9728382 Peters The aim of this research is to determine how the macromolecular organization of fibronectin fibrils and its biological activities are regulated. As one of the major proteins found in the extracellular matrix, fibronectin in organized into an insoluble fibril where it plays a major role in promoting cell adhesion, migration, and growth in vertebrates during embryogenesis. At least twenty different isoforms of fibronectin are expressed during different developmental stages. Although the functional significance of these isoforms are unknown, it is speculated that they regulate the conformation and assembly of fibronectin fibrils so as to favor, or discourage, certain biological activities. The PI recently found that fibronectin fibrils have at least two different conformations, suggesting that the conformation of the fibrils may regulate its biological activity. She plans to study 1) the conformation of fibronectin isoforms and how they affect the assembly of fibrils; 2) the macromolecular organization of the fibrils; and 3) whether the fibrils are flexible structures that undergo conformational changes that regulate the expression of biological domains on their surface. High resolution immunoelectron microscopy, protein biochemistry, and molecular biology will be applied to this problem. Fibronectin is one of the major proteins found in the extracellular matrix, where it forms fibrils that play a vital role in regulating cell adhesion, migration, and growth in vertebrates during embryogenesis. This project addresses the hypothesis that regulation of these diverse biological activities by fibronectin varies with different forms of fibronectin as well as with different conformations of the fibrils. Electron microscopy as well as biochemical and molecular biological techniques will be employed.

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Application #
9728382
Program Officer
Parag R. Chitnis
Project Start
Project End
Budget Start
1998-03-01
Budget End
2002-02-28
Support Year
Fiscal Year
1997
Total Cost
$270,000
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53715