The FEST Distinuished Young Investigator grant program is administered through the Office of the Vice President for Research and Graduate Studies and aims to reward faculty in their first three years at U.Va. with funding for their pioneering research proposals.
Heart disease is the leading cause of death in the U.S. Researchers know that individual chemical reactions within the heart affect its function and dysfunction but much about the specifics of these interactions and communications remains unknown. “My lab is trying to understand how chemical reactions organize in the heart in order to better understand how the heart responds to disease,” explains Saucerman.
Saucerman is using high-tech approaches to understand these complex biological systems, both experimentally and computationally. Using live-cell imaging technologies, his group can observe individual heart cells growing in cell cultures and monitor how the cells respond to different pharmaceutical drugs. With his powerful, robotized assay, Saucerman will be able to test as many as 96 combinations of drugs in one experiment.
Saucerman will build a number of interdisciplinary ties with the FEST project. Ian Macara, professor of microbiology, will mentor the research. “He [Macara] has been a real leader in the field — integrating models and experiments to understand how cells function,” says Saucerman. In addition, a collaboration with Scott Acton, professor of electrical and computer engineering, will enable the conversion of heart cell images into quantitative data. This automated processing and analysis is accomplished by use of complex algorithms. The resulting data will be used to create computer models that illustrate how the heart and its corresponding pathways respond to therapeutics.
“This is a much more complete way of studying the system,” says Saucerman. “New, sophisticated models will allow us sort through hundreds of candidate drug targets systematically. We hope to substantially reduce the time it takes to make a new drug discovery.”
Saucerman’s lab will begin by testing drugs that are known to affect heart cells in a particular way in order to test and validate the system. Then they will move on to look at combinations of different drugs to determine if they cross-react in positive or negative ways. This will allow insights into whether combinations of drugs will be more effective or have lower side effects, or whether the drugs counteract one another. The FEST funding will be used to fund a graduate student to assist with the project, as well as supplies for the experiments.
This project could open many promising lines of research. “Jeff can indeed make an extraordinary leap forward in systems biology by defining pathway organizational principles per se,” says Tom Skalak, chair of the Department of Biomedical Engineering. “These are likely to be applicable to other disease states and cell types in the future. This is something that is hard to achieve funding for in typical grant venues, yet is the very thing that will lead to non-incremental breakthroughs in the field overall.”Written by Melissa Maki, research communications coordinator for the Office of the Vice President for Research and Graduate Studies.