PDRA - In Situ Structural Biochemistry (10266)



    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. As a Postdoctoral Research Associate within the Structural Biology theme of Rosalind Franklin Institute, you will drive research into the molecular basis of complex post-translational modifications such as glycosylation, by characterizing the relevant enzymatic machinery within native contexts.

    The Role

    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.

    Responsibilities

    - Drive the development of methods to specifically tag proteins of interest, using chemical, biochemical, genetic and/or other relevant methods.
    - Investigate the application of labelling methods to live intracellular systems.
    - Learn and apply cryo-electron tomography and/or other imaging methods to detect labels, ultimately within intracellular contexts.
    - Design and carry out experiments in collaboration with other researchers within the Franklin, as well as institutions around the UK and globally.
    - Publish research findings in leading academic journals.
    - Present research findings in UK and worldwide at academic conferences.
    - Take a formal or informal role in the supervision of research students and other junior lab members.
    - Any other duties that come up in the normal running of the facility and that can be reasonably requested of the post-holder.

    In return we offer:

    - 25 days holidays plus Christmas Company Holiday
    - Hybrid working
    - Generous pension scheme (employer’s contribution currently up to 18%)
    - Training and development opportunities for staff at all levels
    - Bus pass discount scheme
    - Access to employee discount platform via Perkbox
    - Access to wellbeing resources through Thrive
    - Subsidised on-site canteen
    - Free on-site parking
    - Campus location in beautiful countryside with social and sports clubs open to staff

    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 this page.

    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.

    At the Rosalind Franklin Institute we welcome applications from all around the world!

    Closing date: Monday 10th April 2023.

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

    Applicants should refer to our Candidate Privacy Policy: https://www.rfi.ac.uk/candidate-privacy-policy/

    Area Scientific
    Location Harwell
    Type of Post Full Time
    Period of appointment 3 years fixed-term in the first instance
    Salary £33,500 - £41,000 per annum
    Closing Date 10/04/2023
    Ref No 10266

    Documents
    Job Pack 10266: https://opportunities.rfi.ac.uk/wd/plsql/wd_portal.view_blob?p_web_site_id=6400&p_web_page_id=517534&p_type=JOBDOC&p_id=431227&p_show=N
    (PDF, 843.21kb)


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