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Manipulation of membrane traffic by bacterial pathogens – Bacterial-Tactics
Characterize the structural and biochemical determinants of toxins from bacterial pathogens that hijack small GTPases pathways; study their interactions at the surface of membarnes We study proteins from Legionella pneumophila et de Coxiella burnetti. We have characterized structural features, inter
Deciphering early and late stages of mammalian mitochondrial Fe-S cluster assembly. – FRATISCA
Objective 1: To obtain an integrated vision of the molecular mechanisms of the initial stage of mitochondrial Fe-S cluster assembly. In particular, we aim at determining the role of frataxin during the formation of Fe-S cluster on the scaffold ISCU. Objective 2: To obtain an integrated vision of t
Imaging and modeling the Bacterial Mitosis – IBM
Our goals are to unravel the in vivo organization and dynamics of the nucleoprotein complex and of the Walker A cytomotive ATPase responsible for DNA segregation, using a minimalistic and representative bacterial segregation system, the ParABS system of the F-plasmid. To achieve this goal, we will u
Biological and synthetic nanostructures investigated by solid-state Nuclear Magnetic Resonance – NanoSSNMR
The design of new architectures and especially the tuning of their properties is a formidable task that requires understanding and ultimately controlling the thermodynamic and kinetic parameters associated with the molecular assembly / disassembly process. Non-covalent weak interactions - e.g. van d
Role of H1 and his partners in the structure and epigenetic properties of chromatin – ChromComp
Our genetic heritage goes far beyond the sequence of our genome. Our development, phenotypical characteristics and cellular functions depend critically on the way the genetic information encoded by DNA is packaged and organized into chromatin within the nucleus. The fundamental unit of this organiza
Massive Parallelization of STED Nanoscopy to study the fast spatiotemporal orchestration of proteins in cell adhesion – FastNano
Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on neighboring cells and extracellular matrices (ECM) cells control their microenvironment, shape and movement. I
RNA-protein and Protein-protein interactions within the replication complex of Influenza A Virus – RNAP-IAV
By handling RNA and by developing innovative biological, biophysical and structural tools, the two partners involved in the project want to address important questions relative to viral proliferation. Recent advances in generating high quality complexes of partly truncated PA-PB1 heterodimers are es
Trm112, a unique methyltransferase at the interface between ribosome synthesis and function – TrMTases
Over the past years, many of the factors regulating ribosome biosynthesis and translation have been identified, yielding to a better understanding of these processes. Several of these factors, either as single domains or isolated proteins, have been studied by functional and structural approaches. H
Direct measurements of mutation rates and mutation fitness effects in single living cells – SingleCellMutation
Use microfluidics, time-lapse microscopy, and Escherichia coli to study for the first time directly at the level of single cells the dynamics of appearance of spontaneous mutations and their effects on fitness. Characterize using this approach and non-parametrically the whole distribution of spontan
Zooming in on the conformational details of a membrane efflux pump – BmrA-NMX
In this project, we would like to contribute to a deeper understanding of conformational events which allow drug export from cells via ABC transporters. The questions we aim to answer are: • What are the key residues acting as conformational switches in the different conformational states involved
Structural and functional analyses of two membrane molecular motors present in Gram-negative bacteria. – BacMolMot
The project aims at deciphering the structure and function of the Tol and Ton complexes, two membrane protein complexes that transmit energy across the Gram-negative bacterial envelope. Tol and Ton transduce energy from the inner membrane (IM) to the outer membrane (OM) to assume essential functions
Molecular mechanism of lipid transport and its role in vesicle biogenesis – AsymLip
P4-ATPases are integral membrane transport proteins that catalyze active transport of lipids across membranes. P4-ATPases do not act alone in lipid translocation as they have been shown to physically interact with members of the Cdc50 protein family. The function of Cdc50 proteins in phospholipid tr
Functional and structural study to understand how CDPSs hijack aa-tRNAs for peptide synthesis – CDPS-hijacker
The unique properties of CDPSs make these enzymes an original and challenging subject of study. Many questions regarding the CDPS catalytic mechanism for cyclodipeptide formation and the molecular bases of the interactions between CDPSs and their aa-tRNA substrates remain to be addressed. CDPSs are
Type IV pili and pseudopili: structure, dynamics, assembly and molecular function – FiberSpace
The capacity of microorganisms to colonize and transform their environment is largely due to their ability to transport macromolecules and assemble surface organelles that promote motility and adhesion to substrates. In bacteria, type 4 pili (T4P) and type 2 secretion systems (T2SS) perform these fu
