Neurogenetics PhD: Comparing Brain Changes Across Chromatin Disorders

Neurogenetics PhD: Comparing Brain Changes Across Chromatin Disorders

Research checked: 3 November 2026

Quick Decision

This project compares three chromatinopathies to identify shared brain pathways and ask whether treatment changes them. The proposed work spans mouse frontal-cortex single-nucleus and bulk transcriptomics, chromatin profiling, behavioural tests and patient/control-derived neuronal cells. It suits applicants interested in neurodevelopmental genetics, epigenetics and functional genomics. The three disorders, candidate drug, sequencing status and the second institution mentioned in the project wording remain unidentified.

Research Problem and Doctoral Work

What is unresolved

Chromatinopathies are a group of more than 180 rare genetic disorders caused by variants in genes encoding chromatin-remodelling factors. Many involve neurodevelopmental features such as developmental delay, intellectual disability or autism. The project description says that most have no treatment. Rather than develop a separate therapy for every disorder, the team proposes testing whether some conditions converge on shared pathways. Its preliminary mouse work is described as showing that a class of drugs can rescue neurodevelopmental phenotypes in relevant models. The public project PDF does not name the three prioritised conditions, drug class or supporting preliminary data; the stated rescue is a rationale for the study, not a result this PhD is guaranteed to reproduce. Project PDF.

Advertised work and methods

The central question is how each disorder changes the brain's transcriptome and epigenome, and how those changes respond to treatment. The student is expected to identify affected cell types, genes and chromatin features, and test whether the mouse models share pathways. The PDF names:

• Parse single-nucleus RNA sequencing (snRNA-seq) and bulk RNA-seq, to examine gene expression at cell-resolved and tissue-wide scales.
• CUT&Tag-seq, to profile chromatin features and relate them to gene-expression changes.
• Baseline and treated mouse frontal-cortex samples, with comparisons across the selected models. Some sequencing data have already been collected; the precise inventory is not stated.
• Mouse behavioural assays spanning anxiety-like behaviour, activity, repetitive and social behaviour, motor function, and learning and memory. Treatment comparisons are intended to test whether molecular changes align with phenotype.
• Patient- and control-derived induced pluripotent stem cell (hiPSC) neuronal data, including treated cells, for comparison between human-cell and mouse responses.

The student is expected to work closely with an expert postdoctoral researcher. The project PDF names mouse lines from the Basson and Banka groups, human iPSC lines and post-treatment RNA-seq/CUT&Tag data from the Banka group, Exeter mouse and behavioural facilities, high-performance computing at both institutions, and clinical-grade drug supplied by an unnamed pharmaceutical company. These are project-level resources; sample numbers, student-specific access, hands-on animal responsibilities, sequencing duties and the identity of the second institution are not specified. Official project PDF, Hatherly Laboratories, Siddharth Banka's University of Manchester profile.

One possible analytical angle is to test whether signals in bulk tissue are driven by particular cell populations, then compare molecular responses across mouse and human-derived neuronal models. CUT&Tag and RNA-seq could help connect chromatin changes to expression, while behaviour adds an organism-level outcome. This is an interpretation of the design, not a promised output. The PDF does not give a statistical plan, cell or animal counts, treatment schedule, compound names, or a division of existing data work between the student and postdoctoral scientist. Even if a molecular signature appears in both treated mice and hiPSC-derived neurons, it would remain preclinical evidence rather than proof of clinical efficacy or safe dosing. Ask how the group will interpret discordant results and what would count as rescue.

School, Programme and Field Context

The project PDF identifies the University of Exeter as the primary institution and Clinical and Biomedical Sciences as the department. Exeter lists an MPhil/PhD Clinical and Biomedical Sciences route, as well as separate research routes in Genetics and Genomics and Neuroscience. The exact degree title, registration unit and campus for this studentship should be confirmed in the offer documents. The project mentions high-performance computing at “both institutions” and names a Banka group, but does not identify a second institutional host or promise joint registration. Participation in the wider DLA network does not establish a joint or double degree.

Relevant Exeter research themes include neuroscience, genes and molecular biology, and research methods, data science and bioinformatics. The Clinical and Biomedical Sciences department describes work on molecular and genetic disease mechanisms through potential treatment. Hatherly Laboratories are used by neuroscience groups, including neurophysiology and neurodevelopment research, and list Albert Basson among principal investigators. Exeter's Rare Disease Genomics activity provides adjacent context in sequencing, variant interpretation and NHS-linked research; a placement there is not promised. The DLA adds shared training, scientific meetings, networking and collaboration across six UK core institutions. Clinical and Biomedical Sciences PhD, department research, Hatherly Laboratories, Rare Disease Genomics, FGx-DLA programme.

Exeter reports 136th overall in the QS World University Rankings 2027. Its REF 2021 profiles include 45% 4-star and 48% 3-star for Clinical Medicine; 53% and 39% for Psychology, Psychiatry and Neuroscience; and 41% and 49% for Biological Sciences. These are broad university or submitted-unit indicators, not ratings of Basson's group, this studentship or an individual student's experience. Exeter rankings, REF 2021 results.

