Principal Investigator (PI)
The Foundation is providing £150,055 in support.
Dr Emily Grace Armitage
GSK provides in-kind contributions, including scientific expertise in leishmania to obtain the extracts from in vitro parasite culture, and access to Biosafety Level 3 facilities and to GSK's collection of compounds.
Screening of compound libraries for potential new antimicrobial agents has demonstrated the superiority of whole organism (phenotypic) screening to identify hits for further development. Such screens require compounds to already demonstrate key pharmacological criteria required for parasite killing, including an ability to enter cells and find targets in situ. However, phenotypic screens are hampered by the fact that drug targets are not known. This can hinder our ability to progress from hit to lead to drug, where target knowledge can guide medicinal chemistry in improving efficacy. In recent years metabolomics has been applied to drug target discovery and also to identify resistance mechanisms. This project aims to use metabolomics to identify modes of action of new compounds identified by phenotypic screening against Leishmania. Hits from the GSK anti-Leishmania screening campaign will be analysed firstly to allow clustering of drugs according to how they alter the metabolome and then focusing on a limited set of representatives to identify individual drug targets. The proposed duration of the project is 18 months and will involve a close collaboration between the Universidad San Pablo CEU, the University of Glasgow and GSK’s Medicines Development Campus at Tres Cantos.