Marine Biology Seminar: Dr. Gerard Wong (University of California, Los Angeles: Department of Bioengineering, Department of Chemistry and Biochemistry, and the California NanoSystems Institute at UCLA)
"Innate immunity, autoimmunity, and self-assembly"
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 to just 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 the molecular designs are changed for marine AMPs that must work at high salinity.