Accelerating the discovery of the next generation of polymers for membrane protein extraction

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

Background

Membrane proteins (MPs) are vital for the transport of molecules across cell membranes and intracellular communication and are often key targets for drug discovery. Under natural conditions, MPs exist within compositionally complex lipid membranes which mutually influence each other. For detailed structural and functional studies, isolation and purification of MPs needs to be performed whilst maintaining their stability and activity. When compared to the isolation and purification of soluble proteins, this is a significantly more laborious task. Traditionally, protein extraction has been performed using detergents. However, they tend to strip away the native lipid membranes and often lead to protein instability. Therefore, efforts have been focused on new methodologies to improve the solubilization and stabilization of MPs.

One approach that has seen a major uptake in the last decade, is the use of amphiphilic copolymers to solubilize MPs directly in their natural environment in the form of polymer-bound lipoprotein nanoparticles.¹ Amphiphilic copolymers, in contrast to harsher detergents, preserve the native lipid environment of MPs, affect their structure to a lesser degree, and allow direct extraction of MPs from biological membranes avoiding the use of detergents at preliminary steps. The approach is not without limitations, the most widely used copolymer, styrene-maleic acid (SMA), is sensitive to low pH & divalent cations, which hinders the formation of the lipoprotein nanoparticles. Furthermore, free SMA can interfere with protein binding or inhibit activity and may restrict the full dynamic function of proteins. Therefore, new amphiphilic copolymers need to be designed to overcome the limitations of SMA-based polymers.

The expansive chemical space available to polymer chemists makes it hard to know what areas to start looking at. Automation has emerged as a powerful tool for high-throughput polymer synthesis and has enabled faster and more efficient polymer discovery. Furthermore, by combining automation with machine learning algorithms a closed loop can be created allowing the platform to act autonomously without the need for human intervention.²

Aims and Methods

This project looks to leverage the power of automation to create libraries of new polymer candidates as alternatives to SMA polymers for membrane protein extraction. The project aims to:

·      Develop automated platforms for the synthesis of amphiphilic copolymers.

·      Create and automate assays to assess the viability of new polymer candidates for membrane protein extraction.

·      Incorporate machine learning algorithms to allow for autonomous design of new polymers for membrane protein extraction.

References

1.   L. Unger, A. Ronco-Campaña, P. Kitchen, R. M. Bill; A. J. Rothnie, Biochem Soc Trans, 2021, 49, 3, 1349–1359.

2.    S. T. Knox, S. J. Parkinson, C. Y. P. Wilding, R. A. Bourne, N. J. Warren, Polym. Chem., 2022,13, 1576-1585

 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.

The ideal candidate would have experience in one or more of the following areas:

·      Organic synthesis

·      Polymer chemistry

·      Membrane protein extraction

·      Computer programming (Python)

·      Computer vision

Contact information

For formal enquiries about this project contact Sam Parkinson at s.parkinson1@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 – Engineering Systems” 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