Defining the Membrane Protein Folding Rulebook

PhD

Programme length: 4 years

AlphaFold has transformed our understanding of protein structure, but how proteins fold during synthesis remains elusive. In this unique project, you will capture structural snapshots of human membrane proteins as they fold into bilayers, combining advanced bioanalytical approaches with real-time measurements to identify the key molecular players and mechanisms involved.

Course type
Full-time
Location
Birmingham
Funding Type (PhD)
Fully-funded
Discipline
Health & Life Sciences
School of Medicine, Pharmacy and Biosciences

Start date

Aston Institute for Membrane Excellence

At Aston Institute for Membrane Excellence (AIME), we are passionate about equity, diversity, and inclusion and are dedicated to cultivating a diverse cohort of PhD researchers from a range of academic backgrounds.

AIME is a first-of-its-kind institute that synergistically combines world-leading expertise in membrane biology and novel polymer chemistries. No other institute in the global research and innovation landscape has the platform, potential or promise for major breakthroughs that AIME heralds.

We welcome students from diverse pathways, whether recent graduates or professionals returning to academia.

We are particularly focussed on recruiting and training female scientists in this exciting multi-disciplinary arena, acknowledging current gender disparities. All AIME PhD projects feature:

  • Flexible working.
  • Comprehensive mentorship for all students.
  • Supported opportunities for secondments in international labs.
  • Diverse scientific and transferrable skills training, equipping all graduates for leading roles in academia or industry.

If you have any questions about this opportunity, please contact AIME Manager Paul Knobbs for a chat at p.r.knobbs@aston.ac.uk

Project details

 

Membrane proteins are essential for cell signalling, transport, and drug targeting, yet how they fold correctly as they are synthesised remains poorly understood. This fully funded PhD will investigate the cotranslational folding of membrane proteins, a fundamental process with important implications for understanding disease and protein misfolding.

This highly interdisciplinary and collaborative Leverhulme Trust funded project will combine native nanodisc technology, proteomics, lipidomics, and biophysical approaches to capture and study membrane bound ribosome nascent chain complexes from human cells. By analysing how nascent membrane proteins interact with lipids, chaperones, and the translation machinery, the work will reveal key mechanisms that govern membrane protein folding and membrane integration.

Additionally, surface enhanced infrared absorption spectroscopy (SEIRAS) will be used to monitor membrane protein folding in real-time during in vitro translation. By coupling cell-free expression with synthetic bilayers or nanodiscs, SEIRAS enables direct observation of structural changes as human nascent proteins fold and insert into membranes. This provides a powerful way to connect molecular interactions identified by multiomics approaches with dynamic folding behaviour. SEIRAS will be carried out alongside world-leading researchers at King’s College London (KCL).

The student will be primarily based in the Aston Institute for Membrane Excellence (AIME) and will work in newly established laboratories designed for membrane protein research. Training will include advanced methods in mass spectrometry, membrane biochemistry, and structural biology. The project will use state of the art instrumentation including the Orbitrap Ascend Tribrid mass spectrometer at AIME and SEIRAS at KCL.

Project objectives

  • Produce snapshots of MPs folding on the ribosome and purify in their natural setting so we can study their physical properties.
  • Understand the environment in which these MPs fold, using a mix of biochemical tests and advanced analytical techniques.
  • Examine the MP intermediate structures closely to see how certain factors affect how they fold.
  • Follow structural changes as they happen in real-time to better understand the process.

Supervisory team

  • Dr Grant Pellowe (Primary Supervisor), Aston Institute for Membrane Excellence
  • Dr Ivana Milic, (mass spectrometry), Aston Institute for Membrane Excellence
  • Dr Alice Rothnie, (membrane proteins and native nanodiscs), Aston Institute for Membrane Excellence
  • Prof. Paula Booth, (membrane proteins and SEIRAS), King’s College London

The project offers training in interdisciplinary approaches spanning cell biology, proteomics, lipidomics, and membrane biophysics, while maintaining strong collaborative links between Aston University and King’s College London, and would suit a student with a strong interest in molecular biology, biochemistry, structural biology or mass spectrometry.

