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Institute of Advanced Study

Dr Christophe Verlinde

COFUND Senior Research Fellow at Hatfield College, Durham University (January - March 2015)

Dr Christophe Verlinde is an Associate Professor, Departments of Biochemistry and Biological Structure, University of Washington, Seattle. Dr Verlinde is an expert in structure-based drug design, author of more than 135 papers, and is widely cited. His focus is mainly on developing drugs for neglected diseases and his design work has led to bioavailable and selective nanomolar inhibitors of various enzymes of trypanosomatid organisms: glycolytic enzymes, kinases, protein farnesyl transferases and as of lately methionyl-tRNA synthetase. 

Toxoplasma gondii is an obligate, intracellular protozoan parasite which has emerged as an opportunistic pathogen and toxoplasmosis is an important disease in immunocompromised patients. The target for drug discovery in this area is the serine palmitoyl transferase (SPT) which catalyzes the first, rate-determining step in the vital process of sphingolipid biosynthesis. Durham, has identified, cloned, expressed and purified several constructs of SPT from Toxoplasma gondii. The protein samples were used to extensively characterize the enzymatic mechanism and overall protein structure by a range of biochemical and biophysical methods. 

The overall aim of this project is to develop novel SPT inhibitors (SPT) from Toxoplasms gondii (TgSPT). In the first step novel inhibitors will be identified by high-throughput in-silico screening methods using a homology model of TgSPT based on the known crystal structure of a related bacterial enzyme. In the second step we will characterize binding and inhibition properties of our new inhibitors by biochemical and biophysical methods.