The University of Sheffield
Synthetic Biology@Sheffield

MATEs

Microbial Applications to Tissue Engineering

The University of Sheffield is the host institution for a multidisciplinary network aimed at using Synthetic Biology to create novel solutions for the tissue engineering field named MATEs - Microbial Applications to Tissue Engineering.

MATEs is one of six research council funded networks aimed at placing the UK at the forefront of Synthetic Biology research. Its members are drawn from a number of scientific, engineering and social science backgrounds and from a range of UK and European universities.

MATEs Projects

Development of synthetic chimeric flagellin for tissue engineering applications

A grant for this interdisciplinary synthetic biology project was awarded via responsive mode BBSRC funding for £119,000 to develop novel adhesive protein fibres for tissue engineering applications.

This is lead by the Dr Graham Stafford, in conjunction with Professor Phillip Wright (CBE, CHELSi) and Professor Sheila Macneil (Kroto). (Who?)

This proposal grew from the MATEs synthetic biology network and will focus on the use of bacterial protein fibres to present adhesive peptides to aid the adhesion of human skin cells with future applications in the improvement of skin grafting and tissue engineering.

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Development of a high throughput one-step protein secretion system

m2Secretion into culture media is a desirable route for biomanufacturing proteins employing a prokaryotic host, as they will be free from cytoplasmic contaminants. In gram negative bacteria, fusion of target proteins to a classical signal peptide will result in export or accumulation in the periplasm, possible proteolysis, complicated downstream processing or unpredictable secretion that hinders scale up.

The bacterial flagellum is not only a highly efficient nanomotor but also an efficient secretion machine, extruding flagellar subunits through the lumen before assembly at the distal growing tip. It handles several thousand monomers of flagellin (FliC), making FliC one of the most abundant extracellular proteins in E. coli and illustrating its high secretion capacity. Flagellar secretion is well characterised and thus amenable to engineering into an efficient protein secretion device. We have constructed strains with a truncated flagellar structure that we are transforming into a streamlined secretion conduit and have demonstrated secretion of eukaryotic and prokaryotic proteins. We have thus developed a prototype generic secretion platform capable of delivering a wide-range of proteins to the culture media, ready for facile downstream processing.

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Links to the Funding bodies:

ahrc epsrc esrc bbsrc
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