Organisation/Company: Imagerie Moléculaire et Stratégies Théranostiques UMR 1240, INSERM, UCAResearch Field: Biological sciences » Biology Chemistry » BiochemistryResearcher Profile: Recognised Researcher (R2) Established Researcher (R3)Country: FranceApplication Deadline: 29 Nov 2024 - 22:00 (UTC)Type of Contract: TemporaryJob Status: Full-timeOffer Starting Date: 6 Jan 2025Is the job funded through the EU Research Framework Programme? Not funded by a EU programmeIs the Job related to staff position within a Research Infrastructure? NoOffer DescriptionContext and description of the project: Isocitrate dehydrogenases (IDH) are enzymes that catalyse oxidative decarboxylation of isocitrate to a-ketoglutarate with subsequent reduction of NADP co-factor to NADPH. IDH are involved in several biological processes such as cellular metabolism, cellular defense against oxidative stress, oxidative respiration, and oxygen-sensing signal transduction. However, mutated IDH enzymes (mIDH) have been observed in several cancers including glioma, acute myeloid leukemia (AML), intrahepatic cholangiocarcinoma, and chondrosarcoma. Mutated IDHs confer neomorphic activity, converting a-ketoglutarate to the oncometabolite D-2-hydroxyglutarate, involved in tumorigenesis. High cellular levels of 2-HG can inhibit, for example, enzymes implicated in DNA-demethylation, histone-demethylation, and subsequently impair normal cellular differentiation and promote tumor development. Targeting mIDHs has emerged as a promising therapeutic strategy and three mIDH inhibitors (vorasidenib, enasidenib, olutasidenib) have been approved by FDA and/or EMA in various protocols of therapy (glioma, AML, …). Accurate evaluation of mIDH status is essential for effective patient management. Currently, the presence of mIDH1 is determined either by invasive biopsy or indirectly by measuring the mIDH-derived 2-HG using magnetic resonance spectroscopy. Non-invasive imaging techniques for the detection of the mIDH1 protein using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) could be of valuable help to provide information on the mutational status of patients' tumours, to select admissible patients for anti-mIDH therapies and to determine the efficacy of therapeutic inhibitors in order to facilitate precise medicine.This international project will be performed in close collaboration with the neuroradiopharmacy laboratory of the HZDR (Research site Leipzig, Germany, Drs W. Deuther-Conrad and B. Wenzel).Minimum RequirementsApplicants should have a Ph.D. degree or equivalent in biology or biomedical sciences.Candidates are expected to have:Strong background and PhD training either in cancer biology, molecular biology, or biochemistry.Experience in common biological assays, including cell culturing, Western Blotting, immunohistochemistry and statistical analyses.Knowledge of handling radioactive material.Experience with in vitro characterisation of radiotracers (uptake, competition assay).Experience with tumor imaging or preclinical disease models for molecular imaging procedures.Willingness to work with animals (mice handling, intravenous injection, tissue processing) and possession of the authorization to conduct experiments on animals - Level 1 or 2.Strong commitment to experimental bench research.Naturally collaborative and self-motivated style to work effectively in a multidisciplinary and integrated team.Excellent communication and writing skills in English and/or French language.Additional InformationWork Location(s)Number of offers available: 1Company/Institute: Imagerie Moléculaire et Stratégies Théranostiques UMR 1240, INSERM, UCACountry: FranceCity: Clermont-ferrand
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