My research focus is on the biochemical pathways of one-carbon (1-C) metabolism and the molecular, nutritional and genomic factors which influence these pathways. One-carbon (1-C) molecular units are used in DNA synthesis and in methylation reactions that are key elements in processes such as cell signalling and control of gene expression. This 1-C metabolic system involves a multi-layered interaction of micronutrients including the vitamins folate, cobalamin (vitamin B12), riboflavin (B2), pyridoxal phosphate (B6) and choline in order to operate effectively. Our laboratory uses metabolic and genetic profiling as tools to understand the complex relationship between nutritional status of these micronutrients and optimal function of this biochemical network. A key goal of my research is to identify common genetic variants in 1-C pathways that alter metabolite concentrations or fluxes through the system and, as a consequence, may alter an individual’s risk of having a birth-defect affected pregnancy or of developing chronic disease conditions of ageing.
One specific area is the role of folate and vitamin B12 in prevention of neural tube defects and possible associations of these vitamins with other congenital disorders such as orofacial clefts and congenital heart disease. In this research, our laboratory has received major funding over nearly twenty years and continues to collaborate with two institutes of the National Institutes of Health in the USA, both National Institute for Child Health and Human Development (NICHD) and the National Human Genome Research Institute (NHGRI). With NHGRI, our group carried out a genome-wide association study of healthy young Irish individuals, primarily for the purpose of studying genomic determinants of blood quantitative traits that are linked to nutrient status. This valuable data set is now been used in wider collaborations with researchers in Europe and in the USA.
A second research area is in exploring how disturbances of one-carbon metabolism due to inadequate vitamin status might increase risk of chronic disease in the elderly (such as cognitive decline, bone disease and hypertension). This research is part of a major collaboration between TCD and St James Hospital, with UCD, UCC and University of Ulster at Coleraine as co-investigators in the Joint Irish Nutrigenomics Organisation (JINGO) consortium, designed to establish a National Nutrition Phenotype Database and funded by the Irish Department of Agriculture and Fisheries (DAFF). The cross border collaboration of JINGO with University of Ulster has also been substantially funded under the Northern Ireland Department for Employment and Learning (DEL) Cross Border R&D Funding Programme.
Another specific area of interest is the development and application of new techniques for analysis of folate and vitamin B12 related metabolites in clinical practice and an evaluation of the relative utility of such markers. Our laboratory has received international recognition as a centre of excellence in measurement of folate status and has collaborated with the US NIH and also the Centers for Disease Control (CDC) in Atlanta, USA in relation to analysis of folate in US populations. I have also acted as technical advisor on folate at several consultations hosted by the World Health Organisation, both in relation to prevention of birth defects and in assessing the folate status of different populations. AMOLLOY[AT]tcd.ie
