Blaine Mooers, associate professor of biochemistry and molecular biology at the University of Oklahoma Health Sciences Center, has won this year’s Farrel W. Lytle Award for advancing synchrotron science and RNA editing research at the Department of Energy’s SLAC National Accelerator Laboratory.
The annual award recognizes dedicated staff members and users of the Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science user facility.
Over his many years doing experiments at SSRL, Mooers has galvanized the facility’s research community and spoken in support of SSRL at many national and international meetings, said Graham George, professor and Canada Research Chair in X-ray Absorption Spectroscopy at the University of Saskatchewan, and previous chair of the SSRL User Executive Committee (UEC).
“Blaine has been instrumental in organizing SSRL workshops, and has been an enthusiastic contributor to every recent users’ meeting,” George said. “Not only that, he is an accomplished scientist with a growing track record of elegant research.”
In 1999, Mooers began experiments at SSRL while working as a postdoctoral researcher at the University of Oregon. Since his first trip here, the facility has had him hooked, thanks to its supportive staff and data collection tools, he said.
"When we go to SSRL, we can count on coming home with a lot of publication-quality data," Mooers said. "We also like the cooperation of the facility’s staff — they go the extra mile to help you get the best possible data.”
Along with researching and teaching, Mooers is the director of the Laboratory of Biomolecular Structure and Function at University of Oklahoma Health Sciences Center and the chair of the SSRL UEC.
Chasing bizarre parasites
Mooers’ RNA work focuses in part on parasitic infections that can cause severe illness and often death if not treated early. Protozoan parasites known as trypanosomes can lead to African sleeping sickness, Chagas disease or Leishmaniasis, and currently threaten 600 million people worldwide.
To develop new and safer treatments, Mooers group is targeting a critical part of parasites’ survival: their RNA editing systems in their mitochondria. All trypanosomes have similar RNA editing systems in their mitochondrion that are not found in humans. Understanding how these systems work could allow researchers to develop drugs that kill the parasites without harming infected people.
To see a parasite’s RNA, Mooers’ team crystallizes the RNA fragments and then zaps the crystals with SSRL’s bright X-rays. So far, they’ve been using the molecular structure of these fragments to screen chemical libraries for potential drugs that bind tightly to the RNA. These bound drugs could halt the RNA editing process. The absence of fully edited mRNA will kill the parasite.
"There are about 2,400 positions in 12 mRNAs that have to be edited correctly for the parasite to survive," Mooers said. "This elaborate system requires a lot of precision on the parasite’s part, which means it’s a strong target for drug treatments. If we dismantle the RNA editing pathways, we can help heal people.”
Mooers’s group also studies cancers that can become drug-resistant. Last year, his team helped develop two types of drugs, which have since been approved by the Food and Drug Administration, to treat advanced lung cancer. The crystal structures of the two protein-drug complexes were determined with X-ray diffraction data collected at SSRL Beam Lines 7-1 and 14-1.
"These results underscore the vital importance of experimentally determining molecular structures when designing drugs to treat cancer," Mooers said. “The crystal structures provided valuable insights into how these two second-generation drugs can overcome cancer cells that have become drug-resistant.”
Mooers and his collaborators are now racing to discover a third generation of drugs, which can fight mutations in cancer cells that are resisting these second-generation drugs.
Going beyond research to support others
Mooers’ dedication to supporting SSRL has been steadfast for many years, Aina Cohen, SLAC senior scientist, said. He always takes the time to test new software and automation – often being the first to report bugs or issues, she said.
“His feedback and advice on how we can improve our beamlines has been extremely valuable, helping us improve our program for all users,” Cohen said. “He is very observant and frequently communicates helpful suggestions, wisdom, software and articles.”
Going forward, Mooers plans to continue studying potential drug treatments for parasitic infections and cancer at SSRL. He is also excited about his role as chair of the SSRL User Executive Committee, a position that allows him to spend time on something he cares about as much as scientific discovery – promoting a facility and staff that continues to solve challenges that benefit society.
The award was presented at the 2022 SSRL/LCLS Annual Users’ Meeting at SLAC on September 29. SSRL is a DOE Office of Science User Facility.
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