, tenascin-C and fibronectin, in vivo and apply this knowledge to recapitulate angiogenesis ex vivo. Goal is to block or normalize aberrant angiogenesis in the future. Thi
Deciphering the molecular dynamics & organization of the Ras signaling node in the control of the analog/digital signal processing – nanoDIGICODE
nanoDIGICODE is a project aiming at realizing breakthroughs at both the conceptual and technological level in the field of biology and health through the strong collaborations between the three teams. The events of cellular signaling, in answer to the integration of many stimuli, constitute the b
Overcoming cancer cell resistance to death receptor ligands by modulating plasma membrane sphingolipids. – SphingoDR
Background: Sphingolipids (SLs) are ubiquitous ceramide-derived lipids, which modulate membrane functions, cancer cell growth and death. Death receptor (DR) ligands such as CD95L and TRAIL play a crucial role in anti-cancer immune response. DR engagement triggers apoptotic cell death, which is assoc
Menin and alpha-cell plasticity: identification of cellular and molecular bases of a-cell transdifferentiation into insulin-expressing cells triggered by Men1 inactivation – ABC-Trans
We have demonstrated that Men1-disruption specifically in alpha cells resulted in their transdifferentiation into insulin-secreting cells. This may renders the conversion of alpha cells into beta cells possible. The current research program is focalised on identification of mechanistic bases of the
Molecular mechanisms governing the meiosis entry in mammals – molmechmeiosis
Central to the process of germ cell (GC) differentiation, meiosis allows the mixing of genetic material between male (XY) and female (XX) individuals. In mammals, XX GC meiosis is initiated during foetal life, at a time when XY GC become quiescent in the G0/G1 phase of their cell-cycle. Then in fema
Control of the Expression of the “AFL” REgulatory network and Seed development – CERES
Les graines représentent une source majeure pour l'alimentation humaine et animale. En tant que semences, elles déterminent le rendement de la plupart des grandes cultures. Dans ce contexte, la compréhension des mécanismes génétiques et épigénétiques contrôlant le développement de la graine et son m
In vitro, ex vivo and in vivo analysis of TGFbeta-induced podosomes in aortic endothelial cells – VASCULOSOMES
Scientific background and objectives Podosomes are adhesive actin-based microdomains of the plasma membrane located at the ventral side of the cell. Like focal adhesions, numerous structural proteins and signalling components are found at podosomes. However, podosomes differ from classical adhesi
Role of ubiquitination in the regulation of intracellular MHC class I traffic and in cross-presentation – MARCHxIRAP
The goal of the MHC I antigen processing pathway is to load MHC I molecules with thousands of different peptides for display on the cell surface. This goal is accomplished by merging two distinct pathways: one for generating peptide-receptive MHC I molecules in the endoplasmic reticulum and another
Dissecting the molecular mechanisms of epithelial architecture and plasticity – ARCHIPLAST
This project aims at deciphering the molecular mechanisms of epithelial stability and remodelling. Epithelia are composed of polarized cells with junctions segregating apical and lateral surfaces. They serve essential functions in separating different physiological environments in the adult. At the
Cell and structural biology of Rab GTPases/molecular motors interactions – Motorab
The general objective of the present proposal is to use a combination of cell biology, biochemical and biophysical approaches to assemble a comprehensive model for the functional basis of Rab GTPase interaction with their molecular motor partners throughout their functional cycle during intracellula
Structural studies of cellular membrane fusion proteins involved in C. Elegans organogenesis – CellMemFusion
Essential processes in developmental biology, such as embryogenesis or organogenesis, rely in specific and tightly controlled cell-cell fusion events. Events like sperm-egg fusion for fertilization, myoblast fusion to form myotubes in skeletal muscle formation, monocyte fusion to form osteoclasts in
Nuclear siRNA in chromatin dynamics – Nuclear siRNAs
Fifteen to 30 nucleotide-long RNAs lie at the core of a vast silencing network in animals and plants. These small silencing RNAs bind to a member of the Argonaute family of proteins to form RNA-induced silencing complexes (RISC), which they guide to complementary targets. Small RNAs regulate many es
Tolerance of DNA replication stress – TODS
1. We aim at reconstituting in vitro signalling cascades implicated in the response to DNA replication stress. We wish to dissect protein assemblies implicated in DNA damage signalling and to unveil key structural features of damaged DNA that triggers the assembly of DNA damage signalling complexes.
