Seminar speaker – Dr. Catherine Grimes, Department of Chemistry and Biochemistry, University of Delaware
Title of the Talk: Chemical Tools for Studying the Activation of the Intracellular Innate Immune Protein Nod2
Time and Location: Wednesday, April 6, 11:00 am – 12:00 pm, Room C121
Abstract:
Chronic inflammatory disorders, such as Inflammatory Bowel Disease, arise from an inappropriate immune response to bacteria. In order to treat these diseases, we need a better understanding of how the innate immune system senses and responds to bacteria. It has long been known that muramyl dipeptide (MDP), a fragment of bacterial cell wall (peptidoglycan), is able to generate an immune response. Recently, it has been shown that the intracellular, mammalian protein Nod2 is involved in sensing the presence of MDP in the cell, leading to activation of the synthesis of inflammatory molecules. Nod2 is an important protein to human health, as mutations in the gene have shown an increased incidence of Crohn’s disease.
The mechanism of activation of the Nod2 signaling pathway by MDP is not understood. For example, it is not known if MDP directly interacts with Nod2. We have taken a chemical biological approach to this problem by synthesizing tagged versions of MDP. This tool was then utilized to probe for an interaction between Nod2 and MDP. We describe the development of a variety of binding assays and present a model for Nod2 activation via MDP. Our approach has led to a deeper understanding of the biophysical mechanisms used by the innate immune system to sense bacteria.