My part in the Nutrigenomics Project involves an analysis of the effects of various nutritional impacts on the gene expression programme of several mouse models of human colon disorders. This analysis will involve the use of boutique and global gene expression platforms, as well as quantitative real-time PCR analysis of transcript levels. My group has been involved in these types of analyses with respect to human disease modelling using the zebrafish.
My background is in molecular genetics with a focus on heritable human diseases. During the past few years I have moved into the area of human disease modelling using zebrafish as our modelling species-of-choice. Our focus of disease modelling has concentrated on three disorders: Duchenne muscular dystrophy (X-linked recessive, neuromuscular), Adrenoleukodystrophy (autosomal recessive, neurodegenerative) and Huntington Disease (autosomal dominant, neurodegenerative). These interests have required investments in hardware and expertise in multiple areas in order to establish: a zebrafish facility, a quantitative real-time PCR platform, enhanced sequencing capability for the University of Auckland, a microarray facility with supporting analytical equipment for University of Auckland staff. These investments have supported my current research programme, which can be divided into three themes.
The first theme concerns the development of gene targeting in the zebrafish. We have been using peptide nucleic acids as effectors of targeted mutagenesis, while we have also examined the means by which RNA interference can be used to effect transient gene down-regulation in the zebrafish. These latter studies have been successful, and we are currently designing DNA constructs with appropriate reporter genes to study the expression and effect of double stranded RNAs on endogenous gene expression in zebrafish embryos.
The second theme is related to the first in that we are concerned with the analysis of impacts we impose in the zebrafish in attempting to model diseases. The analytical platforms we have worked on have required investment in establishing quantitative real-time PCR and microarray-based analysis. We now have both systems running well, while latterly we have moved from the construction of boutique microarrays to using Affymetrix slides for our studies. The use of microarrays will form a significant part of our research in the future.
The third theme concerns the use of the zebrafish as a model species for chemical genomics. In particular, we are studying the effect of marine bioactive compounds on biological pathways, and as possible therapeutic reagents for zebrafish models of human disease. The expectation is that our research strategy can offer an improved diagnostic platform for the assessment of the efficacy of chemicals/drugs in a model of vertebrate development.
We have published recently on all three themes. Importantly, our research in the future will encompass proteomic analysis of zebrafish embryos that will complement our microarray-based studies. This analytical platform must also be underpinned by protein and small molecule arrays in order to gain a better picture of protein:protein and protein:small molecule interactions.
(Total number of peer-reviewed publications 82; non peer reviewed publications 17)