CAREER: A Cell-Based Biosensor for DNA Damaging Agents

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

The objective of this proposed research is the creation of cell-based sensors of DNA-damaging agents. Eukaryotic cells have evolved extremely sensitive and rapid mechanisms to sense and respond to DNA damage. The first stage of this project will quantitatively determine the dose and time-dependence of DNA damage-sensitive gene transcription in the budding yeast Saccharomyces cerevisiae in response to a panel of selected damaging agents. Clusters of genes sensitive and selective for DNA-damaging agents will serve as the basis for biosensor design. Next, the damage-regulated genes will be replaced with reporter genes to facilitate measurement of gene transcription. The third stage of the project will enhance the sensitivity of the cells to DNA damage by disabling endogenous DNA damage pathways. Finally, this project will create new laboratory materials in molecular and cellular bioengineering for undergraduate engineering and high school students. The labs will illustrate the ability to quantitatively control how cells respond to environmental stimuli by altering the genetic makeup of the cells.