Search - Caractérisation des structures et relations structure-fonction des macro-molécules biologiques - 2022

The cell wall is important for bacterial survival and shape, and its biosynthetic mechanism is the target of antibiotics such as beta-lactams and vancomycin. The spread of resistant strains, however, has thwarted the usefulness of these drugs and calls for efforts towards the understanding of proces

Mitochondria coordinate central functions in the cell and have a crucial role in energy metabolism. Fatty acid ?-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are redox processes driven by mitochondrial protein complexes to generate ATP. How these pathways are coordinated remains unknown. A

Scientific background. The oligomerization of membrane proteins is required for signaling and trafficking functions in normal or diseased tissues. From a fundamental perspective, extensive theoretical work has been devoted to determine the physical mechanisms that drive this process, in particular m

An organism’s capacity to survive depends, at least in part, on its ability to sense and respond to sudden changes in its environment. This is particularly true for bacteria, that have devised a wide range of strategies to respond to stress, including the capacity to rapidly remodel and compact thei

In all living organisms, surface cell movements are essential for environmental exploration and multicellular development, and are also at the origin of cancer cell dissemination. In Bacteria, surface cell movements are mediated by a class of widespread nanomachines called Type-IV Pili (Tfp). Import

Endocytosis is the general mechanism by which cells internalize micronutrients and cell surface receptors. Importantly, viruses, toxins, and bacteria often hijack the endocytic machinery to access the host cell. Increasing evidence points out that unconventional endocytic mechanisms exist parallel

Synaptic dendritic spine formation is often defective in autism spectrum disorders (ASD) and intellectual disability (ID). Several Rho GTPases, and their RhoGEF activators, control synaptogenesis by regulating actin cytoskeleton dynamics. We established a novel functional link between the DOCKD fami

Red algae have sulfated galactans (carrageenans or agars) in their cell walls. The bicyclic 3,6-anhydro-D-galactose is found in carrageenans, its enantiomer, 3,6-anhydro-L-galactose, is found in agars. The 3,6-anhydro-bridge introduces strict structural constraints and thus the alpha-linkage is main

Non-vesicular lipid transport mediated by lipid transfer proteins (LTPs) at membrane contact sites (MCS) is emerging as a key mechanism to preserve the membrane identity of cellular organelles, especially in the case of mitochondria (Mito) and Lipid droplets (LDs) that are not integrated into the cl

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has re-emerged in many parts of Africa, Asia and America causing large-scale epidemics in the last decades. CHIKV is increasingly recognized as an important public health problem, due to rapid spread of infection that characterizes epidem

Interactions of proteins with nucleic acids are central in a large variety of biomolecular processes. When the nucleic acids and proteins form together large polymers, the underlying structural events remain poorly characterized, because of the complex choreography of combined polymerization and nuc

The emergence and the spread of antibiotic resistance are natural phenomena of bacterial adaptation to antimicrobial exposure. The last decades, the inappropriate use of antibiotics in human and veterinary medicine has accelerated these processes, leading to the emergence of pathogenic bacteria that

Fluorescence cell imaging benefited from the Green Fluorescent Protein revolution in the early 1990’s, which saw the development of genetically-encoded fluorophores covering the whole visible spectrum. 15 years later, another family of fluorescent proteins (FPs) were developed from the chromophore-b

The biggest challenge in the pharmaceutical industry R&D is preclinical drug target validation. A poorly selected target?often due to poor probes used in target validation assays?is the main source of failure in drug development. This project aims to determine whether transmembrane ceramidases could

Cellular mRNAs bind to the ribosome during translation initiation and are involved in the regulation of protein synthesis in different manners. While translation initiation in eukaryotes mainly takes place through a cap-dependent process, 10% of human mRNAs, coding for key regulators of cell physiol

Serial electron diffraction (SED) and serial synchrotron nano-crystallography (nano-SSX) are just-emerging methods in structural biology, whereby data are collected from protein nanocrystals using a sub-micron-sized electron or X-ray beam, respectively. These methods are set to lead the future of na

