This program is devoted to understanding the way in which blood coagulation is initiated when blood contacts damaged tissues. In general, it is thought that the mechanism involves the formation of a complex between tissue factor, a specific glycoprotein found on many cell types, and factor VII, a protein that circulates in the blood. In project 1, we will be focussing on the mechanisms and kinetics of this interaction both in traditional, static systems, and an """"""""open"""""""" flow system developed in our laboratory. In project 2, measurements of this interaction will be made utilizing fluorescence and other biophysical techniques. In project 3, we will be studying the regulation of the tissue factor gene in vascular tissue. In project 4, the kinetics of feed-back regulation on the tissue factor pathway of coagulation will be studied. Project 5 is devoted to the flow reactor with a special emphasis on flow profiles. Here, both experimental data and computer simulation of laminar flow and disturbed flow will be evaluated. In project 6, the emphasis will be on producing mutations in the tissue factor protein that will be used for structure/function studies in the other projects. Taken together, these projects will enable us to describe this important initiation reaction in terms of the physical chemistry, biochemistry, genetics and regulation.
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