Postdoc New anti-inflammatory drug approach stabilizing the 14-3-3Pyrin complex (V50.2901)

Postdoc New anti-inflammatory drug approach stabilizing the 14-3-3Pyrin complex

Postdoc position: New anti-inflammatory drug approach by stabilizing the 14-3-3/Pyrin complex.
Position
(Post-doctoral) Researcher
Departments
Department of Biomedical Engineering
FTE
1,0
Date off
30/04/2017
Reference number
V50.2901

Job description

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

Job requirements

  • 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).

Conditions of employment

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). 

 

Information and application

For further information please contact c.ottmann@tue.nl.