> Simultaneous with the explosion in computer speed and ability, >the biological sciences have been undergoing a revolution. There has >also been an explosive increase in the quantitative understanding of the >fundamental building blocks of life. The emergence of molecular biology >has defined biology with mathematical precision through the genetic >code. We now have the tools to study and manipulate biology at the level >of individual molecules. This has resulted in an explosion of data. This >project examines how one class of molecules, ion channels generates, >controls and coordinates normal and abnormal electrical activity in the >heart. Recently developed techniques in molecular biology can tell us the >tissue distribution of an ion channel type over the entire heart, down to >microscopic resolution. Previous techniques could only provide >resolution down to a few millimeters and the currents from only a few >cells could be measured within this space. Thus, molecular biology has >provided us with a several orders of magnitude increase in information >concerning the density, cellular and tissue distribution of the excitable >elements in the heart. This is a several orders of magnitude increase in >information over that available only a couple of years ago. It is a major >computational challenge to organize, display, interpret and utilize this >new information. This project will develop the computational tools to >analyze this molecular information from a systems point of view. This >proposal seeks to develop the mathematical and computational tools to >integrate this emerging data from molecular to organ function in cardiac >muscle. It will develop efficient methods to look at how patterns of >electrical activity in individual cells are coordinated across the entire >heart and how slow molecular processes, i.e. memory, influence events >which occur on millisecond time scales during regular beating of the >heart. > Ion channels are found in all living cells. Coordinated ionic >responses arising from multicellular interactions are an integral part of >the physiology of many organs. Chaotic behavior and abnormal electrical >activity is not only a problem in the heart where it may underlie fatal >arrhythmias, but also plays a role in neurological disorders such as >seizures. Action potentials and electrically coordinated activation of ion >channels occurs across a wide variety of species. Similar mechanisms >govern the leaf closing touch response of the Mimosa, heliotropism and >solute transport in root systems. Thus, the mathematical formulation of >coordinated ion channel activity in heterogeneous systems is of wide >application across biology.
