Merck Genome Research Institute Grant Helps Fox Chase Cancer Center Develop Laboratory Tools to Test for Protein Interactions in Cells

PHILADELPHIA (November 2, 1998) -- Dr. Erica A. Golemis, a molecular biologist at Fox Chase Cancer Center who lives in Oreland, Pa., has received a one-year, $84,700 grant from the Merck Genome Research Institute (MGRI) at West Point, Pa., for further development of research tools to study cellular protein interactions.

Within each cell of our bodies, genes order the production of thousands of proteins to carry out or halt particular biological processes. Since many proteins act in concert with other proteins, studies of these diverse interactions are fundamental to determining what individual proteins do and how defects may lead to cancer or other diseases. For example, if a gene that normally shuts down cell division or growth is damaged, this mutant gene may give rise to cancer by generating a protein that functions abnormally or failing to produce enough normal protein to suppress tumor growth.

Golemis uses yeast cells as tools to determine how such anticancer genes and their proteins function. She has devised a genetic screening system based on introducing a "library" of human genes into yeast-cells. She then looks for characteristic changes in cell shape and growth patterns that might predict cancerous changes in human cells.

Working with other investigators, Golemis has also invented the "Interaction Trap," a type of yeast "two-hybrid" system for identifying the interaction of two proteins. Scientists use two-hybrid systems to study a number of protein classes.

With the support of the new MGRI grant, Golemis is working to refine the two-hybrid technique by developing new reagents--proteins or chemicals used to detect the presence of another substance--that will improve the accuracy and speed of the test.

"We are in the process of creating a second-generation reagent set that should considerably enhance the reliability and general utility of two-hybrid systems," she said.

The new system incorporates controls for false positives or non-specific interactions in a single step. Called a "Dual-Bait System," the advanced Interaction Trap-based test will also allow efficient simultaneous testing for a protein interaction with two related or non-related partners in a single cell.

This latter feature would permit simultaneous comparison of both a normal and a mutant form of the same protein. Such a test may be of particular use in conjunction with the development of highly targeted new drugs.

The nonprofit Merck Genome Research Institute was established to support the development of scientific technology that will expedite the analysis and understanding of human genetic traits and help determine the biological function of genes associated with specific diseases. The Institute encourages and sponsors projects that enable scientists to develop innovative assays and methodologies aimed at improving the accuracy and speed in which functional associations can be made with gene sequences. Further information about MGRI and its programs can be found at www.mgri.org.

Fox Chase Cancer Center is one of 34 National Cancer Institute-designated comprehensive cancer centers in the nation. The Center's activities include basic and clinical research, prevention, detection and treatment of cancer and community outreach programs.