MRC Human Genetics Unit
Medical Research Council Human Genetics Unit
MRC Human Genetics Unit
Institute of Genetics and Cancer
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Duncan Sproul Research Group

Epigenetics in Human Disease

D.Sproul
Dr Duncan Sproul - CRUK Career Development Fellow

Research in a Nutshell 

Our work focuses on using interdisciplinary approaches to understand the role of epigenetic dysfunction in human disease, particularly cancer. Epigenetic marks signpost the DNA and are believed to help cells switch genes on and off. For example, to ensure that the genes that make haemoglobin are switched on in blood cells but not brain cells. Alterations in the levels of epigenetic marks, are an intrinsic hallmark of many human diseases. However, we do not currently understand the role of epigenetic dysfunction in human disease and how it can be targeted to treat patients.

Our main focus is on understanding the molecular mechanisms underpinning the widespread alterations in the distribution of the repressive epigenetic mark DNA methylation observed in cancer. We combine computational analysis of large datasets, mathematical modelling and focused experiments in the laboratory. While we principally work on DNA methylation in cancer, we have also examined DNA methylation in aging and Mendelian disorders in collaboration with other research groups.

 

Research Programme

Duncan Sproul Research Group

People

  
Duncan Sproul Group Leader
Hazel Davidson-Smith Research assistant
Francesca Taglini Postdoctoral scientist

Ross Hannah

 PhD student

Lyndsay Kerr

 Postdoctoral scientist
Adrian Lee Research assistant
Andreanna Wright PhD student
Christine Rodger PhD student

Contact

d.sproul@ed.ac.uk

Publications

  1. Kerr L, Sproul D*, Grima R (2021) Cluster mean-field theory accurately predicts statistical properties of large-scale DNA methylation patterns. Submitted, Royal Society Interface. Kerr L, Sproul D*, Grima R (2021) Cluster mean-field theory accurately predicts statistical properties of large-scale DNA methylation patterns. Submitted, Royal Society Interface 19:20210707.
  2. Masalmeh RH, Rubio-Ramon C, Taglini F, Higham J, Davidson-Smith H, Clark R, Wills J, Finch AJ, Murphy L, Sproul D (2021). De novo DNA methyltransferase activity in colorectal cancer is directed towards H3K36me3 marked CpG islands. Nature Communications, 12:694. doi: 10.1038/s41467-020-20716-w.
  3. Heyn P, Logan CV, Fluteau A, Challis RC, Auchynnikava T, Martin CA, Marsh JA, Taglini F, Kilanowski F, Parry DA, Cormier-Daire V, Fong CT, Gibson K, Hwa V, Ibáñez L, Robertson SP, Sebastiani G, Rappsilber J, Allshire RC, Reijns MAM, Dauber A, Sproul D*, Jackson AP (2019) Gain of function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions. Nature Genetics, 51:96-105
  4. Rafique S, Thomas JS, Sproul D*, Bickmore WA (2015) Estrogen-induced chromatin decondensation and nuclear re-organization linked to regional epigenetic regulation in breast cancer. Genome Biology 16:145. * Corresponding author
  5. Benveniste D, Sonntag HJ, Sanguinetti G, Sproul D (2014) Transcription factor binding predicts histone modifications in human cell lines. PNAS 111:13367-72

Full publication list can be found on Research Explorer: Duncan Sproul — University of Edinburgh Research Explorer

Partners and Funders

  • Cancer Research UK Career Development Fellowship

Scientific Themes

Epigenetics, DNA methylation, Bioinformatics, Cancer

Technology Expertise

Epigenomics, Genome editing, Machine learning, Bioinformatics

 

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