Structural Immunology

Elucidating the Basic Principles of Self vs Non-self RNA Discrimination by the Immune System

The ability to distinguish “self” from “non-self” is fundamental to proper functioning of both the innate and adaptive immune systems. Several pattern recognition receptors in the innate immune system are responsible for the initial detection of foreign molecules such as bacteria-specific membrane components or viral nucleic acids. One challenge in using nucleic acids as discriminators is that they are also present in high concentration and structural diversity in the host, raising the question: what features of nucleic acids distinguish self and non-self.

Our lab is interested in understanding the mechanisms by which pattern recognition receptors recognize foreign nucleic acids and trigger down stream signals for antiviral response. We use a combination of X-ray crystallography, computational modeling/ simulation and a variety of biochemical and biophysical methods. Our goal is to determine the structures, dynamics and functions of these receptors in isolation, in complex with RNAs and in higher order complexes with functional partners in the signaling pathway.