Glucocorticoids (GC) are widely prescribed drugs for chronic inflammatory conditions, including rheumatoid arthritis, multiple sclerosis and asthma that have revolutionized the field of medicine. However, long-term treatments have important side effects as they induce diabetes, osteoporosis and musc

The bacterial ribosome is a major antibiotic target. Although drugs that target the ribosome have largely been regarded as general inhibitors of translation that prevent the synthesis of all proteins with the same efficiency, a more nuanced view of antibiotic action has emerged in recent years. Inde

Multidrug efflux pumps are major players in antibiotic resistance. Despite a better understanding of their global functioning mechanism, how they work in vivo (with respect to the bio-availability and partition of the drugs in the bacteria) and what is their intimate molecular mechanism (spectrum of

Post-translational modifications provide proteins with an extended repertoire to modulate their stability and function. A new modification of the eEF1A translation elongation factor: glutaminylation of a single glutamate, was reported recently. The synthesis, function and distribution of this origin

Transcription initiation is a major regulatory step in eukaryotic gene expression. The DNA in eukaryotic cells is organized into chromatin, a highly conserved polymer that controls many crucial functions of the genome. The accessibility of DNA to the transcription machinery is regulated by the degre

The entry of enveloped viruses is achieved by the fusion of viral and cellular membranes, a critical step in infection that provides targets for vaccines and therapeutics. Viral fusion is catalyzed by a specific protein termed fusion protein, which associate with other proteins on the viral surface

Lyssaviruses (LYSV) are enveloped viruses that belong to the Rhabdoviridae family. LYSV cause deadly encephalitis, and rabies virus (RABV), the most famous of this genus, is responsible for 59000 annual deaths. Lyssaviruses are divergent enough to escape the immune response induced by current anti-r

In addition to their degradative role, lysosomes act as signaling hubs which sense and signal internal cues, such as intracellular amino acids, to coordinate cell responses. A well-characterized example is the activation of the mechanistic target of rapamycin complex 1 (mTORC1), a master growth regu

We propose to elucidate structure and function of the poxvirus DNA replication machinery by single particle cryo-electron microscopy (cryo-EM). The poxvirus family comprises members with a strong potential of spillover from the animal kingdom, such as cowpox and monkeypox, which leads to local epide

Iron-sulfur (Fe-S) centers are protein cofactors involved in a multitude of essential biological processes. They are synthesized by highly conserved multi-protein machineries via a still elusive multi-step process. Due to their critical roles, any defect in their biogenesis leads to severe diseases

The Bacteroidetes phylum is a dominant member of the Human gut microbiota, where it has a key role in regulating its composition and maintaining good health. Many of these bacteria harbor a type VI secretion system (T6SSiii) that delivers protein effectors to other bacteria. This allows commensals t

Cells established a spectacular protein network that enables them to receive and process signals. Among the essential proteins orchestrating signaling, the family of small GTPases plays a central role by functioning as molecular switches that alternate between an inactive form bound to GDP and an ac

Photo-switchable fluorescent protein markers provide crucial tools for a wide range of applications in advanced fluorescence microscopy such as super-resolution and multiplexed microscopies. A major challenge for the optimal use of these molecules in cellular applications is the dependency of their

Microtubules (MTs) are cytoskeletal elements that are essential to a variety of functions, including cell motility, compartmentalization and division, that they ensure thanks to their dynamic instability. We recently developed a new method based on dual-axis cryo-electron tomography followed by segm

The alpha-beta-tubulin heterodimer protein is the microtubule building block. The hydrolysis of the GTP molecule bound to the beta subunit that accompanies assembly makes microtubules intrinsically dynamic. This dynamics is controlled in the cell by several families of regulatory proteins, most of t

Silver antimicrobial properties have been used for thousands of years, from the Chaldeans as early as 4000 B.C.E. Despite this long-standing history and its demonstrated activity against Gram-negative bacteria, the complete bactericidal mode of action of silver remains unclear. To counteract the tox