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

该提案概述了教学和研究的综合计划，将为获奖者未来对教育和科学的贡献奠定坚实的基础。 第一个本科教育目标是发展获奖者的教学技能，并利用西北大学塞尔卓越教学中心的资源改进当前的本科细胞生物学课程。 第二个本科教育目标是提供本科生的研究机会，有一些建议的研究目标由夏季本科研究人员进行。 研究生教育的目标包括组织一个新的发展遗传学课程和一个新的演示系列。拟议的研究重点是了解上皮和内皮管的形态发生的机制。 尽管正确的管直径和长度对器官（如血管系统、肺和肾）的功能很重要，但对复杂的细胞骨架和细胞外基质变化、细胞-细胞连接的动态重排或产生特定尺寸管的协调细胞形状变化的了解甚少。 为了识别和研究管大小控制所需的基因的功能，拟议的研究将使用分子/遗传方法来研究果蝇气管系统的形态发生，这是一个上皮管的分支网络，作为一个组合的肺/血管系统。 以前，已经确定了一组8个基因的突变，这些基因专门控制气管导管的大小。 现在已经确定，这些基因之一编码Na+ K+ ATP酶转运蛋白的b亚基，并且Na+ K+ ATP酶a亚基a-ATP酶（93 A）的突变导致类似的气管大小缺陷。 初步数据表明，Na+ K+ ATP酶是组织气管细胞连接所必需的，这是Na+ K+ ATP酶的一个新作用。 为了更好地理解上皮管大小控制的机制和Na+ K+ ATP酶的作用，将研究a-ATP酶（93 A）在气管形态发生中的遗传和细胞生物学功能。 此外，遗传上位性实验表明与Na+ K+ ATP酶平行作用的气管导管大小控制基因varicose将被克隆和表征。 总之，a-ATP酶（93 A）和静脉曲张的分析将提高对上皮和内皮管尺寸控制的基本细胞生物学和分子机制的理解。

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.