Supervisor and Lab Assessment

The named lead is Professor M. Albert Basson, Professor of Neuroscience and Epigenetics in Exeter's Clinical and Biomedical Sciences department. The project PDF refers to resources from the Basson and Banka groups; it does not name Siddharth Banka as co-supervisor or specify the supervision split. Banka's University of Manchester profile describes iPSC-based neurological disease work, including cortical-neuron differentiation in KMT2D-related disorders. This gives context for the human-cell component but does not establish a formal supervisory or degree arrangement. Exeter staff listing, Exeter news on Basson's appointment, Banka profile.

Recent research that helps frame the project

1. Pérez-Sisqués et al., 2026, Science Advances. In a KDM5B-deficient mouse model, the authors combine RNA-seq and snRNA-seq to characterise neurodevelopmental features and report increased NMDAR2D expression; an NMDA-receptor antagonist produced limited rescue on some behavioural measures. This is a close methodological analogue for integrating cell-resolved sequencing with behaviour. It concerns one KDM5B model and a specific antagonist, not the three unnamed disorders or drug in this studentship. Study record.
2. Cuvertino et al., 2025, PLOS Genetics. The team studies KMT2D-related Kabuki syndrome patient iPSCs, neuronal progenitors and cortical neurons, reporting stage-dependent epigenome and transcriptome changes. Siddharth Banka is a co-author. This supports the relevance of human-derived neuronal models but does not test this project's treatment. Paper.
3. Pérez-Sisqués et al., 2024, Journal of Neuroscience. This study links Kdm5b loss and hippocampal knockdown to memory consolidation, activity and gene-expression differences. It shows adjacent experience relating chromatin regulators to behavioural and molecular phenotypes, but uses adult hippocampus rather than this project's frontal cortex and multi-disorder comparison. Study record.
4. Pérez-Sisqués et al., 2025, bioRxiv preprint. This preprint on ORY-1001 in aged mice reports learning and memory findings. It is not peer reviewed, concerns ageing rather than chromatinopathies, and does not identify the current project's compound. Treat it as emerging adjacent work, not established therapeutic support. Preprint record.

Together, these papers show nearby expertise in chromatin regulators, mouse neurobiology, single-nucleus expression profiling and patient-derived neuronal models. They do not establish the candidate drug's identity, response across the three selected disorders or clinical potential. Ask what training will cover sequencing analysis, behavioural protocols and animal work, and how the student will coordinate across groups.

Research Direction and Career Context

Functional genomics combines disease models and genetic variation with cell-specific expression, chromatin profiling and computational analysis. The UK Human Functional Genomics Initiative describes a broader programme using gene editing, disease-relevant cell models, spatial transcriptomics, multimodal screening and data science. This project has a narrower preclinical focus: molecular changes in three disease models and treatment response across mouse and hiPSC-derived neuronal systems. Potential outputs could include prioritised shared pathways or a clearer account of which cell populations respond, but these are hypotheses about what the design could produce, not guaranteed results. Initiative overview, UKRI programme investment.

Career relevance is strongest for combining molecular neuroscience, sequencing-data interpretation and experimental-model literacy. Skills England and the Office for Life Sciences estimate that life-sciences priority occupations could grow by about 66,000 jobs (44%) from 2025 to 2035, with another 52,000 workers expected to leave and be replaced. The report highlights digital, numerical and specialist scientific skills. This is a broad sector projection, not a forecast for genomics PhD graduates. An Association of the British Pharmaceutical Industry report discusses bioinformatics, statistics and data-analysis capability in genomics; it is an industry-body assessment rather than a vacancy or salary forecast. The DLA connects academia, the NHS and industry, but does not guarantee an industry placement or post-PhD job. Skills England life-sciences assessment, ABPI genomics workforce report, DLA researcher network.

Funding, Application and Living Cost

Item	Published position	Decision relevance
Entry and duration	September 2027; four years full-time (part-time study is also available)	Confirm whether this specific project allows part-time registration.
Deadline and route	Applications opened 26 October 2026 and close Tuesday 5 January 2027; apply once through Exeter and submit the DLA questionnaire	The questionnaire allows up to three project preferences; duplicate applications are not accepted.
Stipend	£21,805 per year for 2026/27, updated annually	UK Research Council minimum benchmark, not a guaranteed four-year total.
Tuition and research support	UK tuition fees plus up to £5,000 per year for research training and support	The national FGx-DLA page states Exeter international students do not need to supplement UKRI funding; confirm the final offer and annual fee statements. The support allowance is not described as personal income.
Exeter international fee reference	£29,800 full-time for 2027/28; Home fee TBA	Published university fee for the route; the national DLA page says Exeter students do not pay the UKRI/international fee difference. Confirm the offer reflects that rule.

