Objectif This action aims to discover a novel class of autophagy inhibitors and newly develop chemical probes that can identify theirprotein targets and dissect their biological mode of action. Autophagy dysregulation is intrinsically linked with majorEuropean healthcare challenges, including cancer. The identification of new classes of druggable autophagic proteins willhave broad implications for the development of novel and more effective cancer therapeutics. To address the aims of thisaction, this proposal seeks support to initiate a pioneering and holistic chemical biology programme, which combines thenewest technologies in synthetic chemistry and cell biology. Phenotypic investigations in the host lab recently identified newinhibitors of autophagy based on a novel scaffold, which modulates autophagy through an exciting but unknown pathway. Inthis action the use of a newly introduced sp2-sp3 cross-coupling reaction will allow systematic variation of the scaffold,exploration of its structure-activity relationship, and improvement of the potency of these inhibitors to facilitate thepreparation of high-quality chemical probes. A focused compound collection (>100 compounds) will be prepared andinvestigated in cell-based assays, with the aim of establishing a broad, potent and selective class of inhibitors. The inhibitorymode of action will then be rationalised through identification, validation and engagement of the associated biological targetsusing further cell-based investigations and biophysical assays. Chemical probes will be generated from the most activeinhibitors and used to identify and interrogate the druggability of a novel protein target with potentially huge significance forbiomedical science. My ambition is to become an independent academic researcher in chemical biology at a leadingEuropean institution, and this Fellowship provides a vital opportunity for me to advance my scientific and career potential. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologymedical and health sciencesclinical medicineoncology Mots‑clés autophagy chemical biology synthetic organic chemistry chemical probes biological target identification cell biology cell machinery biological mechanisms cancer metastasis Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2017 - Individual Fellowships Appel à propositions H2020-MSCA-IF-2017 Voir d’autres projets de cet appel Régime de financement MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinateur MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Contribution nette de l'UE € 171 460,80 Adresse HOFGARTENSTRASSE 8 80539 Munchen Allemagne Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 171 460,80
