Capitol News

To some, the metabolome is akin to "dark matter," an unexplored domain in biochemistry. This term refers to the array of small molecules, or metabolites, present in a biological sample. Many chemical signatures identified during metabolomic analysis remain unidentifiable, with only a fraction being chemically annotated.

Aleksandra Skirycz, an associate professor at Michigan State University's Department of Biochemistry and Molecular Biology, aims to uncover the functions of these metabolites. "When we talk of dark matter, we're really talking about the functions of metabolites," she stated. The roles of many known metabolites are still unknown.

Skirycz's research is supported by a $1.91 million Maximizing Investigators' Research Award from the National Institutes of Health. This funding will aid her lab in exploring interactions between metabolites and proteins using an analytical method called PROMIS.

While protein-protein interactions have been extensively studied, protein-metabolite interactions remain less understood. Skirycz explained that understanding these interactions could reveal metabolite functions: "More often than not a metabolite needs to target a protein to execute its function."

Previously at the Max Planck Institute in Germany, Skirycz began mapping these interactions in various organisms. These maps help visualize potential metabolite-protein interactions.

Skirycz's approach involves comparing interaction networks across four model organisms: nematode C. elegans, yeast S. cerevisiae, bacteria E. coli, and plant A. thaliana. By identifying common pairings across networks, researchers can focus on significant interactions relevant to organismal health.

Mass spectrometry will be used for this untargeted analysis approach, allowing researchers to measure a broad range of metabolites and proteins without predefining targets.

The process developed by Skirycz's group is called PROMIS—PROtein-Metabolite Interactions using Size separation—which builds on co-fractionation/mass spectrometry for global interaction analysis.

Ultimately, this research could illuminate unknown aspects of the metabolome and contribute to healthier plants and animals. Reflecting on her experiences in Brazil, Skirycz noted the importance of understanding molecular functions: "If we know that these molecules act by interacting with certain proteins, we can speed up identification of interesting and beneficial compounds."