Measuring small molecules such as fats, sugars, and amino acids — and how changes in them can tip the balance between health and disease — is now possible thanks to the new Trans-NIH Metabolomics Core. The Core is making its unique assays and data analysis tools accessible to researchers at the 27 institutes and centers that make up the National Institutes of Health (NIH).
The new facility expands the portfolio of -omics technologies available at NIH beyond RNA (transcriptomics), protein (proteomics), and epigenetic marks (epigenomics) to include metabolites (metabolomics). Intramural researchers can now leverage the Core’s expertise and resources to conduct large-scale studies of metabolites, which are small molecules made when the body breaks down food, drugs, and chemicals.
Environmental Factor recently spoke with NIEHS scientists Michael Fessler, M.D., and Alan Jarmusch, Ph.D., about what intramural researchers most need to know about the Core’s services, costs, and future expansion plans.
Environmental Factor (EF): What capabilities are offered by the Metabolomics Core that researchers can’t find elsewhere?
Jarmusch: The Trans-NIH Metabolomics Core offers untargeted metabolomics. This unique capability that we're bringing locally to NIEHS, and across the NIH, leverages the power of modern chemical instrumentation to make a lot of concurrent measurements without a researcher having to know beforehand exactly which chemicals or metabolites they want to measure. Using statistics as well as software, code, and scripts developed by the core, we can back out the meaningfulness of those measurements and what is changing in the system. We process the data to give researchers a leap into exploring the biological questions that they’re most interested in.
Fessler: The strength of this untargeted approach is that you get a broad sweep of the levels of small molecules, which is anything other than protein and nucleic acid, in cells and tissues at a given time. The core can piece that data together with software to make sense out of it. The approach is hypothesis generating, but it can also be hypothesis confirming if you are expecting metabolism to be dysfunctional.
Jarmusch: The Trans-NIH Metabolomics Core also offers a complementary type of analysis referred to as targeted metabolomics, where you specifically know what you want to measure and can obtain absolute quantification of metabolites. This coordinated effort to leverage expertise and resources of Ruin Moaddel, Ph.D., at NIA [National Institute of Aging] is a huge benefit to researchers.
EF: What is the cost to use the Metabolomics Core?
Fessler: For untargeted analyses, we currently charge $120 per sample, which is much cheaper than most alternatives in academia and industry to get this type of analysis done. There are some companies that charge in excess of $400 a sample, and if you want follow-up analyses, or if you have a question about your data, you pay more at each step. Our collaborative model — more of a back-and-forth interaction with scientists — is a major advance in that regard.
EF: What types of projects would benefit from small-molecule analysis?
Jarmusch: Any kind of tissue or biofluid you can put in a tube can be analyzed in theory. We’ve analyzed human plasma and serum, cell lines with specific genes knocked out, mouse organs and breast milk, T cells isolated from tissues, feces, and yeast to name a few. We evaluate the small molecules in the sample, and how they may change in response to the environment, exposures, or drugs. For example, we can look for known and unknown metabolic markers of tobacco smoke exposure and correlate that exposure with a health outcome.
Fessler: Our untargeted platform also borders on exposomics, a recently coined term for methods that make global measurements of small molecules in the environment. There's the external exposome — for example, what's in pond water — and then there is the internal exposome, namely, exogenous compounds from the environment, metabolized and not, that are found in internal bodily sources such as serum. Alan’s technique is largely agnostic to detection of exogenous (e.g., chemicals and medications) versus endogenous molecules. It detects both.
EF: How sensitive is your approach to capture chemicals in samples?
Jarmusch: The latest generation mass spectrometer that we use is very sensitive and allows us to detect thousands of chemicals at the same time. But it's also kind of tricky to work with because it is so sensitive. How people handled the samples can make a difference, and we can see what is on their fingertips — from medications to personal care products — if they are not wearing gloves.
EF: What most excites you about the future of the Metabolomics Core and the field in general?
Jarmusch: We now have the experts, equipment, and funding support to facilitate more science and to be the catalyst for biological discoveries. We're just scratching the surface of what we can do with this data and the kind of information we can glean from it. I see this approach someday being part of predictive models to understand why people have unique responses to the environment.
Fessler: Modern biomedicine is in the midst of exciting times, particularly when it comes to the potential for advancing personalized medicine and also for deriving more specific and sensitive signals from biological systems. Most of the things we do in science are bulk — you take a tissue, and it has a whole bunch of different cells in it, and you just measure the average. But if you can look at the level of the cell, study populations of cells that are talking to one another, and map where the glucose or the amino acid is in specific cells, you can derive all sorts of new insights. And that's where the future lies.
(Caroline Stetler is Editor-in-Chief of the Environmental Factor, produced monthly by the NIEHS Office of Communications and Public Liaison.)