Many if not most human organs have ducts or tubes that contribute to organ function. The molecular and genetic mechanisms that direct cells to form the walls of tubes surrounding open lumens are not fully elucidated. This project aims to address the question "How do cells form tubes?" There isn't just one answer to this question because the cellular rearrangements contributing to tube formation in different organs and even within different areas of a single biological tube are varied. However, it is important to understand multiple specific examples of tube formation because failure of these biological programs can result in birth defects (for example, lack of connection between two tubes such as the esophagus and the stomach), and excess activity of these programs can contribute to disease (for example, blood vessel formation promotes tumor growth). This project will focus on understanding tube formation in the reproductive system in the microscopic nematode C elegans. Genetic approaches will allow discovery of new genes affecting tubulogenesis. By using microscopy on live developing tissues, the specific changes in cell structure that accompany tube formation will also be determined. Many biological mechanisms first revealed in C. elegans have proven relevant to all metazoans. Thus, the project has broad intellectual merit because tubulogenesis principles elucidated in C. elegans will have corollaries in other systems and, thus, wide-reaching significance to our understanding of organ formation. A core part of this project is a formal course with an integrated research component that will serve to recruit and train undergraduate students to pursue advanced degrees in biology. Similarly, graduate students will be trained in preparation for independent science careers. Thus, the project has broad merit in the educational realm as well. An important outcome from the completed study will be the preparation of the next generation of scientists.
