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Deep learning-powered functional analysis of the membrane-bound DNA entry gate for bacterial natural transformation – DeepTransfo
Horizontal gene transfer through natural transformation (NT) is a major driver of bacterial evolution. In many pathogenic species, it is the main mechanism for the spreading of antibiotic resistances and virulence factors. Despite the importance of NT in bacterial pathogenesis, many players and aspe
Allosteric modulation of GPCR conformational ensembles and signaling selectivity by the cellular environment – DYNALAND
G protein coupled receptors (GPCRs) are the largest family of membrane receptors for hormones and neurotransmitters. As such, they are also major targets for new therapeutics for a broad spectrum of indications including cancer, inflammatory, cardiovascular, respiratory and gastrointestinal diseases
Searching for the ancestral Iron-Sulfur Biogenesis systems – First-FeS
Iron-sulfur (Fe-S) clusters are ancient and ubiquitous protein cofactors essential for life. It is thought that Fe-S clusters spontaneously assembled in the early Earth anaerobic environment rich in iron and sulfur. Rise of oxygen levels (after oxygenic photosynthesis) would have yield to unfavorabl
Programming condensates to sequester lipid droplets in cells and control their metabolism – ControLD
Lipid droplets (LDs) are unusual cellular organelles that are at the nexus of cellular lipid metabolism. In addition to carbon and energy storage, they play major roles in various processes such as lipid metabolism, protein storage and degradation, as well as resistance to biotic and abiotic stress.
The ForCE molybdoenzymes: New opportunities for CO2 reduction – FORCE
Formate dehydrogenases (FDHs) catalyze the reversible oxidation of formate into CO2 and can be used as biocatalysts in carbon capture and in CO2 conversion. They harbor molybdenum or tungsten at the active site as well as [Fe-S] cluster(s). Importantly, the reaction mechanism for FDHs remains unclea
Chemical Biology for the Functional Exploration of Antibiotic Targets – ChemBioTic
Modern medicine relies on the efficacy of antibiotherapy which is compromised by the emergence of bacterial resistance often due to modifications of drug targets, such as the penicillin-binding proteins (PBPs) and L,D-transpeptidases (Ldts). These essential enzymes catalyze the cross-linking step of
Biochemical Cycle of Uranium in Bone and Kidney – BioCUBK
Uranium (U) is a non-essential heavy metal widely distributed in the environment due to its natural occurrence and its use in various human activities, including nuclear power plants. Natural U exerts chemical toxicity on its target organs, the two main ones being the kidney and the skeleton. To dat
An integrated view on the mycobacterial Rho-dependent transcription termination (RDTT) machinery: groundwork for future pathogen-specific therapeutics – MYCRHO
Transcription termination mediated by the ATP/RNA-dependent motor protein Rho (RDTT) is an essential regulatory mechanism in many bacteria. RDTT is specific to bacteria and thus constitutes an attractive target for the development of antibacterial prophylactic/therapeutic strategies. Our understandi
Zinc-Responsive Bioinspired Magnetic Resonance Imaging Contrast Agents – ZINC-ESPIONAGE
Imbalance of zinc homeostasis is associated to several diseases. It would be highly interesting to image zinc by a non-invasive technique for early diagnosis of these diseases. The ZINC-ESPIONAGE project aims at developing novel bioinspired contrast agents for the detection of zinc by MRI. The propo
Targeting Aminoacyl-tRNA Synthetases of Pathogenic Gram-positive Bacteria To Fight Antibiotic Resistance – BoronTrap
Pathogenic bacteria represent a worldwide public health concern, not only because of the frequency of infections but also because of the phenomena of drug resistance. Today, it is estimated that more than 50% of infections in intensive care units are caused by bacterial pathogens. Here we will focus
Chemical genetics tools for investigating DNA junctions – InJUNCTION
Alternative nucleic acid structures encompass all DNA structures that deviate from the canonical Watson-Crick double helix, or duplex-DNA. These structures are currently being actively studied to understand where, when and how they fold in human cells and to identify the biological processes they ar
