Metabolomics: What's Happening Downstream of DNA
Metabolomics: What's Happening Downstream of DNA
The decoding of the human genome gave rise to genomics and proteomics"global" studies of genes and proteins, respectivelywhich are often touted in terms of their enormous clinical potential. In the midst of a growing shift toward translational studies in today's biomedical research scene, yet another "-omics" science has come to the fore. The science is called metabolomics, and its protagonists say it offers a cheap, rapid, and effective way to diagnose illness and monitor patient therapy.
Metabolomics is the study of metabolite profiles in biological samples, particularly urine, saliva, and blood plasma; scientists are interested in all, rather than some, of the metabolites in a given sample. Metabolites are the by-products of metabolism, which is itself the process of converting food energy to mechanical energy or heat. The number of different metabolites in the human is unknown; estimates range from a low of 2,000-3,000 to a high of around 20,000, compared to an estimated 30,000 genes and 100,000 proteins. Of particular interest to metabolomics researchers are small, low-molecular-weight compounds that serve as substrates and products in various metabolic pathways. These "small molecules," as they are called, include compounds such as lipids, sugars, and amino acids that can provide important clues about the individual's health.
The metabolomethe collection of all metabolites in a cell at a point in timereveals much about that cell's physiological state at the time of sampling, and humans have trillions of cells of many different types, all with potentially different metabolomes. Whereas genes and proteins set the stage for what happens in the cell, much of the actual activity is at the metabolite level: cell signaling, energy transfer, and cell-to-cell communication are all regulated by metabolites. Furthermore, gene and protein expression are closely linked, but metabolite behavior more closely reflects the actual cellular environment, which is itself dependent on nutrition, drug and pollutant exposures, and other exogenous factors that influence health. Explains Bill Lasley, a professor in the Department of Population Health and Reproduction at the University of California (UC), Davis, "Genomics and proteomics tell you what might happen, but metabolomics tells you what actually did happen."
As in the other "-omics," metabolomics data are gathered with high-throughput methods; nuclear magnetic resonance (NMR) spectroscopy and mass spectroscopy (MS) using robotic automation are the dominant analytical techniques used in the field today. "Metabolomics is a beautiful approach for rapidly acquiring a vast amount of information about the molecular composition of a sample," says Mark Viant, a research fellow in the School of Biosciences at the University of Birmingham, United Kingdom. "If you have a disease, it's likely that your metabolism is going to be affected. The same is true if you get hit with a toxicant. To be honest, the diagnostic potential is staggering."
Other researchers apparently agree: metabolomics research activities are now becoming more widespread. The NIH Roadmap for Medical Research, a broad set of initiatives intended to focus the organization's agenda for the next several years, includes an initiative called Metabolomics Technology Development, which is headed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This initiative, currently in the planning stages, will fund several extramural research projects this year, says Maren Laughlin, who directs the NIDDK Metabolism and Structural Biology Program. A new international association established to promote the field, the Metabolomics Society, was announced in March 2004. This international organization of experts from academia, government, and industry is headed by Rima Kaddurah-Daouk, cofounder and vice president for biological research at Metabolon, a company that applies metabolomics techniques to clinical uses. According to Kaddurah-Daouk, the society will bring together leaders from different disciplines with the ultimate goal of building the metabolomics technology and integrating metabolomics with the broader universe of systems biology. "The activities included under the umbrella of the Metabolomics Society will encompass metabolic profiling, metabolite flux analysis, biochemical modeling, and more," she says.
Industry research is also on the rise, as pharmaceutical and biotechnology companies investigate metabolite profiles as potential tools for drug development. Their efforts have been guided in part by researchers at London University's Imperial College of Science, Technology, and Medicine, including Jeremy Nicholson, a professor of biological chemistry who is widely regarded as one of the field's leading figures. Nicholson was among the first to apply the tools of metabolite analysisfirst NMR and now also MSto the assessment of metabolite changes in biofluids over time.
