Overcoming disease with moving pictures and molecular building blocks

If a picture is worth a thousand words, a moving picture might be worth a million. That was the impression James Fraser, PhD, left with the audience during the opening to his 2020 Byers Award Lecture in Basic Science. Before diving into the science, Fraser displayed a snapshot of his two sons happily playing in the backyard—only for the photo to move, showing the two tussling over the same toy.

Similarly, putting motion into microscopic images of proteins, Fraser explained, could be one of the keys to overcoming antibiotic resistance in bacteria.

Fraser delivered the lecture, in celebration of receiving the Byers Award, on March 3, 2020, at the UC San Francisco Mission Bay campus. The audience of scientists and PhD students also included UCSF Chancellor Sam Hawgood, MBBS, and philanthropist Brook Byers, who established the award with his family.

Fraser, a faculty member in the School of Pharmacy’s Department of Bioengineering and Therapeutic Sciences, has recently applied his expertise in structural biology to the growing problem of antibiotic resistance, which can make deadly infections impossible to treat with available drugs.

Fraser uses cryo-electron microscopy and X-ray crystallography to peer into every nook and cranny of the proteins that make bacteria tick. He’s found that combining these techniques can produce moving pictures that reveal how these proteins behave, and even identify where scientists might target small-molecule drugs to defeat drug-resistant bacteria.

Fraser described the serendipity of his collaboration with chemist Ian Seiple, PhD, a faculty member in the School’s Department of Pharmaceutical Chemistry, who has developed a system for building new antibiotics from small, chemical building blocks. Using Fraser’s moving pictures and Seiple’s modular antibiotics, the two can tailor new drugs to jam specific molecular gears inside of bacteria.

In early experiments, Fraser and Seiple “identified two compounds that can kill non-resistant bacteria and—excitingly for the first time—also kill the resistant bacteria,” Fraser explained.

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James Fraser Delivers 2020 Byers Award Lecture on the War Against Antibiotic-Resistant Infections (UCSF News)