Xinyun (Sherry) Cao, a postdoctoral researcher in the lab of biochemistry professor Robert Landick, was awarded a Pathway to Independence Award (K99/R00) from the NIH.
The initial award (K99) provides up to two years of mentored, postdoctoral support. The second phase (R00) provides up to three years of independent research support and is activated when the awardee accepts a full-time tenure track (or equivalent) faculty position. Cao’s K99/R00 is focused on understanding how Clostridioides difficile (C. diff) transcribes its DNA code into RNA using a multi-subunit protein called RNA polymerase (RNAP). RNAP is a proven drug target but is still poorly understood in pathogenic bacteria. Cao’s research will provide knowledge scientists need to discover new drugs that target C. diff RNAP and understand drugs’ mechanisms of action, thereby improving antibiotic treatments for C. diff.
Cao plans to investigate functional relationships between RNAP and other factors, use genomic-scale mapping techniques and biochemical assays to understand RNAP transcription regulation, and build an in vitro platform to enable high-throughput screening of C. diff RNAP inhibitors. Work Cao performed during her postdoc was instrumental in developing this research plan.
"The groundwork of my K99/R00 is based on research we published earlier this year showing the structure of a narrow-spectrum antibiotic that targets C. diff,” Cao says.
That study, which was published in Nature, revealed the structure of the narrow-spectrum antibiotic fidaxomicin. Cao’s contributions allowed the research team to more easily produce C. diff RNAP and opened the door to similar studies involving other bacterial pathogens.
"Sherry’s K99/R00 is a testament to her strong work ethic, perseverance, and creativity,” Landick says. “When she joined our group, Sherry undertook an entirely new project to establish the study Clostridioides difficile RNA polymerase biochemically. Her success not only produced a landmark Nature paper, but also opened a path to find new ways to attack this pernicious pathogen. NIH has rightly recognized her tremendous scientific potential with this award.”
Cao received her Ph.D. in biochemistry in the lab of professor John Cronan at the University of Illinois Urbana-Champaign. Cao thanks her postdoctoral mentors and collaborators, including UW–Madison biochemistry professor Robert Landick, UW–Madison bacteriology associate professor Federico Rey, The Rockefeller University associate professor Elizabeth Campbell, Texas A&M University biology professor Joseph Sorg, and UW–Madison senior scientist Spencer Ericksen, for their support.