Molecular signatures of sex differences in the human brain. MRC GW4 BioMed DTP PhD studentship for 2026/27 Entry, Department of Clinical and Biomedical Sciences Ref: 5633

Supervisors

Lead Supervisor:  Professor Jonathan Mill - University of Exeter - Department of Clinical & Biomedical Sciences 

Co-Supervisors:

Professor Nicholas Bray - Cardiff University - School of Medicine 

Dr Ann Babtie - University of Exeter - Department of Clinical & Biomedical Sciences 

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:

Why do males and females show different risks for brain disorders like schizophrenia, depression, autism and Alzheimer’s? This project explores how sex chromosomes shape gene expression and epigenetic regulation in the human brain across development and aging. Using cutting-edge multiomic and single-cell datasets generated by our team and collaborators this bioinformatics project will investigate how the X and Y chromosomes drive molecular differences at the cellular level. You'll also examine sex-specific changes in brains affected by neuropsychiatric and neurodegenerative disease. Join our dynamic research team to uncover the biological foundations of sex differences in brain health and disease. 

Description:

It is well established that many brain disorders are characterised by sex differences, influencing disease prevalence, symptomatology, progression, and treatment response. For example, conditions such as autism spectrum disorder and Parkinson’s disease are more prevalent in males, while Alzheimer’s disease and major depressive disorder disproportionately affect females. While hormonal influences have long been recognized, emerging evidence points to sex-specific regulatory genomic mechanisms, including differences in chromatin accessibility, DNA methylation, histone modifications, and non-coding RNA expression, as being key contributors to these disparities. These regulatory differences can shape gene expression programs in a sex- dependent manner across brain development and aging, potentially conferring differential vulnerability or resilience to disease.

Understanding how sex-specific epigenetic and transcriptional landscapes interact with genetic risk factors offers a powerful framework for elucidating the biological basis of sex biases in brain disorders and for informing more personalized approaches to diagnosis and therapy.

This bioinformatics-focussed PhD project aims to uncover how sex- specific differences in gene regulation contribute to brain development, function, and disease. The student will leverage unique epigenomic and transcriptomic datasets generated by the supervisory teams in Exeter and Cardiff, including bulk and single-cell data from both human brain tissue and disease models. They will receive training in state-of-the-art computational approaches, including integrative multi-omic analysis and machine learning, and will work within a dynamic, collaborative environment that prioritises open and reproducible research practices. The project will be structured around three interrelated objectives, each forming the basis of a core data chapter in the PhD thesis:

•    Characterising sex differences across brain development and aging: The student will perform integrative analyses using existing epigenetic (DNA methylation, ATAC-seq) and transcriptomic datasets from fetal and postnatal human cortex to map sex-associated differences in gene regulation across key developmental stages and into aging. The student will be encouraged to propose novel ways of integrating datasets and source replication datasets from other groups.

•    Dissecting cell-autonomous sex effects using mosaic Klinefelter Syndrome tissue: Using a rare and uniquely powerful single-cell dataset generated from mosaic brain tissue of Klinefelter’s syndrome (XXY) individuals—where both XX and XY cells are present in the same genetic and environmental background—the student will directly compare gene regulation between male and female chromosomal complements at the cellular level. This will allow unprecedented insight into sex chromosome-driven effects on gene expression and chromatin structure in the human brain. The student will take a lead role in defining analytical strategies for comparing XX and XY cells (e.g., clustering, pseudotime, or trajectory inference) and may pursue additional validation using external datasets or cell-type deconvolution methods.

•    Identifying sex-specific regulatory changes in brain disorders: The student will apply integrative multi-omic approaches to large-scale datasets generated in Exeter and Cardiff across a range of neurodevelopmental (e.g., autism, schizophrenia) and neurodegenerative (e.g., Alzheimer’s, Parkinson’s) disorders. This aim will focus on identifying regulatory elements, genes, and pathways that show sex-specific alterations in disease states, potentially highlighting mechanisms underlying sex differences in risk, progression, and therapeutic response. The student can select which disease(s) to focus on based on their interest, and explore innovative computational methods to identify novel insights.

While the project is focused on testing key hypotheses and supported by available datasets, there is substantial flexibility for the student to steer the direction of the work based on their interests and findings. For example, they may choose to: focus on specific cell types (e.g., glia, neurons, immune cells) or brain regions with strong sex-bias signals; extend findings to in vitro or model systems in collaboration with experimental labs; develop or benchmark new bioinformatics tools for detecting sex effects; lead data visualisation or science communication initiatives related to the project. The student will become part of several extensive international networks via the supervisory teams role in the UK Human Functional Genomics Initiative, the APEX (autism prenatal sex differences) consortium, and the Psychiatric Genomics Consortium.

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