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The Research within FRABio

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The multidisciplinary environment of Villeneuve d' Ascq's campus allowed the emergence of a scientific community in Biology aiming to study the structure-function relationships of biomolecules. Its research and training activities lie on both cutting-edge technological equipment and unique expertise. The Federation of Research FRABio (Structural and Functional Biochemistry of the Biomolecular Assemblies) arose from the will to structure the strengths of the laboratories of the campus involved in basic research in Biology. This research is clearly multi-model (microbial, animal and plant biology), multi-scale (from atoms to organisms) and multidisciplinary (most particularly a strong interface between biology and chemistry).

FRABio results from a remodeling of the former Federative Institute of Research "Proteomics, Post-translational Modifications and Glycobiology" (IFR 147 in 2002-2013, FRE3637 CNRS in 2014) based on both technology and expertise in structural and functional biochemistry (10 facilities and services, among which 3 are common with the Federation Chevreul (chemistry)), and gathering 4 research laboratories contractualized with CNRS and INSERM (UGSF, MSAP, PHYCELL and PRISM).

The main mission of FRABio aims to facilitate the basic research activities in Biology on the Campus while satisfying the needs of the regional, national and international scientific communities, as well as industrial partners. This mission is clearly in line with the process of construction of the University of Lille by the year 2018.

Using the excellence and the fields of expertise of its laboratories, the scientific project of FRABio is based on both characterization and understanding of the macromolecular mechanisms which govern the functioning of life, at the molecular, cellular and organism levels. The scientific project of FRABio is based on the activities in basic research defined within the framework of the former IFR 147: Glycobiology, Cell Regulation Networks, Functions and Pathologies, and Plant Biodiversity.

The leading scientific themes of FRABio’s laboratories are at the heart of its project: animal, plant and microbial glycobiology, physiology of ion channels, proteomics and inflammatory response.

All these themes aim to decipher the mechanisms of intra-and extracellular signaling connected to the post-translational modifications of biomolecules (glycosylation, phosphorylation) (UGSF, PHYCELL), to the molecular actors involved in ion homeostasis and signaling (calcium and ion channels) and membrane transport (PHYCELL, UGSF), and to the molecular complexes involved in gene transcription, cell cycle regulation, cell recognition and metabolism (UGSF, PRISM).

The scientific strategy of FRABio articulates with 3 levels of experimental and analytical approaches by which are realized the key projects of the units:

arrow Approaches in structural biochemistry

UGSF, MSAP and PRISM are national and international leading laboratories in structural analysis in the fields of glycobiology and post-translational modifications, proteomics, membrane transporters, and signal transduction. In this context, powerful tools were acquired and implemented on the campus of Lille, in structural biology (NMR and X-ray crystallography), chemical synthesis, MS and proteomics.

As regards glycobiology and post-translational modifications, UGSF implements and develops structural biochemistry methods using MS and NMR for solving the clarification of the linear structure of sugars free or conjugated. A remarkable outcome of this expertise was the emergence in 2012 of the PAGés facility, which is GIS-IBISA certified (national certification) since 2014. PAGés takes advantage of the expertise and the technological development of UGSF, and also of a complete technological environment in the perimeter of FRABio (NMR and MS facilities (UGSF, MSAP, PRISM). The following projects of FRABio’s laboratories are concerned :

  • Structural studies of adhesins and bacterial lectins (UGSF)

  • Structure-function relationships of tau protein (Alzheimer) (UGSF): study of the structural and functional impact of the O-GlcNAcylation of the tau protein on tubulin assembly; study of the interactions of tau with Pin1, Bin1 and DNA (Labex DISTALZ)

  • 3D structural studies and structure-function relationships of the enzymes of starch synthesis (UGSF)

  • Structural and glycomic studies of glycosylation modifications met during the physiopathological stages of inflammation and infection of bowels, in connection with colorectal cancer (UGSF)

