About the Project
Proteins are bionanomachines, acting in isolation or as part of larger, often complex machinery, performing their function through structural and mechanical changes. Mechanical properties are essential for biological scaffolds, where cell behaviour can be controlled by designing material scaffolds incorporating specific structural and mechanical cues. The ability to tune protein mechanics provides new opportunities to understand the role of force in biological systems, and to create bespoke scaffolds for biomaterial applications.
The aim of this studentship is to investigate the structure and mechanics of folded protein-based networks, using a combination of experimental, computational and theoretical methods. By understanding the properties of the building block (the proteins) we will have predictive control of the biomaterial. This approach will bridge the gap between single molecule mechanics and material biomechanics, revealing how the mechanical properties of individual components are translated to the properties of macroscopic materials. We will investigate a range of candidate chemical and enzymatic approaches to cross linking including the use of sortase and SpyTag/SpyCatcher to install covalent peptide and isopeptide linkages
For more information on the research group: http://www.mnp.leeds.ac.uk/lorna-dougan.html
References
Tych KM, Batchelor M, Hoffmann T, Wilson MC, Hughes ML, Paci E, Brockwell DJ, Dougan L Differential effects of hydrophobic core packing residues for thermodynamic and mechanical stability of a hyperthermophilic protein. Langmuir 32 7392-7402, 2016
Tych KM, Batchelor M, Hoffmann T, Wilson MC, Paci E, Brockwell DJ, Dougan L Tuning protein mechanics through an ionic cluster graft from an extremophilic protein. Soft Matter 12 2688-2699, 2016
Hoffmann T, Tych KM, Crosskey T, Schiffrin* B, Brockwell DJ, Dougan L Rapid and Robust Polyprotein Production Facilitates Single-Molecule Mechanical Characterization ofβ-Barrel Assembly Machinery Polypeptide Transport Associated Domains. ACS Nano 9 8811-8821, 2015*MBiol project student
T. Hoffmann, K.M. Tych, M.L.Hughes, D.J. Brockwell and L. Dougan, Towards design principles for determining the mechanical stability of proteins, Physical Chemistry Chemical Physics, 15, 15767-15780 (2013)
Extraction of accurate biomolecular parameters from single-molecule force spectroscopy experiments. Farrance, O.,
Paci, E., Radford, S. and Brockwell, D. (2015) ACS Nano 9: 1315-1324.
Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein. Gruszka,. D., Whelan, F., Farrance, O., Fung, H., Paci, E., Jeffries, C., Svergun, D., Baldock, C., Baumann, C., Brockwell, D., Potts, J. and Clarke, J. (2015) Nat Commun 6, article no. 7271.
A force-activated trip switch triggers rapid dissociation of a colicin from its immunity protein. Farrance, O., Hann, E., Kaminska, R., Derrington, S., Kleanthous, C., Radford, S. and Brockwell, D. (2013) PLoS Biol, 11, e1001489.
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