WSU researchers on a quest to investigate the critical role carotid bodies play in controlling breathing
Like Sir Galahad searching for the Holy Grail in the Arthurian legend, Christopher N. Wyatt, Ph.D., is on his own quest… to discover how the carotid bodies control breathing. In fact, he has been on a crusade to unlock the mysteries of these tiny oxygen-sensing organs since 1991.
“Defining the oxygen-sensor in the carotid body is like questing for the Holy Grail,” said Wyatt, a researcher and assistant professor in the Department of Neuroscience, Cell Biology, and Physiology. “Actually, there seem to be lots of little Holy Grails in carotid body research,” he admitted.
The size of a grain of rice, the carotid bodies are located at the bifurcation of the carotid arteries in the neck. They sense oxygen and carbon dioxide levels in the blood. If the blood oxygen level falls, these neurotransmitter-rich organs fire and send a signal to the respiratory control center in the brain, which ultimately corrects the pattern of breathing. This is known as the hypoxic ventilatory response.
“We’ve known that carotid bodies are sensitive to oxygen for decades, and we know parts of the mechanism, but we still don’t really know how it works,” he explained. So Wyatt is extending the studies into how the carotid body actually senses changes in oxygen.
“My recent research has indicated that the energy-sensing enzyme AMP-activated protein kinase (AMPK) is critical in the transduction of hypoxic-signaling by the carotid body,” he said. “We believe this enzyme is very important.”
Funded by the National Institutes of Health and the American Heart Association, Wyatt and his research team are testing a hypothesis that low oxygen is sensed by mitochondria in the cells of the carotid body, and that the mitochondria are linked to cellular excitability by AMPK. They compare the hypoxic ventilatory response in normal mice with mice that have the AMPK enzyme knocked out. In their studies, normal mice breathed faster during hypoxia, while the enzymedeficient mice did not.
Research is proving the hypothesis to be true. Wyatt and Heidi Jordan, a Ph.D. student he supervises, will present their most recent findings at the 18th meeting of the International Society for Arterial Chemoreception in Hamilton, Ontario, Canada, this summer.
“Once we understand how this mechanism works, then we can start to look at how it goes wrong,” he added. Future applications of this research could address medical problems such as sleep apnea and sudden infant death syndrome (SIDS).
“One of the reasons I’m achieving my goals is that I have good collaborations both within Wright State and internationally,” Wyatt noted. His chief collaborator is Professor Mark Evans at the University of Edinburgh, Scotland, UK, but a joint project with Tom L. Brown, Ph.D., associate professor in the WSU neuroscience, cell biology, and physiology department, is also producing interesting data. He added that he couldn’t complete his research without his students Heidi Jordan, Ryan Shapiro, and Thao Tran, and especially Barbara Barr, his lab manager and technician.
A third-generation scientist, Wyatt’s love of research is no surprise. “It’s like being paid to do a hobby; it’s just constantly interesting,” he said. His oxygen-sensing research has been published in many scholarly journals, and he has been invited to present at numerous conferences, both here and abroad.
Wyatt hails from Britain, having been born in Manchester, England. After earning a degree in pharmacology from the University of Bath in the United Kingdom, he earned a Ph.D. from the University of Leeds, UK. But he didn’t stop there; he pursued postdoctoral work at University College London, Oxford University, and the University of St. Andrews, uniquely positioning him to compete for research opportunities.
One of those opportunities came from across the “Pond” in 2006. Robert W. Putnam, Ph.D., a researcher and professor in the Department of Neuroscience, Cell Biology, and Physiology at Wright State, sent an email soliciting applicants for research positions to some of his British colleagues. One of them shared it with Wyatt, who applied and was accepted. He soon left the remote Scottish fishing village where he was living to accept a position at Wright State.
Today he lives in Yellow Springs, Ohio, with his wife and their two sons. “I do like that Ohio has seasons; I love the seasons,” Wyatt said. “Scotland only has one season… and summer lasts a day.” VS