The Physics of Genome Mapping in Nanochannels
Kevin D. Dorfman
Chemical Engineering and Materials Science, University of Minnesota
January 27, 2017, PSB 160/161, 4:00-5:00pm
Abstract: Genome mapping by nanochannel confinement is an emerging method for obtaining large-scale genomic information at the single molecule level. In this method, large pieces of contiguous genomic DNA, hundreds of kilobase pairs in length, are labeled with a sequence-specific fluorescent probe while the backbone is labeled with a second color. Upon injection into a nanochannel, the labeled molecule stretches due to confinement and the locations of the probes (the “barcode”) are read by fluorescence microscopy.
Engineering DNA barcoding requires understanding two key properties: (i) the fluctuations of the DNA extension, which sets the lower bound for the error in reading the distance between barcodes; and (ii) the friction of the confined DNA, which set the minimum time scale for making uncorrelated measurements. While these quantities are well understood in the case of strong and weak confinement, nanochannel mapping takes place in moderate confinement, where the channel width is commensurate with the length scale for bending the DNA. This is a challenging regime for polymer physics, since there is no separation of length scales, and fluid mechanics, since there is no solution for the Green’s function of the Stokes equation in channel confinement. I will present our experimental and theoretical progress towards understanding the thermodynamics and hydrodynamics of this technologically relevant regime of confined polymers.
Biosketch: Kevin Dorfman is a Professor of Chemical Engineering and Materials Science at the University of Minnesota. He received his PhD in chemical engineering from MIT in 2002, working with Howard Brenner. From 2002-2005, he was an HFSP postdoctoral fellow with Jean-Louis Viovy at Institut Curie in Paris, France. He has been on the faculty at the University of Minnesota since 2006, where his research focuses on microfluidics, biophysics, and polymer physics. His work has been recognized by a number of awards, most notably a Packard Fellowship and the Colburn Award of the AIChE.