Receptor Tyrosine Kinase (RTK) signaling to actin cytoskeleton
Bacterial pathogens and some viruses hijack actin cytoskeleton of the host cells. They propel themselves with actin comet tails or attach to the protruding actin pedestals. Most of these pathogens exploit a signaling pathway through the adaptor protein Nck. We developed an antibody-mediated aggregation system to induce localized actin polymerization. We also have a quantitative model of the actin comet tail which reproduces experimentally observed results. I study differences between the locally induced actin comets and pedestals. Understanding these differences will shed light on signaling, dynamics and molecular mechanisms taking place in localized actin structures.
Regulation of actin dynamics by Cofilin and Capping proteins
Actin polymerization underlies many biological processes. It is controlled by numerous actin binding proteins. Capping protein caps barbed (fast growing) ends of actin filaments. Cofilin severs actin filaments into smaller fragments. Our computational model predicts how these two proteins act together to promote or inhibit actin polymerization. I am designing an experimental system to manipulate Capping and Cofilin concentrations in motile cells. I will use this system to test the modeling hypothesis and learn how actin dynamics is co-regulated by Cofilin and Capping proteins.
Quantitative and mechanistic aspects of Nck function in tyrosine kinase signaling to the actin cytoskeleton.
Tyrosine kinase signaling leads to the post-translational modification of proteins and their binding partners. These modifications recruit tyrosine kinase binding partners, promoting an increase in their local concentration, which results in a cellular response to the phosphorylation of tyrosine residues. Nck, an adaptor protein, functions in tyrosine kinase signaling by linking tyrosine phosphorylation on the membrane with binding partners that function in facilitating actin nucleation and polymerization. However, quantitative and mechanistic aspects of signaling through Nck remain poorly understood. To explore Nck linkage to the actin cytoskeleton, our lab developed a system in which Nck SH3 domains can be aggregated on the plasma membrane following antibody application. Aggregation of Nck SH3 domains results in localized actin polymerization in the form of actin comet tails. Using the Virtual Cell, we have built a comprehensive, quantitative actin cycle model. With this model, we have produced predicted results that have been confirmed in vivo. This model predicts experimental comet tail length, actin distribution within the comet tail, and maximum actin concentration in the tail based on the number of molecules in the aggregate and the speed at which the aggregate is moving across the cell surface. The combination of modeling and experimentation provides unique insights into the relationship between increased local concentration of Nck and resulting localized actin polymerization.
Favorite thing about UCHC/Hartford Area
Parks, tranquility, proximity to New York.
Find me on LinkedIn Hobbies: soccer, camping, American football, crochet, cooking Languages: Russian