EpiBrain

Published article, 2023: Caffrey A, Lamers Y, Murphy MM, Letourneau N, Irwin RE, Pentieva K, Ward M, Tan A, Rojas-Gómez A, Santos-Calderón LA, Canals-Sans J, Leung BMY, Bell R, Giesbrecht GF, Dewey D, Field CJ, Kobor M, Walsh CP, McNulty H. Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies. Nutr Bull. 2023 Jun;48(2):267-277. doi: 10.1111/nbu.12611. 

The Outstanding External Collaborative Research Team Award 2024, Ulster University was awarded to Prof Helene McNulty on behalf of the EpiBrain project team. The award celebrates the achievements of staff at Ulster University and recognizes how the development of lasting external collaborations can achieve excellent outputs and impact both inside and outside the University. The winning team was honoured at the Research Excellence Awards ceremony in May 2024. 

Generating Impacts beyond academic for wider societal benefit is at the forefront of our collaborative research efforts in this partnership with academics and scientists in Canada and Spain. Through our flagship EpiBrain project (UK-Canada-Spain), a particularly successful focus of our research efforts within Biomedical Sciences at Ulster has been the interface between epigenomics and nutrition. The EpiBrain project has provided greater understanding of mechanisms contributing to risks and benefits of folic acid supplementation in Canada, Spain and the UK; three countries with different public health approaches, food fortification programs and recommendations for the dosage of duration of folic acid supplementation for pregnant women or ageing adults. The collaborative research is well aligned with the goal of promoting health and wellness across the lifespan in global populations. Moreover, work to date in this area and associated research income, as a result of the collative expertise from transatlantic HEIs, has made valuable contributions to the mechanisms underpinning an important research impact case study which is being further developed for REF2029. 

The EpiBrain project has substantial reach and significance, directly contributing to UK society, economy and culture, and demonstrates leadership of this UK research by bringing together researchers with expertise in nutrition, epigenetics and neurodevelopment to engage in diet and health research at a pan-European and international level. This research so far (as described in our Folic acid Impact Case Study submitted in REF2021) has been pivotal in bringing international policy discussions to a successful conclusion and helped formulate policy for the European Food Safety Authority and the Food Safety Authority of Ireland (FSAI) to establish international dietary recommendations. Optimising folate and related B-vitamin status in older populations (through fortification or supplementation programs) may have particular impacts on neuropsychiatric health and in turn help to preserve better quality of life in ageing. However, the biological mechanisms explaining the relationship of these nutrients with the brain remain unclear, hence the precedence of this international collaboration. 

Notably, this international partnership can achieve much more than is possible by any country working on its own, relying on national funding only, and is anticipated to make important contributions with impacts for the health of citizens across the lifecycle and thus beneficial to society as a whole at an international level. The EpiBrain project has improved scientific capacity and capability via the establishment of a critical mass of expertise in this research area and the sharing of innovative approaches and infrastructures. The teams have generated significant volumes of richly profiled human intervention trial data, which included epigenome-wide profiling, magnetoencephalography imaging data, and psychological profiling. The epigenome-wide data is publicly available upon publication. This is of significant value to the scientific community and aligns with a call from the European Food Safety Authority that prioritised the need for interdisciplinary collaboration and a targeted exploitation of available human epidemiological and clinical data to investigate the association between epigenetic changes and health effects. In their report outlining a ‘A Cross-Council vision for Food, Nutrition and Health research’ the Research Councils in the UK reported that many of the mechanisms underpinning the effects of food and nutrition on long-term health were under-investigated and called for multidisciplinary partnerships to deliver a robust and authoritative evidence base crucial to the development of healthier food products, optimisation and stratification of dietary guidelines, and determination of effective intervention strategies.

Regarding societal impact and awareness, the project is providing data to make evidence-based guidelines for periconceptional and prenatal supplementation and formulation of supplements. The minimally effective dose and duration of supplemental folic acid for neural tube defect prevention and other birth outcomes has been identified as a knowledge gap in a recent Canadian workshop on challenges and solutions to aligning supplemental folic acid intakes with current evidence-based recommendations. The teams have carried out significant, wide-reaching, national and international dissemination of research findings and knowledge exchanges to key stakeholders including the scientific community, policy makers, and public-health authorities. Knowledge exchanges have occurred tri-monthly between partners largely via videoconferencing for sustainability and environmental considerations, and in order to minimise costs and time spent on travel.

