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About the Lab Understanding the genesis of abnormal rhythms in organ systems that require precisely timed electrical signaling for normal function has been a long and widely sought goal. The wealth of genetic information accumulated in the last decade has enabled the identification of precise genetic origins for a number of diseases that arise from abnormal electrical activity. While revelation of the genetic basis of disease is crucial, a major challenge is to understand precisely how genetic abnormalities disrupt normal functioning of cells and organs to cause disease. A common approach for making connections between genes and systems is through experimentation on animals. Our goal is to develop novel theoretical approaches. To this end, we aim to develop mathematical models of specialized proteins, called ion channels, which control electrical activity in cells and organs. |
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| An example is the heart, where precisely timed electrical signals determine heart rhythm. In the brain, electrical signals are required for many normal brain functions, including memory storage and retrieval. Precisely timed "turning on" and "turning off" of ion channels allows controlled movement of ions across membranes, a property that is required for healthy organ function. Genetic mutations in regions of DNA that contain instructions for building ion channel proteins can lead to abnormal protein structure and disrupt the opening and closing. The behavior of normal and abnormal channels can be described using mathematical expressions that are derived from experiments. We can then integrate these channel models into "virtual cells" to begin to address the following questions, "How do these abnormal openings and closings lead to the disease? What are the effects of abnormal protein functioning on cellular, tissue and organ level electrical activity?" |
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