Structural biology and biophysical characterization of stabilizing molecules acting on 14-3-3 PPIs

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. In the Innovative Training Network TASPPI (Targeted Stabilization of Protein-Protein Interactions) we aim in a consortium of 5 universities (Dundee, Eindhoven, Leeds, Lille, Prague, Siena), 3 pharma companies (AstraZeneca, GSK, UCB), and 2 SMEs (LDC, Taros) to identify and optimize small-molecule 14-3-3 PPI stabilizers as novel tools for basic research and starting points for drug development. The position described here is to be filled at Eindhoven University of Technology, The Netherlands. The successful candidate will work together with 12 other PhDs within TASPPI and will be included in a network-wide training and secondment programme. As part of the MSCA mobility requirements candidates are eligible for this position when they have spend no more than 12 months of their main activity (work, study) in the last three years in The Netherlands.

Tasks include
  • Purification of full-length 14-3-3 proteins as well as target protein constructs
  • Co-crystallization of 14-3-3 proteins in complex with protein partners, 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 diploma and/or a master’s degree 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
  • TUE will offer the PhD student 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.
  • The successful candidate will also participate in the network’s training activities and work placements at the laboratories of other participating academic and industrial teams.

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