CAREER: Investigating Epithelial Tube-Size Control Mechanisms Using the Drosophila Tracheal System

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The proposal outlines an integrated plan of teaching and research that will provide a solid foundation for the awardee's future contributions to education and science. The first undergraduate educational aims are to develop the awardee's teaching skills and to improve the current undergraduate cell biology course using the resources of Northwestern University's Searle Center for Teaching Excellence. The second undergraduate educational aim is to provide undergraduate research opportunities by having some of the proposed research aims performed by summer undergraduate researchers. The graduate education aims include organizing a new developmental genetics course and a new presentation series. The proposed research focuses on understanding the mechanisms underlying morphogenesis of epithelial and endothelial tubes. Despite the importance of correct tube diameter and length to the function of organs such as the vascular system, lung and kidney, there is little understanding of the complex cytoskeletal and extracellular matrix changes, dynamic rearrangement of cell-cell junctions, or coordinated cell shape changes that create tubes of particular sizes. To identify and study the functions of genes required for tube-size control, the proposed research will use molecular/genetic approaches to investigate morphogenesis of the Drosophila tracheal system, a ramifying network of epithelial tubes that functions as a combined pulmonary/vascular system. Previously, mutations in a group of eight genes that specifically control tracheal tube size have been identified. It has now been determined that one of these genes encodes a b-subunit of a Na+ K+ ATPase transporter and that mutations in the Na+ K+ ATPase a-subunit a-ATPase(93A) cause similar tracheal tube-size defects. Preliminary data suggests that the Na+ K+ ATPase is required to organize tracheal cell junctions, a novel role for a Na+ K+ ATPase. To better understand the mechanisms of epithelial tube-size control and the roles of the Na+ K+ ATPase, the genetic and cell biological functions of a-ATPase(93A) during tracheal tube morphogenesis will be investigated. In addition, the tracheal tube-size control gene varicose that genetic epistasis experiments suggest acts in parallel to the Na+ K+ ATPase will be cloned and characterized. Together, the analyses of a-ATPase(93A)and varicose will improve the understanding of the basic cell biological and molecular mechanisms of epithelial and endothelial tube-size control.