BCOOL (Biological Chemistry, Organic and Organometallic Lecture) Series

Malaria is a devastating disease that affects over half a million people each year mostly children under five years old and pregnant women.

Antimalarial drug discovery by and large is focused on the identification of novel drugs to treat and prevent the disease due to the emergence and spread of Plasmodium strains resistant to existing medicines. In particular artemisinin resistance which has now spread from Southeast Asia and is firmly established in Africa (as reported at ASTMH in Seattle Oct 2022).

The Merck Research Labs (led by Dr. David Olsen) and the Walter and Eliza Hall Institute of Medical Research (WEHI) (led by Prof. Alan Cowman), have teamed up to invent novel drug candidates by targeting the Plasmodium parasite via newly identified essential aspartyl proteases.  The team has been greatly assisted in this endeavor with generous funding for the collaboration from the Wellcome Trust (UK).  The team was successful at identifying potent dual protease targeting hits that lead to the identification of an important tool compound WM382 with subnanomolar inhibitory potency in vitro. This was accomplished through targeted phenotypic screening and structure-guided medicinal chemistry to optimize orphan (mechanism of action unknown) hit compounds. WM382 was also used to establish impressive in vivo proof-of-concept efficacy not only on blood stage parasitemia but also potent pharmacodynamic effects in the sexual/mosquito and liver stages of replication. Finally, Justin Boddey’s team at WEHI determined that defective parasites under WM382 drug coverage yield some interesting immunological effects in mice in vivo. Further optimization of potency and pharmacokinetic and selectivity profiles resulted in the invention of clinical compound MK-7602 (PhI), a very potent PMIX/X dual inhibitor with robust in vivo efficacy in mice at the three stages of the malaria parasite lifecycle and excellent off-target activity and resistance profiles.

This seminar will tell the story of how a few simple oxygen atom transfer reactions, paired with expertise in materials engineering and synthetic biology, led to far reaching implications in recycling and remanufacturing carbon fiber composite materials and waste plastics. While a powerful approach to cleaving polymer waste, catalytic oxidation leaves room for improvement as it typically generates disordered and low value materials from polymer feedstocks. This talk will explain how a combination of engineering and biological strategies enabled us to resolve this complexity and introduce polymer recycling processes that are beginning to permeate the marketplace.

Travis Williams is Professor of Chemistry at USC and science advisor of Catapower Inc. and Closed Composites Inc. He received his Ph.D. at Stanford with Paul Wender before a postdoctoral appointment at Caltech. He came to USC as an assistant professor in 2007. His research program spans the cleantech space, including H2 on demand, benign fine chemicals, and polymer recycling. He has received research awards from NIH (NRSA), NSF (CAREER and BRITE), and DOE (2022 H2 Technology of the Year). He is a fellow of USC’s Loker Hydrocarbon Research Institute and Wrigley Institute for Environment and Sustainability. Travis is a high school dropout and has been struck by lightning and bitten by a shark.