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Towards a New Frontier in Autophagy Inhibition: The Development of a Novel Class of ChemicalProbes and Identification of Their Associated Biological Target

Objective

This action aims to discover a novel class of autophagy inhibitors and newly develop chemical probes that can identify their
protein targets and dissect their biological mode of action. Autophagy dysregulation is intrinsically linked with major
European healthcare challenges, including cancer. The identification of new classes of druggable autophagic proteins will
have broad implications for the development of novel and more effective cancer therapeutics. To address the aims of this
action, this proposal seeks support to initiate a pioneering and holistic chemical biology programme, which combines the
newest technologies in synthetic chemistry and cell biology. Phenotypic investigations in the host lab recently identified new
inhibitors of autophagy based on a novel scaffold, which modulates autophagy through an exciting but unknown pathway. In
this 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 the
preparation of high-quality chemical probes. A focused compound collection (>100 compounds) will be prepared and
investigated in cell-based assays, with the aim of establishing a broad, potent and selective class of inhibitors. The inhibitory
mode of action will then be rationalised through identification, validation and engagement of the associated biological targets
using further cell-based investigations and biophysical assays. Chemical probes will be generated from the most active
inhibitors and used to identify and interrogate the druggability of a novel protein target with potentially huge significance for
biomedical science. My ambition is to become an independent academic researcher in chemical biology at a leading
European institution, and this Fellowship provides a vital opportunity for me to advance my scientific and career potential.

Call for proposal

H2020-MSCA-IF-2017
See other projects for this call

Funding Scheme

MSCA-IF-EF-ST - Standard EF

Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Address
Hofgartenstrasse 8
80539 Muenchen
Germany
Activity type
Research Organisations
EU contribution
€ 171 460,80