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Propriétés physiques locales du biofilm et leur rôle dans la dynamique interne de l'édifice sondé par des micro-colloïdes magnétiques insérés. – DynaBiofilm
Bacterial biofilms are communities of bacteria associated with biological or artificial surfaces. They form by a nucleation - growth mechanism coupled with the production of polysaccharide-rich extracellular matrix likely to both protect and stabilize the formed edifice. These bacterial cells assemb
Cellular Orientation in Non-homogeneous Environments – CONE
The main goal of the current project is to advance fundamental understanding of the mechanisms allowing living cells to orient in the effective ways observed in nature. The widespread and basic nature of the motility function makes that fundamental questions are naturally spurred and have direct imp
Mapping and modelling of chromosome dynamics – Chromodyn
The spatial organization and dynamics of genes and chromosomes in nuclei of eukaryotic cells is not random and plays an important role in gene expression, genome maintenance and replication, with many implications for fundamental biology and biomedical processes. Yet, this dynamic organization still
Conception d'un microsystème basé sur des sondes électrochimiques ultra-sensibles pour une multi-détection sans marquage d'acides nucléiques: application au génotypage HCV – VirProbe
The project concerns the construction of a miniaturized diagnostic platform (microsystem) dedicated to hepatitis C virus (HCV) genotyping. With 170 millions of infected people (3% of population worldwide) including 600 000 persons in France, HCV has become a major problem of public health. HCV infec
Lésions oxydatives tandem de l’ADN, formation réparation et mutagénèse – TODNAL
Oxidative DNA damage is continuously generated in cells as a consequence of oxidative stress and this phenomenon is associated with several pathologic disorders. Generated reactive oxygen species could react with biological molecules including DNA the molecule bearing the genetic information. Cells
Structures, interactions and interferences in the immediate and long-term protection by innate immune macromolecular complexes. – STR-ASS-DEF-COL
The mammalian immune system has evolved innate and adaptive components that cooperate to protect the host against microbial infections. The innate system involves constitutive recognition molecules able to sense danger signals and to trigger effector mechanisms aimed at limiting early infection and
Mechanisms of podosomes/invadopodia auto assembly : theoretical and experimental investigations – ROSETTE
This project will focus on a poorly known type of adhesive structures but that have been described to be essential in physiological and pathological cell invasion of cohesive tissues. These structures are named podosomes in osteoclasts and macrophages and invadopodia in metastatic cancer cells. Poso
Real-time protein dynamics in DNA processing enzymes – RETID(Y)NA
Changes in protein conformation play a vital role in biochemical processes. They can range from small localized motions during electron transfer to large scale domain movements often encountered in enzymatic catalysis. In this project delocalized motions of enzymes, substrates and products will be s
Causes and consequences of protein aggregation in cellular degeneration – PAGDEG
In this project, we propose interdisciplinary approaches to improve our understanding of cellular degeneration in relation to aging and, in parallel, to antibiotic treatment of Escherichia coli. This bacterium is not only the best-known organism but also the simplest aging model available. We thus
Chemical Nano-Imaging of the Dopaminergic Cell – NANOCHEMCELL
The general context of this project is the development of advanced chemical imaging to understand complex biological processes, such as the chemistry of the dopamine neuron. The project is based on cellular multimodal chemical imaging with techniques of unprecedent spatial resolution, and sensitivit
Predicting MOONLIGHTing proteins from protein-protein interaction networks – Moonlight
Some proteins perform several apparently unrelated functions in the cell or the organism. These multifunctional proteins are collectively named 'moonlighting proteins', referring in the human society to a second job held in addition to a regular one. Because protein function is mostly investigated e
Migration cellulaire en milieu confiné – MICEMICO
The ability to migrate in confined spaces is essential for the function of leukocytes, the main components of the immune system. In addition, this type of motility can be adopted by the most malignant tumor cells and contributes to their capacity to invade healthy tissues. We propose here a trans-di
Intégration de données hétérogènes pour la détermination de la structure de complexes macromoléculaires : application à TFIID. – Puzzle-fit
This project aims at developing new computational tools to integrate diverse experimental and in silico data to decipher the architecture of large multi-protein complexes in general and particularly those involved in the regulation of gene transcription. We focus in this project on the general trans
Développement et validation d?une chimiothèque focalisée enrichie en inhibiteurs d?interactions protéine-protéine via des approches in silico et in vitro – PPIFocusDb
Protein-protein interactions (PPIs) are essential for most cellular processes. Aberrant PPIs contribute to most disease states and as such, PPIs represent a highly populated class of essentially untouched potential targets for drug discovery. About 650,000 PPIs are expected in the human body and mos
Bases moléculaires de la régulation de l'activité de Deubiquitination des histones – HISTONEDUB
Post-translational modifications of core histone proteins are crucial for transcriptional regulation in eukaryotes. A strong emerging picture is that defects in these cellular mechanisms lead to various diseases, including cancer. Different histone modifications are observed that influence both chro
Molecular and membrane processes in gamete interaction : a biophysical approach – InterGame
