A complete understanding of animal development and physiology requires examining many cells of the same type in culture. These cells allow detailed investigations that are not possible while the cells are within their tissue in an intact animal. This work is being performed in Drosophila melanogaster, which has been an important genetic model for over a hundred years and for which it has not been possible to make cell lines. A novel strategy is being used to generate Drosophila cell lines, which will benefit many types of investigations. These lines will be distributed to the scientific community through by the Drosophila Genomics Resource Center. In addition to enabling many new types of important research, this project will enhance the development of the scientific workforce by including students in the project. In particular, undergraduate interns in a summer research program, drawn from all over the country, will work on developing and characterizing the cell lines. The summer program is co-directed by the investigator and is targeted to students from other universities and colleges who have limited access to research and are from groups underrepresented in science.
This EAGER project is using an innovative strategy to produce Drosophila cell-type specific cell lines. This strategy involves manipulating the expression of tumor suppressor genes via a new drug-inducible system. It is expected that expressing RasV12 reversibly in a tissue-specific manner will enable the generation of cell-type specific cell lines. Accordingly, each cell line will be allowed to propagate with high RasV12 expression, and then allowed to differentiate by turning off RasV12. These methods will be used on starter cells derived from different embryonic tissues to produce cell lines of three major cell types: epithelium, muscle and neuron. The lines will be validated, characterized, and distributed to investigators. They will enable many novel and essential experiments, such as genome-wide screens for new genes involved in epithelial cell polarity, myoblast fusion, and neurite outgrowth.