By Sophie Rentschler | Division of Research
In the stomach, digestive enzymes tuck themselves into craters in large proteins like a puzzle to break down molecules.
This interplay between proteins in the digestive system is vital to turning food into energy, and it is central to Xiaoqin Zou’s study of protein interactions to develop novel, molecular medicine at Mizzou’s Dalton Cardiovascular Research Center.
“These digestive enzymes are like molecular scissors that break proteins into smaller pieces,” said Zou, a Curators’ Distinguished Professor of physics and biochemistry. “Without these enzymes, the digestion of a protein would take thousands or even millions of years to occur.”
Zou studies craters, or deep pockets, in proteins that make it possible for other proteins or small molecules to latch onto them. She models these protein interactions with physics, bioinformatics and machine learning techniques, to understand how proteins interact with various drugs and therapies.
Proteins function as building blocks of life — they give structure to our bones and muscles while also being capable of breaking down other proteins (enzymes) and regulating bodily processes (hormones). An enzyme is just a specialized protein that speeds up chemical reactions for digestion, metabolism and energy production within an organism. Its ability to not be broken down in the process of digestion sets it apart from the proteins that make up the food it helps deconstruct. Drug molecules, typically small chemicals, work by fitting into pockets on disease-related proteins to block or enhance the molecule’s functions.
Zou looks for small molecule drug candidates to precisely target protein mutations for precision medicine applications in cardiac arrhythmias and neurodegenerative diseases. She does so alongside collaborators at Washington University in St. Louis, Stony Brook University and Duke University. This and other protein projects have garnered Zou and her collaborators more than $7 million in direct grants from the National Institutes of Health since 2023.
A background to build on
Zou’s experience sets her up well for this sort of science.
Since high school, Zou showed a strong interest in the physics behind biology and how to cure diseases with effective strategies.
She came to the U.S. as part of the CUSPEA (China-U.S. Physics Examination and Application) program, coordinated by Nobel laureate Tsung-Dao Lee as a bridge between China and the western world. In Zou’s year of applying to the program, 76 of the country’s physics students were chosen to pursue their PhDs in physics at U.S. institutions.
She completed her postdoc at the University of California San Francisco 26 years ago, where she learned from Irwin D. Kuntz, the founder of a famous computational area of study in drug discovery called molecular docking. Like Kuntz, Zou also established her own new techniques to study structure-based protein interactions.
She developed computational methods to model how proteins latch onto other proteins — despite the surface of a protein being very flat — and for proteins and peptides to bind to each other.
Science that’s paying off
The development of her own protein interaction techniques and her reputation have paid dividends in terms of Zou and her collaborators securing funding.
NIH R01 grants — the oldest, most prestigious grants awarded to scientists conducting biomedical research — currently provide about $367,000 in direct costs per year toward Zou’s work supporting the development of drug design. Zou and her collaborator also directly received an NIH R21 grant — given to high-risk, high-reward exploratory research — and the renewal of her R35 grant meant to provide long term support to experienced investigators with an outstanding record of research productivity. Within the month of September alone, she has submitted three grants. As a professor with four joint appointments across Mizzou — Dalton, MU’s Department of Physics and Astronomy, Department of Biochemistry, Institute for Data Science and Informatics — her months as a researcher usually look this way: fast-paced, with work often spilling into the weekends.
Kevin Cummings, interim director of the Dalton Cardiovascular Research Center, said Zou’s research area is vital to the center in its ability to foster collaboration on cardiovascular physiology.
“What we value in Zou and all of our investigators at Dalton is bringing a unique skill set or experience that can be harnessed by others,” Cummings said.
Being an apprentice of the founder of an area of study inspired her to create her own biological techniques, and that creation fuels her long-term goal of developing a drug that yields success with patients.
When asked if she has any scientists that she looks up to, Zou said she has stopped looking up to scientists. She said she stays fixated on her research, extending the advice to stay focused to other researchers seeking success in their work.
“When you have exciting ideas, you don’t just leave them on the desk,” Zou said.
Cummings said Zou’s unique expertise continues to lure other researchers in, explaining the “exponential growth” across her grants.
“You can take your research into something you never really thought it would turn out to be,” Cummings said about collaborating with scientists with niche research interests.
Centers, like Dalton, achieve this reality by bringing researchers together in close proximity, feeding off each other's successes and progress.
“That’s why we have centers,” Cummings said.
Zou said the most important thing for researchers who strive to be the leading scientist in their field is to have “their own niche in their research.”
“When a kind of research is brought up, your name will come to mind,” Zou said.
Zou said she is proud and grateful for her exceptional current and former team members, who are the driving force behind these exciting research programs. Her 25 years in the highly interdisciplinary environment of the Dalton Cardiovascular Research Center have also been instrumental in advancing her research on rational drug design for cardiovascular and neurological diseases. Zou also extends gratitude to her cross-institution collaborators and those across MU: Jianmin Cui of WashU, Ira Cohen and Richard Lin of SBU, Huanghe Yang of Duke and Xiao Heng and Hongmin Sun at MU.