Project Officer Position in Biomolecular NMR
Structural studies of signal transduction in Wnt pathway. Molecular Biology and High Resolution NMR
The interaction between beta-Catenin, Tcf family members and BCL9 proteins is crucial for the Wnt signal transduction pathway, which is commonly mutated in cancer. Beta-Catenin forms a complex with BCL9, which activates the transcription of known proto-oncogenes. The HD2 domain from BCL9 proteins can compete with BCL9 at the beta-Catenin complex, which potently inhibits the Wnt pathway in colon cancer cells. We will create an efficient drug-design platform targeting beta-Catenin/BCL9 interactions in the Wnt-pathway, which is capable of establishing structural requirements of possible anti-cancer drugs as well as biophysical characterization of drug binding and effects on the cells in cell culture. We will use NMR to refine the solution structure of the individual components as well as the beta-Catenin/BCL9-HD2 complex and to characterize its dynamic structural changes induced by interactions. NMR structural models will be used in several in-silico structure based drug design rounds. The obtained high affinity binders will be assayed in cell cultures resulting in generation of potential drug leads for animal trials.
Candidates with strong background in biochemistry or molecular biology or NMR are welcome. Please contact:
Konstantin Pervushin, Ph. D
Associate Professor
School of Biological Sciences
Phone (office): +65-65141916
Fax: +65-6791 3856
Nanyang Technological University
60, Nanyang Drive,
Singapore 637551
e-mail: kpervushin@ntu.edu.sg
Updated 05 Mar 2009