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The project involves 2 CNRS groups of chemists from Nantes and Le Mans, and a group of immunobiologists (Inserm U892-CRCNA). The collaboration has already been ongoing for three years, supported by the «Cancéropôle Grand Ouest» program, the regional research grant 2006 «CIMATH» and ARC (Ass. Against

The aim of this project concerns the development of a new laser Doppler velocimeter (« Laser Doppler Flowmetry » : LDF) for renal graft monitoring, in order to quantify the renal perfusion during removal and transplantation. The advantages of this system over classical echo-doppler methods rely on t

Our efforts to clone an angiotensin III receptor led to the cloning of a gene encoding a rat seven transmembrane domain receptor exhibiting 95% sequence identity with that of the human orphan APJ receptor. The ligand for this receptor was identified en 1998 and and was named apelin. We characterized

Infectious diseases leading to colonization of the blood by the infectious agent are a major burden to society. Such infections lead to a wide array of devastating clinical manifestations including septic chocks, hemorrhagic syndromes and infection of the brain (meningitis). Pathogens triggering suc

In 2007, the FDA approved only 17 new drugs, of which 4 were indicated in the treatment of cancer and 2 for the treatment of CNS-related diseases. Beside increased levels of regulatory caution, the scarcity of new drugs also results from the lack of novel targets. To overcome this target shortage, s

Cancer is the second mortality cause in developed countries with colorectal and breast cancers causing high rate of mortality. Approximately 90% of all cancer deaths arise from the metastatic spread of primary tumours. Of all the processes involved in carcinogenesis, local invasion and the formation

Photodynamic therapy (PDT) is being assessed as a therapy for the treatment of malignant gliomas. Despite conventional treatments, local relapses remain higher than 80%. PDT relies on the light activation of a photosensitizer (PS) localized in the tumor site. The treatment involves two steps. In the

Scientific background and objectives Controlling gene expression in space and time is a much sought after goal in biology. Inducible gene expression systems have been used but they remain limited by the technology associated to the inducer delivery. Ideally, the latter should be noninvasive, fast, l

Over the ~23k genes present in a human cell, only a few thousands are expressed at a given time in order to specify a cellular function integrated in an organism. The regulation of gene expression is ensured by specific transcription factors (TFs). TFs control the genes that are silenced or activate

The project « High-speed Bio Atomic Force Microscopy: structure and dynamics at the single molecule level » aims at the development of high-speed atomic force microscopy (AFM) setups in a collaborative consortium for the investigation of structure and dynamics of biological samples. Conventional AFM

Scientific context: Shigella flexneri are enteroinvasive Gram negative bacteria responsible for endemic shigellosis, or bacillary dysentery. To fight this major burden, especially in children under 5 years of age, vaccines ensuring multi-serotype coverage are in demand. New glycovaccines based on sy

The mitochondrial ADP/ATP translocator (ANT) plays a central role in aerobic eukaryotic cells and can be involved in human pathologies. Four isoforms with tissue-specific expressions have been identified in humans. Based on cellular pharmacology, biochemistry and isoform-specific over-expression exp

The hexosamine biosynthetic pathway is associated with the side effects of diabetes through its end-product UDPGlcNAc. The rate limiting step of this pathway, i.e. the conversion of fructose-6P into glucosamine-6P, is catalyzed by glucosamine-6P synthase (hGfat). This enzyme is therefore considered

Tumor vasculature brings nutrients to the tumor and also constitutes the main entry path for chemotherapy. Tumor vasculature usually fails to meet the demands of the tumor cells for oxygen and nutrients and this failure results in tumor blood flow heterogeneity often inducing intermittent hypoxia, a

Specific human tissue targeting by therapeutic agents, whatever the field of application, remains a challenge for biologists and chemists. These agents must avoid biological transformations leading to rapid clearance out of the body and, at the cellular level, active molecules must distinguish betwe

Hypothesis - Understanding the biosynthetic pathway of glycosaminoglycans (GAGs) is a major issue in cell biology since this process determines the composition of GAG chains that govern the signalling functions of these complex polysaccharides in health and disease. Of special interest is their cruc

Perturbation of protein kinase-mediated cell signaling pathways can lead to various disease states. Protein kinase CK2 is a multifunctional kinase of medical importance as it is found dysregulated in many cancers. Therefore, CK2 is now considered to be a relevant target supporting the development of

Aging is an intrinsic feature of living organisms which is at least partly genetically determined. Despite considerable efforts to identify the mechanisms that govern the transition to senescence, a precise and quantitative understanding at the cellular level is missing, mainly because it has been

G protein-coupled receptors (GPCR) represent the single largest family of cell surface receptors involved in signal transduction. They therefore represent major targets for the development of drug candidates with potential application in all clinical fields. In fact, more than 50% of the drugs presc