  • Structural studies of the heparan motifs of immune cells during the inflammatory process; synthesis of biomimetics of inflammatory factors (UGSF)

  • O-GlcNAcylation (UGSF): identification by ETD-MS of the sites of O-GlcNAcylation of proteins involved in cellular pathways; co-crystallization studies of the OGT-beta catenin complex

  • Structural biology studies of membrane transport and signal transduction (UGSF)

  • Modelling and statistical data analysis of protein-protein interactions (UGSF) ; improvement of 3D-structure predictive models of the macromolecular complexes (docking protein-protein CAPRI) (UGSF)

  • Study of the inhibitors of protein-protein interactions between CDK5 and CDK5 / P25 (UGSF)

  • Study of the molecular interactions between Myt1 kinase and the Cdc25 phosphatase involved in cell cycle regulation (UGSF)

  • Study of the control of Ets transcription factors by the mediator complex and the DNA repair complexes (UGSF)

  • Structural analysis of transfusional plasma proteins (MSAP)

  • Localization by MS of the modifications of starch and plant polysaccharides (IEED IFMAS) (MSAP / UGSF)

arrow Approaches in functional biochemistry

The approaches in functional biochemistry intend to establish a relationship between the structure of biomolecules and their functions within cells and bodies. The main research themes of UGSF, PHYCELL and PRISM are directly connected to these approaches, more particularly those concerning the mechanisms of intracellular and extracellular pathways: neuro-inflammation, ion channels, glycobiology and post-translational modifications, membrane transporters, cellular cycle... The omics approaches, such as proteomics, glycomics and glycoproteomics are essential for the identification, the quantification and the follow-up of biomolecules in cells and tissues. The MS-imaging developed by PRISM (CLIC-Imaging facility) is a key technology among these omics approaches. The following projects of FRABio’s labs are concerned by the approaches in functional biochemistry :

  • Study of the catabolism of mycobacterial enzymes (UGSF)

  • Study of the role of bacterial adhesins and lectins in the adhesion of bacteria to epithelial cells (UGSF)

  • IEED IFMAS project (UGSF - structural biology, MS and proteomics facilities): study of the molecular mechanisms governing the synthesis of starch in Arabidopsis thaliana and potato; analysis of the catabolism of starch in Chlamydomonas.

  • Study of the biosynthesis and the role of the OPGs in bacteria by in vivo and in silico studies (UGSF)

  • Functional studies of the mechanisms permitting the terminal glycosylation of proteins and lipids, and study of the role of this glycosylation in pathologies (UGSF- cell imaging facilities)

  • Studies of the regulation of heparan motifs synthesis in immune and inflammatory cells; synthesis of biomimetics of inflammatory factors (UGSF)

  • Study of the molecular and cellular mechanisms governing the glycosylation steps in the RE and the Golgi in normal and pathological models (CDG) (UGSF - cell imaging facilities / calcium imaging facility / MS and proteomics facilities)

  • O-GlcNAcylation (UGSF / cell imaging facilities / MS and proteomics facilities): functional studies of the role of O-GlcNAcylation in intracellular pathways and cell cycle; study of the role of glucose metabolism in the O-GlcNAcylation of tau (Alzheimer's disease); study of the cellular mechanisms of OBP O-GlcNAcylation and its role in OBPs functions.

  • Studies of the cellular mechanisms of glycosylation of the linen plant wall fibers (UGSF / cell imaging facilities / MS and proteomics facilities)

  • Study of the mechanisms of cell cycle regulation in alphaproteobacteries (UGSF- structural biology facility / cell imaging facilities / MS and proteomics facilities)

  • Characterization of new partners and functions of the oncoprotein Ets-1 (UGSF- structural biology facility / cell imaging facilities / MS and proteomics facilities)

  • Characterization of the conjugation pathway ubiquitin / FAT10 (UGSF- structural biology facility / cell imaging facilities / MS and proteomics facilities)

  • Study of the mechanisms of regulation of cell cycle and division signals( UGSF- structural biology facility / cell imaging facilities / MS and proteomics facilities)

