Biomolecular Pathways

Essential biological molecules—like proteins, lipids, RNA, and metabolites—create the language of gene expression and energy exchange that leads to healthy cells, organisms, and living systems. EMSL’s Biomolecular Pathways Integrated Research Platform connects these biomolecules to their communication signals, biological roles, and energy functions to better explain and understand the trillions of small interactions that make up the world as we know it. This essential knowledge provides an enhanced understanding of cellular communication to improve resource use and create a more resilient environment.

The science

The collective biomolecules in plants, fungi, and microbes determine an organism’s structure, function, and dynamics. EMSL has integrated capabilities to quantify the functional components of complex systems and probe biological molecules with unknown functions through increasing the rate, dynamic range, and resolution by which we analyze proteins and metabolites. Our accelerated throughput—with integrated metabolomics, proteomics, and lipidomics—provides ultrasensitive measurements that explain the molecular mechanisms behind biological processes. With this capability, our research community explores biological complexity and diversity in the quest for more efficient bioproduct synthesis and robust environmental nutrient cycling predictions.

How we do the science

EMSL’s Biomolecular Pathways expertise includes a breadth of cutting-edge capabilities.

We combine advanced mass spectrometers, nuclear magnetic resonance (NMR) spectrometers, and data processing and integration to conduct high-throughput proteomics, metabolomics, and lipidomics for biological discovery investigations. We provide comprehensive and integrated characterization of complex biological and environmental systems using a combination of protein, metabolite, and lipid analyses.

• Combining quantitative bottom-up proteomics and top-down proteomic approaches yields an expanded quantitative survey of the protein complement and understanding of molecular assemblies.
• We perform in-depth structure and function studies of intact proteins using high-resolution mass spectrometry (MS) and NMR spectroscopy.

• Our combined approach using NMR spectroscopy and liquid chromatography-MS, gas chromatography-MS, and ion mobility spectrometry-MS yields greater metabolome coverage and more accurate metabolite identifications than any one technique alone.
• Our MS imaging capabilities combine spatial, qualitative, and quantitative molecular information to study metabolites within specific locations.

• We use mid-range scientific computing-based advanced data analytics and visualization software to more effectively translate large amounts of molecular measurements and multiomics data to essential biological understanding.

Research in action

Elucidating the role of riverbank microbes in carbon and nitrogen cycling 

Sediment along the river’s edge—known as the hyporheic zone—contains numerous microbes that can transform pollutants and influence river health. Researchers from EMSL and Colorado State University used advanced instrumentation—such as nuclear magnetic resonance and mass spectrometers—to find out which microbes are involved in carbon and nitrogen cycling. Analyzing samples collected from the hyporheic zone of the Columbia River near Richland, Wash., the team identified specific genes within microbes that play a role in greenhouse gas emissions. The researchers then created a conceptual model detailing the roles of different microbes in organic matter decomposition, carbon sequestration, nitrogen mineralization, nitrification, and denitrification.

Producing precursors to sustainable fuels 

Replacing fossil fuels with sustainable alternatives can reduce human-made greenhouse gas emissions. However, producing sustainable alternatives at an industrial scale is challenging. Researchers from the Agile BioFoundry—a consortium of Department of Energy national laboratories—identified a viable strategy for producing muconic acid, a precursor chemical for bioproducts and petrochemicals. They engineered a strain of bacteria to produce cellular machinery that converts plant sugars into muconic acid. They also found that overexpression of certain genes involved in membrane transport would increase muconic acid synthesis. They achieved up to 92 percent of the maximum theoretical yield of muconic acid—bringing this process one step closer to commercial reality.

Investigating underground interactions between plants 

The area immediately surrounding plant roots—the rhizosphere—is teeming with microorganisms. Plants influence the composition of this microbiome through root secretions. Research from Michigan State University and EMSL shows that neighboring plants of different species can also affect each other’s rhizospheres—especially when the plants compete for resources. Their study showed that changes in root secretions—known as exudates—and the surrounding rhizosphere were most significant when neighboring plants were highly competitive.