Research Associate in protein design in cells

The role

Post-doctoral research assistant in protein design in cells

As part of a recently funded BBSRC grant with Dr Mark Dodding (Biochemistry, Bristol), a post-doctoral Research Associate position is available to develop de novo designed motor proteins that operate in eukaryotic cells. Funding for this post is available immediately and for 30 months. The position is in the protein design laboratory of Prof Dek Woolfson (Chemistry and Biochemistry). The post holder would work in the newly refurbished laboratory of the Max Planck-Bristol Centre for Minimal Biology (MPBC), which is housed in the School of Chemistry. However, it is anticipated that the successful applicant would work seamlessly between the Dodding and Woolfson labs and in a team of ≈6 people from the two groups who will collaborate on the design and engineering of motor proteins in eukaryotic cells.

What will you be doing?

Specifically, the work will be to design de novo peptides and protein modules that fold, assemble and function in eukaryotic cells. The intention is that the synthetic peptides and proteins will interface with endogenous motor proteins to probe and augment their functions. The project will build on Woolfson's set of de novo coiled-coil domains (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; and Thomson et al. (2014) Science 346 , 485-488 DOI: 10.1126/science.1257452). The aim is to use these and new design modules to construct components of self-assembling motor proteins that work in living cells. The designed proteins will be used: (1) to help understand the molecular mechanism of natural kinesin-1 motors; and (2) to design semi-synthetic motor proteins that work alongside endogenous motors in cells. The project builds on a successful collaboration between the Dodding and Woolfson labs on designing peptides that penetrate cells, seek out and bind to the kinesin-1 motor, and, in doing so, hijack the motor to transport targeted cargoes in cells. For more background see: Cross et al. (2021) Cell Chem Biol 28, 1347-1355. DOI: 10.1016/j.chembiol.2021.03.010; and Rhys et al. (2022) Nature Chem Biol In Press. DOI: 10.1038/s41589-022-01076-6.

You should apply if

The position would be best suited to a talented and ambitious early career researcher with an interest in applying de novo protein design in chemical and synthetic biology. Essential skills for this role include: experience in molecular cell biology in bacteria and/or eukaryotic cells, including the design and expression of synthetic genes in E. coli and/or mammalian cells or similar; plus biochemical and biophysical characterisation of proteins in cells using light and electron microscopy. Experience in the preparation and structural characterisation ( e.g. solution-phase biophysical methods, X-ray crystallography, and/or cryoelectron microscopy) of synthetic or natural peptides and proteins would be desirable, but are not essential initially to take up this post.

For informal enquiries, please contact: d.n.woolfson@bristol.ac.uk

Details of the MPBC can be found at: tinyurl.com/2p93wftj

We welcome applications from all members of our community and are particularly encouraging those from diverse groups, such as members of the LGBT+ and BAME communities, to join us.