Understanding the Biochemistry of Innate Immunity
We study the activation of the innate immune system by bacterial threats. The innate immune system is
the body’s first line of defense against invading pathogens. This ancient system has evolved to live in a
symbiotic relationship with some commensal bacteria and at the same time recognize and destroy
virulent bacteria. Understanding the molecular details of this system is extremely important, as chronic
inflammatory disorders, such as Inflammatory Bowel Disease, arise from an inappropriate immune
response to bacteria.
Our program focuses on a class of proteins in the innate immune system known as the Nod-Like
Receptors (NLRs). These proteins police the intracellular space of the cell for bacteria and/or their
traces. NLRs are called receptors and are assumed to bind bacterial-derived fragments. However, no
biochemical or biophysical data exist for these proposed interactions.
For each NLR that we study, we ask three fundamental questions:
(1): How and where are the immunostimulatory molecules of bacterial cell wall generated?
(2): Do these bacterial molecules interact with a given NLR?
(3): How is the NLR activated for down-stream signaling?
In order to answer these questions, we make use of a variety of techniques such as protein expression,
solution and solid phase binding assays and mass spectrometry.