Unravelling the structure and conformational dynamics of membrane proteins using H/D-exchange mass spectrometry and cryo-EM

Project Description

A dynamic studentship which includes experience working in both academic and pharmaceutical industry environments: the project is performed in partnership between laboratories at both King’s College London and UCB Pharma (Slough, 20 miles West of Central London). The ideal candidate will enjoy creative and multidisciplinary approaches to answering questions. The objective of the PhD project is to employ techniques such as molecular biology, structural biology, and mass spectrometry. Students will liaise with industrial partners and academics to ensure research is translational and aligned to medical outcomes.

Membrane proteins are biological macromolecules that are present within dynamic and complex cellular membranes. They have diverse complex cellular functions and represent more than half of drug targets; however, the molecular mechanisms governing their modes of action remain poorly understood. Most membrane proteins are highly dynamic and undergo structural and conformational rearrangements to perform their function. Whilst HDX-MS and cryo‐EM each provide unique information, both techniques complement and validate each other providing static pictures as well as dynamics and flexibility information of large and complex systems. This project focuses on the elucidation of the structure and conformational dynamics of membrane proteins important for human health through the development of HDX-MS and cryo-EM workflows.

This PhD includes the participation of KCL, a world class research and post-graduate training university, and industrial expertise from a leading multinational biopharmaceutical company, UCB Pharma. The student will become a member of the Dr Eamonn Reading group at the Department of Chemistry, King’s College London (https://www.ereadinglab.com/) and will work in partnership with Dr Zainab Ahdash at UCB Pharma (https://www.ucbpharma.co.uk/). The project will include time spent at UCB Pharma, where appropriate, for knowledge transfer and technical training.

Funding Information

This project is funded by a 3-year studentship sponsored by UCB Pharma; applicants should ensure they have understood the funding eligibility criteria for these studentships. Tuition fees are covered at the UK fee rate of £5000 per year.

Eligibility Requirements

Essential criteria:

  • Minimum of 2:1 in first degree and/or Master’s degree in Molecular biology/Structural biology/Chemistry or Biochemistry or related disciplines.
  • Research experience in at least one of the following subjects: molecular biology, microbiology, biochemistry, enzymology, organic/pharmaceutical chemistry.

Desirable criteria:

  • Excellent verbal and written communication skills (ranging from informal 1:1 discussion to formal presentations).
  • Experience in analytical chemistry (mass spectrometry, HPLC).
  • Experience in molecular biology (DNA cloning, protein overexpression and purification).
  • Ability to work as part of a team.
  • Awareness of the values of Equality, Diversity and Inclusion.

Application Process

1. Send your CV and cover letter to [email protected]

2. Complete an online application on the King’s College myApplication system (https://apply.kcl.ac.uk/):

  • Register a new account/login
  • Once logged in, select Create a new application
  • Enter ‘Chemistry Research MPhil/PhD (Full-time/Part-time)’ under Choose a programme. Please ensure you select the correct mode of study.

3. CV submission and online application MUST both be completed by the deadline.

All relevant information regarding eligibility, including academic and English language requirements, is available from the online prospectus.

The deadline for applications is 30th April 2021. References must be submitted by the 7th May. We aim to hold interviews in early May. If you require support with the application process, please contact the Chemistry Postgraduate Administrator Cairn Macfarland [email protected]

References

Reading, E., Ahdash, Z., et al. Perturbed structural dynamics underlie inhibition and altered efflux of the multidrug resistance pump AcrB, Nat. Commun., (2020) 11, 5565.
Engen, J. R. & Komives, E. A. Complementarity of Hydrogen/Deuterium Exchange Mass Spectrometry and Cryo-Electron Microscopy. Trends Biochem. Sci. 45, 906-918 (2020).
Reading E., Assessing Membrane Protein Structural Dynamics within Lipid Nanodiscs, Trends in Biochemical Sciences, (2019) 44(11):989-990
Reading, E., et al. Interrogating Membrane Protein Conformational Dynamics within Native Lipid Compositions. Angew. Chem. Int. Ed. Engl. 56, 15654-15657 (2017).

To apply for this PhD, please email eamonn.reading@kcl.ac.uk.

Before sending your email, please double check you have followed all guidelines in this listing and have included a reference number if asked to do so.

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