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. Pyrin is a key innate immune receptor recently found to be repressed via interaction with 14-3-3 proteins. Therefore, stabilising the Pyrin/14-3-3 interaction would prevent inflammation. In this project Eindhoven University of Technology (TU/e) and GlaxoSmithKline (GSK) join forces to identify and optimise small molecules that bind to the interface of the inhibitory complex between 14-3-3 and Pyrin consequently inhibiting the pro-inflammatory activity of Pyrin.

The postdoc will be hired initially for one year with the possibility to extend the contract by additional 2 years. Place of work will be TU Eindhoven (The Netherlands). A 3-months secondment to GSK Stevenage (United Kingdom) is planned for the first year with possible further secondments in year 2 and 3.

Tasks include:

Purification of full-length 14-3-3 proteins as well as Pyrin constructs

Co-crystallization of 14-3-3 proteins in complex with Pyrin constructs, Pyrin-derived peptides and small molecules

X-ray crystallography fragment-based ligand identification

Biophysical characterization of complexes by Surface Plasmon Resonance and Isothermal Titration Calorimetry

Have a PhD in biology, biochemistry, or biotechnology.

Have excellent track record from their previous studies along with experience and expertise in at least one of these fields: biochemistry, protein expression, x-ray crystallography, protein biophysics. Good knowledge on chemistry is a plus.

Fluent in English language (spoken and written/proficiency level).

Our Offer

TU/e and GSK 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.

Full-time employment at a dynamic and ambitious university

A position for a period of 1 year. After a good evaluation your contract can be extended.

The gross monthly salary is in accordance with the Collective Labor Agreement of the Dutch Universities (scale 10), depending on your experience.

An attractive package of fringe benefits, including excellent work facilities, childcare, moving expenses, sports facilities, an extra holiday allowance (8%, May), and an end-of-year bonus (8.3%, December).