Grant: Operating Grant

We study how signals in a tissue environment govern the proliferation and behavior of the cells within the tissue. We focus on a molecule called the epidermal growth factor receptor (EGFR), whose excessive activity is associated with tumor growth. These studies, carried out in the fruit fly model system, will help us to understand the factors that influence whether cells can respond to EGFR activity, thus improving our understanding of cancer mechanisms. For example, identifying a molecule that makes cells resistant to EGFR activity in the fruit fly may provide useful insight for the development of strategies to block this activity in tumor cells. Previous work in the fruit fly ovary has shown that certain cell behaviors are restricted to specific regions of the tissue where EGFR is activated. However, later work showed that switching on EGFR activity parts of the tissue where it is not usually active does not necessarily result in the expected changes in cell behavior. These findings prompted the hypothesis that some cells in this tissue are naturally resistant to EGFR activity. To investigate the cause of this resistance, we will study these cells further by using a variety of experimental tools to artificially activate EGFR and observe the effect on cell behavior. In addition, we will study a mutant strain of fruit flies in which this tissue seems to be inherently more sensitive to EGFR activity; by identifying the gene that is mutant, we will learn which more about why normal cells can be resistant. This work will advance our knowledge of how sensitivity to EGFR activity is regulated. Increased EGFR activity is found in a variety of human tumors and is one of the most common defects associated with breast cancers. Since fruit fly genes are so similar to human genes, understanding the factors that inhibit or promote responsiveness to EGFR in this system may provide important targets for therapies, complementing those that target EGFR activity.