Modulation of Protein-Protein Interactions (PPIs) with small-molecules is one of the most promising and challenging areas in Chemical Biology and Drug Discovery. Whereas inhibition of PPIs is meanwhile a well-documented and successful strategy, the opposite approach of small-molecule stabilization of PPIs has not been followed systematically. The adapter protein 14-3-3 acts as a “hub” by interacting with several hundred partner proteins in human cells. These 14-3-3 PPIs are implicated in a number of diseases ranging from cancer and neurodegeneration to inflammation and metabolic syndromes. A minimal system to pharmacologically recruit and stabilize 14-3-3 protein on any site of interest in a target protein would allow new therapeutic concept validation in the absence of chemical matter for the specific site. Such a minimal system has to have two features: controllable phosphorylation and pharmacological 14-3-3 stabilization. This chemical biology/protein engineering approach will be highly useful for therapeutic concept validation and prioritization of binding sites for drug development in 14-3-3/partner protein complexes.
The postdoc will be hired for two years, place of work will be TU Eindhoven (The Netherlands) with the possibility of short term stays at the oncology group of Boehringer-Ingelheim’s Regional Center Vienna (BI RCV).
TU/e and Boehringer Ingelheim will offer the postdoc a unique opportunity to gain world class knowledge and hands-on experience in various applications of chemical biology and drug discovery at the forefront of biomedical research and development.
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