BSB Seminar: A chemogenetics platform for antimalarial drug target identification and hit discovery

Malaria is a major global health problem, with 247 million cases and 619,000 deaths estimated in 2021. Antimalarial drugs are critical for malaria treatment and eradication efforts. However, resistance to clinically approved drugs is rapidly spreading, and the pipeline of new antimalarial drugs is relatively limited. Phenotypic screens are valuable for discovering promising lead compounds, but target identification is a separate, time-consuming process. To overcome this bottleneck in lead compound discovery and optimization, we are combining genetic engineering, synthetic biology and chemical screening approaches to rapidly identify functional interactions between compounds and their molecular targets. In this way, we simultaneously obtain evidence of a compound's antimalarial activity and likely mode of action. We illustrate the potential to scale this target-based screening approach, and to integrate it with increasingly higher throughput screening activities towards improving the efficiency with which new and promising antimalarial compounds can be identified.

Biography

Jacquin Niles is the Whitaker Professor of Biological Engineering and Director of the Center for Environmental Health Sciences at the Massachusetts Institute of Technology (MIT), and an Associate Member of the Broad Institute of MIT and Harvard. He completed combined medical and PhD training at Harvard Medical School and MIT, respectively, and postdoctoral studies at University of California at Berkeley. His lab focuses on engineering enabling genetic and molecular technologies, and leverages these novel tools in combination with chemical biology and other molecular approaches to study malaria. His research aims to improve our understanding of malaria parasite metabolism, and to catalyze early stage target-based antimalarial drug discovery. His work has been recognized with several awards, including the NIH Director’s New Innovator and HHMI Faculty Scholars Awards.