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Center for Nonlinear Studies |
My research combines experimental and theoretical techniques to understand the molecular basis of the initial signaling events in mast cells. Biochemically, the signal is initiated when IgE receptors on the cell's plasma membrane are cross-linked by antigen, forming a cluster of receptors. The plasma membrane itself, consisting of liquid ordered and liquid disordered lipid phases, is then thought to play a role in mediating the initial recruitment of kinase to the IgE cluster. I developed a theoretical framework based on the Ising model to quantitatively study the role of the plasma membrane in biochemical reactions. Given a cluster of receptors in a particular configuration, the model calculates how strongly a kinase of the same lipid phase preference is recruited to the cluster. Using this framework, I predict how features such as cluster size, receptor spacing, and composition of the membrane affect the extent of kinase recruitment. To test these ideas experimentally, I visualized this signaling system in intact cells using STORM, a super-resolution fluorescence microscopy technique with 20 nm resolution. This allows for quantification of IgE clustering, as well as the ability of clusters to recruit signaling partners such as the kinase Lyn. Cells are stimulated with structurally defined ligands to form IgE clusters of well-defined size and receptor density. I evaluate what stimulation conditions lead to most effective kinase recruitment, and compare these results with the predictions from the Ising model.
Host: Bill Hlavacek