Polymerization of actin filaments is the underlying mechanism of various biological processes such as cell growth and motility. In this project we construct a series of computational models, with increasing level of detail and complexity, in order to analyze the dynamics of the polymerization process. We will find the conditions under which stochasticity plays a significant role, and will analyze the sensitivity of the system to perturbation in the various kinetic parameters.

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The contractile function of the heart is determined by factors including cavity volume, wall thickness, internal pressure, intrinsic muscle property, and circumferential stress and strain. In this study, we used the Law of Laplace to investigate how left ventricular (LV) geometry and the heart’s intrinsic properties impact chamber function during passive inflation. The geometric parameters were identified by means of image analysis of MRI scans of a healthy and failing mouse heart, while the end-diastolic pressure (EDP) and muscle property parameters were identified from literature.

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Changes in cardiac action potential duration and morphology can result in the development of arrhythmias. These changes are either a result of a congenital disorder, such as Long QT Syndrome, or the result of a pharmacological agent which blocks one or more channels in the ventricular myocyte membrane. Predicting the multitude of effects from specific channel blocks can be difficult and expensive to test experimentally. One way in which one can observe the effects of these blocks is to use a computational model and quantifiably block channels at different drug affinities. I used the TNNP model of the human ventricular myocyte and the computational program Matlab to run these hypothetical experiments. This predicted how the action potential duration and morphology were altered when more than one channel was blocked at a time. I then performed a partial least squares (PLS) linear regression on the TNNP model, which showed which ion channels had the greatest effects on action potential duration and morphology. Finally, I compared slopes taken from normalized action potential duration curves with the linear regression coefficients in order to see if there existed a correlation between combinatorial drug blocks and the results of the linear regression analysis.

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My project is the construction of a spatial model based on partial differential equations and using the software Virtual Cell. My goal is to simulate ERK nuclear translocation and explore two different theories on MEK's control over ERK localization in the MAP kinase pathway. I will use Virtual FRAP, a software tool to analyze FRAP experiments and estimate diffusion parameters.

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In this project we have developed a Flash-based cell signaling pathway viewer which provides interactive web-based display of cell signaling pathways. The viewer accepts XML input files to display pathways on any web-page. To demonstrate the usability of this viewer we implemented PathwayGenerator2, a web-based system that automatically generates cell-signaling pathways from mammalian cells connecting multiple receptors to multiple transcription factors.

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Many cardiac arrhythmias are thought to result from disruptions in intracellular calcium (Ca2+) cycling, specifically from increased "leakiness" of the ryanodine receptor (RyR), the key intracellular Ca2+ release channel in the heart. I am using an integrative mathematical model of Ca2+ cycling in ventricular myocytes to explore how RyR leak interacts with Ca2+ entry into cells and triggering of Ca2+ release to either increase or decrease arrhythmia risk.

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