PDRA - In Situ Structural Biochemistry (10266)

PDRA - In Situ Structural Biochemistry (10266) - Rosalind Franklin Institute (rfi.ac.uk) 

We are interested in understanding the cellular basis underlying biosynthesis of the glycosaminoglycan polysaccharide heparan sulfate (HS), a complex heterogenous molecule involved in vital physiological processes. The biosynthesis of HS is known to take place in the Golgi compartment of cells. Many of the enzymes responsible for HS construction are now characterized, but a unified picture of how they act together in cells remains lacking. 

Cryo-electron tomography, coupled with focused ion beam milling, offers a powerful route towards in situ structural characterization (e.g., Berger et al, Nat Comms, 2023). However, smaller proteins, such as the enzymes involved in HS construction, are still difficult to identify within information dense tomograms. There is thus a pressing need to develop methods to tag proteins of interest in native contexts, so they can be recognised even within the crowded intracellular environment. 

Your primary task will be to develop new methods to modify proteins of interest, to facilitate their detection by cryo-electron tomography and associated techniques. Working with researchers across the Franklin, you will utilize chemical, biochemical and/or genetic methods to add tags such as fluorophores or heavy atoms to proteins in a site selective fashion. You will develop strategies to apply your tagging methods within intracellular milieu and use multiple imaging modalities to verify successful incorporation and detection. Although early stages of the project will focus on in vitro models, your ultimate targets will be intracellular Golgi enzymes involved in heparan sulfate construction.  

This post would suit an ambitious candidate with expertise in protein (bio)chemistry, who wishes to apply their knowledge to complex cellular systems. It is envisioned the successful candidate would bridge existing interests in the Franklin regarding both protein modification and complex multimodal imaging. You will be afforded training on high end electron imaging methods, with access to cutting edge and beyond state-of-the-art EM platforms. 

Before submitting your application, please ensure you read the Job Information Pack for full details of this role by clicking on the attachment at the bottom of our job advert:

PDRA - In Situ Structural Biochemistry (10266) - Rosalind Franklin Institute (rfi.ac.uk) 

About us: The Rosalind Franklin Institute is a new national Research Centre, funded by the UK government through UK Research and Innovation, dedicated to bringing about transformative changes in life science through interdisciplinary research and technology.  

Location: The Franklin is based in Harwell Campus, UK’s innovation hub and well-established as one of the leading science and innovation campuses in Europe.   

Closing date: Monday 10^th April 2023

Interviews will be held w/c 24th April 2023.

Area: Scientific

Period of appointment: 3 years fixed term in the first instance

Advert information