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Tooth diseases: Porphyromonas active secretion of toxin effectors – TOOTHPASTE
Periodontitis and gum diseases are considered as major public health concerns as roughly 36% of the world population (20% in industrialized countries) suffer of serious tooth tissue damages and tooth decay. The main microorganism responsible for periodontitis and gingivitis is the oral pathogenic ba
Pseudomonas aeruginosa–induced hemorrhagic pneumonia: deciphering novel virulence strategies – HemoPseudo
In this project, we undertook an integrated study of CLJ1-like P. aeruginosa clinical isolates from microbiological, biochemical, cellular, tissular and structural viewpoints, combined with genome-wide approaches, with the objective of delineating the mechanisms of bacterial pathogenesis utilized by
Analysis of the GABAergic synapse using structural and genetic strategies in the C. elegans model organism. – GABAREL
GABA is the primary inhibitory neurotransmitter in the nervous system. Changes in GABAergic neurotransmission contribute to the etiology of prominent neurological and mental disorders including epilepsy, anxiety and schizophrenia. Despite extensive molecular and pharmacological characterization of G
A new approach to inhibit ErbB2 signaling and design new drug candidates: targeting the EGF domains of its membrane partner, the MUC4 mucin – DRUG_MUC4
The general goal of the DRUG_MUC4 project is to study the structure-function relationship of the MUC4-ErbB2 complex and propose new small inhibiting therapeutic molecules targeting MUC4-EGF domains. The main aim of that project is to understand for the first time how the EGF domains of MUC4 interac
Sequence and structure of the packaging signals of the influenza A virus genome – PSiFlu
Influenza A viruses (IAVs) are responsible for recurrent flu epidemics and occasional devastating pandemics in human and animal populations. In addition to seasonal flu, which claims 250,000 to 500,000 lives yearly, new IAVs with high pandemic potential regularly emerge. Evolution of seasonal viruse
Structural basis of viperin-induced changes in lipid synthesis upon virus infection – VipVir
Viperin (virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible) is an interferon-stimulated gene that has antiviral activity against a variety of pathogenic enveloped viruses including cytomegalovirus, influenza A, dengue virus and HIV-1. Its precise mode of action is larg
Resolution of meiotic recombination intermediates from yeast to mouse – Resolve
A key question is to identify all actors directly involved in dHJ resolution, a reaction that requires two cleavage reactions each of two DNA strands, and to understand why the cleavage is made only asymmetrically, such that only crossovers are produced. This differs from the mechanism proposed for
Bacterial Cell Remodeling by Viral Infection – BacVirRemodel
Our previous work provided a cytological description of the bacteriophage SPP1 multiplication process in the bacterium Bacillus subtilis and identified most of its effectors and their interactions network. The present research proposal builds in this basic knowledge to dissect in real time the assem
Structural investigations of the HTLV Tax protein – SinTax
The Tax protein plays a central role in the pathogenicity of HTLV-1. Resolving its atomic structure would give insights for the development of new anti-HTLV-1 therapies. However, given the fact that Tax shows pleiotropic functions, it is anticipated that it may harbor different structural conformati
The bridge and the shuttle : structure and dynamics of the membrane contact site formed by the sterol/PI(4)P exchanger OSBP – SwingBridge
The overall goal of the project is to obtain the first 3D functional structural and dynamical model of OSBP in MCS. We want to highlight two particularly innovative aspects of this project. The first is the use of cryo-EM to determine the MCSs structure. Cryo-EM will provide 3D models of both protei
Functional dynamics of a nanomachine involved in proteome quality: a combined NMR/SAXS/SANS study of the PAN unfoldase – PROTstretch
The specific degradation of proteins in cells is one of the major mechanisms, along with transcription and expression control, that regulates an ensures a healthy proteome (i.e. the ensemble of proteins) in living cells. A key step in this process is the specific recognition of deleterious proteins
The role of spatio-temporal nano-organization in regulating the specificity of JAK/STAT signaling – NANOSTAT
We will unravel the determinants of type I(IFNAR) and type II(IFNGR) IFN-R assembly and endocytic trafficking. We believe that the type I (IFN alpha/beta) and type II (IFN gamma) IFNRs represent one of the best paradigms to investigate the complexity of these mechanisms since IFNAR and IFNGR both ac
High resolution characterization of bacterial chromosome structuring – HiResBaCS
The main goal of HiResBaCS is to unravel the interplay between the multiple levels of organization of bacterial chromosomes and the impact of this organization on the regulation of DNA-management functions such as gene expression, DNA replication, and segregation. To achieve this general goal, the p
Structure, Activity and Genome-wide Analysis of the SAGA co-activator – SAGA2
Our objective is to decipher the structure and the function of the transcriptional coactivator SAGA in regulated gene expression by combining cryo-electron microscopy, genome wide transcriptional profiling and in vivo mutational analysis. Regulation of gene expression at the transcriptional level is
Ribosome Fidelity and Structure studied by X-ray analysis. – RFS
Protein synthesis is a tightly regulated cellular process that affects growth, reproduction, and survival in response to both intrinsic and extrinsic cues. Molecular mechanisms responsible for differences in longevity between living organisms are largely unknown, but it was shown that it is related
