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Thursday, February 08, 2018
2:00 PM - 3:00 PM
CNLS Conference Room (TA-3, Bldg 1690)

Seminar

Model-driven characterization of immunoreceptor signaling dynamics

Ryan Suderman
T-CNLS

The immune response is driven in part by cellular response to antigens. Immune cells display antibodies bound to immunoreceptors on their surfaces for antigen detection. In particular, mast cells display the antibody immunoglobulin E (IgE), which is well-known for its role in anaphylaxis. We developed a series of dynamical models to examine the interaction between FcεRI (the IgE-bound immunoreceptor) and Syk (an intracellular signaling protein). This interaction is a key step in regulating degranulation, which is the release of inflammatory agents into the local extracellular environment. Experimental evidence shows that a mutant form of Syk, which inhibits degranulation, has a slightly shorter lifetime of interaction with FcεRI compared to wild-type Syk. In our models, we look at potential mechanisms of signal quality control that may explain how a seemingly small difference in interaction lifetimes results in completely different cell behavior. As simple models cannot explain this behavior, we propose a new mechanism for the Syk, FcεRI interaction, consistent with available experimental data and based on the physical structure of the FcεRI immunoreceptor.

Host: Chris Neale