Functional and molecular exploration of the carbohydrate sulfatases diversity – S-PLORE
Sulfated polysaccharides found in micro- and macro-algae (i.e. agars, carrageenan etc.) or secreted by marine bacteria represent the most abundant marine biomass. Even though, they are less abundant in terrestrial organism, sulfated polysaccharides are involved in many biological pathways (e.g. glyc
Host glycan breakdown by fungal CAZymes from the human gut MYCobiota – CAZyMYC
The human gut microbiota (HGM) is a complex community of microorganisms, which plays a major role in many aspects of human health. Notably, it is now established that the HGM is involved in the shaping of the intestinal epithelium and maintenance of its integrity, energy harvesting, regulation of h
The membrane hypothesis of schizophrenia and receptor oligomer theory: investigations at the membrane level – SCHIZOLIP
Schizophrenia is a severe psychiatric disease, that affects more than 23 million persons in the world and close to 600 000 in France. That represents around 1% of the global population, with men being more affected than women. Schizophrenia is characterized by psychopathological, cognitive, and neur
Ultra-Fast Fluorescent Turn-ON Detection of Bacteria with Targeted Bioconjugates – ULTRON
Infectious diseases are the third cause of mortality and the first cause of morbidity in the world. Advanced methods for fast and sensitive detection and phenotyping of pathogenic bacteria in patient specimens are urgently needed to implement the precision medicine approach, where personalized anti-
Photosynthesis redox regulation in microalgae revealed by in-cell real-time Nuclear Magnetic Resonance – PhotOxIN
CO2 assimilation in the Calvin-Benson-Basham (CBB) cycle is dependent on light and the availability of ATP and NADPH, produced upon the photochemical phase of photosynthesis. It is inhibited in the dark by the oxidation of thiol groups of some of CBB enzymes, by pH shift, and by proteins-proteins in
Rational approaches to disrupt the functioning of the replication machinery of Respiratory Syncytial Virus – RSV-RAPstop
Human Respiratory Syncytial Virus (RSV) is the main viral agent responsible for bronchiolitis in young children. This virus is also recognise as a major pathogen of elderly and immunocompromised persons, responsible for acute respiratory infections (pneumonia). Despite the impact of these infections
Role of the interaction of gangliosides with synaptotagmin in nerve terminal exo-endocytosis – RoSane
Synaptotagmin is a synaptic vesicle protein that regulates neurotransmission. The poorly studied intravesicular domain of this protein is transitorily exposed to the extracellular milieu upon exocytosis. We recently identified a direct interaction of this domain with glycolipids of the neuronal plas
Targeted environment-sensitive fluorescent probes for biomolecular condensates – PROBIC
Biomolecular condensates (BCs) are microscopic intracellular fluidic bodies that are formed by certain proteins and RNAs in the process known as liquid-liquid phase separation (LLPS). Biomolecular condensates play many roles in normal cell physiology and homeostasis, whereas misregulation of LLPS ha
Towards more selective compounds targeting a prototypal GPCR, the V2 vasopressin receptor – V2Cure
G protein-coupled receptors (GPCRs) are key players in intercellular communication. Agonist binding promotes the recruitment of two major intracellular proteins, G proteins and Arrestins, which activate two distinct signaling pathways. "Biased" agonists can selectively activate one pathway with the
Expansion of the phosphoinositide toolbox to decipher class II PI3K biological functions – NEWPI
Phosphoinositides (PIs) are quantitatively minor phospholipids of cell membranes, yet involved in almost all aspects of a cell’s functions. PIs have a highly active metabolism strictly controlled by a set of phospholipases, kinases and phosphatases. Importantly, PIs mediate their effect by recruitin
Analysis of the relationship between the new snoRNA-jouvence in the gut, the metabolism, the neurodegeneration, and the lifespan – Aging-jou
Aging, longevity, and metabolic disorders are major concerns of public health. They result of complex biological processes of accumulation of different damages at molecular, cellular, tissue and organ levels. This leads to the perturbation of certain physiological functions increasing the vulnerabil
