University of NOTTINGHAM

The University of Nottingham is a pioneering university that provides an exceptional research-led education (TEF Gold), and an outstanding student experience.

Short biography principal investigator

Prof. Dr. Kevin Sinclair

Prof. Dr. Kevin Sinclair

Kevin is a member of the Future Food leadership team. Kevin’s research interests lie in metabolic programming during early mammalian development, where epigenetic outcomes are determined in embryonic cells and tissues, and long-term developmental consequences assessed in offspring. His group were the first to discover that developmental anomalies following embryo culture, leading to Large Offspring Syndrome (LOS) in cattle and sheep, were due to errors in genomic imprinting. They were also first to demonstrate that reductions in folate and vitamin B12 in maternal diets (sheep and rats) lead to epigenetic modifications to DNA methylation associated with hypertensive and insulin-resistant offspring. They subsequently demonstrated that paternal malnutrition epigenetically modifies DNA methylation and adversely affects cardio-metabolic health in mouse offspring. Kevin’s ongoing work is assessing the nature and extent of aneuploidy and epigenetic dysregulation during bovine embryo culture, and transgenerational epigenetic consequences of exposure to real-life mixtures of environmental chemicals in sheep grazing pastures treated with biosolids.

Key Research Facility and Equipment

From testing laboratories to scientific equipment, our facilities are supported by researchers who can guide you through set-up and analysis.

Current involvement in Research and Training Programmes

Ongoing research is addressing the hypothesis that maternal nutritional effects in developing oocytes and embryos, and procedures used in assisted reproduction, can program fetal development and adult health via heritable epigenetic changes to DNA methylation at specific gene loci in the oocyte and pre-implantation embryo. First to discover that developmental anomalies following mammalian embryo culture were due to errors in genomic imprinting (Nature Genetics, 27: 153-154). Similar phenomena have since been reported in human IVF pregnancies. Work supported by the National Institutes of Health (USA) demonstrated that reductions in folate and vitamin B12 in the diets of intending mothers (rat and sheep) lead to epigenetic modifications to DNA methylation and adult offspring with increased body fat and blood pressure, altered immune function and insulin resistance (showcased to the NICHD Advisory Council in Washington DC in January 2007; PNAS, 104: 19351-19356).

Provided the first detailed report of cardio-metabolic and musculo-skeletal health in aged cloned (by somatic-cell nuclear transfer (SCNT)) offspring (Nature Communications 7: 12359; Scientific Reports 7: 15685) and, most recently, provided details of concordant DNA methylation in embryonic and somatic-cell lineages (PLOS Genetics. 13: e1007060). Ongoing work is determining if the nature extent of (a) mtDNA heteroplasmy and (b) DNA methylation in different cell types can explain observed differences in metabolic and musculoskeletal health within and between cloned animals

Additional EU-FP7 – sponsored studies in sheep and mice assessed the effects of exposure to real-life levels of environmental chemicals on development of the fetal hypothalamic-pituitary-gonadal axis. Studies in sheep were initially based on animals grazing sewage-sludge treated pastures at various intervals during pregnancy (Scientific Reports. 6: 22279). From these studies specific groups of chemicals (e.g. phthalates and PCBs) were identified as being particularly harmful and have since been studied in separate studies. Exposure to these chemicals has a profound effect on testis development, with more subtle effects observed in the fetal ovary. Molecular studies are assessing global changes in gene and protein expression associated with such effects.

Current BBSRC funded studies are investigating the genetics of one-carbon metabolism in sheep in relation to productivity, fertility and health. Also, seeking to generate generate cytogenetically ‘normal’ and developmentally competent bovine and porcine sexed-embryos that have undergone genomic evaluations in order to promote the production of livestock that are genetically superior for a number of health and production-related traits.