With the new Trans-NIH Metabolomics Core, it is now possible to measure small molecules such as fats, sugars and amino acids and how their changes tip the balance between health and disease. Core is making its unique testing and data analysis tools available to researchers at 27 National Institutes of Health (NIH) institutes and centers.
The new facility expands the portfolio of omics technologies available at NIH beyond RNA (transcriptomics), proteins (proteomics) and epigenetic markers (epigenomics) to include metabolites (metabolomics). On-campus researchers can now leverage core expertise and resources to conduct large-scale studies of metabolites, the small molecules produced when the body breaks down food, drugs and chemicals.
![The Trans-NIH Metabolomics Core can measure changes at the level of small molecules in a cell or tissue sample and then piece together the meaning of those changes using software developed in the core. (Image courtesy of Yurchanka Siarhei/Shutterstock.com)](https://factor.niehs.nih.gov/sites/niehs-factor/files/2024/01/science-highlights/nih-metabolomics-core-body1.jpg)
Environmental Factor recently spoke with NIEHS scientists Michael Fessler, MD, and Alan Jarmusch, PhD, to discuss what campus researchers need to know most about core services, costs and plans for future expansion.
To learn more about how the Trans-NIH Metabolomics Core can support your on-campus research project, please complete the Project Initiation Form and email it to the Core.
Environmental factors (EF): What capabilities does Metabolomics Core offer that researchers can’t find elsewhere?
![Michael Fessler, MD](https://factor.niehs.nih.gov/sites/niehs-factor/files/2024/01/science-highlights/nih-metabolomics-core-body2.jpg)
Jarmusch: The Trans-NIH Metabolomics Core provides untargeted metabolomics. This unique capability we are introducing at NIEHS, and across NIH, harnesses the power of modern chemistry instrumentation to make large numbers of concurrent measurements without researchers knowing exactly in advance which chemicals or metabolites they want to measure. Using statistics, along with core-developed software, code, and scripts, we can infer the meaning of these measurements and the changes that are occurring in the system. We process data to enable researchers to quickly explore the biological questions that interest them most.
Fessler: The advantage of this non-targeted approach is that you can get a broad picture of the levels of small molecules (anything but proteins and nucleic acids) in cells and tissues at a given time. The core can piece this data together with software to make sense of it. This method is hypothesis generating, but it can also be hypothesis testing if you anticipate metabolic dysfunction.
Jarmusch: The Trans-NIH Metabolomics Core also offers a complementary type of analysis called targeted metabolomics, where you know exactly what you want to measure and can obtain absolute quantification of metabolites. This coordinated effort leverages the expertise and resources of NIA (National Institute on Aging) Dr. Ruin Moaddel, which is a huge benefit to researchers.
![Dr. Alan Jarmusch](https://factor.niehs.nih.gov/sites/niehs-factor/files/2024/01/science-highlights/nih-metabolomics-core-body3.jpg)
EF: How much does it cost to use the Metabolomics Core?
Fessler: We currently charge $120 per sample for non-targeted analyses, which is significantly cheaper than most alternatives for completing this type of analysis in academia and industry. Some companies charge more than $400 per sample, and if you want to do follow-up analysis or have questions about the data, you’ll pay more at each step. Our collaborative model—more of a back-and-forth interaction with scientists—is a major advance in this regard.
EF: What types of projects would benefit from small molecule analysis?
Jarmusch: Any type of tissue or biological fluid that can be put into the tube can theoretically be analyzed. We analyzed human plasma and serum, cell lines in which specific genes have been knocked out, mouse organs and breast milk, T cells isolated from tissue, feces and yeast, and more. We evaluate small molecules in a sample and how they change in response to environment, exposure, or drugs. For example, we can look for known and unknown metabolic markers of tobacco smoke exposure and correlate that exposure with health outcomes.
Fessler: Our non-targeted platform also borders on exposomes, a recently coined term that refers to global measurements of small molecules in the environment. There is the external exposome (e.g., substances in pond water) and then there is the internal exposome, i.e., exogenous compounds from the environment, whether metabolized or not, that are present in internal sources (e.g., serum). Allen’s technology is largely agnostic to the detection of exogenous (such as chemicals and drugs) versus endogenous molecules. It detects both.
EF: How sensitive is your method for capturing chemicals in your sample?
Jarmusch: The latest generation mass spectrometers we use are so sensitive that they allow us to detect thousands of chemicals simultaneously. But it’s also a little tricky to use because it’s so sensitive. How people handle samples can make a difference, and if they aren’t wearing gloves, we can see what’s on their fingertips – from medications to personal care products.
EF: What excites you most about the future of metabolomics core and the field as a whole?
Jarmusch: We now have the experts, equipment and financial support to facilitate more scientific research and be a catalyst for biological discovery. We’ve only scratched the surface of what we can do with this data and what information we can glean from it. I think this approach could one day be part of predictive models to understand why people respond uniquely to their environment.
Fessler: Modern biomedicine is in an exciting era, especially when it comes to the potential to advance personalized medicine and obtain more specific and sensitive signals from biological systems. Most of the things we do in science are batch – you take a piece of tissue and there’s a bunch of different cells in it and you just measure the average. But if you can look at the cellular level, study groups of cells talking to each other, and map where glucose or amino acids are in a particular cell, you can get all kinds of new insights. This is where the future lies.
(Caroline Stetler is editor-in-chief of Environmental Factors, a magazine published monthly by the NIEHS Office of Communications and Public Liaison.)