UKRI's general guidance says its grant contributes only up to home-fee rates and international students may have to contribute more. The national FGx-DLA page adds a programme-specific exception: it names Exeter among the institutions where international students do not need to supplement UKRI funding. That resolves the general-versus-project ambiguity for this Exeter DLA, while the written offer remains the operative confirmation. FGx-DLA funding terms, national international-fee guidance, Exeter Clinical and Biomedical Sciences fees, UKRI student support, Exeter PGR fees.

Exeter estimates basic living costs at £1,300–£2,000 per month for a single student. Self-catered halls are listed at £150–£270 a week including bills; private rooms are £135–£250 a week before bills, based on local spend in April 2026. The £21,805 stipend averages about £1,817 a month over 12 months: roughly £517 above the low estimate and £183 below the high estimate. This is an arithmetic comparison, not a personal budget; initial setup, visa/health costs, travel, rent timing and annual stipend changes matter. Check current rents and contract periods in the university's accommodation room finder. Exeter living-cost estimate, accommodation room finder.

Applicant Fit and Preparation

Official requirements

The FGx-DLA calls for at least a 2:1 honours degree or international equivalent in a relevant subject. Listed areas include genetics, molecular biology, biomedical science, human biology, biochemistry, medicine, healthcare professions, pharmacology, bioinformatics, computer science and statistics. The English threshold is typically IELTS 7.0 overall with no component below 6.5, or equivalent; evidence is due by the application deadline. Applicants submit one Exeter online application and a completed DLA questionnaire, where they may list up to three project preferences. Two academic references are required and must not come from the prospective supervisory team. If referee details are supplied first, letters are expected after shortlisting; shortlisted candidates must arrange direct institutional-email submission seven days before interview. Documents must be in English, with certified translations of qualifications. The questionnaire asks applicants to describe any generative-AI use. Check the current official page for full document rules and questions. FGx-DLA application criteria.

Suggested preparation, not additional formal requirements

The project does not publish mandatory sequencing, animal or coding prerequisites. Applicants can show relevant experience in molecular biology, neurodevelopmental or genetic disease, RNA-seq or epigenomic data, experimental design, statistics, coding and reproducible analysis. Distinguish hands-on methods from coursework or planned learning. A concise application narrative can explain interest in the cross-model design, relevant research experience, how to approach negative or divergent results, and methods to learn. The advertised methods describe the doctoral work; they are not automatically entry requirements.

The project may be less directly aligned with applicants seeking a purely computational project, a patient-intervention study, or a fully specified compound and disease scope at application stage. This is an interpretation of the advertised work, not an admissions rule. Ask how computational, wet-lab and behavioural components are weighted and whether the emphasis can change.

Next Actions and Questions to Verify

Before applying

1. Ask the supervisor for the names of the three prioritised disorders and the treatment, or why these cannot yet be disclosed, plus a summary of the preliminary mouse evidence.
2. Confirm which sequencing data are already generated, which experiments the student will lead, and the balance among analysis, wet-lab, mouse behaviour and postdoctoral collaboration.
3. Confirm expected start date, Exeter degree/registration route and any English-equivalency documents. Submit one application and the questionnaire by 5 January 2027; list up to three preferences only if each is acceptable.

At interview

• How will shared pathways be distinguished from model-specific effects, and what happens if mouse and hiPSC data disagree?
• Which behavioural assays, animal procedures and analysis tools will the student learn and perform? What training is available?
• Who is on the supervisory team, and what are the roles of the Banka group, second institution and postdoctoral researcher?
• What evidence will count as treatment response, and how will null or partial-rescue results be interpreted?

Before accepting an offer

• Obtain written confirmation of the international-fee rule, stipend schedule and increments, four-year duration, and conditions attached to the £5,000 research-support allowance.
• Confirm the degree-awarding institution, registration, work location, access to animal/HPC facilities, and any cross-institution travel or residence expectations.
• Compare current Exeter housing contracts and personal spending with the confirmed stipend; the £1,300–£2,000 estimate is a range, not a guaranteed personal cost.

Evidence and Sources

Project, institution and programme

• Official chromatinopathies project PDF
• MRC Functional Genomics Doctoral Landscape Award — University of Exeter
• FGx-DLA postgraduate and international-fee guidance
• Clinical and Biomedical Sciences PhD route
• Clinical and Biomedical Sciences research
• Hatherly Laboratories
• Clinical and Biomedical Sciences staff
• Exeter Rare Disease Genomics
• Exeter rankings
• Exeter REF 2021 results
• Exeter neuroscience expansion news

Supervisor and publications

• Siddharth Banka — University of Manchester
• KDM5B mouse study — PubMed
• KMT2D Kabuki syndrome iPSC study — PLOS Genetics
• Kdm5b and hippocampal memory — PubMed
• ORY-1001 aged-mouse preprint — PubMed record

Funding, costs, field and careers

• Exeter PGR fees
• UKRI support for funded students
• Exeter student budgeting
• Exeter accommodation room finder
• UK Human Functional Genomics Initiative
• UK functional genomics researcher network
• Skills England life-sciences assessment
• ABPI genomics workforce report
• UKRI investment in the Human Functional Genomics Initiative