Detailed information about NuNZ achievements

NuNZ operates its research programme in four closely-interwoven objectives. Each has made tremendous scientific progress in less than four years. As described in our top four outputs, this means that we now have all the elements in place for a capability platform that can work with industry to develop a whole new export-focused 'personalised food' sector.

Objective 1 has developed the infrastructural platform necessary to deliver the bioinformatics, biostatistics and database resources for NuNZ. This has involved establishing a relational database that can be interrogated for relationships between genetic variation and disease states, plus the impact of diet in human populations. It has also involved developing a formal infrastructural platform for bioinformatics and database resources in order to analyse microarray and proteomics data on gene expression patterns, identify clusters of affected genes, discover human analogues and thereby extrapolate this information to human health or disease. A highlight of this objective has been the establishment of the nutrigenomics wiki, which acts as a responsive source of information and communication across the programme. A data stewardship committee meets by teleconference once a month in order to develop priorities for data analysis.

We have also done important and necessary fundamental work on methods for analysis, especially in relation to the selection of methods for single nucleotide polymorphism analysis  and whole genome association studies . We have very critically compared available genotyping platforms, to conclude that much of the confusion in several prominent and apparently contradictory studies has been caused by technical artefacts associated with some of the commonly used methods  This investigation led us to bring in Charles Cantor, CEO of Sequenom, as a lead speaker at our 2006 conference and to play a key role in the business case to bring the Sequenom and Affymetrix array technologies to Auckland. NuNZ has integrated our own resources and expertise to lead innovative foods insight by building linkages across New Zealand that extend beyond the programme. Our initial links were with gastroenterology clinics at Christchurch and Auckland, in order to develop collaborative studies, initially relating genetic factors in Crohn's disease to clinical phenotypes and outcomes. Our secondary aim in these collaborative studies is to establish gene-diet relationships of relevance to Crohn's disease and other endpoints of chronic inflammation. Our initial collaborations with Drs Barclay and Gearry, Christchurch Hospital, have led NuNZ to publish 5 papers, with several others having been submitted to high impact journals that provide clinical evidence for the genes important for Crohn's Disease in New Zealand, and the way in which the genotype interacts with dietary needs and intolerances. We have been contributing to the education of New Zealand's food industry and other end-users so that they realise the potential value of nutrigenomics.

We have developed an undergraduate training option in nutrition, majoring in nutrigenomics, through Auckland University and postgraduate courses at both Auckland and Massey University, to train the next generation of New Zealand's innovators. This is supported by a very extensive training programme for postgraduate and postdoctoral scientists. We also offer a workshop programme each year that provides an opportunity for various industry and other professional groups to learn about nutrigenomics. This knowledge is extended to the public through a series of popular articles, media releases, TV and radio interviews held by several programme members. Our linkages also extend internationally. We are organising or co-organising a series of international conferences in the Asia-Pacific region, that link science providers in nutrigenomics with food industry and consumer end-users. The 2006 conference was held in New Zealand and we will also host another conference in 2010. We also played key roles in the 2005 conference in Singapore and the 2008 conference in Australia.

Objective 2 has interrogated human population data for genetic variations relating to Crohn's Disease in New Zealand, and used the information thus generated to design cell line models in order to validate genetically-led nutritional interventions with the potential to minimise the adverse symptoms of Crohn's Disease in this country. This objective has linked closely with Objective 1 in relating the genetic variation among individuals with Crohn's Disease to disease phenotypes and dietary responsiveness. We have determined the genetic variations primarily in the form of single nucleotide polymorphism and haplotypes, and used linkage analysis to establish the relationship between the target gene and the phenotypes of interest. Cell culture models have allowed us to assess the response of those individual polymorphisms to defined nutrients, foods and food components. We have developed a series of cell-based nutrient sensor arrays that are being used for high throughput (HTP) screening to identify nutrients or food components that alleviate (initially) the Crohn's Disease phenotype. We have deliberately selected several genes that appear to be involved in more than one disease state within New Zealand so that the information being gained in the initial studies on Crohn's Disease can subsequently be applied to several other diet/genome targets appropriate to gut health, inflammation and/or disease. Each of the genetic variants that we have developed into screens has led to the identification of some key foods or nutrients that will become components of putative genotype-specific smart foods. These food components are currently being subjected to further testing in both in vitro and in vivo models.

