World of Metabolites: Lawrence Berkeley National Laboratory developed Imaging Technique for their Capturing
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 9/27/2017
From: “Dr. Larry Bernstein” <larry.bernstein@gmail.com>
Reply-To: “Dr. Larry Bernstein” <larry.bernstein@gmail.com>
Date: Tuesday, September 26, 2017 at 10:45 AM
To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>
Precision or personalized medicine seeks to provide the right drug to the right patient at the right time. Hence the significance of the principal omics: disciplines of genomics, proteomics, and last but not least metabolomics, as diagnostic enablers.
Primacy among the ‘omics is debatable, but the notion that metabolomics reflects the most accurate picture of disease states has reached significant momentum. “Almost every factor affecting health exerts its influence by altering metabolite levels,” says Mike Milburn, Ph.D., Chief Scientific Officer at Metabolon (Morrisville, North Carolina, USA).
Where clinical chemistry blood tests typically quantify individual species for example, glucose or cholesterol, metabolomics measures hundreds or even thousands of metabolites to provide a nuanced view of disease states.
Metabolon employs standard liquid chromatography-mass spectrometry (LC-MS) for metabolomic studies. Its proprietary informatics and processing platform, Precision MetabolomicsTM, overcomes the “big data” challenge, a natural consequence of measuring hundreds or thousands of small-molecule entities with widely differing concentrations in a single sample. Precision Metabolomics enables “n of 1” studies — meaningful clinical trials on a single patient, Milburn adds:
Diagnostic metabolomics resembles other medical testing, where results are compared against readings from healthy individuals or a reference population. Many metabolites serve that purpose but none on its own is sufficiently specific or diagnostic for a diagnosis — otherwise it would comprise a standalone test. Hence the reliance on metabolite panels or networks, which together may provide a clearer view of disease states than any single diagnostic molecule.
Imaging technique captures ever-changing world of metabolites
The kinetic world of metabolites comes to life in this merged overlay of mass spectrometry images. It shows new versus pre-existing metabolites in a tumor section (yellow and red indicate newer metabolites). Image: Lawrence Berkeley National LaboratoryWhat would you do with a camera that can take a picture of something and tell you how new it is? If you’re Lawrence Berkeley National Laboratory scientists Katherine Louie, Ben Bowen, Jian-Hua Mao and Trent Northen, you use it to gain a better understanding of the ever-changing world of metabolites, the molecules that drive life-sustaining chemical transformations within cells.
They’re part of a team of researchers that developed a mass spectrometry imaging technique that not only maps the whereabouts of individual metabolites in a biological sample, but how new the metabolites are too.
That’s a big milestone, because metabolites are constantly in flux. They’re synthesized on-demand in order to sustain an organism’s energy requirements. When you eat lunch, metabolites momentarily fire up in various cell populations throughout your body to fuel your day. But they also have a dark side. Cancer cells tap metabolites to drive tumor development.
Unfortunately, the current ways to clinically analyze metabolites don’t capture their kinetics. Microscopy maps the cells and biomarkers in a tumor section. And traditional mass spectrometry reveals the abundance and spatial distribution of molecules such as metabolites.
But these images are static snapshots of a highly dynamic process. They’re blind to how recently the metabolites were synthesized, which is a key piece of information. The metabolic status of a cell population is a good indicator of what the cells were up to when the sample was taken.
To image the ebb and flow of metabolites, the scientists paired mass spectrometry with a clinically accepted way to label tissue that uses a hydrogen isotope called deuterium.
As reported in Nature Scientific Reports, they administered deuterium to mice with tumors. Newly synthesized lipids (a hallmark of metabolic activity) became labeled with deuterium, while pre-existing lipids remained unlabeled. The scientists then removed tumor sections and analyzed them with a type of mass spectrometry.
The resulting images look like freeze-frames of a slow-motion fireworks show. They reveal when and where metabolic turnover occurs in a tumor section, with the brighter colors depicting newly synthesized lipids.
The scientists also found that regions with new lipids had a higher tumor grade, which is a good predictor of how quickly a tumor is likely to grow.
“Our approach, called kinetic mass spectrometry imaging, could provide clinicians with quantifiable information they can use,” says Bowen.
The scientists are now applying their imaging technique to study metabolic flux in other biological systems, such as microbial communities.
Source: Lawrence Berkeley National Laboratory
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