Rachel Patton McCord, Ph.D., Professor of Biophysics, University of Tennessee, Knoxville, "Analyzing 3D Genome Structure in Times of Stress"

Speaker:

Rachel Patton McCord, Ph.D.

Professor of Biochemistry

University of Tennessee, Knoxville

Faculty Host: Renata Dos Reis Marques

Title: Analyzing 3D Genome Structure in Times of Stress

Abstract:

The 3D folding of human chromosomes inside the cell nucleus affects numerous fundamental biological processes, including gene regulation, DNA repair and replication, and even the physical properties of the nucleus. Recent research is beginning to define the key molecular factors that build the genome structure, but less is known about how this structure responds to physical stresses experienced by cells and nuclei. The 3D genome structure in healthy cells must withstand or respond to perturbations such as physical forces and nuclear shape changes. Disruptions in genome structure and nuclear architecture can lead to cell fate changes and diseases such as cancer or premature aging. Our research has shown that A375 melanoma cells that have migrated through multiple rounds of constrictions experience stable epigenetic, 3D genome structure, and nuclear lamin alterations that associate with a more mesenchymal and migratory cell phenotype. By integrating microscopy, epigenetic profiling and disruptions, and the chromosome conformation capture (Hi-C) approach, we are investigating the factors that contribute to encoding and maintaining the memory of this altered cell phenotype. We further compare disruptions caused by constricted migration to 3D structure changes in other stresses such as low or high salt, cancer drug treatment, or irradiation. Our observations begin to shed light on the robustness of the 3D genome structure to perturbation and how the network of 3D contacts in the genome can accomplish both gene regulatory functions and contribute to necessary physical properties of the nucleus.

Bio:

Rachel Patton McCord received her B.S. in Biophysics from Davidson College and a Ph.D. in Biophysics from Harvard University.  She began working with large scale genomic data during her doctoral work under the mentorship of Dr. Martha Bulyk, analyzing transcription factor sequence preferences from protein binding microarray data.  Realizing that information along the linear DNA sequence has limited ability to explain complex human gene expression, she pursued postdoctoral research exploring genome architecture in Dr. Job Dekker’s lab at UMass Medical School.  She joined the Biochemistry & Cellular and Molecular Biology faculty at the University of Tennessee Knoxville in 2016, where her lab combines experiments and computational analyses to study the influence of physical perturbations on 3D genome structure.