Regulatory strategies for rational design of whole cell biosensors. Genetic engineering is widespread and commercially valuable but has so far proceeded on an ad hoc basis. The past several decades of work in molecular biology have provided the knowledge to begin rationally designing artificial systems. The theoretical and practical underpinnings to do this are still emerging and this provides opportunities at the interface of well-established engineering design principles and biology. One of the challenges of biological systems is that they are inherently noisy and this poses challenges for the design of robust systems. Groundwork has already been laid both from theoretical and practical perspectives (1, 2). This project will take a hybrid approach including both modelling and experimental validation. The starting point for the project will be whole-cell biosensors: living cells which produce a detectable response to a target analyte (3). Such systems are tractable for both modelling and experimental manipulation. Deterministic and stochastic regulatory models of biosensors will be constructed. Simple regulatory motifs will be constructed in vivo to facilitate model validation. Progress has already been made in establishing a proof-of-concept arsenic biosensor in this lab (4). Later the project will include analysis of promising new circuit components such as CRISPRs and TALENs (5, 6).
- Lestas I, Vinnicombe G, Paulsson J. 2010. Fundamental limits on the suppression of molecular fluctuations. Nature 467:174–178.
- Elowitz MB, Levine AJ, Siggia ED, Swain PS. 2002. Stochastic Gene Expression in a Single Cell. Science 297:1183–1186.
- French CE, Mora K de, Joshi N, Elfick A, Haseloff J, Ajioka J. 2011. SYNTHETIC BIOLOGY AND THE ART OF BIOSENSOR DESIGN. Text.
- The Arsenic Biosensor Collaboration (http://arsenicbiosensor.org/).
- Joung JK, Sander JD. 2013. TALENs: a widely applicable technology for targeted genome editing. Nat. Rev. Mol. Cell Biol. 14:49–55.
- Barrangou R. 2012. RNA-mediated programmable DNA cleavage. Nat. Biotechnol. 30:836–838.