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The functions of all cells in the human body are regulated by hormones and neurotransmitters (extracellular messengers) and transmitted within the cell by intracellular messengers. Intracellular messengers include the nucleotides cyclic-AMP (cAMP) and cyclic-GMP (cGMP). In many diseases, the balance

Homologous enzymes are defined by a set of highly conserved “core” residues that are required for function. The catalytic properties (catalytic rates, Michaelis constants, susceptibility to inhibitors, and even bidirectionality) are frequently determined by non-conserved residues remote from the act

Human respiratory syncytial virus (hRSV) infections primarily affect infants, the elderly, and immunocompromised patients. They are a major cause of morbidity and mortality worldwide and represent a significant social and economic burden. However, we still lack a complete understanding of the key mo

Negamycin, a specialized metabolite of the hydrazine family, is produced by the actinobacterium Kitasatospora purpeofusca. In addition, two metabolites of the negamycin family, 3-epi-deoxynegamycin (3-Dneg) and leucyl-3-epi-deoxynegamycin (L-3-Dneg) produced by the actinobacterium Streptomyces goshi

Microglia are the brain resident immune cells that maintain brain homeostasis by responding to cytokines and eliminating substances by phagocytosis. Microglial activation and phagocytotic clearance of aggregated amyloid ß (Aß) and tau aggregates limits Alzheimer’s disease (AD) pathology. There is an

Understanding the chemical processes involved in enzymes is a challenge that requires, in most cases, the use of complementary experimental techniques. This knowledge is often crucial for the development of biotechnological applications. The aim of the IRMA application is to perform a precise struct

Recent studies conducted in the team of Pr Gilles Favre at the CRCT have highlighted a potential role of the small GTPase RHOB in the resistance to Epidermal Growth Factor Receptor (EGFR) therapies. RHOB overexpression reduces cell sensitivity to erlotinib in a dose-dependent manner by restoring cel

Therapeutic antibodies (Abs) are a very potent class of newly developed and approved drugs. The discovery and development of these large-size biologics require the characterization of endogenous Abs, which remains a difficult and tedious task. This key step includes the identification of the Abs’ am

SensiGut: Programmable bacterial biosensors for gut metabolites monitoring. Increasing evidence describes how gut microbiota influences human physiology. The emerging picture suggests that the interplay between the human genome and the microbiome is continuously regulating metabolic pathways and

Post-translational modifications dramatically expand the chemical repertoire of ribosome-synthesised polypeptides and enable otherwise inaccessible molecular functionalities. Some of them are remarkably conserved. For example, the universal ribosomal protein uS11, which in humans is involved in incu

Methanol is an attractive low-cost substrate for biotechnology. Although methanol-based cell factories have been established, there are still major gaps in understanding methylotrophy itself. Thus, limiting their use at industrial scale. In methylotrophic yeasts like Komagataella phaffii, the entire

Brown and beige adipocytes can generate heat from chemical energy, independently of canonical thermogenesis processes. These adipocytes feature a creatine-based adaptive thermogenesis process activated not only after short-term cold response and long-term cold acclimation, but also possibly by diet.

Nucleic acids (NA) form an essential class of macromolecules for storage, transmission and expression of the genetic information of a cell. While deoxyribonucleic acid (DNA) encodes the information cells need to make proteins, ribonucleic acid (RNA), conformationally more variable, play multiple cel

Context. Oligosaccharide fragments derived from pathogens, and those derived from host glycoconjugates, can be immunogenic. In mammalian cells, free oligosaccharides (fOS) are produced normally during the biosynthesis of N-glycoproteins in the endoplasmic reticulum (ER), but under certain circumstan

The aim of this project is to expand the chemical universe of biopolymers used for aptamer synthesis, selection and amplification, by using a much larger library of elementary bricks modified on the nucleobase. The resulting aptamers will have an increased stability and specificity. The choice of b

