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Molecular characterisation of the assembly and functioning of a membrane complex: the NADPH-oxidase – PROTOTYPE NOX
In general, reactive oxygen species (ROS) are classically considered to have both beneficial and deleterious (cytotoxic, mutagenic or oxidative stress-inducing) properties and, thus, their amount must be severely controlled. As professional ROS producing systems, the NOX enzymes are at the centre of
Molecular ortheses for the crystallization of membrane proteins. Application to multi-drug efflux pumps. – X-Or
Membrane proteins have widely diverse, essential functions and constitute a major class of molecular targets for therapeutic research. However, membrane proteins remain challenging for structural studies as all steps, from expression to structural studies, are potentially complicated by their obliga
Structural characterization of both closed and open forms of a ligand-gated ion channel of the cys-loop family and molecular mechanism of the transition – Nico_chimera
Objectives : Molecular basis of the gating mechanism of an ion channel and its modulationby allosteric effectors. We aim at deciphering the molecular basis of gating, modulation and ion permeation in pentameric ligand---gated ion channels that are essential in fast chemical signalling between nerv
Searching of Antagonist Ligands Switching of the Angiogenesis by interacting with the VEGFR-1 d2 domain. – SALSA
This project aims at designing new vascular endothelial growth factor (VEGF) antagonist raised again the VEGF receptors (VEGF-Rs). More precisely we will target the receptor 1 that is implicated in tumoral angiogenesis i.e the formation of new blood vessels that are widely up-regulated in cancer and
Radiation therapy with photon activation of heavy elements – RAPHAELO
Glioma is the most common type of brain tumor in adults. Today the average life expectancy of patients with high-grade glioma is less than a year. The treatment of brain tumors is complicated by their resistance to conventional treatments (chemotherapy and radiation) and their location; with a delic
Identification and molecular characterization of secretion signals in the virulence proteins secreted by the bacterial type 2 secretion system – SecPath
The type II secretion system (T2SS) is widespread in Gram-negative pathogenic bacteria and is used to secrete toxins and lytic enzymes. These secreted virulence proteins are directly involved in pathogenesis and in many of these bacteria are the main virulence factors. T2SS is a multiprotein nano-ma
Development of magnetic resonance and optical imaging probes and their in vivo validation in detecting enzymatic activity in infection – ENZYMAGE
(i) To rationally design and synthesize lanthanide-based imaging probes with enzyme-activated response in Gd-enhanced/PARACEST MRI or optical imaging. (ii) To provide their complete in vitro physico-chemical characterization with regard to applications as Gd-enhanced or PARACEST MRI agents or optic
Role of TRF2 and its partners in the formation and the processing of the t-loop of human telomeres – TELOLOOP
The ends of human chromosomes are composed of specialized structures called telomeres that play crucial roles in aging and cancer. These structures are essential for genome stability. They shorten at each cell division to a critical size incompatible with their functions leading to cell division arr
Spatial and temporal control of synapse formation through the neurexin/neuroligin adhesion complex – Synapse-2Dt
Our principal contribution has been to develop new biomimetic systems based on these purified adhesion molecules, to induce synaptic differentiation in controlled time and space. The use of numerical simulation tools and super-resolution microscopy techniques has allowed us to quantify these process
Cotranslational processing mechanisms: towards a dynamic 3D model – RIBO-Dyn
Among non-ribosomal proteins, ribosome-associated protein biogenesis factors (RPBs) are molecules acting as soon as a nascent polypeptide reaches the tunnel exit of the ribosome. RPBs are involved in the so-called cotranslation events including protein folding, modifications and/or translocation in
Observing the T cell receptor (TCR) activation in real time: monitoring the intracellular domain orientation dynamics of the receptor complex in live cells with polarized time-resolved fluorescence imaging – ReceptOrient
We study the process of activation of TCR - initiation of intracellular signaling cascades following receptor engagement by pMHC ligand. Recent studies in model systems suggest that an essential early step in the activation of the TCR involves conformational change / re-orientation of the CD3epsilon
Treatment of bone metastases by combining low intensity ultrasound and bisphosphonates – MOTUS
