We believe that modelling animal nervous system in prokaryotic chassis has a wealth of potential applications in synthetic biology. Using ion channels can reduce the lag between input and output inherent in systems that rely on changing gene expression, and instead provide rapid response to stimuli. This is the focus of the Voltage section of our project, that aims to integrate glutamate-sensitive potassium channels in E.coli, and in future, explore other signalling molecules, and use voltage-sensitive channels that could enable action potential propagation.
The nervous system also offers a strong example of the significance of self-organisation in development, an important factor in determining how the few precursor cells grow into an extremely complex and dynamic network.
We plan to implement a simple two-component Reaction-Diffusion system in the gram-positive model organism Bacillus subtilis. In 1952, Alan Turing famously described this system and suggested it as the basis for self-organization and pattern formation in biological systems. The simplest of these patterns, which we are planning to model in bacteria, mimic the spots and stripes seen on animal coats. We intend to use two well-characterized bacterial communication systems to generate this behavior. The agr peptide signalling system from S. aureus will serve as our activatory signal (pictured), while the lux system from V. fischeri will serve as our inhibitor. Bacillus subtilis serves as an excellent chassis for this project because of the ease with which chromosomal integration can be performed. This project will focus on a tight integration of modeling and experiment; we will test different promoter strengths and other variables, feed these system parameters into our multi-cell models, and then use those models to tweak the regulatory machinery that will control signal production.
The aim of this project is to work towards an interface between biological and electric systems. We hope to do this by measuring a voltage change due to the presence of a certain substance. In the first instance, this substance will be glutamate, as it acts as a ligand for a prokaryotic gated potassium channel. Our idea is to sequester K+ inside E.coli cells by using leak channel knock-out mutants, and over-expressing K+ influx pumps. Then, when glutamate is present it will open K+ channels, allowing an efflux of potassium and causing a small but measureable change in voltage in the medium.
We are investigating the formation of magnetosomes (membrane bound magnetite particles) in magnetotactic bacteria. This process is believed to take place in the following steps: i) production of invaginations along the inner membrane ii) uptake of iron into these invaginations iii) biomineralisation of the iron into magnetite crystals of a specific size and shape iv) axial alignment of the magnetosomes.
This mechanism gives the bacteria the ability to align itself like a compass needle along geomagnetic field lines. We are attempting to engineer the uptake of soluble iron into membrane invaginations in E.coli, and stimulate formation of magnetite using genes from Magnetospirillum. The ulitmate aim of the project is to cause E.coli to align and form extended neuron-like chains.
NOTE: unfortunately, the Magnetic project had to be discontinued. This was caused by the need to concentrate team resources and manpower on fewer projects.