SURF 2018: Evolutionary Stability of Genetic Circuits

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2018 SURF project description

  • Mentor: Richard Murray
  • Co-mentor: Andy Halleran

Evolutionary Stability of Genetic Circuits Synthetic biology’s heralded inception 15 years ago promised synthetic biology would revolutionize practically every field, from agriculture and manufacturing to medicine. However, all synthetic biology faces an uphill battle: synthetic circuits require host resources, inevitably slowing host growth. Therefore, mutants that disable the synthetic circuit grow faster than cells faithfully carrying out the programmed function. This causes mutants to outcompete engineered cells, bringing an end to the synthetic program. This universal feature of synthetic biology imposes a limit on the lifetime of programmed cellular functions. Improving the lifetime of synthetic circuits is of fundamental importance to the field of synthetic biology.

The goal of this SURF project is to characterize the mutational stability of existing synthetic circuits, followed by design and implementation of biomolecular feedback systems to improve circuit lifetimes. SURF students would work on developing techniques for characterizing mutational stability (flow cytometry, high throughput sequencing, etc.), mathematical modeling of the escape phenomenon (time to mutation, effect of load and circuit copy number on time to escape), and gain experience in synthetic circuit design and implementation.

Useful previous experience: Molecular biology (cloning, heterologous gene expression, etc.), coding in python / matlab / etc., math modeling, deterministic / stochastic simulations

Relevant background literature: https://www.biorxiv.org/content/early/2017/08/20/177030

http://www.sciencedirect.com/science/article/pii/S1097276510003266