RATIONAL ENGINEERING OF SYNTHETIC ELECTRON TRANSFER CIRCUITS IN BACTERIA.

Electron transfer of fundamental importance to all cells, and for many industrially relevant bio-electrochemical systems such as MECs (Microbial Electrolysis Cells) and MFCs (Microbial Fuel Cells). Despite this, the details of these processes are poorly characterised, and synthetic biology currently lacks a consistent framework within which to design and engineer with electron transfer components. Such a framework is required since 'traditional' synthetic biology has until now (and with great success) focused on the engineering of genetic circuits, whose dynamics differ enormously in some key aspects.

Of particular importance for industrial applications is the interaction of bacteria with solid electrodes. For this reason, the project will focus on the model exoelectrogens /Geobacter/, which rely on electron transfer to and from extracellular substrates (such as electrodes) for their survival. The unique abilities of these bacteria also offer an opportunity to interact electronically with any synthetic biological constructs they host.

This project will develop foundational tools in the form of mathematical models derived from both existing models of non-biological electrochemical processes, and models of the genetic and metabolic processes already used by synthetic biologists. The aim is to provide a unified framework for the rational design of synthetic biological constructs in /Geobacter/ using electron transfer and genetic components. In this regard, five particularly important aspects of naturally occurring electron transfer circuits have been identified as targets.

1) Signal generation via electrode potential or reactive oxygen species.

2) Activation of receptor components which connect the intracellular environment to the generated signal.

3) Transduction of the (electronic) signal into a genetic response.

4) Output as either a modulation of gene expression, or metabolic activity that results in electronic output (current).

5) Signal termination through either deactivation of receptor components, or clearance of reactive oxygen species.

The outcome will be a novel framework for the description of each of these components separately, their composition into larger synthetic biological designs, and the prediction of their behaviour in man-made
bio-electrochemical systems such as MECs and MFCs.