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

Our laboratory investigates the molecular mechanisms of the vertebrate immune system. We are particularly interested in protein aggregates, namely “functional aggregates”, that play increasingly important and common functions in immune systems. Our interest in functional aggregates started with our investigation of the innate immune receptors, RIG-I-like receptors, which recognize viral RNAs during infection and activate the antiviral immune response. We discovered that RIG-I-like receptors and their downstream signaling molecules assemble into higher order oligomers (i.e. filaments) during viral RNA detection and signal transduction. We additionally showed that their functions depend upon tightly controlled assembly and disassembly processes to prevent aberrant protein oligomerization/aggregation and immune activation.

These findings have also led us to explore other functional aggregates in different biological contexts, such as transcriptional regulation in the adaptive immune system. Our on going work on one such transcription regulator, AIRE, suggests a novel mechanism in which functional protein aggregation plays an important role in transcriptional remodeling during T cell development.

Altogether, our work continues to focus on identifying new molecular principles of functional aggregates in the immune system involving nucleic acid biology: (A) antiviral innate immunity and (B) transcriptional regulation of immune functions.

Recent publication highlight: Ahmad et al, Cell 2018

Read more at https://vector.childrenshospital.org/2018/02/mda5-autoinflammatory-disease/