Tools under development
We have 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, including the relationships between diet and IBD, and to integrate transcriptomics, proteomics and metabolomics data on gene expression patterns in mouse models.
This work also includes our skills in metabolomics and identification of biomarkers for dietary compliance and for determining animal and human state of health. In this area we have accessed mouse models of inflammation used to find biomarkers of inflammation using metabolomics.
Human clinical trials
By interrogating human population data for genetic variations relating to Crohn's Disease in New Zealand, 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 target genes and the phenotypes of interest.
We have also focused on establishing relationships between the diet and IBD patients reactions to these diets, and have built up a significant database of dietary preferences and foods to be avoided, associated with genotype.
We are now entering human trials to establish capability and measure the ability of some of our ‘hits’ to reduce inflammatory biomarkers in human trials.
Testing foods in model systems
We use model animal systems to determine the effect of selected nutrients, foods and food components on the expression of disease, health or performance-related genes, proteins and metabolites, and relate these to changes in gut inflammation. We have used three animal models of genes known to be involved in human Inflammatory bowel disease (IL-10, NOD2 and MDR knockout mice). A 2x2 experimental design allows NuNZ to determine the effects of specific food components at the molecular level in these models. 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.
Developing new foods
We take food samples, extracts and fractionates and use cell based models to discover foods and fractions that can reduce inflammation, preferably in a gene specific context. This provides the knowledge base for developing customised foods to improve performance and ameliorate predisposition to genetic disease. 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. We have developed a standardised food and food-component tracker and 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.
The cell based models used in our systems include two NOD variants, a TNF-alpha promoter variant and a JAK2 based assay, all of which are genetic variants found in our IBD populations as well as in other inflammatory diseases. These cell based models have allowed us to assess the response of those individual polymorphisms to defined nutrients, foods and food components. Identified food components in the cell based assays are subjected to further testing in both in vitro and in vivo models (objective 3).