Study of signal transduction mechanisms through investigation of receptor conformational changes – ARCHITECT
The G protein-coupled receptors (GPCR) constitute the largest family of integral membrane proteins, participate in the regulation of most physiological functions and are the targets of most currently marketed drugs. A better knowledge of their functioning at a molecular level upon ligand binding (ho
Role of Greatwall in mitotic entry and progression – GREATWALL
Mitosis is tightly regulated by the protein phosphorylation and dephosphorylation (addition or withdrawal of phosphate residues to a protein respectively). These biochemical modifications assure the correct spatio-temporal development development of this phase of the cell cycle. Alterations of these
Chromosome attachment and aneuploidy – chromocatch
Do you know that while you are reading this paragraph, more than 20 millions of cells in your body are dividing? Do you know that during each cell division, these cells have to faithfully segregate 23 chromosomes? Any mistake during this process can be really serious. Indeed, an increased frequency
Role of the Drosophila Pmi and human TMEM11 proteins in mitochondrial fusion/fission. – Mitopim
La mitochondrie est un organite impliqué dans de nombreux processus essentiels de la cellule. Des résultats démontrent l'impact de la morphogenèse mitochondriale sur de nombreux aspects de la fonction de l'organite tels que la production d'ATP et de ROS. Même si des progrès importants ont été effect
Cellular functions of STOP proteins: towards a functional and molecular understanding of microtubule effects on synaptic transmission and neuronal organisation – CBioS
MAP6 proteins are major effectors of microtubule whose deletion in mice leads to serious impairment of higher mental functions with cognitive defects sensitive to antipsychotics. STOP KO mice is widely used to study different aspects of the pathophysiology of schizophrenia. The challenge now is to
Translational control in the Drosophila germline and early embryo – GermlineRNA
Translational regulations are essential at multiple steps during oogenesis and early development. In particular, these regulations are crucial for germline stem cell biology and for early embryogenesis which depends on maternal mRNAs and their regulations. One major regulatory mechanism involves cyt
Epigenetic control of centromere functions : The centromere "histone code". – EpiCentr
During cell division, either during embryonic development or during the replacement of dead cells of the adult organism, the chromosomes are distributed equally in the two daughter cells. Control of this distribution is carried out by molecular machines located at a particular location of the chromo
Function and Regulation of Telomeric Transcripts – FURETT
Telomere length is tightly regulated and decreases during aging. Changes to this regulation are associated with genetic diseases, malignancy and cellular senescence. It is therefore important to identify factors involved in controlling telomere length and function. From this perspective it was
Evolution of nuclear hormone receptors ligand binding abilities : the contribution of the amphioxus model – AmphiNR
Nuclear receptors constitute an important family of transcription factors and their activation depends on binding of small molecules like hormones. Dysfunction in NRs-associated intracellular pathways may induce proliferative, reproductive or metabolic diseases. Currently, studying NRs promise a wid
Absicisic acid synthesis and signaling in Arabidopsis seed development – ABSIG
In seeds, ABA is synthesized in tissues which are genetically distinct, the testa is constituted of maternal tissues derived from ovule integuments, whereas the triploid endosperm and the diploid embryo both result from double fertilization and contain maternal and paternal genome equivalents. In ad
A tissue specific study of the functional engagement of the transcription/repair factor TFIIH – FreTNet
Answer to questions such as: - Are there new partners of the TFIIH complex that can regulate its function? - What role does TFIIH plays in ribosome biogenesis? - What is the impact of the amount of TFIIH in transcription and DNA repair - How hormones can control TFIIH functions in vivo. During
Characterization of PARP-3 in genomic stability and epithelial plasticity. – PARP-3