Molecular basis of rhabdovirus entry into the host cell – MoBaRhE
The objective of this project is to characterize the molecular bases of the rhabdoviruses entry into their host cell. It comprises two axes aimed at: 1) Investigating the interaction between vesicular stomatitis virus (VSV) and rabies virus (RAV) glycoprotein and their identified receptors (LDL-LLD
New light-driven channels and transporters for optogenetics – NEWOPTOGENETICSTOOLS
Optogenetics is one of the most important technological recent advances in biology. It revolutionized our ability to study the mechanisms of processes in neuronal circuits, promising new approaches to the treatment of different diseases and handicaps. The core tools of optogenetics are light-driven
Ribosomal RNA maturation and its link to quality control of ribosome assembly – ARNr-QC
Ribosomes, the large ribonucleo-protein complexes that carry out protein synthesis, are essential for life. In rapidly growing cells, the biosynthesis of ribosomes accounts for most of cellular transcription and consumes a major portion of the cell's energy. Mistakes in ribosome assembly are thus un
Development and application of high-speed force spectroscopy for biology – BioHSFS
The development of nanotechnologies opened the field of single biomolecule mechanics. Atomic force microscopy (AFM) combines force measurements and imaging capabilities with piconewton sensitivity and nanometer resolution. However, the response time in force is still limited to the millisecond times
Investigating Biomolecular Interactions by PICOsecond Fluorescence in PICOliters – PICO2
Biomolecular interactions are characterized by structural heterogeneity, i.e. coexistence of different conformers, and structural dynamics over time scales from picoseconds to over minutes. The detailed investigation of these interactions is of essential biological relevance for the design of new th
NMR studies of the role of intrinsic disorder in mitogen- activated protein kinase cell signalling pathways – NMRSignal
Over the last decade, classical structural biology has experienced a shift towards a more dynamic paradigm with the realization that a protein can be fully functional even in the absence of a stable, folded structure. It is estimated that up to 40% of the proteins encoded by the human genome are int
Biochemical and Structural characterization of MnmE/MnmG and GTPBP3/MTO1 protein complexes involved in redox modifications of bacterial and human tRNAs – MiGRATe
We choose to focus our project on MnmEG and GTPBP3/MTO1complexes for several reasons: The reaction mechanism catalyzed by MnmEG is still a matter of discussion. Regarding GTPBP3/MTO1, nothing has been done in the biochemical and structural characterizations. This reaction is performed by a protein
Principles of molecular recognition between Polycomb protein SCML2A and human long-non coding RNAs – lincRNPs
Polycomb repressive complexes 1 (PRC1) and 2 (PRC2) are evolutionary conserved regulators of embryogenesis and stem cell differentiation. They repress transcription by marking chromatin at key positions of target genes with chemical modifications, such as ubiquitination and methylation, respectively
Basal body anchoring in ciliogenesis: structure-function analysis – ANCHOR
we propose multi-disciplinary approaches, combining biochemical, molecular and cell biology techniques with cryo-electron and STEM tomography. We plan: 1) to identify interacting protein partners involved in the anchoring process using the proximity dependent biotin identification (BioID) technique
Characterization and physiological importance of ubiquinone biosynthesis in different oxygen tensions – (An)aeroUbi
E. coli, like many microorganisms, is a facultative anaerobe: it can grow under anaerobic (absence of dioxygen) or aerobic conditions in order to adapt to the varying oxygen tensions met in different environments. Ubiquinone (UQ) is known to contribute to aerobic metabolism but is also produced in a
Toward an Integrated View of Transcription Terminator Rho Functions and Mechanisms – IntegRhoMe
The emergence of hyper-virulent and/or multi-drug-resistant bacteria calls for renewed efforts to understand the mechanisms that allow bacteria to evolve by incorporating and expressing foreign genes. Improving such understanding is an obligate step toward the development of alternative antibacteria
Unraveling the Cross-Talk between Chromatin and Protein Homeostasis Combining Coevolution and High-throughput Interfaces Perturbations for Structural Biology. – CHIPSeT
It will first focus on newly discovered physical interactions ensuring the cross-talk between chromatin remodelers (INO80) and proteostasis pathways (Cdc48/VCP/p97). Combining large scale proteomic screens and genome-wide CHIP-seq technologies, partner 2 found that both machineries act in a concerte
Label-free (N)on-(L)inear (O)ptical Imaging of (M)etabolism and (M)yelin distribution in (I)ntact (T)issues – NLOMMIT
Multiple Sclerosis (MS) induces destruction of intrinsically normal myelin (demyelination) and disrupts cellular metabolism leading to neurodegeneration. Myelin is an ubiquitous lipidic structure within the nervous system essential for the normal conduction of impulses along axons and the energetic
Assembly of MHC class II molecules: A structural investigation of protein-protein and protein-lipid interactions within the membrane bilayer – InMembrane
The function of membrane proteins depends on interactions both inside and outside the lipid bilayers into which they are embedded. While protein-protein interaction modules within the membrane are described, much less is known about specific interactions of protein transmembrane domains (TMDs) with