Single Granule oMics to support starch synthetic biochemistry – SinGraMics
Starch is a main storage form of carbon for plants. It is composed by glucose polymers forming water insoluble granules that harbour a wide range of sizes and morphologies regarding to their origin (e.g., plant species, organs, tissues, cells). In addition, starch granules contain minor fractions of
IRon Uptake Pathways in Pseudomonas aeruginosa: phenotypic switches and mechanism of regulation – IRUPP
One of the bottlenecks in antibiotic development is the ability of the drugs to enter bacteria. Iron uptake pathways are considered as promising gates for the import of antibiotics into bacteria and a nice example is the Cefiderocol developed and commercialized by Shionogi. To access iron, an essent
Photosynthetic energy networks for the functioning and regulation of the algal CCM – AlgalCCM
Microalgae account for nearly half of the CO2 annually fixed by the Earth’s ecosystems. Because CO2 diffusion is slow in water and the CO2-fixing enzyme of photosynthesis (Rubisco) has a low affinity for CO2, the efficiency of microalgal photosynthesis greatly depends on a mechanism that concentrate
[Fe-S]-dependent tRNA sulfuration and cellular stress – sulfo-tRNA
Post-transcriptional modifications of transfer RNA (tRNA) are essential for translational fidelity and their regulation is critical for adaptation and cell survival, notably under stress conditions. We will focus on sulfuration of uridine at position 34 in tRNA, catalyzed by MnmA-type enzymes (named
Deciphering the nuclear receptor NHR-8 metabolic functions in Parasitic nematodes to overcome Anti-infectious drug Resistance – DePAR
Resistance to ivermectin (IVM), the most important broad-spectrum antiparasitic drug in use today, is widespread in parasites to the extent that it compromises successful control of human and animal parasites. We identified the orphan nuclear receptor NHR-8 of nematodes, known as a key player in cho
Integrative structural and functional study of the two major histidine kinases controlling PA infection modes – TARGETS
Pseudomonas aeruginosa (PA) is a major human opportunistic pathogen. It causes infections in immune-compromised patients, cystic fibrosis patients and is responsible for many nosocomial infections worldwide. PA provokes acute and chronic infections. The choice between these two modes of infection de
Tuning the shape of wall-less minimal cells: From spheres to helices – WallesShape
Understanding fundamental mechanisms of cell shape maintenance would enable to get novel insights into basic cell processes such as division or resistance to stress. In most bacteria, the cell wall plays a prominent role in cell shape determination and complicates studies aimed at deciphering the ro
Regulation of cellular sphingomyelin dynamics – SPHINGODYNA
Our body contains thousands of different lipid species. These lipids are not randomly distributed in a cell. Even in one membrane, the lipid composition of the outer and inner leaflets of the lipid bilayer is different. However, how this asymmetry is built, maintained and regulated remains poorly un
Full affinity mapping of the Human PDZ-PBM interactome and interactome-phenotype relationship of the viral HPV oncoprotein E6. – Full-PDZ-PBM-HPVE6
Many protein-protein interactions boil down to domain-motif interactomes. For instance, in human, the 266 PDZ domains (the PDZome) and their 4000 putative C-terminal PBMs (PDZ-Binding Motifs) mostly situated at the C-termini of partner proteins define a network of one million potential interactions,
Fluorinated foldamers: synthesis, structuration and capacity to interact with amyloid proteins and biomembranes – FluFOLD
FluFOLD aims to design and synthesize fluorinated peptidomimetic foldamers which have so far been under-explored in organic chemistry and unexploited in medicinal chemistry. The effects of the rational assembling of specific and original fluorinated amino acids in foldamers will be evaluated for the
Selective single-cell transcriptomic analysis of targeted cells – Sel-scRNA-seq
Studying populations of cells at the single-cell level is essential to fully understand normal function and disease in humans, or any other multicellular organism. The ability to analyze transcriptomes by single-cell RNA sequencing (scRNA-seq) is revolutionizing cell biology. For, example, in cancer
