Biological Physics of DNA Bending

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

Title: Biological physics of DNA bending DNA is one of the essential molecules of life, carrying the genetic information of a cell. The mechanical properties of DNA are related to the ability of different protein complexes to bind to DNA, and control gene expression and DNA repair. Understanding DNA mechanics, especially at short length scales, ends up being more complicated than the mechanics of more classic materials such as an elastic rod, given the double-helical nature and inhomogeneous building blocks of DNA. This research will produce physical insights that will advance our understanding of the relationship between DNA mechanics and several important DNA-related biological processes. In this project, the PI will investigate how sharp DNA bending promotes tight packaging of the genome, local defects in the double helix, and protein transport between DNA sites, all features that have implications on gene expression and DNA repair. The PI will train undergraduates in his lab and offer scientific demonstrations to K-12 students. Despite the current atomistic-level knowledge of DNA structure, conformational changes and fluctuations of DNA at short length scales are not trivial to understand. Especially, spontaneous looping of DNA is highly sensitive to sequence, intrinsic curvature, and length scale. In this project, the PI will investigate how biophysics of spontaneous DNA looping impacts DNA-protein interactions. In the first aim, the PI will measure stability of small DNA loops as a function of nucleosome preference. This aim will address whether the sequence rule of nucleosome formation can be better understood from DNA mechanics in the strong bending regime. In the second aim, the PI will measure stability of small DNA loops with and without highly meltable regions. This aim will address whether strong DNA bending can enhance local melting of duplex DNA. In the third aim, the PI will measure association and dissociation kinetics of DNA binding proteins in various DNA constructs. This aim will address whether DNA looping can facilitate protein transfer. The PI will use single-molecule fluorescence techniques and coarse-grained DNA models to conduct this research.