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Functional and Systems Biology

Structural Biology

All living systems rely on the tiniest of cellular functions to maintain health and vigor. When these functions break from disease or other stresses, the whole organism suffers. Structural biology allows us to study the relationships between cellular proteins, how they communicate, and their functions. With a better understanding of these cellular roles, we can look for ways to improve crops for food, biofuels, and bioproducts in a resource-constrained future.

The science

Our Structural Biology Integrated Research Platform focuses on examining the assembly, structure, and function of proteins and protein complexes at the nanoscale, down to ångströms, across space and time.

With high-resolution images, we can see details in the molecular organization of a biosystem in three dimensions. We can also map the chemical processes involved in micronutrient exchange both within and between cells and their environment, revealing links between proteins' structural and biochemical dynamics, protein complexes, and other biomolecules. These views help us understand how changes in morphology and composition affect biological systems.

How we do the science

EMSL’s structural biology expertise includes a breadth of cutting-edge capabilities.

  • Using atom probe tomography, we can produce three-dimensional images of elements and molecular fragments—at the atomic scale—within soft biological materials.
  • With high-resolution cryo-electron microscopy (EM), we can determine the atomic-scale structure of proteins and protein complexes greater than ~100 kilodalton (kDa). With this information, we can uncover and understand the molecular mechanisms regulating cellular processes. We also use cryo-EM to determine cellular ultrastructure in microbial systems—giving us clues into how organisms respond within a microbial consortium or to environmental stresses.
  • Working with nuclear magnetic resonance spectroscopy, we can measure the distance between protons to determine the structure of small proteins less than ~50kDa.
  • Employing mass spectrometry, we can study the organizational relationship between protein complex subunits—providing clues to the molecular mechanisms driving enzymatic reactions in these complexes.

Combined with mid-range scientific computing and complementary expertise in other areas, EMSL’s structural biology expertise is expanding to include correlative multi-modal imaging and analyses.

Research in action

Unearthing soil viruses soil viruses

Soil is rich with microbes—from fungi to viruses. The roles of these microbes are not fully understood. Researchers from EMSL, Stanford University, Lawrence Berkeley National Laboratory, Mammoth Biosciences, Oregon Health & Science University, and Washington State University found that soil viruses carry a set of genes called auxiliary metabolic genes that are not involved in viral replication. Instead, these genes appeared to help metabolize chitosan—a molecule closely related to chitin found in insect exoskeleton and fungal cell walls. The researchers cloned the genes and expressed the proteins to determine the protein structure using X-ray crystallography. Then they compared the structure to other enzymes responsible for chitosan metabolism to validate its function. Their study supports the hypothesis that soil viruses carry genes that can support host metabolism.

Characterizing wildfire smokewildfiresmoke

Up to 20 percent of the phosphorus emitted annually worldwide comes from wildfires. With changes in climate and fuel availability, wildfires are predicted to increase in occurrence. The phosphorus from wildfires can end up in water systems and impact aquatic ecosystems—too much of the element can create harmful algal blooms that deplete oxygen in the water. Researchers from Michigan Technological University and EMSL used an ultrahigh resolution, custom-built 21 Tesla Fourier transform ion cyclotron resonance mass spectrometer to characterize the organic aerosols in wildfire smoke for the first time.

Examining particles from wild grass soil microbes

Living organisms can release a variety of biological particles into the atmosphere—from cell debris to bacteria. A multi-institutional team of scientists led by EMSL researchers characterized the biological particles released from the wild grass Brachypodium distachyon. They collected particles from eight different developmental stages of the plant’s life cycle and analyzed the particle morphology, elemental composition, and abundance. Their studies revealed that fungal spores were most prevalent during the stage just before flowering, while bacteria were more abundant during flowering and fruit development.