SURF 2011: Effects of Topology on DNA Transcription

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2011 SURF project description

A goal of synthetic biology is to predict the operation of a designed biological circuit in a cell. However, there are a number of cellular effects for which we have few/no accurate predictive models, including the change in gene translation that results from topological changes in DNA. Circular "plasmid" DNA takes on a number of distinct topological states as it supercoils. Previous work has shown that the distribution of topological states occupied by the DNA in cells can impact the expression of different genes, and that the distribution of topological states over time.

This project will focus on developing a physical model for the relationship between DNA topological state and transcription. This may involve engineering biological circuits that rely on coiling effects for their operation as a proof-of-concept. There are commercially available enzymes to coil, uncoil, and cut DNA outside of cells, and experimental tools to measure the rate of translation from DNA and to measure the distribution of topological states for the DNA.

Students interested in this project must be proactive and willing to work with both experiment and theory. Lab experience is not necessary but very helpful.

References

  1. Krasilnikov et al, Large-scale Effects of Transcriptional DNA Supercoiling in Vivo, Journal of Molecular Biology, 1999
  2. Vijayan et al, Oscillations in supercoiling drive circadian gene expression in cyanobacteria, PNAS, 2009
  3. Koster et al, Cellular Strategies for Regulating DNA Supercoiling: A Single-Molecule Perspective, Cell, 2010