Supervisors: Dr D Sproul, Dr Hannah Long, Dr M Wilson
Deadline: Monday, November 16, 2026
Funding: Funded PhD Project (Students Worldwide)
About the Project
DNA methylation is a repressive epigenetic mark whose genomic pattern is established early in mammalian development. The correct patterning and maintenance of DNA methylation is vital for development to proceed normally and disruptions cause disease. However, we do not currently understand why DNA methylation defects cause abnormal development.
DNA methylation is patterned by DNA methyltransferase enzymes (DNMTs) which are recruited and regulated by multiple pathways. Our recent work has dissected and defined these pathways providing the opportunity to understand which DNMT functions are required for development to proceed correctly.
This project focuses on dissecting the role of DNMT3B, the enzyme primarily responsible for methylating the genome during early development. DNMT3B knockout is lethal in mice and human mutations cause the recessive genetic developmental condition Immunodeficiency centromeric instability facial anomalies syndrome type 1 (ICF1) (Rolls et al 2024). We have recently delineated a novel pathway recruiting DNMT3B to constitutive heterochromatin (Taglini et al, 2024).
To understand why DNMT3B is critical for development, we will generate human embryonic stem cell (hESC) lines with separation-of-function mutations targeting different DNMT3B recruitment pathways before characterising their epigenomes and transcriptomes. We will then differentiate these hESC lines to understand how DNMT3B defects impact on development. As DNMT3B mutations affect facial patterning in ICF1, we will focus on differentiating hESCs to cranial neural crest which are a key cell type for facial patterning (Long et al, 2020). This project lays the groundwork to understand the molecular basis of why correct DNA methylation patterning is vital for human development.
The project is a close collaboration between the Sproul, Long and Wilson groups at the University of Edinburgh. The successful applicant will work within the vibrant, interdisciplinary research community at the Institute of Genetics and Cancer. It would ideally suit those with a strong interest and background in gene regulation, chromatin and epigenetics with quantitative skills. Applicants with other training backgrounds who are motivated to learn the necessary skills will also be considered. During the PhD, the student will gain experience in hESC culture, genome editing, Nanopore sequencing, CUT&Run, scRNA-seq and computational analysis of the resulting data.
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP). Detailed guidance on the application process, and the EASTBIO Application and Reference Forms can be found at How to Apply | Biology.
Please send your completed EASTBIO Application Form along with a copy of your academic transcripts (as a pdf) to student-admin@igc.ed.ac.uk. You should also contact your referees and ask them to submit their references (on the EASTBIO reference form template) to student-admin@igc.ed.ac.uk by the application deadline of 16th November 2026.
Funding Notes
This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees. The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees. There is a cap on the number of international students the DTP recruits. It is therefore important for us to know from the outset which fees status category applicants will fall under when applying to our University.
Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
References
Long et al 2020, https://doi.org/10.1016/j.stem.2020.09.001
Rolls et al 2024, https://doi.org/10.1042/BST20231017
Taglini et al 2024, https://doi.org/10.1038/s44319-024-00061-5
Project supervisors
Dr. Duncan Sproul
Career overview
Dr. Duncan Sproul is a programme leader and CRUK Career Development Fellow at the MRC Human Genetics Unit and Institute of Genetics and Cancer. They studied Genetics at the University of Edinburgh before being awarded an MRC pre-doctoral fellowship to undertake a PhD on the regulation of gene clusters under the supervision of Prof. Wendy Bickmore at the MRC Human Genetics Unit. During postdoctoral training at the Edinburgh Breakthrough Breast Cancer Research Unit with Dr. Andrew Sims, they applied emerging epigenomic technologies to understand the role of epigenetic dysfunction in breast carcinogenesis. Dr. Sproul joined the MRC Human Genetics Unit in 2013 as a research fellow and was awarded a Career Development Fellowship from CRUK in 2016. They are also an alumnus of the Scottish Crucible.
