BME Lecture Series: Gerard C. L. Wong, UCLA

Abstract: Antimicrobial peptides (AMPs), which directly kill pathogens have long been known to also modulate the immune system, but the precise mechanisms are not clear. The recognition of pathogen-associated molecular patterns (PAMPs) by immune receptors has been one of the paradigmatic examples of specific binding in molecular biology. This is exemplified by the recognition of pathogen nucleic acids by Toll-Like Receptors (TLRs) of innate immunity, the first responders to infection. We show that TLRs recognize and respond not just to the chemical patterns on individual ligand nucleic acids they are designed to detect, but also to nanocrystalline complexes in which AMPs organize nucleic acids into spatially periodic arrays for optimal presentation. Since the immune receptors are detecting crystalline arrangements of dsDNA and dsRNA in a multivalent manner, the resultant immune response can be highly amplified, leading to a broad range of health outcomes, including inflammation induced by heart disease, neutrophil apoptosis and autoimmune diseases. We will also discuss how machine learning can be used to map out the undiscovered sequence space of AMPs and how this knowledge may be used to create new molecules against multidrug-resistant pathogens by renovating existing obsolete antibiotics.

Bio: Gerard C. L. Wong is a professor in the Departments of Bioengineering and Chemistry at UCLA. Wong received his bachelor's degree and doctorate in physics at Caltech and Berkeley. He joined the Departments of Materials Science and Physics at the University of Illinois at Urbana-Champaign in 2000 and was recruited to UCLA in 2009. His research recognition includes a Beckman Young Investigator Award and an Alfred P Sloan Fellowship. He is a fellow of the American Physical Society, the American Academy of Microbiology, and  the American Institute for Medical and Biological Engineering.