About the Project
Supervisors: Dr. Eamonn Reading (Primary supervisor – KCL), Mr. Malcolm Anderson (Industrial supervisor - Waters Corporation), Prof. Paula Booth (Secondary supervisor – KCL)
Contact: Dr. Eamonn Reading. E-mail: [Email Address Removed] Tel: 020 7848 7508
Membrane proteins are ubiquitous biological macromolecules which reside within dynamic and highly complex cellular lipid membranes. They carry out a multitude of essential, complex biological functions with exquisite specificity within their cell membrane environment and concurrently are key targets for more than half of modern drugs. This makes understanding their fundamental processes a vital task. Currently, most of our structural insights on membrane proteins are gained within purified membrane mimetic systems which lack the context of the native lipid environment. Being able to achieve structural insight into these fundamental biomolecules within more native environments, including in live cells, would be a huge step forward in understanding how they shape cellular function.
The student will develop structural mass spectrometry and protein engineering approaches to decipher native membrane protein structural behaviour. The project will involve advancement and training on cutting-edge H/D eXchange mass spectrometry (HDX-MS) for HDX structural analysis of membrane protein dynamics. With an emphasis being placed on understanding the role of drugs and the lipid metabolism on protein function. Importantly, the student will perform molecular biology and biochemical investigations alongside technology development to fully understand membrane protein behaviour and function.
This project is performed in partnership with Waters Corporation which will include a 3-month placement at the Waters Mass Spectrometry Headquarters facility at Wilmslow, UK. During their placement, Waters Corporation will provide education and training on how a large scientific company is organised and run. This will include meeting members from a variety of departments and disciplines, both formally and informally, to understand their business strategy, hierarchy, and how teams work together.
Please see Reading group website for updated publications list and news from the group of Dr Eamonn Reading: https://www.ereadinglab.com/
Student profile
Applicants must hold, or be expected to achieve, a first or high upper second-class undergraduate honours degree or equivalent (for example BA, BSc, MSci) or a Masters degree in a relevant subject. At least a 2:1 honours degree or equivalent. Students with backgrounds in biological, chemical or physical sciences are welcomed.
Applicants should hold a BSC or Msc in Biochemistry, Biophysics or Chemistry, and have an understanding of protein (bio)chemistry and analytical methods. Experience in protein mass spectrometry and/or protein biochemistry will be a strong advantage. Candidates must have a fascination for interdisciplinary research, excellent communication skills and work well in a team.
Apply
Deadline for applications is 23rd March 2020. We might accept later applications until the position is filled.
Information about the programme’s application procedure can be found on the Centre for Arts & Sciences Admissions webpage: http://www.kcl.ac.uk/study/postgraduate/apply/course-types.aspx.
Candidates should apply for a PhD in Chemistry in the usual way through King’s myApplication system: https://myapplication.kcl.ac.uk/
Funding Notes
This project is funded by a 4-year BBSRC studentship, applicants should ensure they have understood the funding eligibility criteria for these studentships. Unfortunately, international students are not eligible for programme funding on this project.
Eligibility: This scheme only covers funding for Home/EU students.
References
E Reading, Assessing Membrane Protein Structural Dynamics within Lipid Nanodiscs, Trends in Biochemical Sciences, (2019) 44(11):989-990
Martens, C., Shekhar, M., Borysik, A., Reading, E., Lau, A. M., Tajkorshid, E., Booth, P. J. & Politis, A. Direct protein-lipid interactions shape the conformational landscape of secondary transporters. Nat. Commun., (2018) 9:4151.
Reading E., Hall Z., Martens C., Haghighi T., Findlay H., Ahdash Z., Politis A., Booth P. J., Interrogating membrane protein conformational dynamics within native lipid compositions, Angew. Chem. Int. Ed., (2017) 49:15654-57.
A.V. Hateren, M. Anderson, A. Bailey, J.M. Werner, P.J. Skipp, T. Elliott. Direct evidence for conformational dynamics in Major Histocompatibility Complex class I molecules, Journal of Biological Chemistry (2017) 292(49):20255–20269.
A Laganowsky, E Reading, TM Allison, MB Ulmschneider, MT Degiacomi, AJ Baldwin, CV Robinson, Membrane proteins bind lipids selectively to modulate their structure and function, Nature, (2014) 510 (7503):172.
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