A high performance GC-MS platform for metabolite analysis in animal health and disease

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Low molecular weight metabolites ultimately represent the end products of gene expression and can be regarded as important indicators of phenotype. The emerging science of metabolomics is concerned with characterising global changes in a broad range of metabolites and represents a radical shift from single metabolite monitoring to complex metabolite profiling and pattern recognition. Metabolomics therefore has the potential to provide a more comprehensive view of the response of biological systems to a variety of genetic and environmental influences. Metabolomics is developing into a priority area for research funding bodies. At present, the focus of these studies has been on plant, microbial and human systems. The Faculty of Veterinary Science at the University of Liverpool provides an outstanding research environment and has established a substantial programme in the application of basic sciences to animal health. This proposal is submitted by a multidisciplinary group of investigators with considerable expertise in mass spectrometry and basic and clinical animal science. The overall focus of this application is to create a new technology platform that will allow rapid and comprehensive analysis of changes in the metabolome of the normal and diseased animal and enhance our capabilities in mammalian semiochemistry and further our study of the molecular pathogenesis of infectious disease. Our goal is the accurate profiling of low molecular weight metabolites in samples from companion, laboratory and large animals and in vitro systems, including those volatile molecules that are responsible for the complex information transmitted during chemical communication. The wide range of low molecular weight metabolites in complex biological systems demands a variety of analytical platforms for detection, identification and quantification. Suitable techniques must be sensitive, robust and have the capacity to acquire data on metabolite profiles from large populations of samples. We have already established a comprehensive suite of LC-MS instrumentation; we now have a pressing need to establish research grade GC-MS capabilities (separation, identification and resolution) for metabolomic investigations (for the global analysis of metabolites) in animal and veterinary science. We request funding for a Waters Micromass GCT gas chromatography-time-of-flight-mass spectrometry (GC-ToF-MS) system. Metabolite profiling using state-of-the-art technologies will offer a bottom up view of the healthy and the sick animal and we will integrate the proposed research programme with existing post-genomic (transcriptomic and proteomic) studies. Investigations of such `gene-to-metabolite¿ networks will provide further insights into the aetiology of disease processes, the molecular basis of chemical communication in animals and the opportunities for exploitation of this information. This approach, focusing on metabolite expression, is a logical strategy in meeting our research goals.