THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION (Taken from applicant's Abstract) The broad, long-term research interests for the principal investigator are (1) correlations between normal bladder structure and function (both epithelium and bladder wall are of interest), (2) pathophysiology leading to abnormal structure, (3) relationships between abnormal structure and functions. The specific focus of this project will be how bladder wall smooth muscle and connective tissue development is affected by increased intravesical pressure (created by ligating the urethra and ureters of fetal bladders in organ culture). The project will also include normal bladder development because little is currently known about normal development. The underlying hypothesis is that normal bladder development follows a specific program of changes, and that this program is accelerated by ligation. The changes include (1) decreased ratio of collagen to smooth muscle, (2) shift in collagen fiber type and organization to promote flexibility, (3) increase in elastin fibers, (4) increase in smooth muscle a and g actin isoforms while b actin decreases, (5) replacement of fetal-type myosin light chain (LC-23) with adult type (LC-17), (6) change in myosin light chain phosphorylation from fetal to adult pattern. The plan is to evaluate bladder structure on macroscopic, microscopic and ultrastructural levels, and to compare the above features under different conditions of bladder development.
Specific Aim 1 will determine the normal in situ developmental program.
Aim 2 will compare in situ bladders with bladders grown in organ culture.
Aim 3 will compare bladders in organ culture: unligated vs. with the urethra and ureters ligated.
In Aim 3, intravesical pressure will also be compared for the two conditions. The project has clinical relevance because intravesical pressure changes are thought to affect bladder wall smooth muscle and collagen in several disease states such as spina bifida and benign prostatic hyperplasia. In addition, useful extension are planned including (1) correlation of structural with functional changes in this model and (2) expanding this model to study bladder epithelial development and the roles of stromal- epithelial interactions.
