Directed evolution of proteins in vivo
In this project, a new phage-based directed evolution approach will be used to evolve proteins with properties to make them suitable for use in synthetic circuit applications, such as in vivo biosensing or construction of bistable switches.
Directed evolution allows for the rapid selection of new protein function. By iterative rounds of mutagenesis and selection under conditions which favour the desired property/activity, variants can be selected from a large library without any requiring detailed structural information.
A recently published method for directed evolution using filamentous phage should allow a wide variety of selection schemes to be employed. For example, it should be possible to convert a transcriptional repressor into a transcriptional activator, or to improve the strength of a particular protein-protein interaction.
Study synthetic biology, biochemistry, genetics and mathematical modelling
Our research integrates biochemistry, genetics and mathematical modelling to characterise fundamental mechanisms of gene control and how these elements are combined to create gene regulatory circuits with complex functions.
Having a toolbox of well characterised genetic components allows us to ‘rewire’ them in a rational way in order to construct new genetic circuits with predictable behaviour for use in synthetic biology applications.
The lessons learnt in the construction of artificial genetic circuits in turn give us a deeper understanding of how natural biological systems work.