MRC International Nutrition Group Quinquennial Renewal

Malnutrition represents the greatest modifiable threat to global health. This is especially so among children in the world's poorest nations where malnutrition and infections act hand-in-hand leading to high mortality and preventing children from reaching their full potential.

Many of the solutions to nutritional deficiencies are already known, and require political will, economic advancement and operational research to achieve a resolution. However, a host of unsolved scientific questions remain and these are critically inhibiting the design and implementation of interventions that could potentially bring immediate health benefits and save millions of lives. The MRC International Nutrition Group's mission is to overcome these barriers through research that illuminates the mechanisms linking diet to disease (see www.ing.mrc.ac.uk). Our vision is to improve the health of nations, especially in Sub-Saharan Africa, through research that will translate into medical and public health advances.

MRC ING is based at the London School of Hygiene & Tropical Medicine (LSHTM) and runs a major permanent fieldstation at MRC Keneba in rural Gambia. In a remarkable partnership between researchers and the local population the MRC has supported internationally pre-eminent research at Keneba for over 65 years leading to numerous seminal advances.

Our research falls under 4 themes:
The Early Growth and Development theme focuses on mothers and babies and seeks to understand the effects of nutrient deficiencies throughout the lifecourse (from before a baby is conceived through pregnancy, lactation and childhood) on growth, immunity and brain development. It seeks to define critical windows of opportunity when nutritional supplements would be most effective, and to define the optimal nature of such foods.
The Iron, Infection and Anemia theme is exploiting the recent discovery of hepcidin - a hormone that acts as the master regulator of iron metabolism - to try to understand how humans and their pathogens (bacteria, viruses and protozoa) compete for this essential nutrient. This battle for iron can lead to serious adverse outcomes if iron is administered to children living in infectious environments.
The Calcium, Vitamin D and Bone Health theme seeks to understand how bone health is affected by nutrition and other environmental factors. Populations consuming little dairy produce adapt to living on very low calcium intakes and can show paradoxically harmful effects of calcium supplementation. Understanding how calcium and vitamin D affect bone health and related problems such as osteoporosis is of crucial importance in developed nations and will become so in emerging societies as populations transition towards more Western diets and start to live longer.
The Nutritional Genetics theme uses genetic studies to try and pinpoint the key metabolic pathways that link diet with health and disease. The manner in which a person's genes are expressed throughout life can also be influenced by nutrition (so called epigenetics). Understanding these processes have profound implications for human health. They are thought to hold the clues as to how early-life nutrition affects lifelong health. ING is making important contributions to the science of epigenetics.

Modern science requires collaborations across numerous technologies and areas of expertise. Based upon the exceptional research opportunities at MRC Keneba, ING is able to attract world-leading scientists to assist us in our discovery mission.

Although focussed primarily on the nutritional issues of Sub-Saharan African our research contributes to globally-relevant problems because it focuses on making basic discoveries about how foods and nutrients affect human health.

The MRC International Nutrition Group (ING) is based at LSHTM and MRC Keneba in rural Gambia, with additional externally-funded research in Tanzania and Kenya. ING's central objective is to gain novel insights into the basic mechanisms linking malnutrition to metabolic and infectious diseases. We focus on discovery science in the strong belief that major knowledge gaps regarding causal pathways in nutrition are barriers to implementing effective solutions. Methodologies include clinical studies, epidemiology, long-term population surveillance, and randomised controlled trials. ING maintains its own infrastructure in Keneba including major research platforms: the Keneba Biobank (rising to n=12,000+ individuals); the West Kiang DSS; an integrated clinic-electronic registration system linked to genetic databases; and an antenatal outreach service allowing early recruitment of pregnant women. Technologies in Keneba range from imaging and body composition methods to clinical chemistry, immunology and microbiology. Genetic and epigenetic analyses, and specialist assays, are conducted by ING's international collaborations. MRC Keneba offers exceptional research opportunities due to the continued interplay between malnutrition and infection, a seasonal 'experiment-of-nature', long-term demographic records spanning 65y, and excellent community relations. Research is conducted across 3 focus areas (Early Growth & Development; Iron, Infection & Immunity; and Calcium, Vitamin D & Bone Health) with a 4th cross-cutting theme on Nutritional Genetics. The ultimate goal of ING's research is to provide a stronger theoretical basis for effective community-based and clinical interventions in deprived populations worldwide and thereby to contribute to medical and public health advances. Although primarily focussed on Sub-Saharan Africa our research contributes more generally to globally-relevant health challenges because it is focussed on general mechanisms linking diet and disease.

