MBIB News

Atomic-scale structural analyses performed at Berkeley Lab’s Advanced Light Source (ALS) are helping scientists understand the inner workings of the enzyme “assembly lines” that microbes use to produce an important class of compounds, many of which have uses as antibiotics, antifungals, and immunosuppressants.

These cellular machines, known as nonribosomal peptide synthetases (NRPSs), are large, multi-enzyme clusters that synthesize compounds by passing a precursor molecule from one module to the next, with each “station” catalyzing a change in the molecule. In the past decade, researchers have learned a great deal about how individual NRPS modules work, but an understanding of how the assembly lines function as a whole has been lacking. In the hopes of eventually engineering custom NRPSs to make new and improved medicines, a team led by McGill University began investigating the bacterial NRPS that synthesizes the antibiotic gramicidin.

A team of scientists led by Elizabeth Boatman at the University of Wisconsin Stout used X-ray imaging and spectromicroscopy performed at Berkeley Lab’s Advanced Light Source (ALS) to demonstrate how soft tissue structures may be preserved in dinosaur bones – countering the long-standing scientific dogma that protein-based body parts cannot survive more than 1 million years.

In their paper, now published in Scientific Reports, the team analyzed a sample from a 66-million-year-old Tyrannosaurus rex tibia to provide evidence that vertebrate blood vessels – collagen and elastin structures that don’t fossilize like mineral-based bone – may persist across geologic time through two natural, protein-fusing “cross-linking” processes called Fenton chemistry and glycation.

A team led by Harald Hess at the Howard Hughes Medical Institute (HHMI) Janelia Research Campus and Eric Betzig, a senior faculty scientist in the Molecular Biophysics and Integrated Bioimaging (MBIB) Division, has devised a technique that combines cryogenic super-resolution fluorescence microscopy and focused ion beam–milling scanning electron microscopy. In a report in the journal Science, the researchers describe their technique, called cryo-SR/EM, and display some of exquisitely detailed three-dimensional images they captured of the complex innards of cells.

Jennifer Doudna, faculty scientist in the Molecular Biophysics & Integrated Bioimaging Division, will share the 2020 Wolf Prize in Medicine, a prestigious international prize awarded in Israel for unique contributions to humanity. Doudna, who is also UC Berkeley professor of molecular and cell biology and of chemistry, and colleague Emmanuelle Charpentier, director of the Max Planck Institute for Infection Biology in Berlin, Germany, were honored for their 2012 invention of the CRISPR-Cas9 gene-editing technology. 

Seeking to develop a direct inhibitor of a mutant protein caused by errors in the KRAS gene, researchers at Amgen conducted X-ray crystallography of KRAS(G12C) proteins using the Berkeley Center for Structural Biology (BCSB) beamlines at the Advanced Light Source (ALS). The high-resolution structural maps generated from the data acquired revealed a small pocket on the molecule. Now, an investigational cancer drug that binds in this pocket will be evaluated in phase 2 clinical trials.