  • Studies of the molecular mechanisms of activation and recruitment of microglial cells at the lesion site of nervous system; search for markers of microglial activation; study of microglial functions in leech; study of microglial secretomes (PRISM - cell imaging facilities / MS and proteomics facilities)

  • Functional studies of ion and calcium channels: identification of new agonists and antagonists of calcium channels TRPM8, TRPV2, TRPV6, ORAI1 and ORAI3; study of the control of channels trafficking in prostate cancer; functional study of the intracellular channels; study of the role of channels TRP and ORAI in the migration of epithelial and endothelial cells in prostate cancer and angiogenesis (PHYCELL - cell imaging facilities / calcium imaging facility).

arrow Approaches in integrative biology

Understanding the complexity of living requires multi-scale studies: molecules, biomolecular assemblies, cells, tissues, organisms and populations. FRABio gathers resources and expertises of the laboratories to promote integrative approaches associating experimental and structural studies, omics (proteomics, glycoproteomics and glycomics), in vivo and in silico studies.

This integrative approach takes advantage of i) the diversity of the biological models (animals, plants and microbes), ii) the diversity of the pathological models (glycopathologies, cancer, canalopathies, neurodegenerative and behavioral diseases), and iii) the pluridisciplinarity of the laboratories within FRABio, the university of Lille1, and the scientific community of Lille.

The integrative approach lies on the 3 technological clusters of FRABio (for the experimental studies on molecules, cells and tissues), on the animal housing facility permitting the physiological and behavioral experiments on rodents, and the use of aquatic models (for the experimental studies on whole organisms), and on the biocomputing service of FRABio (for the in silico studies on databases, data handling, and computational biology and modelling studies.

All FRABio’s laboratories are involved in this integrated biology approach, most particularly on the following projects :

  • Study of the molecular and cellular mechanisms of the expression of Golgi glycosyltransferases using the Zebrafish model (UGSF); phylogenetic studies of the origin and evolution of Golgi glycosyltransferases (UGSF); functional genomics of the expression of the sialyl-transferase B4NLNT2 in cancer cells (UGSF - coll. Verona, Italy)

  • O-GlcNAcylation, brain, cognitive ageing and Alzheimer (UGSF): study of the premature programming of the ageing caused by prenatal stress to the rat; study of the role of ocytocin and glucocorticoids on the regulation of glucose homeostasis in brain; characterization of the relationships between metabolic changes and pathological ageing using Alzheimer mouse models; study of the phosphorylation and O-GlcNAcylation of the tau protein in mouse.

  • Stress and olfaction (UGSF): study of the effect of the prenatal stress on the expression phenotype of Odorant-Binding Proteins (OBPs) in mouse by proteomic and transcriptomic studies.

  • Glycosylation of linen plant wall fibers (UGSF): studies of genome and transcriptome data for the identification of the genes responsible for glycosylation in the answer to stress and to environmental conditions.

  • Molecular biology of the regulation of genes in eukaryotes (UGSF).

  • Molecular and cellular modelling (UGSF): molecular modelling and dynamics of proteins and proteins-lipids systems; modelling of the regulation of genes in prokaryotes and eukaryotes; modelling and statistical data analysis of protein-protein interactions (UGSF); fluctuations in structured coulombic fluids.

  • Evolution and diversity (UGSF): integrative and compared study of cell cycle regulation in prokaryotes and eukaryotes using alphaproteobacteries, human cells and Xenopus models; in silico modelling of the cell cycle.

  • Immunity and repair mechanisms of the nervous system (PRISM): compared proteomic study of microglial cells from leech (Hirudo medicinalis) and mammals (mouse).

  • Cancer and ionic channels (PHYCELL): molecular targeting of the calcium channels involved in tumor formation and metastatic development using in vivo models (mouse); study of the impact of environmental factors on the ion channels in connection with the progress of prostate cancer (mouse).

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