The decoding of the human genome gave rise to genomics and proteomics"global" studies of genes and proteins, respectivelywhich are often touted in terms of their enormous clinical potential. In the midst of a growing shift toward translational studies in today's biomedical research scene, yet another "-omics" science has come to the fore. The science is called metabolomics, and its protagonists say it offers a cheap, rapid, and effective way to diagnose illness and monitor patient therapy.
Metabolomics is the study of metabolite profiles in biological samples, particularly urine, saliva, and blood plasma; scientists are interested in all, rather than some, of the metabolites in a given sample. Metabolites are the by-products of metabolism, which is itself the process of converting food energy to mechanical energy or heat. The number of different metabolites in the human is unknown; estimates range from a low of 2,000-3,000 to a high of around 20,000, compared to an estimated 30,000 genes and 100,000 proteins. Of particular interest to metabolomics researchers are small, low-molecular-weight compounds that serve as substrates and products in various metabolic pathways. These "small molecules," as they are called, include compounds such as lipids, sugars, and amino acids that can provide important clues about the individual's health.
The metabolomethe collection of all metabolites in a cell at a point in timereveals much about that cell's physiological state at the time of sampling, and humans have trillions of cells of many different types, all with potentially different metabolomes. Whereas genes and proteins set the stage for what happens in the cell, much of the actual activity is at the metabolite level: cell signaling, energy transfer, and cell-to-cell communication are all regulated by metabolites. Furthermore, gene and protein expression are closely linked, but metabolite behavior more closely reflects the actual cellular environment, which is itself dependent on nutrition, drug and pollutant exposures, and other exogenous factors that influence health. Explains Bill Lasley, a professor in the Department of Population Health and Reproduction at the University of California (UC), Davis, "Genomics and proteomics tell you what might happen, but metabolomics tells you what actually did happen."
As in the other "-omics," metabolomics data are gathered with high-throughput methods; nuclear magnetic resonance (NMR) spectroscopy and mass spectroscopy (MS) using robotic automation are the dominant analytical techniques used in the field today. "Metabolomics is a beautiful approach for rapidly acquiring a vast amount of information about the molecular composition of a sample," says Mark Viant, a research fellow in the School of Biosciences at the University of Birmingham, United Kingdom. "If you have a disease, it's likely that your metabolism is going to be affected. The same is true if you get hit with a toxicant. To be honest, the diagnostic potential is staggering."
Other researchers apparently agree: metabolomics research activities are now becoming more widespread. The NIH Roadmap for Medical Research, a broad set of initiatives intended to focus the organization's agenda for the next several years, includes an initiative called Metabolomics Technology Development, which is headed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This initiative, currently in the planning stages, will fund several extramural research projects this year, says Maren Laughlin, who directs the NIDDK Metabolism and Structural Biology Program. A new international association established to promote the field, the Metabolomics Society, was announced in March 2004. This international organization of experts from academia, government, and industry is headed by Rima Kaddurah-Daouk, cofounder and vice president for biological research at Metabolon, a company that applies metabolomics techniques to clinical uses. According to Kaddurah-Daouk, the society will bring together leaders from different disciplines with the ultimate goal of building the metabolomics technology and integrating metabolomics with the broader universe of systems biology. "The activities included under the umbrella of the Metabolomics Society will encompass metabolic profiling, metabolite flux analysis, biochemical modeling, and more," she says.
Industry research is also on the rise, as pharmaceutical and biotechnology companies investigate metabolite profiles as potential tools for drug development. Their efforts have been guided in part by researchers at London University's Imperial College of Science, Technology, and Medicine, including Jeremy Nicholson, a professor of biological chemistry who is widely regarded as one of the field's leading figures. Nicholson was among the first to apply the tools of metabolite analysisfirst NMR and now also MSto the assessment of metabolite changes in biofluids over time.