See full details in the attached case for support, Section 1.1.4.5. Some brief examples of our impact have been extracted here:

Science policy: We have argued strongly for the incorporation of mechanisms/explanatory research into large scale clinical trials in nutrition. The Director adopted this theme for his EV McCollum International Prize Lectureship Series titled: 'Trials and Tribulations: Interpreting unexpected outcomes from micronutrient interventions' delivered to large audiences in Washington, Nairobi and New Delhi, and internally to the Bill & Melinda Gates Foundation's Seminar Series.

ING has also been very active in steering the research agenda on iron and calling for greater investment in this critical micronutrient. The Director chairs the NIH/NICHD Research Review Committee overseeing the Iron & Malaria portfolio, and will present progress at the International Congress of Nutrition 2013. He will lead the iron track at the 2014 Micronutrient Forum World Congress in Addis Ababa.

Science funding: In line with our mission to build more informative mechanistic research and sub-group evaluations into large-scale trials we lobbied WHO to top slice a $20m funding package for 3 large trials of neo-natal vitamin A supplementation (NNVAS) in India, Tanzania and Ghana (n=100,000) and to issue an RFP for ancillary mechanistic trials. Despite a very tight time line the RFP received 47 applications of which our NNVAS mechanisms trial in Sukuta (twinned with a trial in Bangladesh) was one of 3 funded (see 1.2.3.1).

ING plays a prominent role in assisting BMGF to identify critical research gaps and formulate RFPs. We were commissioned to prepare 4 briefing documents as they prepared their Healthy Group call for proposals, and advised also on the Gut Function RFP. Similarly we conducted a major landscape analysis on nutrition and vaccine efficacy. Prentice sits on the Gates Foundation's 7-strong Discovery Expert Group for Global Health. He is also a member of the Wellcome Trust's Expert Review Group for Physiology in Health and Disease.

Health policy: ING continues to play a significant advisory role at WHO; our next input will be at the NNVAS Consultation in Sept 2013. We have played a prominent role in WHO's various consultations on Iron and Malaria and through membership of the NIH/NICHD Iron and Malaria Technical Working Group now feed in detailed advice.

We work in very close collaboration with the National Nutrition Agency (NaNA) in The Gambia holding regular coordinating meetings.

Dr Ann Prentice is Chair of the UK's Scientific Advisory Committee on Nutrition (SACN) and a member several of its sub-committees.

Clinical practice: Our recently completed trials on Zn and severe pneumonia, physician-prescribed LNS, NNVAS and PUFA supplementation in infancy will all have an impact on the evidence base and ultimately on practice. The complex design of the ENID Trial, which has just completed recruitment, will yield numerous clinically relevant endpoints. We are working to clarify the interrelations between infection, inflammation, hepcidin, iron redistribution and anemia in SCD, TB and HIV, which ultimately will have significant impact on clinical practice by guiding appropriate therapies for the anemia of infection.

Academic leadership: The Director holds, and has held, many leadership positions in the world's leading nutrition society, the American Society for Nutrition. He has been President of ASN's International Nutrition Council and has thrice been nominated to stand for the overall presidency of ASN; declining in order to concentrate on core ING activities. The Director has been nominated by Thailand to stand for election to IUNS Council.

Training: We have a very active training programme prioritising capacity development in Africa.