Multivalent chondroitin sulfate oligosaccharides targeting cathepsin K exosites – MODULATE
Osteoporosis is a metabolic bone disease affecting around 200 million people worldwide in which the density and quality of bone are reduced. Human cathepsin K (Cat K) is the major bone-degrading protease. It is a multifunctional protease having, among others, a unique potent collagenase activity tow
Unlocking bioactive microbial products discovery through synthetic biology – UMISYN
Secondary metabolites (SMs) produced by microorganisms have been a critical source of bioactive molecules, with applications in diverse therapeutic areas, from infectious diseases to cancer. Despite an enormous unexplored diversity, discovering new SMs has become increasingly difficult. Genomic tech
Deciphering the Minimal Metalloproteome Essential to Mycoplasma Survival – MIMESIS
Transition metals are required by all life forms to carry out central functions necessary for survival. Moreover, they are at the heart of the host-pathogen battle as the host immune system sequesters essential metals from pathogens. In order to acquire metals and maintain their metal homeostasis, m
Influence of intestinal microbiota metabolic cross-talk on host metabolic allocation during animal juvenile growth – MicroMetabo
The gut microbiota shapes animal growth trajectory in different nutritional environment. Despite recent progresses, the molecular mechanisms behind such mutualism remain poorly understood. This is partly due to the fact that the gut microbiota is a complex ecosystem, mostly composed of bacteria, whi
Enlightening cell migration through the development and applications of photoresponsive molecules to remodel actin networks – SwitchActin
The actin cytoskeleton controls cell shape and motility. A myriad of actin-binding proteins govern the polymerization of globular actin into filaments. To study the role of the actin cytoskeleton in various biological processes, natural and synthetic small molecules are used by biologists. Besides,
Building stimuli-responsive primitive cells – ResponCell
Despite being self-sustaining units of life, cells do not live in isolation. Due to selective membrane permeability, cell survival depends on the ability of membrane-bound biological machinery to regulate the active transport of solutes, process information received from the environment, and mediate
Metal-based Agents for Selective Amyloid Imaging – MASAI
Amyloid aggregates are associated with many pathologies, like Alzheimers’s disease (AD) or Type 2 diabetes (T2DM), respectively involving Abeta and amylin. Recent evidence indicates a link between these two diseases, likely mediated by “cross-seeding” processes when one amyloid protein promotes aggr
Ultrahigh-throughput functional screening of antimicrobial peptides against planktonic and biofilm producing bacteria – bioAMP
Antimicrobial resistance in pathogens has become an increasing burden for public health systems, and new therapeutical molecules are urgently needed to fight bacterial infections. Antimicrobial peptides (AMPs) are among the first line of defense against bacterial infections in all living organisms (
Post-Translational Mycoloylation – PTMyco
Post translational modifications (PTMs) are widespread in all forms of life, where they are critical to various aspects of cell physiology. Our project is focused on a newly characterized PTM specifically found in Corynebacteriales, an order of bacteria that includes numerous human pathogens, such
Phasing-in Protein Acetylation in Nuclear Proteostasis – NuPhAce
Protein misfolding is a constant threat to cellular health and is linked to pathologies. It has been recently demonstrated that misfolded nuclear proteins reversibly translocate into the nucleolus upon stress. This novel cell protective protein quality control pathway involving the nucleolus maintai
Characterization of a new class of ribosomally synthesized and post-translationally modified peptides (RiPPs) involved in resistance to copper – CuRiPP
Ribosomally synthesized post-translationally modified peptides, or RiPPs, display a tremendous diversity of structures and bio-activities. Most classes of RiPPs are produced by bacteria and mediate antagonistic or cooperative interactions between them or interactions with their environment. We have