Parasites infect billions of humans each year and cause several major diseases, largely in underserved populations in developing parts of the world. Malaria, in particular, is a leading cause of deaths worldwide, and its causative agents, Plasmodium parasites, are crafty as they have successfully eluded our defense mechanisms since they first infected us tens of thousands of years ago. They have several different developmental stages and two hosts: mosquitoes and humans. Despite increased efforts at treating and suppressing the disease around the globe, its impact is increasing due to the parasites’ ability to rapidly mutate and develop resistance to first-line antimalarial drugs. Malaria parasites can synthesize over 5,000 proteins, but the functions of these predicted proteins, along with which ones are important at which developmental stage, are largely unknown. The combination of unexplored biology, poorly understood host-parasite relations, and the burden of morbidity and mortality offer multiple opportunities to conduct research with practical implications. Research in the Derbyshire laboratory uses chemical tools and biological methods to uncover novel aspects of malaria parasite biology with the ultimate aim of identifying druggable targets. Projects range from developing assays for phenotypic and target-based screens – forward and reverse chemical genetics – to dissecting biological pathways and identifying small molecules with potential therapeutic value. Our interdisciplinary collaborative program integrates both novel and established methods to address target identification, one of the most challenging aspects of malaria drug discovery. Our lab’s goal is to globally interrogate parasite biology by using chemical biology, molecular biology, and biochemistry to characterize the roles of essential proteins.