Research interests
Dr. Sproul's research focuses on the regulation of gene clusters and the role of epigenetic dysfunction in breast carcinogenesis. They have applied emerging epigenomic technologies to investigate these areas, particularly during their postdoctoral training at the Edinburgh Breakthrough Breast Cancer Research Unit.
Hannah Long
Career overview
Hannah Long began an active interest in research during school, participating in a Nuffield Science Bursary to study the impact of invasive crayfish species on native populations. She completed undergraduate studies in Natural Sciences at the University of Cambridge, where she conducted research with Professor Leonard Zon at Harvard Stem Cell Institute and Professor Akira Nakamura at the RIKEN Institute in Japan. Pursuing interests in development and nuclear processes, she undertook doctoral work at the University of Oxford in the Department of Biochemistry as part of the Wellcome Trust Graduate Programme in Chromosome and Developmental Biology. During her DPhil, she collaborated with Professors Rob Klose and Roger Patient to explore the conservation of non-methylated islands across vertebrate species and investigate DNA sequence features affecting DNA methylation status. For her postdoctoral research, she received a Sir Henry Wellcome post-doctoral fellowship and worked with Professor Joanna Wysocka at Stanford University, alongside Professors Doug Higgs and Jim Hughes at the University of Oxford. Her postdoctoral work focused on utilising human embryonic stem cell and murine models to characterise gene regulatory regions, known as enhancers, that are disrupted in patients with Pierre Robin sequence (PRS), a craniofacial disorder. This research provided insights into disease mechanisms, characterised long-range disease-associated enhancers for the SOX9 gene, and demonstrated how subtle changes in gene expression can lead to morphological alterations. As a Programme Leader Track (PLT) Group Leader at the MRC Human Genetics Unit, her group aims to leverage knowledge of the SOX9 regulatory locus and developed model systems to investigate the roles of combinatorial enhancer function and 3D genome architecture in gene regulation. This research has significant implications for understanding how genetic alterations affect normal human facial development and contribute to disease.
Research interests
Hannah Long's research focuses on the mechanisms of gene regulation in the context of craniofacial development and the role of non-coding regulatory elements called enhancers. They investigate how enhancer perturbation can lead to human congenital craniofacial disorders, particularly through the study of the SOX9 gene, which is crucial for craniofacial morphology. Their work utilises in vitro differentiation of human embryonic stem cells to cranial neural crest cells (CNCCs) and animal models, employing genome-editing, epigenomic analysis, and imaging techniques. The research aims to understand the regulatory mechanisms driving gene expression and how chromosomal structure relates to gene activity, ultimately seeking to predict the impact of non-coding genetic mutations on developmental gene expression and disease phenotypes.
Dr. Marcus D Wilson
Career overview
Dr. Marcus D Wilson is a Sir Henry Dale Fellow and Lecturer in Structural Cell Biology at the Wellcome Trust Centre for Cell Biology, University of Edinburgh, a position held since 2018. Prior to this, Dr. Wilson was a Postdoctoral Fellow at the Francis Crick Research Institute in London from 2016 to 2018. They also served as a Visiting Scientist at the SickKids Research Institute in Toronto, Canada, from 2015 to 2016, and at the University of Wisconsin, Madison, USA, in 2014. From 2013 to 2016, Dr. Wilson was a Post-doctoral Researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada. Dr. Wilson completed a Ph.D. in Biochemistry at University College London (UCL) at the Cancer Research UK London Research Institute from 2009 to 2013, and obtained an MBiochem in Molecular and Cellular Biochemistry from Oxford University from 2005 to 2009.
Research interests
Dr. Wilson's research focuses on understanding how epigenetic marks are placed, read, and interpreted on chromatin. They utilise defined modified chromatin to study individual nucleosome-chromatin protein complexes using single-particle cryo-electron microscopy (cryo-EM), along with biochemical, biophysical, and cell biology approaches to investigate histone marks and DNA methylation.