References

  • doi.org/10.1021/acs.biochem.0c00423
  • doi.org/10.1016/j.bbamem.2019.07.007
  • doi.org/10.1038/s41594-025-01676-5
  • doi.org/10.1038/s41598-017-08522-9

Key words

Protein folding, membrane proteins, structural biology, mass spectrometry, ribosomes, nanodiscs.

Financial Support

This project covers the home tuition fees and includes an annual stipend of £20,780. International applicants may apply for this studentship but will need to pay the difference between the ‘Home’ and the ‘Overseas’ tuition fees each year.

Please note that the successful candidate will be responsible for any costs relating to moving to Birmingham and/or visiting the Aston campus. International students must meet the financial requirements for the visa, flights, and NHS Surcharge. Applicants should be confident that they can meet these costs before applying.

Further information can be found here: Financial Requirements | Aston University

PhD overview

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries and developing lifelong skills. 

At Aston University, our Engineering and Physical Sciences PhD programmes will provide all the support and facilities you will need to develop into a leading researcher in your chosen field.  You will be welcomed into a supportive community with a shared enthusiasm for original research, where diversity and multidisciplinary is championed.

Supervisory team details

Main Supervisor                 Dr Grant Pellowe

Associate Supervisor           Dr Alice Rothnie, Dr Ivana Milic, Prof Paula Booth (KCL)

For enquiries about this project, contact Dr Grant Pellowe at g.pellowe@aston.ac.uk.

 

Person specification

Candidates should have been awarded, or expect to achieve, EITHER:

  • A Bachelors degree in a relevant subject with an award of First Class or 2.1. 

OR 

  • A Bachelors degree in a relevant subject with an award of First Class or 2.1, and a Masters degree in a relevant subject with an award of Merit or higher.

Qualifications from other countries which are considered by Aston University to be equivalent to that described above will be eligible to apply.

Any Desirable / Essential Skills or Experience

 

Essential Skills:

  • A strong background in biochemistry, biophysics, structural biology, or a related discipline
  • Practical laboratory experience in biochemistry
  • Good analytical and problem-solving skills.
  • Ability to work independently & collaboratively as part of an interdisciplinary research team.
  • Strong written & verbal communication skills.

Desired Skills:

  • Previous experience with molecular biology and cloning; mammalian tissue culture; recombinant protein expression and purification (including membrane proteins); use of copolymer technologies; SDS-PAGE and Western blot; protein reconstitution into synthetic lipid systems; cell-free expression systems; mass spectrometry; and development of protein activity assays

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.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.  

Contact information

For formal enquiries about this project, contact Dr Ho Fai Po

group of students talking

Apply now

If you require further information about the application process please contact the Postgraduate Admissions team.

Support services

In addition to the support provided by your supervisory team and the wider research community, the Aston University Graduate School provides a range of support services for both applicants and current research students. This includes:

  • The Student Charter: a summary of the aspirations and expectations of the University and its students. 
  • The Postgraduate Mentoring Scheme: supporting the integration and student experience of newly arriving postgraduate students by matching them with more experienced postgraduate students who act as peer mentors.
  • International Student Support Unit: providing help and advice to students from overseas, both before you join Aston and once you have arrived.
  • Committee representation: our College Research Committee and the University's Graduate School Management Committee has a student member from each School of study.
  • Facilities: in addition to the specialist facilities you will use, we also have a Graduate School Office and Training Room, as well as a Postgraduate Student Common Room, a space designated for you to meet, relax and socialise.

Career prospects

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.

The variety of PhD project topics at Aston means that the destinations of our graduates vary substantially. Some choose to continue into academia, at either Aston or other leading institutions, while others go onto use their newly acquired skills in a range of research, healthcare, industry or charitable fields. When selecting your chosen PhD path at Aston, your supervisor will be able to provide you with relevant career opportunities that could be available to you in your specialist area.

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