Mechanics of ESCRT-III catalyzed membrane fission – ESCRTfission
The structural and functional basis of ESCRT-III membrane remodeling is poorly understood. To provide more insight we propose to pursue the following three objectives: 1. The first objective is to solve the structure of the repeating unit of the 40Å-wide ESCRT-III filaments at high resolution, whic
Photostable probes for imaging proteins with high temporal resolution – Tag-light
Deciphering the complex mechanisms controlling cells and organisms requires effective imaging systems and fluorescent probes to observe and quantify biomolecules in real time with high spatiotemporal resolution. A common strategy for imaging proteins is to fuse them to peptide or protein sequences t
Structural studies of arrested ribosome nascent chain complexes prepared using a flexizyme-based approach – RiboFLEX
Ribosomes are large ribonucleoprotein complexes responsible for translating genetic information into protein in all living organisms. During translation, nascent polypeptides must transit through a long exit tunnel spanning the large subunit of the ribosome in order to reach the intracellular milieu
Hybrid Formal Modelling of Time for Circadian Clock Biology and Chronopharmacology – HYCLOCK
The general objective of HyClock project is (i) to offer the proof of principle that hybrid modelling outperforms classical formal methods for studying the properties of the mammalian circadian timing system and (ii) to apply this approach to better understand the circadian clock-cell cycle-cancer c
Mechanisms of error-free lesion tolerance – GENOBLOCK
We have two main objectives: 1) Pursuing the genetic study of DNA damage tolerance and understanding the molecular mechanisms of DA in bacteria. We expect to better understand the structure of a replication fork encountering a lesion and therefore the molecular mechanisms of lesion tolerance. Combin
Electrochemical Functional Imaging of Multi-Component Enzymatic Systems Organized on Virus Nano-Scaffolds – eVIRZYM
The major scientific goal of this project is to generate new insights into the way spatial organization modulates the efficiency of scaffolded multi-component enzymatic systems. To achieve this goal, experimental nanoscale enzymatic platforms need to be designed and their functional behavior interro
Combining optico-mechanical manipulations, high resolution microscopy and physical modelling to decipher the role of caveolae in mechanosignaling – DECAV-RECAV
Mechanotransduction, that is the translation of mechanical stimuli into biochemical signals, has emerged as a key event in several fundamental cellular aspects, including cell motility, growth and differentiation. How mechanotransduction couples the sensing of mechanical forces with specific cellula
A novel nicotianamine-based metallophore in pathogenic bacteria – ANIBAL
Ensuring the availability of a given metal for growth is a vital microbial process, especially critical when the source becomes scarce like inside a host. Here, we present a project that is dedicated to the study of an operon expected to encode the different functions required for the synthesis, exp
Mechanical connection between the actin cytoskeleton and the nucleus – Actin2Nucleus
In eukaryotic cells, the nucleus is physically connected to the cytoskeleton, which is fundamental for mechanical force transmission and required for multiple nucleus and chromosomes functions. A transmembrane protein of the nuclear envelope, nesprin-2, interacts with the actin cytoskeleton and is t
Reconstitution of the interface between microtubules and cortical actin – ReconstMT-Act
The interaction between microtubules and actin is indispensable for fundamental biological processes such as organ development or wound healing. Defects in proteins that link microtubules to actin are either lethal or cause diseases ranging from skin blistering to cancer. Thus, understanding the fun
P-body structure and assembly – PBODYSTRUC
A major limitation in understanding P-body function stems from their small size and scarcity, but also from the lack of purification protocol. Their known protein components were identified fortuitously or by trial and error, while their RNA content remains a complete blackbox. There is also no info
NMR view of tRNA maturation – NMR-VitAmin
The originality and the challenge of this project reside in the use of in-extracts and/or in-cell NMR to elucidate some critical aspects of tRNA biosynthesis and maturation under the conditions of a living cell. Our main objective is to perform, for the first time, a systematic study of the tRNA mat
Structure-function relationships of a family of histidine kinases controlling P. aeruginosa lifestyle – REGALAD
We plan to characterize the molecular bases dictating specificity in the detection and the H1 cytoplasmic transmitter domains of the four GacS/PA1611/LadS/RetS histidine kinases (HK) in P. aeruginosa to mediate heterodimer versus homodimer formation, an additional control mechanism compared to other
A multidimensional exploration of exoprotein transport and secretion by the type II secretion pathway – 4D-SECRETION
Pathogenic bacteria have developed highly sophisticated nano-machines to guarantee the efficient secretion of virulence factors. The type II secretion system (T2SS) is dedicated to the transport of folded proteins. We previously used in vitro biophysical and biochemical tools to reveal unprecedented