Tuesday, August 16, 2016

Lecture 7: Chris Bohrer (Elijah Roberts & Jie Xiao Labs)

The Chromosomes Fight Against Disorder in E. coli
Transcription in Escherichia coli generates positive supercoiling in the DNA, which is relieved by the enzymatic activity of gyrase. Recently published experimental evidence suggests that transcription initiation and elongation are inhibited by the buildup of positive supercoiling. It has therefore been proposed that intermittent binding of gyrase plays a role in transcriptional bursting. Considering that transcription is one of the most fundamental cellular processes, it is desirable to be able to account for the buildup and release of positive supercoiling in models of transcription.
Positive Supercoiling (PCOIL) is
produced when mRNA is transcribed
(from Bohrer&Roberts,BMC,2016).

In their recent paper, Chris Bohrer and Elijah Roberts from Johns Hopkins Biophysics present a detailed biophysical model of gene expression that incorporates the effects of supercoiling due to transcription. By directly linking the amount of positive supercoiling to the rate of transcription, the model predicts that highly transcribed genes’ mRNA distributions should substantially deviate from Poisson distributions, with enhanced density at low mRNA copy numbers. Additionally, the model predicts a high degree of correlation between expression levels of genes inside the same supercoiling domain.

The model, incorporating the supercoiling state of the gene, makes specific predictions that differ from previous models of gene expression. Genes in the same supercoiling domain influence the expression level of neighboring genes. Such structurally dependent regulation predicts correlations between genes in the same supercoiling domain. The topology of the chromosome therefore creates a higher level of gene regulation, which has broad implications for understanding the evolution and organization of bacterial genomes.
Chris graduated from The Kent State University with a degree in physics and education. He is interested in studying the dynamics of gene regulatory circuits, and so decided to join both Dr. Elijah Robert’s lab as well as Dr. Jie Xiao’s lab at Johns Hopkins University Biophysics, in order to be proficient in both theory and experiments. Chris plays the guitar, runs, and makes sushi when not in the lab.

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