Exploiting novel lipid binding proteins to tackle neurological disorders. MRC GW4 BioMed DTP PhD studentship for 2026/27 Entry, Department of Biosciences Ref: 5642

Supervisors

Lead Supervisor: Professor Michael Schrader - University of Exeter - Department of Biosciences 

Co-Supervisors:  

Dr Gaynor Ann Smith - Cardiff University - Biomedical and Life Sciences – Dementia Research Institute 

Professor Valerie O'Donnell - Cardiff University - Systems Immunity Research Institute 

Professor Stephan Kemp - Departments of Clinical Chemistry and Paediatrics 

The GW4 BioMed2 MRC DTP is offering up to 17 funded studentships across a range of biomedical disciplines, with a start date of October 2026.

These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK and International students.

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 80 students over 4 cohorts in its second phase.

The 122 projects available for application, are aligned to the following themes;

• Infection, Immunity, Antimicrobial Resistance and Repair

• Neuroscience and Mental Health

• Population Health Sciences

Applications open on 1 September 2025 and close at 5.00pm on 20th October 2025.

Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check our website for details.

Studentships will be 4 years full time. Part time study may also be available.

Project Information

Research Theme:  Neuroscience & Mental Health

Summary:  

Successful applicants will join a dynamic, multi-disciplinary research project at the forefront of molecular cell biology, neurobiology, and lipid biochemistry. This cutting-edge project aims to uncover novel connections between organelle membrane proteins, lipid metabolism, and neurodegenerative diseases. Through innovative approaches— including advanced lipid analysis and the study of newly identified lipid- binding proteins—you will help reveal fundamental biological and biomedical principles. The findings are expected to open new pathways for improving lipid uptake and developing potential therapeutic strategies for neurodegenerative disorders. 

Description:

Adrenoleukodystophy (ALD, X-ALD) is a severe neurodegenerative disease, a hereditary condition which results in damage to the membranes that insulate nerve cells in the brain. The birth incidence of ALD is estimated at 1:14,000 and patients suffer from a variety of debilitating symptoms including progressive demyelination and adrenal insufficiency. This can lead to chronic fatigue, hearing and visual impairment, and seizures with rapid degeneration to a vegetative state. The severity and onset of symptoms can vary and the disease, despite being X-linked, can also manifest in carrier females in later life. ALD is caused by mutations in the ALDP gene which encodes a lipid transporter on peroxisomes, which are sub-cellular organelles with key functions in the processing of a range of lipid species including those required for proper function of neuronal membranes. Mutations in ALDP affect transport of lipids into peroxisomes, compromising lipid processing. 

The pathophysiology of ALD is complex but can be attributed to: 1) reduced lipid transport into peroxisomes resulting in insufficient processed lipids at the neuronal membrane and 2) accumulation of the unprocessed lipids in the cytoplasm leading to toxic effects. Currently therapeutic options are limited or in their infancy, and mostly aim at reducing accumulation of unprocessed lipids to limit toxicity. Surprisingly, the ALDP protein itself has no intrinsic affinity for lipids (Baker et al., 2015 Biochem Soc Trans. 43:959). We recently discovered a novel lipid binding protein, ACBD5, at peroxisomes, which appears to act as an ALDP cofactor, allowing increased lipid channelling to the transporter (Costello et al., 2017 J Cell Biol 216:331; Islinger et al., 2020 BBA 1867:118675; Kors et al., 2022 J Cell Biol 221(3):e202003143; Costello et al., 2023 J Biol Chem 299:105013; Kors et al., 2024 BBA-Mol Cell Res 1871:119843). In cooperation with the Amsterdam Medical Centre, we also identified first patients with loss-of-function mutations in ACBD5 (Ferdinandusse et al., 2017, J Med Genet 54:330; Schrader et al., 2020, J Inherit Metab Dis. 43:71; Dawes et al., 2025, Frontiers Mol Neurosci 18:1602343). Removal of ACBD5 results in the accumulation of the same lipid species which are evident in ALD patients. Our findings now enable us to further explore the properties and functions of ACBD5 in lipid metabolism, neuronal function and neurodegeneration. Our exciting discovery of ACBD5 (and related proteins) as a novel peroxisomal membrane protein with lipid-binding properties and a role in transport/uptake of lipids into peroxisomes opens new avenues for the treatment of neurodegenerative disorders, which the student will explore.

Modulation of ACBD5 may be exploited to overcome defects in ALDP and improve lipid uptake in ALD, and possibly other neurodegenerative diseases with aberrant lipid metabolism. The student will be integrated in a multi-disciplinary project combining molecular and biochemical studies (M Schrader, Biosciences, Exeter) with neurobiological approaches/in vivo models (GA Smith, Dementia Research Institute, Cardiff) and expertise in lipid metabolism and lipidomics (V O’Donnell, School of Medicine, Cardiff; S Kemp, Amsterdam Medical Centre, NL). The student will combine molecular cell biology and biochemical approaches to further characterise the properties and functions of ACBD5 in lipid binding and as a cofactor for lipid transport. Cellular approaches will be combined with organismal models (fly, mouse) and mass spectrometry/lipidomics to determine the impact of ACBD5 on neuronal development, lipid composition and neurodegeneration. With this multi-disciplinary approach, we aim to unravel new basic biological and biomedical principles, to understand the properties and functions of ACBD5, and to explore approaches to improve lipid uptake into peroxisomes to combat neurodegenerative disorders such as ALD.

Funding

This studentship is funded through GW4BioMed2 MRC Doctoral Training Partnership. It consists of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£20,780 p.a. for 2025/26, updated each year).

Additional research training and support funding of up to £5,000 per annum is also available.

Eligibility

Residency:

The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD.  All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).

Academic criteria:

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences.  Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English requirements:

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the details in the following web page for further information https://www.exeter.ac.uk/study/englishlanguagerequirements/

Please check the relevant English Language requirements of the university that will host the PhD project.  

Data Protection

If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.

Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).

Further Information

For an overview of the MRC GW4 BioMed programme please see the website www.gw4biomed.ac.uk

Entry requirements

Academic Requirements

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English Language Requirements

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the relevant university website for further information.  This will be at least 6.5 in IELTS or an acceptable equivalent.  Please refer to the English Language requirements web page for further information.

Please check the relevant English Language requirements of the university that will host the PhD project. 

How to apply

A list of all the projects and how to apply is available on the DTP’s website at gw4biomed.ac.uk.  You may apply for up to 2 projects and submit one application per candidate only.

Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’.  If successful, you will also need to make an application for an 'offer to study' to your chosen institution.

Please complete the online application form linked from our website by 5.00pm on Monday, 20th October 2025.  Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the DTP’s website for details and updates

If you are shortlisted for interview, you will be notified from Tuesday, 23rd December 2025.  Interviews will be held virtually on 27th and 28th January 2026.  

Further Information

For informal enquiries, please contact GW4BioMed@cardiff.ac.uk

For project related queries, please contact the respective supervisors listed on the project descriptions on our website.

Summary