Bone metastases are a common complication of breast cancer. These metastases are responsible of complications that can change vital prognosis and affect the quality of life of patients. These bone metastases are osteolytic, i.e. they induce bone resorption. Osteolytic lesions were created due to a s
Membrane signaling complexes : role of transmembrane domain interactions – interferenceTM
More and more data demonstrate the importance of receptor interactions at the cell surface for their activation, which is often abnormal in cancer. The transmembrane domains which anchor the receptors at the cell surface play a role in this activation. In this project, our goal was to study some of
Quinone reduction and supercomplex formation: the two enigma of Rieske/cytb complexes – BIsP
Purification of complexes and /or the supercomplex from Geobacillus and Heliobacteria should be followed by characterization by UV/VIS and EPR spectroscopy and crystallization. Crystallization of a supercomplex would be a first and needs careful preparation of a homogenous protein sample. Heme ci’s
Targeting integrin alpha5beta1 for bone regeneration – Integros
The available therapeutic tools that can promote osteogenesis in bone pathologies (fracture repair, bone regeneration, osteoporosis) which are characterised by decreased bone forming cells, are limited. Mesenchymal cells can differentiate into mature osteoblasts and can be used for cell therapy, bu
High resolution structural studies to understand the chemomechanical transduction mechanism of myosin motors and the critical interactions that regulate their cellular location. – How myosin produces force
The cell comprises several molecular motors that are essential not only for cell division and migration but also for polarized transport, the maintenance of ultrastructures of the cell, or for the anchorage of vesicules or organelles within the cell. The project will focus on the study of the myos
DEAD-box helicases: function, specificity, and mechanism of action – HelicaRN
This research project proposes to study the DEAD-box family of helicases, which are enzymes that are essential for the biology of RNA in nearly all organisms. Indeed, the inappropriate expression of these enzymes can provoke cancer in humans; this reflects the capacity of these enzymes to modify or
Conformational rearrangements of group II ribozymes – GRP2CONF
Bacterial and organelle group II introns are retrotransposons, whose excision from precursor RNAs as branched molecules (lariats) on the one hand, and reverse splicing into DNA targets on the other, are catalyzed by a large, intron-contained ribozyme. Catalysis of both branch formation and exon liga
Study on cyclodipeptide synthases (CDPSs), a new family of tRNA-dependent peptide bond-forming enzymes – CyDiPepS
CDPSs divert aminoacylated tRNAs from their canonical role in ribosomal protein synthesis, for cyclodipeptide formation. CDPSs are unique enzymes that are unrelated not only to aa-tRNA-protein transferases and Fem aminoacyl-transferases, the two enzyme families that use aminoacyl-tRNAs as substrates
Green fibronectin substitute and functionalization of materials – Green Fib
Recent strategies in the biomaterials field aimed to fix on implant’s surfaces molecules recognized by cells like fibronectin (FN). The FN used in the biomaterials field is generally purified from human plasma (pFN). We have recently demonstrated that is was possible to isolate from plants a protein
New tools based on ultrafast spectroscopy and molecular dynamics simulation for investigating the structural dynamics of chaperon protein/DNA complexes – FEMTOSTACK
Voir version française see annexed report see «conclusions« in full report cf. complete list in the attached pdf file The FEMTOSTACK project gathers inter-disciplinary know-how in ultrafast laser spectroscopy, theoretical chemistry and molecular biophysics and sets out to develop new experimen
Ultra-short carbon nanotubes: near-infrared nanolabels for single molecule tracking in live brain tissues – UshortNT
In recent years, the observation of individual molecules has revolutionized optical microscopy. This domain is promised to play a decisive role in understanding biology at the nanoscale. However, current microscopy techniques detecting individual molecules suffer from serious limitations that curren
Control of tolloid proteinase activity in tissue remodelling: structural determination of regulatory mechanisms and design of novel inhibitors and activity-based probes – TOLLREG
Tolloid metalloproteinases play major roles during embryonic development and tissue repair by synchronizing the synthesis of the extracellular matrix with the activation of growth factors. Excessive deposition of extracellular matrix, composed mainly of collagens, is a common characteristic of the m
Mecanism of transcription termination by the Rho factor – TERMINATOR
This project aims to elucidate the mechanism by which Rho acts to prevent the expression of a gene, stopping the transcription of DNA. It is a very general mechanism of gene regulation in bacteria such as E. Coli. In addition, Rho is the prime target for the antibiotic bicyclomycine. - First observa
