188. EFFICIENT DETECTION OF POINT MUTATIONS THROUGH SHEAR-INDUCED UNZIPPING OF HYBRIDIZED DNA

Department: NanoEngineering
Faculty Advisor(s): Gaurav Arya

Primary Student
Name: David Szeto
Email: daszeto@ucsd.edu
Phone: 858-822-5542
Grad Year: 2012

Abstract
Detection of DNA point mutations with high sensitivity and accuracy constitutes a major bottleneck towards the successful diagnosis of genetic diseases like cancer. Recently, our collaborators have devised a novel experimental assay to detect mutations within a single-stranded DNA (ssDNA) target. The assay involves shear-induced unzipping of the target hybridized to ssDNA probe tethered to the surface of colloidal particles, where the probe is designed to be complementary to an unmutated target. The presence of mutations in the target is then detected through fluorescent quantification of the hybridized targets, which gives different results for mutated and unmutated targets. In my research project, I am utilizing coarse-grained models of ssDNA and Langevin dynamics simulations to optimize the design of the probes so as to maximize the difference between the shear-induced hybridization kinetics of mutated and unmutated targets, thereby maximizing the sensitivity of the assay. Our approach involves simulating the effects of mutations introduced at different locations along a dsDNA molecule and varying shear rates. Preliminary results indicate that unzipping rates can change by as much as a factor of 2 depending on the location of the mutations and the applied shear rate. Our results demonstrate the usefulness of computational methods in optimizing next-generation nanoscale diagnostic devices.

Related Files:

  1. TimevsDNAUnzipping.png

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