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Mononegavirales such as Ebola, rabies, VSV and measles virus are non-segmented negative strand RNA viruses causing important public health threats. Although prophylactic or post exposure vaccination is available against a limited set of Mononegavirales, we lack antiviral molecules for the treatment
The homeostasis of the cell and its adaptation to environmental changes rely on tight and coordinated gene expression regulation occurring especially through pathways, which involve not only proteins but also non-coding RNAs. Identifying the different actors of a regulatory pathway but also its dyna
Bacterial elongation and division result from synthesis and remodeling of the peptidoglycan (PG), a three-dimensional sugar and peptide network that surrounds the cell. The PG confers a cell shape adapted to the ecological niche of the bacterium, allowing it to feed, move and multiply in an optimal
Ancestral Allostery
The goal of this project is to use the resurrection of ancestral proteins for investigating the genesis of allosteric regulation. As now accepted, a protein is not a static entity, on the contrary its structure fluctuates, and continuously explores a range of conformations. The relative occupancy of
Androgens and glucocorticoids are two steroid hormones that exert highly pleiotropic effects in mammals. Androgens control cell proliferation, development of sexual characteristics, behaviour and muscle mass and strength, whereas glucocorticoids control the circadian rhythm, glucose, lipid and prote
Most functional modules within the living cells consist of multimeric protein complexes organized into transient interaction networks. Thus, uncovering the structure and dynamics of proteins forming such networks is of critical importance for human health and disease. However, apprehending the macro
Translation and its control in Staphylococcus aureus: consequences on virulence and stress responses
Translational control has become a major attention during the last decade. In bacteria, the determination of the structures of ribosomes led to a better understanding of ribosome functioning and dynamics. New development of methodologies enabling unbiased characterization of the translatome, which r
G-quadruplex (G4) DNA consists in the formation, from guanine rich nucleic acids, of tetrameric structures resulting from the association, via Hoogsteen type hydrogen bonds, of guanine tetrads and their stacking. Numerous studies demonstrate the important biological role of G4, now considered to be
All cells in nature are covered with a dense coating of glycans occuring as modifications of proteins and lipids. This glycome is decoded by specific glycan-binding proteins such as lectins. Lectin-glycan interactions are essential to biological systems, not simply as the “glue” between cells, but a
In eukaryotic cells, the nuclear envelope (NE) isolates the genetic material from the rest of the cell. This double lipid bilayer comprises the inner (INM) and outer (ONM) nuclear membranes, separated by a lumen called perinuclear space (PNS). Anchored in the NE, nuclear pore complexes (NPCs) are th
The control of gene expression is crucial for cells to accurately produce functional proteins at the proper time and in the correct location. As a consequence, eukaryotic cells have evolved a finely tuned “gene-expression factory” that encompasses the routing of nascent transcripts through multimeri
Chaperone proteins are present in all living organisms and are essential to maintain protein homeostasis (also called proteostasis) in the cell. Chaperones are involved in almost every steps in the protein folding process. In particular, they allow the protection, folding, activation, disaggregation
After several decades of continued success of antibiotic therapy against bacterial infections, we are now facing an increasing threat: the accelerated evolution of antibiotic resistance in important human pathogens and the scarcity of new anti-infective drug families. For this reason development of
Microtubules are essential components of the cytoskeleton involved in fundamental processes such as intracellular trafficking or cell division. A large part of these functions is underpinned by their dynamic properties, which allow microtubules to switch rapidly between polymerization and depolymeri
Cells can be considered as reactors in which the continuous biochemical interactions between proteins represent the network of interaction forming the physical and chemical basis of cellular behaviours. On one side, the recent advent in super-resolution microscopy has revolutionized our understandin
Each year, 200 to 400 million clinical cases of malaria are reported globally, causing around 500 000 deaths, largely in the sub-Saharan continent. Plasmodium falciparum and, to a much lesser extent, P. vivax are the main causes of disease and death from malaria. An important difference between P. f
Our first objective is to determine the conformations of the formin FH2 dimer when it is interacting with the barbed end of an actin filament. Our results will be confronted to current predictions and will help understand how a formin can track the growing filament end. Our second objective is to c
