The fundamental goals of this project are to test the hypotheses that: 1) nanoscale topographic features of the substratum underlying corneal epithelial cells modulate the distribution of cytoskeletal elements 2) nanoscale topographic features alter the expression and clustering of integrins at focal adhesion sites 3) inactivation of G-proteins, such as Rho, modulate the impact that nanoscale topographical features of the substratum have on cell behaviors. These investigations will provide insight into the effects of substratum topography on cytoskeletal response and related cell signaling pathways. Completely synthetic matrices will be used that have nanotextured surfaces with features of similar type and dimension to that of the """"""""native"""""""" corneal epithelial basement membrane. This allows the impact of nanoscale substratum topography, independent of specific ligand- receptor mediated events, to be evaluated. It is possible that improved cell performance will be observed on nanoscale textured synthetic surfaces providing preliminary evidence on techniques to improve epithelial cell performance on corneal prosthetics. The candidate of this application has obtained the DVM degree and specialty training in Comparative Ophthalmology. This proposal will coincide with achievement of the Ph.D. degree which will provide a firm foundation for a career as an independent clinician/biomedical researcher. The training environment: In addition to having state of the art facilities, the University of Wisconsin fosters a rich collaborative environment between disciplines. The training program will be focussed on development of the candidate into a successful, independent, biomedical researcher fully prepared to launch a successful career as a clinician/scientist. The majority of supervision will be provided by Christopher J. Murphy, an internationally known investigator in the areas of corneal wound healing and neuropeptides. The mentoring committee consists of respected experts in cell signaling and cytoskeletal interactions, nanoscale topographic surface fabrication, and imaging techniques.
