NORMAN, OKLA. – Yihan Shao, an associate professor of chemistry at the University of Oklahoma, has received a Maximizing Investigators’ Research Award from the National Institutes of Health to develop computer modeling tools for studying the enzymes critical for CRISPR gene editing and biomedical imaging tools for cancer tumors.
CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is a technology that allows researchers to selectively modify the DNA of living organisms. It was adapted from a naturally occurring antiviral defense system in bacteria. Cas proteins use short sequences of RNA to guide the process.
“For gene editing to work properly, CRISPR-Cas technologies need to cut the DNA that exactly matches the guide RNA. The selectivity of this process is not 100%, which means that it will cut some non-matching DNA,” Shao said. “To improve the cleavage selectivity, we will use machine learning to model the chemical process.”
Shao is working alongside Rakhi Rajan, an associate professor in the OU Department of Chemistry and Biochemistry. Her lab's primary focus is to characterize protein-DNA-RNA interactions using CRISPR-Cas systems.
“CRISPR-Cas is important because it has been approved for gene therapy in a few select diseases,” Rajan said. “To make a system that can treat many diseases, we need to fully understand how these guide RNAs work and ensure that the DNA is cut at exactly the spot we need them to be cut.”
In collaboration with Lacey McNally, the vice chair of research advancement in the OU College of Medicine at OU Health Sciences, Shao will also deploy computer models to simulate how different modifications of photoacoustic probes used to detect pancreatic and breast cancer tumors affect their performance. These probes emit sound waves in living tissue that can be detected by imaging technologies, allowing researchers to see what's happening deep inside the body at the molecular level.
“By using these approaches, we can study gene editing and bioimaging process accurately and efficiently and hopefully gain new insights into both processes,” Shao said.
About the project
The project, “Multiscale Modeling of Enzymatic Reactions and Bioimaging Probes,” is funded by an expected $394,119 R35 grant from the National Institutes of Health’s National Institute of General Medical Sciences, project No. 1R35GM153297-01, with an expected total grant amount of $1,868,977 for the 5-year funding period. Shao will employ two graduate researchers and two post-docs. It began on June 1, 2024, and is expected to conclude on May 31, 2029.
About the University of Oklahoma
Founded in 1890, the University of Oklahoma is a public research university located in Norman, Oklahoma. As the state’s flagship university, OU serves the educational, cultural, economic and health care needs of the state, region and nation. OU was named the state’s highest-ranking university in U.S. News & World Report’s most recent Best Colleges list. For more information about the university, visit ou.edu.
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