Cheung’s Research Looks at Protein Linked to Cell Growth and Cell Death

A $1.6 million, five-year research grant to physics professor Margaret Cheung from the NIH’s National Institute of General Medical Sciences will support the study of a protein linked to cell growth and cell death.

“In our project, we are looking at the protein, calmodulin, and mapping how it recognizes and interacts with binding partners inside a cell,” said Cheung, an assistant professor of physics at the University of Houston. 

Calmodulin binds with calcium and then can interact with more the 400 binding partners, or targets. “How does it know which one to interact with in the jam-packed conditions of a cell? How does it know when to stop growth or when to interact to encourage growth? There must be a rule of interaction; that is what we want to learn,” she said.

Through this grant, Cheung is mapping the interactions related to calmodulin’s poorly understood cell signaling cycle.

To learn about calmodulin’s interactions, Cheung is using a computer model to simulate the conditions inside a cell rather than studying the interactions outside the cell in a test tube. These model systems will allow her to explore calmodulin’s interactions with binding partners and to understand the mechanisms behind the interactions.

“We found a way to model the crowded environment of the cell using physics principles,” Cheung said. “This allows us to simulate the interactions under cell-like conditions. Then, we can predict how calmodulin and a new binding partner will behave.” 

Cheung is collaborating with an experimentalist, M. Neal Waxham, Ph.D., and a bioinformatician, Yin Liu, Ph.D., both at the University of Texas Health Science Center in Houston’s Texas Medical Center. Waxham will test and validate the results of the computer simulation from Cheung’s group, and Liu will generalize the findings based on selected targets to all possible calmodulin binding targets in the database.

“If we can identify strategies to manipulate calmodulin, there is the possibility that cell growth and cell death can be controlled by perturbing the cellular environment in a way that activates or suppresses the appropriate calmodulin signaling pathways,” Cheung said. “That information could one day lead to novel therapeutic strategies for cancer treatment.”

- Kathy Major, College of Natural Sciences and Mathematics