Protein design in living cells

Max Planck - Bristol Centre in Minimal Biology

A 4-year PhD studentship is available to develop de novo protein design in bacterial cells. This will be to work with the protein design laboratory of Prof Dek Woolfson (Chemistry and Biochemistry; https://woolfsonlab.wordpress.com/) and in the new Max Planck-Bristol Centre in Minimal Biology.

The proposed project aims to develop de novo proteins that will operate in E. coli and orthogonally to the endogenous proteome and interactome. The project will build on the Woolfson group’s pioneering work in delivering sets of robust de novo coiled-coil proteins (Fletcher, et al. (2012), ACS Synth Biol 1, 240. DOI: 10.1021/Sb300028q; Thomas, et al. (2013), J Am Chem Soc 135, 5161. DOI: 10.1021/Ja312310g; Thomson, et al. (2014), Science 346, 485. DOI: 10.1126/science.1257452); and the group’s use of these to construct peptide- and protein-based systems both in vitro and in cells (Fletcher, et al. (2013), Science 340, 595. DOI: 10.1126/science.1233936; Lee, et al. (2018), Nat Chem Biol 14, 142. DOI: 10.1038/nchembio.2535).

Specifically, the new project will use the de novo coiled coils to construct fibrous and globular scaffolds to build completely new cytoskeletons for bacterial cells. In turn, these will be used as a scaffold to coordinate the assembly of enzyme cascades and to produce bacterial cell factories for potential applications in synthetic biology and biotechnology.

For this studentship, we are seeking applications from bright and enthusiastic students with an interest in applying de novo protein design in cell biology and synthetic biology. The project is likely to include: rational and computational de novo protein design; the synthesis and structural characterisation of synthetic peptides in vitro; the design, construction and expression of synthetic genes in E. coli; and studies of whole bacterial cells using proteomics and light and electron microscopy. Experience in any of these areas would be an advantage but is not essential for applicants at this stage.

This studentship would be best suited to students with undergraduate and/or masters degrees in chemistry, biochemistry or related subjects in the physical and life sciences. Enthusiasm and a keen sense of adventure in science will be key attributes of the successful applicant.