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Details of Grant 

EPSRC Reference: EP/K030574/2
Title: Kinetic Switches: Exploiting Feedback in Enzyme Microparticles
Principal Investigator: Taylor, Professor AF
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Chemical & Biological Engineering
Organisation: University of Sheffield
Scheme: Standard Research
Starts: 01 September 2014 Ends: 28 February 2017 Value (£): 226,081
EPSRC Research Topic Classifications:
Catalysis & Applied Catalysis Physical Organic Chemistry
Synthetic biology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:  
Summary on Grant Application Form
Many biological processes require a rapid transition from one chemical state to another following a supercritical stimulus. These kinetically-controlled cell switches are driven by feedback such as autocatalysis, when a reaction is catalysed by its product. Feedback also lies at the heart of synchronisation of activity in cellular systems such as bacteria and yeast. There has been great interest in the design of reaction networks that produce feedback-driven behaviour, for example, genetic circuits were developed to create a toggle switch, chemical oscillations and synchronisation of oscillations in E. coli cells.

Through computational studies and experiments, we will design bio-inspired switches combining two components: feedback in the reaction kinetics and compartmentalisation of the reaction in microparticles. This research will provide insight into biological self-organisation as well as having potential applications in analytical or "smart" materials science.

The first component of the research involves designing novel reaction networks for chemical feedback and for this we will use nature's catalysts: enzymes. Enzymes offer specificity, efficiency and biocompatibility for widespread applications such as sensors, drug delivery devices and bio-reactors but the wealth of behaviour associated with autocatalysis has yet to be exploited. We will investigate possible advantages such as such as a fast, robust response to a chemical signal in the presence of noise.

In order to create a cellular switch, the enzyme catalyst for the reaction will be immobilised in microparticles. When immersed in a bath of reactants, the microparticles obtain chemical "fuel" from the surrounding solution, naturally maintaining the system far-from-equilibrium in a similar manner to cells. By manipulation of the kinetics, exciting features such as a chemical switch, hysteresis, chemical pulses, patterns or self-motion of the microparticles are possible. Groups of enzyme microparticles interact with each other via the release of chemicals into the surrounding solution, thus creating a new opportunity for the examination of collective behaviours and self-organisation in bio-inspired cellular systems.

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Organisation Website: http://www.shef.ac.uk