This project will take inspiration from nature to design a new class of peptide-based molecular devices. These shape-changing molecules will have applications in biotechnology and synthetic biology.
This is a challenging project, and will require a multidisciplinary approach. Information will be extracted, using computational methods, from known protein structures in order to determine the factors that govern shape-switching processes in nature. This information will then be used to generate designs for small, simplified molecular switches that will exhibit a significant change in molecular shape in response to a chemical input. Target molecules will be synthesised, primarily by solid phase peptide synthesis, but also making use of organic synthesis or molecular biology techniques where appropriate. These molecules will then be analysed by chemical and biophysical methods in order to determine their structure and dynamic switching behaviour. Once a set of prototype molecular switches has been established, applications will be pursued in the sensing and regulation of biochemical processes.
This project is highly multidisciplinary, and as such it will present an excellent opportunity for a motivated candidate to learn techniques spanning traditional discipline boundaries, and to apply these techniques to cutting-edge science.
Applicants should have a good degree (2i or above) in chemistry or biochemistry, and be highly motivated to carry out research at the chemistry/biology interface. Good English communication skills are essential. The candidate will be required to write and modify computer code, so a willingness to learn coding is essential. Existing coding skills will be considered an advantage. Research experience and a demonstrated ability to work independently will similarly be considered an advantage.
This position has been prioritised for funding and covers tuition fees for UK applicants who fulfil the Research Council UK residency requirements, as well as paying a stipend at the Research Council rate (estimated £14,510 for Session 2017-18). EU applicants are also eligible for funding to cover fees and will be considered for a stipend at the Research Council rate.
Some recent publications that give an indication of the approach that this work will take:
A. J. Burton, A. R. Thomson, W. M. Dawson, R. L. Brady, D. N. Woolfson,
‘Installing hydrolytic activity into a completely de novo protein framework’
Nature Chemistry, 2016, 8, 837. DOI: 10.1038/nchem.2555
A. R Thomson*, C. W Wood, A. J Burton, G. J Bartlett, R. B Sessions, R L. Brady, & D. N Woolfson*
‘Computational design of water-soluble α-helical barrels’
Science, 2014, 346, 485-488. DOI: 10.1126/science.1257452
C. W Wood, M. Bruning, A. Á Ibarra, G. J Bartlett, A. R Thomson, R. B Sessions, R L. Brady, & D. N Woolfson*
‘CCBuilder: an interactive web-based tool for building, designing and assessing coiled-coil-protein assemblies’
Bioinformatics, 2014, 30, 3029-3035. DOI: 10.1093/bioinformatics/btu502