Understanding lipid interactions with membrane proteins

Aston Institute for Membrane Excellence

This studentship is supported by the Aston Institute for Membrane Excellence. AIME is a unique, interdisciplinary, intersectoral research and training hub for translational membrane science. AIME is a globally unique, cross-disciplinary institute to develop novel membranes for use in applications as varied as drug discovery and water purification. The team behind AIME believes that the full potential of membranes will only be realised by a research team spanning biology, physics and chemistry that can investigate membranes holistically. No other institute has the platform, potential or promise for major breakthroughs in this area. The vision is for AIME to become a ‘one-stop shop’ for interdisciplinary, translational membrane research through access to its facilities and expertise, ideally located in the heart of the UK.

Details of the Project

Polymer lipid nanoparticles (PLPs) are a new and increasingly popular way to solubilise and stabilise integral membrane proteins (IMPs). The PLP method uses amphipathic polymers such as poly(styrene-co-maleic acid) to disrupt cell membranes and encapsulate IMPs in soluble disc-shaped nanoparticles. A key advantage of this technology is that lipids are retained when the proteins are solubilised from the membrane bilayer. Bilayer lipids are now regarded as an intrinsic part of functional IMP assemblies. However, our ability to purify and characterise proteins using these methods has outstripped our fundamental understanding of how the PLP assemblies form, and their subsequent behaviour in solution. Though these particles certainly contain IMPs and specific lipids from the host cell membrane, there is evidence of rapid lipid exchange between discs. Therefore a major unresolved question in the field is how closely PLPs really resemble the protein/lipid assemblies found in vivo. To answer this question requires us to decipher the composition of the discs upon initial assembly, and also to assess their stability and composition over time.

This project is collaborative between Aston University and the Harwell Science and Innovation Campus. Work at Aston will be under the supervision of Dr Philip Kitchen with co-supervision by Dr Naomi Pollock. Amphipathic polymers will be used to produce lipid-only PLPs and to purify several well-characterised membrane proteins with different sizes of membrane-spanning domain (MSD). Using these we will test the hypothesis that the lipids within PLPs are dynamic, but are stabilised by the MSDs of proteins. We will also access expertise within AIME for lipid analysis by mass spectrometry to identify which lipids are present in the discs.

Neutron reflectometry, and infrared and fluorescence spectroscopy will be used to measure the rate and extent of lipid exchange between discs and other bilayer assemblies. Small-angle neutron scattering will be used to determine the structure of the discs before and after lipid exchange. This element of the project will be led by co-supervisor Dr Stephen Hall, a beamline scientist at the ISIS Neutron and Muon Source at Harwell. The student will have routine access to the analytical techniques available within the support labs of the ISIS facility.

This project would suit a student with either a biological or physical science background who is keen to work collaboratively at the interface of the life and physical sciences.

 Person Specification

The successful applicant should have been awarded, or expect to achieve, a Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution) in a relevant subject.

 Contact information

For formal enquiries about this project contact Philip Kitchen at p.kitchen1@aston.ac.uk

Submitting an application

 We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include:

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor degrees.
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count.
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience.
4. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary.
5. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage.
6. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Apply for this position here

Alternatively, apply here

Please select “ Research – Biomedical Sciences” from the application form options.

 If you require further information about the application process, please contact the Postgraduate Admissions team at pgr_admissions@aston.ac.uk