Supervisor: Gregory Funk
Project: Exploring the mechanisms by which the brain counteracts the life-threatening depression of breathing that accompanies reductions in brain oxygen in prematurity
Bachelor of Science with Honors in Physiology
Why did you choose the degree program you are in?
I chose to enter the Honors Physiology program because in high school I enjoyed learning about how the human body works. I was fascinated by how molecular changes could have a significant impact on whole organ systems and wanted a program that taught me more about the physiology of the entire body. I also chose the honors program because during the summer after my grade 11 year I worked in my first lab at the University of Alberta and realized how much I love research.
How did you stay connected with your supervisor and lab members when the pandemic impacted your project earlier in the summer?
When I was unable to come into the lab I had weekly Zoom meetings with my supervisor where I could ask any questions I had about my project topic. Weekly journal club meetings have allowed me to connect with all the lab members, even when I cannot come into the lab. As well, we have recently started weekly lab meetings to discuss everyone's research in the lab. Finally, now that I am in the lab, I can connect with the other lab members to get help with my project and the techniques required.
What's been the best part of your experience so far?
I have really enjoyed the environment of the lab I am working in because it allows me to feel comfortable asking questions to any lab member. This has helped me better understand the research I am doing and the techniques I am using, which makes the experiments and analysis more interesting.
What impact do you hope this project makes once completed? How will this contribute to improving the health of children?
I hope that my project will increase our understanding of the mechanisms causing the secondary depression of breathing during hypoxia and why this depression is more severe in premature and newborn mammals. Understanding these mechanisms could provide information relevant to developing new treatments for apnea of prematurity (AOP).
Caffeine is a respiratory stimulant that blocks adenosine receptors and is very effective in treating AOP. The clinical problem is that approximately 20 per cent of infants do not respond to caffeine. For these premature babies, there is no alternative and they spend longer in hospitals, more time on ventilators, have poorer lung function and increased incidence of cerebral palsy. This research will hopefully lead to treatments that can improve the acute and long-term health of premature infants who do not respond to caffeine.
My project is part of a larger research program focussed on understanding how purinergic signalling, a form of extracellular signalling, in the brainstem shapes the hypoxic ventilatory response—the increase in ventilation induced by hypoxia that allows the body to intake and process oxygen at higher rates—in premature infants and newborns and how this signalling system might be exploited to develop treatments for breathing disorders that involve the brain.
What's one piece of advice you received from your supervisor/mentor that resonated with you?
My supervisor has repeatedly pushed me to question and analyze experimental techniques used in the research area I am working in. This has allowed me to look at the advantages and disadvantages of every technique I use, which is important in research. Without looking at the caveats of an experimental approach, I cannot accurately apply my results to human physiology, which is why this advice resonated with me.
The brain depends on a constant supply of oxygen to meet its energy needs. If this supply fails for even a few minutes permanent brain damage or death can result. Some infants born prematurely are at risk because they suffer from apnea of prematurity, a condition where breathing slows or stops (apnea) for short periods and oxygen levels fall. Unstable breathing reflects that the brain circuits that produce breathing are immature. Reductions in oxygen levels (hypoxia) during these periods of apnea trigger an adaptive increase in breathing. However, if this increase does not immediately restore oxygen levels, the brain becomes hypoxic and the initial hypoxia-induced increase in ventilation is followed by a secondary phase where breathing is depressed, falling below baseline and becoming potentially fatal in premature infants who suffer from apnea of prematurity.
In many infants, the respiratory stimulant caffeine is used to reduce these apneas and respiratory depression. However, approximately 20 per cent of infants do not respond to caffeine, so alternate treatments are required. Our previous research has shown that hypoxia causes the release of adenosine triphosphate (ATP), the primary carrier of energy in cells, in the brain areas that generate breathing, which stimulates breathing and reduces this hypoxic inhibition of breathing. The objective of this study is to determine how ATP acts in the brain to increase breathing. We will isolate slices of brainstem that generate breathing in a dish and use drugs to identify the ion channels responsible for the excitation of breathing by ATP. These data will guide the development of more targeted, efficacious treatments for apnea of prematurity.