G Protein-Coupled Receptors (GPCRs) are central players in the complex relationship of inter-cellular signaling. They act in concert by activating and influencing each other according to the context or the pathology in a complex web whose figures and meanings remain, even today, often indecipherable

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) affects 10 million people each year and the emergence of resistant TB augurs for a growing incidence. In the last 60 years, only three new drugs were approved for TB treatment, for which resistances are already emerging. Therefore, there i

Glycosaminoglycans (GAGs) are essential biopolymers attached to core-proteins of proteoglycans (PGs), that perform multiple structural and regulatory functions in cell and tissues of multicellular organisms. They are synthesized by the coordinated action of glycosyltransferases (GTs) and partners, w

Insulin resistance (IR) plays a major role in the pathophysiology of type 2 diabetes (T2D) and is mediated by a phenomenon called lipotoxicity. With overweight, excess fatty acids (FA) accumulate in peripheral tissues like muscle, and are metabolized into sphingolipid derivatives such as ceramides (

Excessive inflammation can occur in response to infection and is a hallmark of several diseases. Effective drugs against acute forms of inflammation are scarce. Our data reported an uptake of copper via CD44 by inflammatory macrophages. We identified that mitochondrial copper(II) catalyzes the reduc

The plasma membrane (PM) and the plant cell wall (CW) form together an exocellular continuum that acts as a dynamic barrier against environmental threats. The properties of the PM and the plant CW have been studied independently for several decades but increasing evidence indicates that a continuous

Cyclophilins are a family of proteins that catalyzes the cis/trans isomerization of peptide bonds at proline residues, which facilitates protein folding. CypA, the most abundant cyclophilin isoform, has been described as a key player in viral infection for viruses such as HCV, dengue virus, coronavi

Genome annotations have been based on several main criteria to distinguish “true” ORFs from random events including a minimum length of 100 codons. Recent studies have showed that several genes predicted to be non-coding actually encode sequences for the production of active small polypeptides of le

In general, the efficiency of metabolic pathways is limited by short lifetime, toxicity and diffusion of intermediates, and by other competing pathways. These caveats were met in nature by the evolution of isolated microenvironments as organelles. With the advent of synthetic biology, intended to e

Phosphatidylinositol (PI) is a unique lipid as it is the precursor of phosphoinositides, like PI4P and PI(4,5)P2, which have key roles in the eukaryotic cells. However, little is known about how PI is exported from the endoplasmic reticulum (ER) where it is synthesized, to the Golgi apparatus and th

Proteins play multiple roles in RNA metabolism, regulating almost all aspects of the RNA functions, and form tight non-covalent complexes, mostly mediated by electrostatic charges and hydrogen bonds. In those complexes, oxidative-stress mediated, and highly reactive, chemical groups of RNA and prote

The interdisciplinary MiniToxoAd proposal interrogates how the protozoan parasitic microbe named Toxoplasma gondii interacts with and navigates through a variety of host extracellular matrices to establish intracellularly, which are the two obligatory conditions for guaranteeing T. gondii perpetuati

The fungal cell wall (FCW) is probably one of the most essential and widely shared structure throughout the fungal kingdom. Whether they be involved in plant biomass decay, pathogenesis or symbiotic associations filamentous fungi secrete a wide array of enzymes, so called carbohydrate-active enzymes

Biotransformation capacities of cells are directly linked to cellular metabolism. The enzymatic process of RNA decay participates to metabolism regulation by controlling gene expression post-transcriptionally. Thousands of RNA molecules belonging to three classes (messenger, ribosomal and transfer R

Small interfering RNAs (siRNAs) are specific and effective molecules for gene silencing, but fail to enter cells unassisted due to their negative charges and their high molecular weight/size. The conjugation of siRNA to ligands targeting cell surface receptors is a promising approach to silence gene

