Advancing episignature analysis for chromatin disorders

About the Project

Details of the Project

Epigenetic disorders of development (EDD) are associated with a range of clinical complications including developmental delay, growth and congenital anomalies, endocrine and others. EDDs include both congenital imprinting disorders (CIDs) and conditions caused by germline pathogenic variants (GPVs; mutations) in genes that regulate chromatin structure /function (chromatin disorders=CD). The genetics of CDs are complex and genetic heterogeneity and variable genotype-phenotype relationships make the interpretation of variants of uncertain significance (VUS) in CD genes challenging. However, GPVs causing CDs are frequently associated with altered patterns of DNA methylation (episigntures) that can be detected in blood. Episignature analysis can resolve the pathogenicity of variants of uncertain significance (VUSs) but further algorithm development is required for full-scale clinical application. We have demonstrated that episignature analysis can inform VUS interpretation, have identified novel episignatures and demonstrated that episignatures might inform prognosis and insights into the mechanisms of disease. This project will extend these pilot findings by applying a novel state-of-the-art sequencing technique that provides both DNA sequence and CpG methylation status (Illumina 5-base sequencing) to CDs. This provides much more detailed analysis of methylation status than the methods currently used for episignature analysis and promises to improve the sensitivity and accuracy of episignature detection with the potential for direct translation into clinical diagnostics.

Overseas Applicants

Overseas applicants may apply for this studentship but will need to pay the difference between the ‘Home’ and the ‘Overseas’ tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7. As part of the application, you will be required to confirm that you will provide this additional funding. Please indicate this on the application form in the funding section.

Location

This position will be based on the Aston Campus in Birmingham, UK. The successful candidate will need to be located within a reasonable distance of the campus, and will be expected to visit in person regularly.

Person Specification

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

a] a First or Upper Second Class award in their Undergraduate Degree (Bachelors or UG Masters) from a UK institution, in a subject judged by Aston to be relevant to the proposed research.

OR

b] a Merit (or above)* in a Postgraduate Masters degree in a relevant subject AND an Undergraduate Degree (Bachelors or UG Masters), both from UK institutions.

*where appropriate.

Qualifications from overseas institutions will be also considered but performance must be equivalent to that described above, and the University reserves the right to ascertain this equivalence according to its own criteria.

Contact information

For formal enquiries about this project contact Professor Eamonn Maher at e.maher@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. A Curriculum Vitae (Resume) which details your education and work history.
5. Two academic refereeswho 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.
6. 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.
7. 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.

Apply for this position here

Please select “ Research - Biomedical Sciences” 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

Funding Notes

This project covers the Home tuition fees. Candidates who do not have Home status will be responsible for the difference in tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7.

References

Lee S, Menzies L, Hay E et al. Epigenotype-genotype-phenotype correlations in SETD1A and SETD2 chromatin disorders. Hum Mol Genet. 2023;32:3123-3134
Lee S, Ochoa E, Badura-Stronka M, Donnelly D et al. Germline pathogenic variants in HNRNPU are associated with alterations in blood methylome. Eur J Hum Genet. 2023;31:1040-1047
Ochoa E, Zvetkova I, Lee S et al. Germline variants in UHRF1 are associated with multilocus imprinting disturbance in humans and mice. Proc Natl Acad Sci U S A. 2025;122):e2505884122