In spite of the present decrease in human fertility, the research aiming at understanding fertilisation is limited. The molecular and membrane mechanisms are poorly understood mostly because the classical biological approaches are difficult owing to the difficulty to obtain oocytes in adequate quant
Ion-Channel Coupled Receptors (ICCR): Protein-based bioelectric sensors for the study of G-protein-coupled receptors – ICCR
Using existing proteins as templates, it is possible to create biological objects with novel properties. Our recent publication (Moreau et al., 2008, Nature Nanotech. 3:620-625) introduced Ion-Channel Coupled Receptors (ICCRs), hybrid proteins engineered by assembly of an ion channel and a receptor
Structure et fonction du complexe IFNg/héparane sulfate pour l'ingénierie d'un glyconjugué de synthèse pour inhiber la cytokine – HEPAFERON
Cytokines are small size proteins that, by diffusing in the extracellular space carry distinct signals (activation, inhibition, proliferation, differentiation), and provide cells a system to communicate. Current research increasingly shows that most cytokines, in addition to their specific receptors
Régulation du fonctionnement des RCPG : hétéro-oligomérisation et organisation dynamique des récepteurs dans la membrane – GPCR D-I-F
In recent years, the general mechanism of G protein-coupled receptor (GPCR) signaling has been largely revisited, in part because it was shown that a given receptor could form homo- or heteromers with other GPCRs. In addition, the notion that GPCRs must function in the context of a specific multipro
Understanding the physical basis for pressure effects on protein folding – DELTAV
Defining the physical-chemical determinants of protein folding and stability, under normal and pathological conditions has constituted a major subfield in biophysical chemistry for over 50 years. And although a great deal of progress has been made in recent years towards this goal, a number of impor
Pontage covalent « clickable » optimisé pour la spectrométrie de masse, application à l’analyse structurale des pili de type IV de Neisseria meningitidis – CLICKMASSLINK
Probing the organization of proteins and of their interactions within a living system is essential to understanding the role of these proteins in vivo. In the case of many pathogens, such as N. meningitidis, virulence is primarily dependent on the expression of filamentous organelles called type IV
Microscopie électrochimique à Nanocavité pour l’imagerie fonctionnelle de cascades enzymatiques. – CASCADE
This proposal describes an experimental nanoscale platform to address modern aspects of enzymatic biocatalysis. The aim of this project is to develop new experimental tools to both assemble artificial enzymatic complexes, in a way spatially controlled at the nanoscale, and to probe their functional
Real-Time Studies of Biological NanoMachines in Action by NMR – NanoLife@Work
The study of the structural and functional properties of biomolecular nanomachines remains a considerable practical challenge. The size of the target nanoparticles, complexity of biological substrates and structural rearrangements, all present an array of logistical problems. Structural studies of s
Microscopie des Intermédiaires de Réplication et Recombinaison – MIRR
During DNA synthesis, replication fork progression can be compromised by replication fork barriers (RFBs) which can results from various situations (DNA damage, DNA/protein complexes, DNA secondary structures...). Depending on the nature of the replication block, multiple pathways can be employed to
Signalisation transmembranaire des récepteurs métabotropiques du glutamate – mGluNano
The metabotropic glutamate receptors (mGluRs), a particular family of G-protein coupled receptors (GPCRs), are activated by glutamate, the major excitatory neurotransmitter in the central nervous system. Among the eight types of mGluRs (8 genes encoding for mGluR1 to mGluR8 in human), they are not u
Induction Mécanique des Gènes Tumoraux dans le Cancer du Colon et dans l’Hepato-Carcinome – MECHANO-CANCER
Our understanding of multi-cellular tissue morphogenesis and homeostasis is being challenged by increasing evidence demonstrating the involvement of mechano-sensitive interplay between shape-related strains and state of expression of the genome in tissues. Even though such mechanical cues were demon
MAss Spectrometry imaging Data Analysis in EYE – MASDA-EYE
By combining the advantages of mass spectrometry (MS) and microscopy in a single experiment, the emerging mass spectrometry imaging (MSI) technology brings extraordinarily powerful capabilities to understand the molecular complexity found in both health and disease. Compared to traditional immunocyt
Calcium carbonate Multifunctional Particles elaborated in supercritical CO2 medium. Application to controlled release of therapeutic proteins for tissue engineering – CALCOMED
Osteoporosis and degenerative arthropathies are in constant increase due to population ageing. The important sport practicing in modern societies leads also to articular traumatism with high prevalency. Thus, research in tissue engineering becomes one major axis at the international level. This kind
Chimiokines adhésives: structure moléculaire, imagerie cellulaire et outils thérapeutiques – Adhékines
Rationale and background Among chemokines, which are secreted chemotactic cytokines, CX3CL1 and CXCL16 are exceptions: they are also expressed in transmembrane form. In this form, they surprisingly function (hence the acronym 'adhekines'), with their respective receptors CX3CR1 and CXCR6, as strong
Additifs supramoléculaires de cristallisation des transporteurs ABC de résistance à de multiples agents chimiothérapeutiques – AddX
The structure-based design of highly efficient and selective, therapeutic inhibitors, requires the knowledge of their protein targets at the atomic level, if possible in several conformations, that will reflect the different catalytic steps of a given process. This is a particularly difficult task c
Force associée à la polymérisation d’actine. Aspects biochimiques et mécaniques. – ACTIMAG
The dynamics of actin filaments and networks is a fundamental process involved in many cellular functions. The functionally relevant property of actin is to self assemble with associated ATP hydrolysis in a single turnover reaction. How this reaction is coupled to force production and used by protei