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. 

Tasks include:

• Co-crystallization of 14-3-3 proteins in complex with partner protein-derived peptides and stabilizer tool compounds.
• Biophysical characterization of complexes by Surface Plasmon Resonance and Isothermal Titration Calorimetry
• Cell biology characterization of the effect of enhanced stabilization of 14-3-3/partner protein complexes

Qualifications

• 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: cell biology, biochemistry, x-ray crystallography, protein biophysics.
• Fluent in English language (spoken and written/proficiency level).

We offer:

• A challenging job in a dynamic and ambitious university
• Full-time employment by the Eindhoven University of Technology
• A position for a period of 2 years (starting with a one year contract)
• The gross monthly salary is in accordance with the Collective Labor Agreement of the Dutch Universities (scale 10), minimal € 2.709 and maximum € 4.274 depending on your experience
• An attractive package of fringe benefits, including excellent work facilities, childcare, moving expenses, sports facilities, an extra holiday allowance (8%, paid yearly in the month of May) and an end-of-year bonus (8.3%, paid yearly in the month of December)

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.