Current projects

developmental programming of ribosomal dna epigenetics: a functional link to metabolic disease?

Ribosomal DNA (rDNA) exists in 100s of copies/genome. Specific subpopulations of rDNA in inbred (C57BL/6J) mice can be distinguished on the basis of a sequence polymorphism located within the promoter of 45S-rRNA (represented as A or C). Exposure to malnutrition in early life leads to lifelong epigenetic silencing (black circles) of copies with an A at the polymorphic site. The amount of silencing is proportional to the relative copy number of the A variant within the genome of the individual and also correlates with the extent of growth restriction caused by malnutrition (see Figure). Growth restricted mice have metabolic defects, such as reduced insulin secretion, that emerge as the offspring become adults. Maternal high fat and Western-style diets elicited a similar effect at rDNA, suggesting that it is a conserved target of malnutrition in development (Holland et al., 2016).

We are now developing systems to address what the functional consequences of this are for ribosome composition and function, with a view to establishing how this is causally related to the altered metabolic phenotypes observed in the mice as they age.

Collaborative projects

"intergenerational impacts of paternal obesity"

Collaborators: Dr David Williams, The Institute for Women's Health, University College London Hospital and Prof Vardhman Rakyan, The Blizard Institute, Queen Mary University London

“defining the influence of the extracellular matrix in determining tumour cell behaviour”

Collaborators: Dr Luca Urbani, The Institute of Hepatology, Foundation for Liver Research and Dr Chris Bell, The William Harvey Research Institute, Queen Mary University London

“the role of m6a in viral infection"

Collaborator: Dr Chad Swanson, Department of Infectious Diseases, King’s College London

“modulating epigenetics to enhance oncolytic virus efficacy”

 Collaborator: Dr Michelle Lockley & Dr Gunnel Halldén, Barts Cancer Institute, Queen Mary University London