Objective 3 defines the effect of selected nutrients, foods and food components on the expression of disease, health or performance-related genes. Specifically, NuNZ is considering what variations in gene or protein expression data, in the context of gene changes relevant to inflammation, mean in terms of frank changes in cellular function and ultimate manifestation of inflammatory disease outcomes. Initially concentrating on two animal models of colitis (IL-10 and MDR knock out mice), NuNZ has assessed gene and protein expression profiles in terms of variations in levels of accepted protein bioindicators of nutrient response relevant to inflammatory disease. A 2x2 experimental design is allowing NuNZ to determine the effects of specific food components on gene expression in both these models. Preliminary work has established a need for inoculation with gastrointestinal bacteria in order to more consistently establish colitis, and validate the optimal timing for interventions. NuNZ has determined food component-induced changes in gene and protein expression in appropriate tissues collected from the 2x2 mouse experiments using microarrays and proteomics techniques to identify disease-, health-, or performance related genes. NuNZ is also identifying biomarkers using proteomics and metabolomics techniques to assess the ability of dietary interventions in small animal models of human metabolism or limited human trials to maintain optimal health (and protect against gut inflammation). More recent studies have utilised a knock-out/knock-in mouse model of the most common human variant in Crohn's disease, a frame shift mutation in the CARD15 (Caspase-activated recruitment domain) gene. This can be used to confirm the genotype-phenotype link and to test nutrients or food components for efficacy against prevention or mitigation of Crohn's disease initially, and then other diet/genome targets appropriate to health, performance and/or gut disease.

Objective 4 provides the knowledge base for developing customised foods to improve performance and ameliorate predisposition to genetic disease. We are not aware of any other systems biology applications in nutrigenomics using a pharmaceutical approach (considering food rather than drug libraries), and this research is already attracting international interest and attention. We have made intelligent choices of food sources, fractionating to class fractions and chemically characterising food sources and food components for use in high throughput nutrient sensor arrays. For example, our initial screens imply that kiwifruit and berryfruit might be good sources of extracts to counter Crohn's Disease in specific populations. We have developed a standardised food and food-component efficacy database, integrated into the bioinformatics platform, which can be used to choose material for testing against other diet/genome targets appropriate to health, performance and/or disease. Data from 389 food fractions tested in three screens (21,792 data points) are currently available (29 May 2008) to those within the programme through the nutrigenomics wiki and the number rises constantly as batches are completed and verified. We have prepared our first model food constructs from generated data for application to in vivo and clinical studies. We are also equipped to monitor the biotransformations that occur from ingestion of a food through to some fraction exercising its beneficial Food effects on the body. Two initial foods have been prepared, overcoming the significant technological problems associated with incorporating high levels of genotype-specific food fractions into a gluten-free bread. We have worked with an SME (Venerdi specialist bakery) in developing these prototypes, and will expand our industry contacts further with the next test products.

Global linkages

In developing a world leading Nutrigenomics Centre in New Zealand, it has been vital to develop and maintain global linkages with other leading international research groups.

Dr Jim Kaput, Director, Division of Personalized Nutrition and Medicine, FDA/National Center for Toxicological Research, Jefferson, Arizona has provided an independent evaluation of our work in each of the first two years of the programme. These reports are available to the Governance Board and could be made available to FRST on request.
Dr Ben van Ommen, TNO Nutrition and Food research, Zeist, Netherlands, is the overall coordinator of the European Union Strategic Initiative in Nutrigenomics, (NuGO), which Prof Ferguson reviewed in 2005. Our relationship with Dr van Ommen gives us access to the very wide network of science in the nutrigenomics area in Europe.
Dr Ahmed El Sohemy is Assistant Professor, Department of Nutritional Sciences, University of Toronto, Canada, where he established a research programme in gene-diet interactions and holds the Canada Research Chair in Nutrigenomics. We contributed to his travel costs and arranged for him to address our industry workshop in Aug 2007.

Profs John Hesketh and John Mathers (Professor of Human Nutrition and Director of the Human Nutrition Research Centre at the University of Newcastle; Co-ordinator of the EU Framework 6 Integrated Network, NuGO) have visited our labs, and Dr Emma Bermingham (AgR), a FRST Postdoctoral Scientist in nutritional epigenetics, recently worked in their labs with resultant scientific manuscripts in relation to foods,

The above networks have been explored, particularly during the capability-building phase of this proposal, to seek new techniques and thinking and to benchmark growing capability in New Zealand. As capability in NuNZ has grown, we have attained equivalent status globally, enabling us to deliver benefit to New Zealand industry at a level unsurpassed anywhere.

NZ Linkages

Within New Zealand NuNZ has contracts covering a collaboration with the Canterbury IBD Research Group, Canterbury District Health Board (which provides access to clinical information and DNA of people with IBD and controls); and with the Krissansen Lab, University of Auckland (for confidential access to clinical information and DNA for people with Crohn's disease, and allowing NuNZ to conduct a food preference survey). NuNZ also has agreements with Auckland IBD Research Group, Auckland District Health Board (providing access to clinical info, DNA, and food preference data for additional people with Crohn's Disease), and with Auckland Paediatric Gastroenterologists, Auckland District Health Board (providing access to clinical information, DNA, and food preferences of paediatric cases of people with Crohn's Disease). NuNZ has an enviable record of capability development. NuNZ has been successful in securing additional related co-funding from FRST and industry sources. NuNZ has engaged with end-users and health professionals and is creating a sense of expectancy that New Zealand will become a world leader in the production and trade of nutrigenomic foods