Mycobacterium tuberculosis is a pathogen killing ~1.5 million people yearly. Development of a new therapeutic strategies and identification of the new drug targets necessitates understanding of the molecular mechanisms employed by bacteria to invade host and to survive antibiotic treatment. Virulenc
This project aims at performing a detailed functional and structural characterisation of the mitochondrial translation apparatus in Arabidopsis thaliana. The research on mitochondria attracts considerable attention because these organelles are responsible for the energy production through aerobic
Prior to 2014, there are no suitable µMAS techniques towards metabolomic studies owing to the difficulty of achieving superior spectral resolution (in the order of 0.02 ppm, a prime criterion in NMR-based metabolomics) without sacrificing the sensitivity. This is because of the necessity of spinning
In vivo determination of enzymatic parameters in a multistep synthetic pathway
Enzymatic reactions have long been analyzed in vitro, using pure enzymes and experimental conditions adapted to these measurements. Thanks to the large amount of data generated and collected with thousands of enzymes, enzymology has made enormous progress in understanding the properties of biocataly
Protein ubiquityation is catalyzed by tens of enzymes, termed E2s and E3s, that assemble different types of ubiquitin chains on their substrates. These enzymes interact with each other to form E2/E3 pairs, which constitute functional units. A small number of E2/E3 pairs have been characterized and w
To get a better insight into the structure of the outer cell wall of A. fumigatus, the FUNHYDRO project focuses on the study of the functional amyloids formed by three different hydrophobins named RodA, RodB and RodC. Our objectives are: (A) to describe the structure of the functional state of hydr
C1q-mediated efferocytosis: from molecular and cellular mechanisms to self-tolerance or autoimmunity
The C1q complement protein, first identified as a microbial sensor involved in innate immune defence, is now considered as a multifunctional protein with a prominent role in the safe clearance of altered self-elements. The C1qEffero project focuses on the particular role of C1q in the phagocytosis o
Post-translational protein modifications (PTMs) contribute to all aspects of cell physiology and are a primary source of protein functional diversity in mammalian cells. Such modifications add another layer of coded information that can finely tune the transmission of intracellular signaling. A high
Iron sulfur proteins in giant viruses to seek answers on the origin of life
The first "giant" virus, Mimivirus was discovered in 2003. Its capsid, easily visualized by light microscopy was found to contain a 1.2-Mb-genome as complex as that of many bacteria. In the last 5 years, 3 additional families of giant viruses have been discovered. The amphora-shaped Pandoraviridae h
Our main objectives are to understand : 1-How HSP90 collaborates with R2TP for assembly ? 2-What are the roles of the RUVBL1/2 ATPases ? *Our consortium has discovered the existence of a new R2TP-like co-chaperone, called R2SP (Maurizy et al., Nat Commun 2018). It comprises the proteins RUVBL1
In the context of increasing antibiotic resistance, we propose to gain fundamental knowledge on the biogenesis of the bacterial cell wall in an integrative approach. This project aims at filling the gap between inhibition studies on isolated molecular targets and studies on complete cells. It will p
How do bacteriophages perforate the bacterial cell wall?
Bacteriophages are the most abundant microorganisms in the biosphere. At the origin of major discoveries in modern molecular biology, their study is getting increasingly popular in fields as diverse as ecology, genetics, phylogeny and nanophysics. Moreover, medicine and animal health have a reawaken
Integral trans-membrane proteins are involved in different major cellular functions including e.g. cell homeostasis, cell bioenergetics and cell detoxification. Therefore their dysfunction is associated with serious human pathologies such as neurodegenerative diseases, cancer and virus infections. I
xx xx xx xx Protein quality control is a vital cellular process. Bacteria are exposed to oxidative stress, both endogenous and exogenous, which eventually damage macromolecules, in particular proteins. We recently identified a new enzymatic system, MsrPQ (standing for methionine sulfoxide reductase)
The ribosome is arguably one of the most ancient molecular machines given its universal function in protein synthesis. While its overall structure is remarkably conserved across the three kingdoms of life, ribosome production in eukaryotes has evolved into a more complex assembly process, which incl
Essential biological processes such as gene expression, DNA repair and replication require dynamic assembly and disassembly of nucleosomes. These processes involve several histone chaperones that handle and escort histones. The CAF-1 complex (Chromatin Assembly Factor 1) is the only histone chaperon