Analysis of Mechanisms in Stimulous-Secretion Coupling

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WPC 2 B R V ` Z #| x Courier 10cpi 2 x x x , x @ 8 ; X @ HP Laserjet (25-in-one, Network) HPLASEII.PRS x @ , t 0 NX @ 2 B ~ # x 6 X @ 8 ; X @# ( 9300799 Keizer The long term objective of this project is to understand the molecular mechanisms that control secretion of hormones from cells in response to various types of stimulatory events. These mechanisms, which are currently being uncovered by experimentalists, least to complex phenomena involving oscillations and waves that require the use of mathematical and computational analysis for their understanding. Of particular interest are 1) the mechanisms controlling calcium oscillations and waves in secretory cells; 2) the mechanism involved in agonist stimulation of G protein events, especially, control of ion channels in the pancreatic beta cell; 3) the mechanisms underlying the 2 5 minute period calcium oscillations in insulin secretion from pancreatic secreting cells that are under the control of glucose metabolism; 4) the mechanisms involved in the control of electrical activity and calcium levels in anterior pituitary gonadotrophs; and 5) the mechanisms responsible for the 15 30 period oscillations in insulin secretion from pancreatic islets in vitro. The method employed by the principal investigator involve the development and analysis of ordinary and partial differential equations corresponding to mechanisms uncovered by experiment. Sufficient quantitative information regarding the rates of these five mechanisms is available to justify these calculations, which will continue to be interfaced closely with experimental work. The computational work will be done on a parallel architecture platform. This proposal is being jointly supported by the Cell Biology, the Computational Biology, and the Applied Mathematics programs. ***