Metabolomics is the newest of the omics approaches and perhaps the one that is the closest reflection of what is actually taking place in the living cell. Researchers are looking to this platform, which draws on many different technologies, for new insights into biochemical pathways and hope it will thereby yield products such as biomarkers and new drug targets. Delegates at "metabomeeting 2008," which will take place later this month in Lyon, France, will present a range of specific contributions and approaches to metabolomics research.
John P. Shockcor, Ph.D., director of metabolic profiling business development at Waters
, says that small molecule profiling (as metabolomics is sometimes known) is about four simple questions: what has gone up, what has gone down, what is missing, and what is new?
Waters’ HPLC/UPLC and mass spectrometry technologies can help answer these questions by providing information about the composition of complex molecular mixtures. Thereafter, it is the role of the biochemist to integrate this with proteomics and genomic data to understand the context of these changes that may, or may not lead to the identification of a useful biomarker.
Dr. Shockcor will present Waters’ recent work on ion mobility mass spectrometry—a technology that is the basis of the company’s Synapt high-definition MS (HDMS) system. Ion mobility refers to the diffusion of an ion through a gas under the influence of an electric field. The rate of this diffusion depends upon the charge on the ion and its rotational cross-sectional area—the latter being more relevant to metabolomic work.
The Waters system places an ion mobility separation stage just prior to the mass analyzer, and when combined with UPLC, a type of 2-D separation is achieved. The technology allows fine separation of ions with similar masses, and the output gives an accurate mass compared to the nominal mass, which is the more usual output of MS techniques.
Ion mobility with MS is a tool that Waters has pioneered, according to Dr. Shockcor, and other companies are now following its lead. “Waters will continue to develop ion-mobility mass spectrometry beyond the first generation and will focus upon the utility of accurate mass for analysis of complex mixtures,” he adds.
Synapt HDMS is already being used for a wide range of small molecule studies. Dr. Shockcor will discuss its application to lipidomics at the meeting. “So many of the chronic diseases that plague us, heart disease and diabetes, for instance, are linked to the regulation and absorption of lipids,” he explains. “There is a massive subset of tens of thousands of lipids that are extremely challenging to analyze in metabolomic studies. We are developing tools for looking at these in experiments that have not previously been possible.”
Nuclear Magnetic Resonance
Nuclear magnetic resonance (NMR) is another key technology for metabolomics, and Norbert Lutz, Ph.D., research professor at the Faculty of Medicine of the Université de la Méditerranée, will present some cutting-edge applications.
“Metabolomics is, broadly speaking, the comprehensive study of metabolism in biological tissue,” he says. Such studies are not focused on individual metabolic questions but cover a vast range of metabolic events. Nor is metabolomics restricted to a specific analytical method or statistical tool.
“Metabolomics starts with measuring a large number of metabolite concentrations without selecting a specific pathway or event,” he explains. “It is of interest because it deals with biochemical events that are directly linked to the performance of cells, therefore providing more direct insight into the functioning and malfunctioning of cells, tissues, or organs than genomics or proteomics.”