The main rationale of this project is to gain information about the recognition process between bacterial lectins and oligosaccharides from a coherent point of view involving chemistry, biophysics, microbiology and structural biology. It also involves kinetic, thermodynamic and structural studies of

Mechanical integrity is a critical feature of tissue homeostasis. Cell transformation, tumour growth and metastasis dissemination are systematically associated with cell mechanical deregulation and tissue disorganisation. Mechanical equilibrium within multicellular arrangements depends on the regula

The aim of this project is to understand at the molecular level the link between membrane structures and the actin cytoskeleton. Ezrin, member of the ezrin/radixin/moesin (ERM) family, is a membrane cytoskeleton linker involved in the cellular morphogenesis and motility. ERM proteins are localized i

Structured RNA are major actors of numerous biological processes such as mRNA splicing, protein translation, control of gene expression, replication of viruses, RNA processing , chromosome maintenance… In most documented cases, the corresponding biological processes include one or more essential ste

Protein misfolding and subsequent aggregation is at the origin of over 20 human diseases termed 'conformational' diseases. Although actively studied, the fundamental mechanism of the misfolding of a variety of polypeptides leading to their aggregation and associated diseases is far from being unders

Recent studies have shown that as much as one third of eukaryotic proteins contain long intrinsically disordered regions, with 12% of them being fully disordered. Intrinsically disordered proteins (IDPs) are functional proteins that fulfill essential biological functions while lacking highly populat

Electrochemical Sensor Arrays (ESAs), in which each individual electrode is specifically tailored to sensitively detect a particular analyte, provide an easy access to the development of tools for the simultaneous detection of multiple species. By that way, ESAs offer potential applications for inve

Post-translational methylation of arginine is a widespread epigenetic modification found in eukaryotes that is catalyzed by the protein arginine methyltransferases (PRMTs). PRMTs have been implicated in a variety of biological processes, such as regulation of transcription, translation and DNA repai

Synthesis of the large precursor of the ribosomal RNA is performed by the multimeric RNA polymerase I (RNA Pol I) and represents about 65 % of the transcriptional activity in exponentially growing eukaryotic cells. This essential cellular process is tightly regulated during cell cycle and through th

1-Scientific background & objectives: The efficient exploitation of numerous medicaments is strongly dependent on their overall comportment within the human biosystem, described by their pharmacokinetic ADME (Absorption, Distribution, Metabolism, Excretion). Over the past few decades, the importance

The morphogenesis of developing embryos and organs relies on cells‚ abilities to change shape and to remodel their contacts with other cells. These behaviors stem at the celular level from interplay between the cortical tension and adhesion. In this context, we aim at elucidating how cortical actin

Many vital cellular processes, such as neuronal communication and insulin secretion, rely upon highly regulated fusion events between cargo containing vesicles and target membranes. The core of the fusion machinery consists of the assembly between vesicular (v-) SNARE and target (t-) SNARE proteins

Metals play fundamental role in biology and they are involves in the catalysis of a large variety of reactions in more than one third of the proteins. In metalloenzymes, metal-site reactivity results from a fine balance between the chemical nature and spatial distribution of the ligands. It is the w

Cell migration is a process having a hierarchical spatial and temporal organization. At the cellular, sub-cellular, and molecular levels, migration proceeds through cycles lasting from minutes to seconds. The robustness of these cycles relies on the precise regulation of motions and transient intera

Recent technological advances, such as high magnetic field MR imaging systems, high magnetic field gradient coils and specialized radiofrequency detectors brought the imaging of single biological cells within reach. The application of Magnetic Resonance Imaging (MRI) to the study of small biological

The LPEM has developed for two years a structured illumination microscope that can produce 3D super resolved fluorescent images. The instrument, based on a commercial microscope is actually in a test phase. Lateral and axial resolution gains have been demonstrated independently on model samples, lik

Following engagement by their cognate ligand(s), receptors of the TNF family can either signal survival/ proliferation/ differentiation or cell death. Current challenges in TNFR pharmacology and aim of our project are to understand the molecular basis for the multiplicity of cellular responses contr

RNA, which has long been viewed as a 'passive' information carrier, is now widely recognized as a major actor for the regulation of gene expression. In bacteria, the mRNA is a key player in this process, and the regulation involves mRNA structural elements that directly sense the environmental cues,

Most methods in modern cell biology are implicitly based on the assumption that the behavior of a cell is predominantly determined by its individual biochemical and genetic properties. Moreover, complex processes such as tumorigenesis, are studied by methods that make it quite difficult if not impos

An important current challenge in cellular biology is the understanding of the numerous networks of molecular interactions that regulate cellular processes. Traditionally, molecular interactions between cellular molecules have been measured by in vitro techniques. However, recent developments in con