Mike Pablo | Elston Lab

PhD Candidate, Biological Chemistry at UNC – Chapel Hill, Elston & Hahn Labs
Member of the Molecular & Cellular Biophysics Training Program

mikepab@live.unc.edu
I’m interested in how signaling networks encode the spatiotemporal organization of molecules within cells. I use image analysis, statistical modeling, and computational simulations, in collaboration with Hahn Lab experimentalists, who perform live cell microscopy and optogenetic experiments, to understand mechanisms that shape molecular distributions over time and space. My main focus is on polarity establishment in yeast and FcgR-mediated phagocytosis in mammalian systems.

We investigated the role of molecular fluctuations on yeast polarization by performing particle-based simulations of a Cdc42-centric polarity model. Individual molecules were treated as point particles subject to probabilistic reaction and diffusion; active Cdc42 molecules are shown. Initially, random activation of Cdc42 creates an unpolarized distribution, but competition for molecular components needed to sustain the polarity patch leads to a single resolved site. We found that stochastic effects enhance the speed and robustness of this process versus the corresponding deterministic system.

We are interested in characterizing signaling architectures that can form precisely organized structures. We used phagosynapse formation in FcgR-mediated frustrated phagocytosis as a model experimental setup, in which an F-actin ring forms around a IgG patch printed onto a coverslip. To identify signaling motifs compatible with this behavior, we applied an evolutionary algorithm to generate ensembles of reaction-diffusion PDEs capable of mimicking the F-actin ring on a circular domain. Shown are a variety of ring-forming systems. Applying constraints based on experimentally-observed ring formation dynamics, or the distributions of other molecular species, will allow us to refine our system of models, and characterize signaling motifs consistent with phagosynapse formation.