Molecular Regulation of chloroplast Galactolipid biosynthesis – ReGal
The ReGal project aims at understanding the mechanisms governing the production of the most profuse lipid in photosynthetic membranes, monogalactosyldiacylglycerol or MGDG, being therefore an essential process for agricultural production. Indeed, in 1sqm of leaves, the photosynthetic surface is esti
Tunable Time-Resoved Stimulated Emission Depletion Microscopy for dynamic imaging of interactions at the subcellular scale. – STED-FLIM
L’objectif est de développer un système de microscopie STED à super-résolution accordable en longueur d’onde afin de pourvoir exciter une large gamme de fluorophores d’intérêt biologique, voire plusieurs fluorophores simultanément. En outre, la mesure de la fluorescence pourra être effectuée de mani
RAD51-catalyzed homology recognition and DNA strand exchange: monomer order and dynamics in nucleoprotein filaments assembled on single DNA molecules and during filament interaction with a duplex DNA molecule. – RADORDER
Homologous Recombination is a universal life process essential for maintenance of genome integrity, cell survival and protection against tumorigenesis. Accurate genome duplication, chromosome segregation and repair of DNA double-strand breaks depend on the ability of cells to perform DNA strand exch
MUltisenSIng polymer transistors for in vivo reCording – MUSIC
• To develop multi-sensing probes capable of simultaneous in vivo monitoring of local field potentials and ion currents from neurons. • To develop multi-sensing probes capable of simultaneous in vivo monitoring of local field potentials and glucose concentration. • To add wireless capability
Multiplexed Imaging of Cell Secretions – Mult-I-Cell-S
Ce projet implique 3 partenaires, chacun étant expert dans différents domaines : la Chimie (fonctionnalisation de surface), la Biologie (suivi de réponse immunitaire) et la Physique (micro-technologies et instrumentation). Au delà d’une meilleure connaissance du système immunitaire, nous envisageons
Mitochondrial transport mechanism at the molecular level – MIT-2M
The first structure of AAC was solved in 2003 by one of the partners of the project. It is still the only atomic resolution structure of such a carrier. It shed the first light on mitochondrial carriers by showing the overall fold and the mechanism of inhibition by atractylosides, well-known poisons
Rational design of a sensitive and enantiospecific electrocatalytically-amplified aptasensor for amphetamine-derivatives drugs – ECSTASE
At present, methods of screening for amphetamines and its related metabolites were performed on urine samples. They are mostly based on fast qualitative immunochemical tests associated with a colorimetric measurement (for example by visualizing the formation of a color on a strip) of the activity of
The physics of plant morphogenesis: dynamics and mechanics of the plant cell wall in the meristem – MechaStem
In the past thirty years, we have seen tremendous progress in the field of developmental biology. Today, the main gene families that are responsible for growth patterns and cell and tissue differentiation are known. However, the link between the identity of these genes and shape control remain poorl
Molecular and cellular mechanisms of mechanotransduction and mechano-sensing at cell-cell junctions – MECANOCAD
Transduction of mechanical stress is an underestimated adhesion-associated signal contributing to morphogenesis during development and tissue homeostasis. The transmitted mechanical stress through its effect on cell tension has high incidence on cell adhesion itself, cell migration as well as surviv
Aqueous core capsules: a versatile tool for parallelized 3D confined cell culture – CAPCELL
Nowadays, one of the major challenge in biology is to bring the actual investigations made in Pétri dish on cell monolayers towards a 3D level, physiologically more relevant. The global objective of this project is to develop a new cell encapsulation technology and to realize a tool that is routinel
Revealing complexity of the plant phenolic metabolism : novel routes to the precursors of the cell-wall biopolymers – PHENOWALL
Cytochromes P450 catalyze rate-limiting and irreversible oxidation reactions in the phenolic metabolism. Some of them have duplicated during early seed or monocotyledonous (cereals) plant evolution. These duplicates have been conserved in most plant species. Our aim in the PHENOWALL project was to d
Nanoparticulate formulation of nitrosothiols aimed at improving nitric oxide bioavailability. Toxicological and pharmacological evaluation – NanoSNO
The discovery of nitric oxide (NO) as a physiological messenger has opened a wide field of investigation in therapeutics, especially for the treatment of cardiovascular diseases. NO donors presently available have restricted indications because they fastly release NO, which is very unstable (half-li