The impact for career progression for individuals at all levels and at an organisational level has exceeded all expectations with this project. Prof. Helene McNulty (an elected Member of the Royal Irish Academy since 2008) was elected to Council of the Academy in 2021 – the RIA is Ireland’s leading body of experts in sciences and humanities. Furthermore, in 2021, she was elected Member of the Advisory Council to the international Micronutrient Forum. Notably, Prof. Mary Ward was elected as President of the Nutrition Society of the UK and Ireland in 2023. In addition, Prof. McNulty and Prof Mary Ward are members of the Public Health Nutrition sub-committee for the Food Safety Authority in Ireland, which aims to improve public wellbeing, quality of life or morbidity or survival and changed public attitudes. The teams have a strong focus on supporting progression and mentorship to PhD students and early career researchers. In evidence of the impact in career progression, the teams secured funding for five PhD students, two at Ulster University, one at the University of British Columbia, and two additional students at Universitat Rovira i Virgili, in addition to two postdoctoral researchers. Regarding progression, Dr Aoife Caffrey progressed from PhD student to Postdoctoral Researcher at Ulster University and Dr Miroslava Ondicova to Postdoctoral Researcher at the University of British Columbia, and Dr Rachelle Irwin who was the original Postdoctoral Researcher from Ulster University progressed to a permanent position as a Lecturer in Genomic Medicine at Ulster University.

The collaborative research team have gained international recognition in epigenomics, health and nutrition publishing papers of significant academic merit, receiving attention from scientific and professional communities due to their originality, rigour and impact. To date, the team have published more than 53 peer-reviewed articles, book chapters, editorial and news pieces, within the last 4 years since 2018 in refereed journals, including the American Journal of Clinical Nutrition and with impact factors ranging from 3.7 to 12.2, and all regarded as all regarded as either 4* world leading or 3/4* internationally excellent.

In recognition of leadership in their fields, the team have undertaken more than 35 external engagement activities including international conferences in Vancouver, Spain, Brazil, Turkey, Poland and more, and invited press releases, media interviews, working groups and expert panels such as Prof. McNulty’s invitation and presentation to the US National Academy of Sciences Engineering and Medicine Committee (Food and Nutrition Board, Health and Medicine Division). A recent invited talk in Sao Paolo for the SLACAN 2023 conference, was further funded internally via the attainment of an Ulster University Early Career Researcher Collaboration Award, which has opened avenues of discussion with further international researchers and collaborations with FEA-UNICAMP.

The teams at Ulster, Canada and Spain have been successful in exchanging visits by team members, predominantly early career researchers and PhD students, between the transatlantic HEIs which has strengthened the collaboration and international profile of the research project work at conferences. The teams have been well-recognised for their research efforts; Dr Aoife Caffrey, a post-doctoral researcher on the project, attained the DSM Science and Technology European Bright Science Award, Ulster University Research Recognition Award, Ulster University Best PhD Thesis Award, FASEB Postdoctoral Poster Presentation Award, and the UKRI-Global Food Security Policy Lab award. A senior PhD student, Luke Hilman, attained the Best Poster Presentation Award at the Irish Society of Human Genetics Conference. Professor Michelle Murphy achieved a research prize for Consell Social URV: Modalitat EX-ANTE; Area of health and life sciences. Recently the Ulster team hosted Prof. Lamer’s PhD student a three-week internship exchange in November 2023 to learn techniques, such as pyrosequencing, unique to the internal team here.

The teams have co-developed an open source (general public license) webtool/application known as CandiMeth; a software tool for quantifying and visualising DNA methylation changes. The software has been used in a number of their published papers in collaboration with colleagues from a range of disciplines in both the internal and external teams and is empowering those in the life sciences to carry out their own analyses of epigenetic alterations without the need for extensive bioinformatics support (doi: 10.1093/gigascience/giaa066).

The Reus-Tarragona Birth Cohort Study (RTBC) has observed that maternal cobalamin and folate status around the time of neurogenesis show the strongest associations, out of numerous modifiable factors investigated, with cognitive performance in the offspring during mid-childhood. These results will be submitted shortly for publication.