How cells adapt to an increase in their secretory load sets a delicate balance between health and disease and pave the way for pathologies ranging from cancer to diabetes. The Endoplasmic Reticulum (ER) directs this adaptation through a dedicated signaling: the Unfolded Protein Response (UPR). Adapt

The objective of the Sweet-THioPep project is to develop new biochemical tools as non-hydrolysable and multivalent probes to target lectins or glycosides hydrolases. These tools will be built by biocatalysis, using engineered glycosyltransferases (GT), modified by domain swapping, yielding chimerize

Multidrug-resistant bacteria represent a major public health problem and it is becoming essential to develop new strategies to fight them. A prerequisite is to better understand how pathogens adapt and resist to stresses during infection. Surprisingly, the role of chaperones, major players in protei

Penicillin-binding proteins (PBPs) are the targets of beta-lactams, the most widely used antibiotics such as penicillins, cephalosporins or carbapenems. PBPs are transpeptidases that catalyze the cross-linking of the peptidoglycan (PG), the main component of the bacterial cell wall. Pathogens such

Rare earths elements (REE) are a set of elements with unique properties, used in a variety of high-tech applications and products, and critical to the ongoing energy transition. The recent discovery of enzymes that specifically use REE as a cofactor in a wide range of environmentally important bacte

In aerobic biological hydroxylations, mono-oxygenases activate molecular oxygen to a peroxy intermediate, using bound cofactors such as heme, flavin or metal ions (Fe, Cu). In anaerobic biological hydroxylations, molybdopterin mono-oxygenases activate a water molecule. We have identified a new type

Proximity between proteins plays an essential and ubiquitous role in many biological processes. Molecular tools enabling to control and observe the proximity of proteins are thus essential for studying the functional role of physical distance between two proteins. In this context, chemically induced

Personalized medicine is based on medical biology, whose purpose is to define the metabolic profile of patients to adapt their treatment and minimize secondary effects. These metabolic profiles consist of an ensemble of biomarkers, which allow the early diagnosis of diseases like cancer and establis

Bioenergetic chains that fuel cellular metabolism have experienced dramatic changes since life appeared on Earth, with a diversification of environmental energy sources and the evolution of numerous dedicated enzymes. The mechanism of energy conservation, however, has remained nearly constant. It pr

Neurodegenerative diseases represent a major public health issue that needs to be addressed. Among them, Parkinson's disease (PD) is considered as the most common motor pathology but for which no curative treatment is available. Recently, the gene coding for LRRK2 has emerged as one of the major gen

Ribonucleoprotein particles (RNPs) are made of RNA associated with proteins and play a central role in biological systems (maintenance of cellular homeostasis, establishment of infectious or pathological processes). The identification of the components of these RNPs has exploded over the past decade

One of the most intriguing question is how oxygenic photosynthesis evolved presumably from an anoxygenic, sulfur-based one. Primitive cyanobacteria were the “inventors” of oxygenic photosynthesis, and in an early and not completely oxygenated ocean they were able to perform both oxygenic and anoxyge

Of the four fundamental macromolecular components necessary for life, complex carbohydrates (glycans) are probably the most structurally diverse. Glycans cover each cell in the human body, decorate almost all secreted proteins and have been shown to play roles in nearly every biological and patholog

Autotrophic carbon fixation, the Calvin-Benson cycle (CBC), is the main limiting factor of photosynthesis. It is believed to be impossible to improve and that Evolution reached the best possible fitness in current environment. However, a different maximum fitness of CBC was never ruled out. We will

Recent technological developments have expanded and intensified the use of metals in domains as diverse as renewable energy, computing, and medicine. Among those metals, technology-critical elements (TCEs, including lanthanides) are essential, but scarcer or produced by only a handful of countries.

To evolve in their volatile environment, mammals constantly call on their sense of smell. Odor can be seen as a chemical signal converted by the brain into an electrical signal itself translated into perceptions and emotions. This simplistic view is not representative of the molecular puzzle involve