Fluorescent Probes for DNA Mismatch Detection
Initial Award Abstract
Lung cancer is the leading cause of cancer death for both men and women in California and the entire United States. The development of early diagnostics and screening for lung cancer is imperative to reduce mortality. The incidence of lung cancer is closely related to tobacco smoking. In fact, tobacco smoking is found to cause several other cancers as well. Tobacco smoke contains many carcinogens, which cause DNA damage and render cells prone to cancerous transformations as DNA mismatches and mutations accumulate. Cells that are deficient in DNA mismatch repair ability will be particularly vulnerable to alterations in their DNA caused by carcinogens, and thus are more likely to become cancerous.
In this proposal, we hope to detect DNA mismatches using novel fluorescent sensor molecules. We aim to design and synthesize sensor molecules that will signal the presence of DNA mismatches by both binding at the mismatches and emitting light: strong fluorescence signals indicate the presence of DNA mismatches; in the absence of mismatches, the signals will be too weak to be detected. We will apply the sensor molecules to directly image biological samples with differing degrees of mismatch repair proficiency. Our approach, if successful, would allow rapid, sensitive detection of DNA mismatches and mismatch repair deficiency for early cancer diagnosis. |