Principal Investigator (PI)
London School of Hygiene and Tropical Medicine (Department of Pathogen Molecular Biology)
The Foundation is providing £176,250 in support.
Dr. Francisco Olmo
The aim of the project will be to add value to the lead optimization process by identifying the intra-parasite targets of compounds showing most therapeutic promise, deciphering their mechanisms of action, and assessing the potential for resistance.
Identification of genes involved in resistance to novel compounds from the HTS formerly prosecuted at GSK will be approached through complementary high-throughput genetic methodologies, such as RITseq in T. brucei, CRISPR/cas9 in T. cruzi and construction of a T. cruzi cosmid over-expression library. The set of genetic constructs will be screened against GSK Chagas Box in order to assess the modes of action and/or resistance mechanisms of lead compounds in T. cruzi. Furthermore, in vivo screening can be undertaken to assess physiological relevance