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The overall goal of FluTranscript is to provide a detailed and integrated mechanistic description of viral transcription in vitro and in the cellular context. To achieve this ambitious goal, the Cusack and Naffakh groups will combine their highly complementary expertise in structural biology and mol

The aim of the TOMOCHIKV program is to provide the first functional and structural information on Chikungunya virus (CHIKV) replication organelles. These compartments, derived from the plasma membrane, provide a structural framework for the viral replication machinery, concentrate the viral and cel

Our consortium aims at characterizing a lysosomal transporter involved in nutrient recycling and nutrient sensing using biochemical and biophysical approaches. This work is in progress. This project should help understand the mechanisms underlying the metabolic and signaling roles of lysosomes in he

In that context, the purpose of the project is to decipher how HS biosynthetic enzymes associate to each other to form «nanomachines« committed to specific HS motif assembly. For that purpose we gathered a complementary consortium with the aim to express the HS biosynthetic enzymes, analyze their in

The objectives of this program are to be able to record the different conformational changes of the mGlu2 receptor. This receptor consists of two subunits, and each of them is made of «main structured domains: the binding domain, the cysteine-rich linker, and the membrane domain. We want to record t

In this project, we propose to understand how IntraFlagellar Transport (IFT) proteins, that recently emerged as having both ciliary and non-ciliary functions, at different stages of the cell cycle, could regulate the activity and organization of microtubules and their associated motors. Indeed, desp

Pathogenic microorganisms produce various virulence factors that are responsible for the damage inflicted to the host or that support the colonization of the patient. These pathogenic determinants are viable pharmaceutical targets. Anti-virulence drugs should reduce antibiotic use and, ultimately, d

This project will allow for the first time to characterize with high precision the dynamics of the T4P machinery in action. The methods developed will be broadly applicable to other biological systems. Since the T4P machinery is highly involved in the virulence of numerous bacterial pathogens, the o

Anti-CRISPR-Cas9 proteins are used by bacteriophages (phages) to defend themselves against the CRISPR-Cas9 adaptive immune system of their hosts. The striking sequence diversity of anti-CRISPR-Cas9 proteins identified so far and the absence of homologs with known function raise questions relating to

The ambitious goal of the Nipah-C project is to (i) obtain a structure-based model to explain the functions of NiV C, (ii) to determine the importance of these functions for NiV replication, immune escape and pathogenesis and (iii) to better understand the interdependence in expression of proteins c

There are two main objectives: 1) Identification of lipids compatible with binding using a liposome binding assays 2) Structural characterization of lipids required for fusion either by co-crystallization in presence of lipids with short-acyl chains, or in presence of detergents. We also plan to c

The study of adenoviruses in subgroup B2 is interesting from two points of view. On the one hand, they are responsible for sometimes fatal respiratory infections requiring epidemiological surveillance and, on the other hand, they are used as oncolytic vectors in phase II clinical trials. The discove

By combining fast affinity purification and quantitative mass spectrometry, we recently made a breakthrough in understanding NMD mechanisms. Our approach unambigu­ously demonstrated the existence of two mutually exclusive and successive protein complexes that both contain Upf1. We named the complex

The aim of this project is to decipher the structure and function of the Tol and Ton complexes present in various Gram-negative bacteria, two membrane proteins complexes that transmit energy across the cell envelope. These complexes are involved in essential functions such as nutrient importation, c

Molecular mechanism of DNA breaks formation during meiosis Sexual reproduction requires a specialized type of cell division called meiosis that allows the conversion of diploid cells into haploid gametes. In most species, this requires a specific program of DNA double strand break (DSB) formation

Translational control of gene expression plays a crucial role in the response to stress by blocking translation of most mRNAs. However, alternative translation mechanisms allow enhanced expression of a small group of mRNAs involved in cell survival. This occurs in pathologies such as ischemic heart

Pseudomonas aeruginosa is a causative agent of hospital- acquired infections, calling for the urgent development of new treatments. This grant builds on a very successful ANR project (ended Oct 2017) in which Partner 1 structurally and functionally characterized the first complex between a PBP and a

Bacterial cell division is a temporally and spatially regulated process coordinated by a multi-protein complex called the divisome. The assembly of the divisome is initiated and organized by a highly conserved bacterial protein, the bacterial tubulin homologue FtsZ, which polymerizes to form a dynam

Fatty acid photodecarboxylase (FAP) is a photoenzyme recently discovered and characterized by the coordinator and a partner of this proposal (Sorigué et al. 2017 Science 357:903). FAP catalyses the light-driven decarboxylation of fatty acids into hydrocarbons and CO2. It is only the third photoenzym

The accumulation of stalled and defective ribosomes is induced by stress and is associated with ageing and with many diseases. Understanding how cells get rid of defective ribosomes represent a major challenge in fundamental biology and biomedicine. The PROTE-IN project addresses this pivotal quest

A challenge in modern biology is to understand how circuits of proteins enable cells to monitor information from their environment and make decisions to mount efficient responses. Small GTPases are among the most prominent actors in cellular pathways, and they are involved in the regulation of virtu

The threonylcarbamoylation of the N6 nitrogen of the adenosine at position 37 (t6A) of ANN-accepting tRNAs is necessary for translation initiation and translational efficiency. The biosynthesis proceeds in two steps: YRDC/Sua5 first synthesizes a threonylcarbamoyl (TC)-AMP intermediate, and then the

The Orange Carotenoid Protein (OCP) is modular photoactive protein involved in cyanobacterial photoprotection. Strong blue light induces carotenoid and protein conformational changes causing a spectral shift and leading to carotenoid translocation and separation of two domains. These characteristics

Membrane proteins (MPs) account for 25-30% of proteomes. Their key role in signaling and transport make them the target of 70% of the current drugs and -estimated- 80% of the future ones . Knowing their 3D-structure is a mandatory step for rational drug design, requiring the extraction of MPs from t

Pentameric ligand-gated ion channels (pLGICs) are transmembrane protein assemblies that mediate neuronal signaling by opening an ion pore in response to the binding of a chemical messenger. Understanding their function at an atomic level of detail is key for the development of drug therapies against

Lipid droplets (LDs) are the primary organelles regulating cellular lipid fluxes. They play a central role in cellular lipid/energy metabolism and are thus, by essence, directly implicated in a variety of metabolic disorders linked to obesity, such as type II diabetes, cardiovascular diseases, or li

In all organisms, DNA transcription is controlled by proteins called transcription factors (TFs) that recognize and bind to specific promoter DNA sequences. Many microbes have TFs that contain either cubane [4Fe-4S] or rhombic [2Fe-2S] clusters capable of sensing changes in their environment. Althou

Exploring biomolecules in the context of their intracellular environment has been recognized as being the gold standard to approach the complexity of the cellular milieu. Therefore, obtaining a holistic understanding of protein function requires to probe structural dynamics of proteins and protein i