One of the most fundamental aspects of animal development is the control of the cell division cycle. Without this control there would be no coordination between cell proliferation and the formation of the gross anatomy of an organism. In my lab, we are interested in understanding how the molecular processes that establish pattern formation and determine cell fate decisions during Drosophila development control the cell cycle. We use genetic and biochemical approaches to examine how specific cell cycle regulators (e.g. E2F, cyclins, cdks) function, and then use this information to explore how their activity is influenced by different developmental programs.

In the past several years it has become apparent that the structure and function of molecules controlling the cell cycle are highly conserved between mammals and Drosophila. This allows us to exploit certain advantages that Drosophila has over mammalian systems for studying growth control and cell cycle regulation. One important advantage is the ease with which molecular genetic approaches can be applied to the study of gene function in the context of a whole animal. Another is the relative simplicity of fruit flies: the study of many mammalian cell cycle regulators is complicated by the existence of gene families whose members have overlapping or redundant functions, whereas the Drosophila homologs of these molecules are often encoded by single genes. Genetic analyses of these genes in Drosophila provide a powerful tool for understanding the fundamental roles of cell cycle regulators in controlling cell proliferation. In this way Drosophila can contribute important information for understanding aspects of the deregulated growth typical of cancer.

Current research projects focus on how gene expression is controlled during the cell cycle, with a particular emphasis on the G1-S transition. The E2F family of transcription factors plays an important role in regulating the G1-S transition by controlling expression of genes encoding components of the replication machinery. We have isolated mutations in each of the E2F genes in Drosophila. The consequences of these mutations on cell cycle progression and development in several tissues is actively being analyzed using several techniques, including sophisticated microscopy, molecular genetics, and DNA microarray analysis. We suspect that E2F activation provides a way of linking developmental signals that control cell fate with cell cycle progress. Other projects are designed to understand how histone mRNA expression is cell cycle regulated, and how ubiquitin mediated proteolysis contributes to S phase control.