Details of Grant 

EPSRC Reference:	EP/I016589/1
Title:	BioEngineering from first principles.
Principal Investigator:	Banwart, Professor S
Other Investigators:	Huang, Professor W Scholes, Professor JD Geoghegan, Professor M Romero-Gonzalez, Dr M Rolfe, Professor S Swanson, Dr L Harding, Professor J Biggs, Professor CA
Researcher Co-Investigators:	Dr CL Freeman
Project Partners:
Department:	Kroto Research Institute
Organisation:	University of Sheffield
Scheme:	Standard Research
Starts:	01 February 2011	Ends:	31 May 2012	Value (£):	201,746
EPSRC Research Topic Classifications:	Cells Chemical Biology
EPSRC Industrial Sector Classifications:	Environment Healthcare Pharmaceuticals and Biotechnology
Related Grants:
Panel History:	Panel Date Panel Name Outcome 26 Aug 2010 Cross-Disciplinary Feasibility Account 2010 Announced
Summary on Grant Application Form
The research challenge is to understand the principles that control cell-surface and cell-cell interactions given the enormous variety of macromolecular structures produced by microbial cells and the complexity of their chemical and physical influences on binding interactions. We will predict attachment using computational models and gain understanding why extracellular DNA promotes or inhibits attachment under specific conditions. This is a major challenge with huge rewards if it can be met. A predictive capability of cell attachment would enable new methods of analysis and design in the fields of environmental engineering, process engineering and biomedical engineering.To tackle this challenge, we have recruited multidisciplinary expertise to combine theoretical and experimental techniques from the fields of computational chemistry, surface and polymer physics, molecular biology, polymer chemistry, engineering microbiology, analytical chemistry, X-Ray and vibrational spectroscopy and environmental engineering science.We propose to use computational chemistry techniques for simulation of cell walls, to characterise the behaviour of their individual chemical constituents, and to estimate the physical-chemical interactions that occur with specified solid surfaces. Looking 1-2 decades ahead, the aim is to develop computational methods sufficiently to allow the required interactions to be designed, identify the macromolecular structures necessary for these interactions to occur and identify the necessary gene sequences for their synthesis. This Feasibility Account study will launch theoretical chemistry into the specific challenge of tackling extracellular DNA (eDNA) binding on cells and minerals as one identified mechanism in biofilm formation. The outcome will be an evaluation of this combined approach between multidisciplinary experimentation and theoretical simulation as a case study for predicting cell attachment and growth. With the computational techniques, we shall investigate the binding of nucleic acid sequences to the surfaces using molecular dynamics simulations. Experimentally, we will first characterise eDNA produced by biofilm-forming microbes that we have isolated from environmental samples. We will then remove eDNA from biofilm-forming cells and replace it with synthetic DNA to start to quantify the relationship between the properties of eDNA and cell attachment. This 'synthetic' approach will allow us to vary systematically eDNA length, sequence and concentration and quantify cell attachment to model oxide surfaces such as negatively charged silica and positively charged alumina under defined ionic medium conditions. We will explore how eDNA is arranged on the cell surface and substratum using atomic force microscopy and fluorescence techniques, and we shall explore the use of methods that break the diffraction limit for optical resolution such as SNOM (Scanning Near Field Optical Microscopy) which, to our knowledge, has never been applied to this area. The potential for engineering applications is immense. We anticipate that virtually all fields of biotechnology would potentially profit. We propose to assess this breadth of promise by bringing a wide range of engineering experts together with the project team in a sand pit that will be held 3 months before the project end. We will hold a 2-day workshop to present our results and develop a roadmap for moving this forward as a research area and for practical application. Participants will evaluate our results, identify areas of opportunity for engineering applications, and assess the promise for generalisation across the broad field of BioEngineering through systematic application of our approach.
Key Findings
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Potential use in non-academic contexts
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Organisation Website:	http://www.shef.ac.uk