Investigating the molecular drivers of drug transport and resistance in Non-Tsetse Transmitted Animal Trypanosomes (NTTAT)

Project Description

The overall aim is to establish whether the T. brucei drug transporter models, which identified the TbAT1 and TbAQP2 transporters as chief determinants for diamidine and arsenical resistance apply to T. evansi and T. equiperdum, and whether mutations/genetic variations could potentially contribute to treatment failure with diminazene and cymelarsan.
Laboratory strains will be used initially for this investigation– cloning the T. evansi/equiperdum AT1 and AQP2 genes into corresponding null mutant T. brucei clones. Introduction of specific mutations in the transporter genes to probe transporter function, and testing of alleles from field isolates (samples are available from prof. Philippe Buscher, Institute of Tropical Medicine, Antwerp).