Poly(ADP-ribosyl)ation is a post-translational modification of proteins with key functions in the monitoring and maintenance of genome integrity. This enzymatic reaction was initially discovered by Pierre Chambon in Strasbourg, in the lab of Paul Mandel almost 50 years ago. Very rapidly, the therape
Coordination of Arf and Rab small G protein functions by Rab-ArfGEF-Arf1 cascades in membrane trafficking pathways centered on the Golgi – ArfRabCrosstalk
A major goal of the proposal is to elucidate the mechanisms by which the functions of the two families of small G proteins involved in vesicular trafficking – the Arfs and Rabs – are coordinated. Our project is highly original in that it will demonstrate for the first time a new molecular mechanism
Structure/function studies of the nuclear export factor CRM1: cooperativity, regulation and inhibition – NucExp
The protein CRM1 plays a key role in the cell, as it is responsible for transporting hundreds of proteins from the nucleus to the cytoplasm. This activity, called «nuclear export«, is fundamental for every eukaryotic cell, including human cells. However, precisely how CRM1 exports proteins (called
Structural and functional analysis of the maturation process leading to the production of the eukaryotic small ribosomal subunit – RIBOPRE40S
The ribosomes produce the proteins of all living organisms. Their mode of action and their structure is now understood at the molecular and atomic level. In contrast, numerous aspects of their production in cells containing a nucleus (the eukaryotic cell, the building block of advanced organisms) re
Epithelial stem cell fate and epigenetic reprogramming – EPIStem
This proposal originates from the discovery of the gene, Pw1, implicated in adult stem cells. As described in the preceding sections, our laboratory identified PW1 in a search for early developmental regulators of the skeletal muscle lineage. We subsequently demonstrated that PW1 regulates 2 key cel
Cellular Imaging of Gene Expression – IMAGenEx
Clonal cells sharing an identical environment differ from each other at the phenotypic and gene expression levels. An important part of this variability comes from stochastic variation at the level of gene transcription and this contributes to phenotypic variability at the level of cells and organis
Homeostasis of the intestinal epithelium during a bacterial infection by Serratia marcescens in Drosophila melanogaster – DROSOGUT
A genome-wide genetic screen has identified about 150 genes required in the host defense against ingested Serratia marcescens specifically in the Drosophila midgut. Some of these genes are involved in the compensatory proliferation of intestinal stem cells (ISCs) that allows to maintain the homeost
Ubiquitylation and spatiotemporal control of gene expression – UBIGENEX
Eukaryotic cells such as yeast or human cells, are formed of compartments associated with specific cell functions. The nucleus represents the library of 'knowledge' of the cell whereas the cytoplasm, is the compartment where the library books are translated into cellular actions. The DNA that carrie
Plasticity of Fas receptor signalling in colorectal adenocarconoma – PLAF
Our main aim is to study the fas signaling patways (cell death/cell survival) in colorectal cancer. We observed that Fas tyrosine phosphorylation correlates with survival of CRC cells. Site-directed mutagenesis studies strongly suggest that the dephosphorylation of Fas turns on the apoptosis signal
Mechanisms regulating oocyte apoptosis and follicular differentiation during ovarian early follicular growth – EARLYFOLL
The frame of the EARLYFOLL project concerns the mammalian oocyte and its roles on early follicular development and endocrine function. In mammals, female fertility strictly relies on the pool of primordial follicles, which is definitely established around birth. Soon after the formation of this foll
Molecular and cellular regulation of beta1,4-GalNAcT-II in physiological and pathological states (gastrointestinal cancer) – GALFISH
This project aims at understanding the molecular and cellular mechanisms underlying the supramolecular organization and localization of Golgi-GTs implicated in the biosynthesis of Sda et sLex antigens. These carbohydrate determinants are found in the normal and cancerous gastrointestinal (GI) tract