Research

Our lab's research focus is how the environment interacts with genes in different organisms to bring about changes to the phenotype, which can last a life time. We therefore have projects looking at ageing, obesity and diabetes, as well as more basic scientific research questions, focussing on the mechanisms of gene-environment interactions.

Gene-environment interactions at ribosomal DNA

How our genomes respond to stressful environments has a significant impact on health and disease states. Epigenetic down-regulation of ribosomal DNA has long been known to be a key stress response mechanism in all eukaryotes. We recently found that a suboptimal early-life environment results in increased DNA methylation at the rDNA promoter. This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Our work identified environmentally induced epigenetic dynamics that are dependent on underlying genetic variation. We are now further characterising these effects in mouse models and extending our work to human populations. These experiments include cell biology, long-read sequencing, epigenomics, and computational biology.

INTERGENERATIONAL IMPACTS OF Paternal obesity

We wish to discover if acquired characteristics such as obesity, can be transmitted from father to unborn babies inhuman, as has been shown in mouse models. We have designed a multi-staged, integrated study to discover how an obese father might inhibit the growth of his unborn baby and whether paternal weight loss has the potential to improve fetal growth and provide the ultimate primary prevention of life-long disease in the next generation. This project involves genomic and epigenomic analysis (both computational and experimental) of large human cohorts.

the epigenetic ageing clock

Recent studies have established the existence of aging-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesize that aDMPs are pan-mammalian and  are a dynamic molecular readout of lifespan variation among different mammalian species. In a large-scale analysis of aDMPs in six different mammals, we have shown a a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This represents the first dynamic molecular readout of lifespan differences among mammalian species and suggest that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals. We are currently trying to understand the molecular origins of aDMPs.