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Study of DNA ADP-ribosylation and Its Role in DNA Damage Response – DNAPAR18
Cellular DNA is constantly damaged by exogenous and endogenous factors resulting in base damage and DNA strand breaks. The accumulation of endogenously occurring DNA lesions is a primary factor contributing to aging. Failure to detect and repair DNA strand breaks and other lesions can lead to delete
Molecular and cellular characterization of nanobodies directed against Tau – ToNIC
The aggregation of neuronal Tau protein to form fibrilar structures inside neurons is associated with tauopathies, notably Alzheimer’s disease (AD). A trans-synaptic transfer of Tau may participate in the spatio-temporal progression of the disease and this supposes that Tau is secreted into the inte
High performance MS-based proteomics by reducing stable isotopes complexity in vivo – SLIM-labeling
One of the most challenging problems in modern biology is to address at the experimental level the analysis of the dynamics of proteome variations in composition and structure in order to decipher the fundamental mechanisms of gene expression and regulation in normal and pathological conditions. Usi
New Activity-based Probes for Mass spectrometry Profiling of Metallo Proteases. – ProMaP
Proteomic aims to develop global methods for analysing proteins function within complex biological samples. In the case of Matrix MetalloProteases (MMPs) present in low abundance and subjected to a complex array of posttranslational modifications, this implies to be able to selectively detect their
Detection and quantification of fluorinated pollutants Fluorine NMR – FLUOVIAL
Fluorine is a light and common element, but there is nearly no fluorine metabolism in any living organism. Because of the extreme chemical resistance of fluorinated molecules its use in man-made products is common, and fluorine is present in perfluorinated polymers, in nearly 50% of phytosanitary pr
Role and functional specificities of actin-activated ExoY-like nucleotidyl cyclase virulence factors in gram-negative bacterial infections – activExoY
Many pathogens manipulate the cAMP intracellular signaling of host cells to promote their survival and proliferation in hosts. Bacterial ExoY-like virulence factors represent a new atypical subfamily of nucleotidyl cyclase (NC) toxins. Exoenzyme Y (ExoY) was first identified as a toxin secreted via
Construction and transplantation of semi-synthetic genomes of Bacillus subtilis: towards the development of the next generation of bacterial chassis – Bacillus2-0
Synthetic genetic circuits often fail to function as designed because of unwanted interactions between circuit components and the host system. A promising strategy to foster innovation in biotechnology relies on the construction of adequately streamlined cellular chassis. Ideally, a valuable chassis
Accurate Atomistic Models for Computer-Aided Drug Design – ATMCADD
This project addresses the important problem of the development of accurate atomistic simulation models for computer-aided drug design (CADD). Drug discovery and development are very time and resource consuming processes, which are significantly facilitated by CADD methods. Structure-based CADD meth
Diversity and evolution of oxidosqualene cyclases and prenyltransferases in the latex of Amazonian tree species – AMAZYME
Plant exudates represent a unique system to examine the role of trait diversification on adaptive radiation. Exudates have arisen independently in at least 40 families across six orders and occur in ca. 20,000 plant species (15% of tropical taxa). The evolution of exudates may have driven the succes
A chemical biology approach toward innovative granulysin analogs – GRAN
Granulysin (GN) is a human protein secreted by cytolytic T-lymphocytes and natural killer (NK) cells. GN protein has a broad-spectrum of antimicrobial activities on some Gram-positive and Gram-negative bacteria, fungi and parasites but also strong immunomodulatory properties. Taking advantage of the
Dolichol linked oligosaccharide diphosphatases: orphan enzymes scavenging toxic waste? – DLODESTRUCT
Context: Protein N-glycosylation occurs by the transfer of an oligosaccharide from a lipid linked precursor (Glc3Man9GlcNAc2-PP-dolichol, DLO) onto newly synthesized proteins in the lumen of the endoplasmic reticulum. This process is essential for life and mutations in genes required for biosynthesi
Dual-Input Fluorogenic Probes for Localized Biphotonic Imaging – DIPimaging
Fluorescence imaging has become a widespread mean of observing biological processes thanks to the development of new instrumental techniques and smart fluorescent probes. Biphotonic microscopy using and infrared excitation source has made it possible to perform in vivo imaging in physiological condi
Dissecting the mechanisms whereby the C-type lectin DCIR modulates type I interferon signaling and immunity to tuberculosis – DCIR-TB
Tuberculosis (TB) is a chronic inflammatory disease, mostly of the lung, caused by the airborne bacterial pathogen Mycobacterium tuberculosis (Mtb). A better understanding of host-pathogen interactions in TB, and of anti-mycobacterial immunity in particular, may help developing novel intervention st
Synthetic metabolic and genetic networks for medical diagnostics – SynBioDiag
Organisms have evolved to sense large panels of metabolites and human have used these sensing abilities throughout history. Recently, synthetic biology has expanded and rationalized biosensing by engineering whole-cell biosensors (WCBs) with sophisticated signal processing capabilities. The main adv
Artificial scaffolding proteins for engineering natural product biosynthetic pathways – SCAFFOLD-ART
Natural products (NPs) are small bioactive molecules produced by living organisms, often microorganisms. They are at the origin of many drugs. The diversity of NPs has not been exhaustively explored nor exploited. In many fields (anti-infectives, anti-tumor, ...) new bioactive molecules are actively
Novel Therapeutics for Toxoplasmosis and Malaria Directed to New Parasite Targets – NovoTargetParasite
Current anti-toxoplasmosis drugs have serious limitations: side-effects, low-to-moderate efficacy and poor administration routes. The spread of Plasmodium resistance to artemisinin is now a global health problem. This highlights the desperate need of new classes of drugs, ideally directed to novel t
Deciphering the role of membrane sialidase NEU1 in macrophages – MACRONEU1
Sialidases, or neuraminidases, represent a family of exoglycosidases removing terminal sialic acid residues from glycoproteins, glycolipids and oligosaccharides. Their presence affects the molecular properties and structure of glycoconjugates, modifying their function and interactions with other mol