It lives naturally inside some of us, but under the right circumstances it can grow out of control and cause systemic fungal infections. Systemic infections can be life-threatening with up to a 40 percent mortality rate, especially among immune-compromised individuals.
Candida albicans, a species of yeast, is the focus of Todd Reynold’s research, for which he and Elias Fernandes, associate professor of biochemistry, cellular, and molecular biology, were awarded one of the first Office of Research and Engagement seed funding grants in 2018. Reynolds, associate professor of microbiology at the University of Tennessee, Knoxville, explains that the initial project, “Virulence mechanisms of Candida albicans secreted lipases,” provided enough preliminary data for a subsequent proposal to the National Institutes of Health. From that initial funding through ORE, he and Tim Sparer, associate professor of microbiology, in collaboration with Robert Wheeler, associate professor of molecular and biomedical sciences at the University of Maine, parlayed that success into a recent $2.5 million R01 award from NIH to better understand the fungus.
“This fungus has the ability to hide from the immune system,” said Reynolds. “It is detected by the immune system through a sugar on its outer surface known as beta glucan, but it can mask its beta glucan from detection and make itself less easily detected. We’re interested in how it hides and whether we can get it to unmask itself, through drugs or other manipulations.”
Working closely with Sparer and Wheeler, Reynolds tapped the support services of the research development group and Office of Sponsored Programs in ORE to craft a competitive R01 proposal. The proposal was submitted in October 2019 and funded in May 2020.
Their research project, “Regulation of ß(1,3)-glucan exposure in Candida albicans,” has three specific aims: to understand the signaling pathway that regulates unmasking, study the mechanisms of unmasking, and explore the immune system in an animal model to understand how unmasking decreases the ability of the fungus to cause disease and how the immune system responds to unmasking.
According to the NIH website, the R01 is the original and historically oldest grant mechanism used by NIH, providing support for health-related research and development based on the mission of the NIH.
Reynolds says that Kiley Compton, research development manager, and Stacey Wade, sponsored programs administrator, helped him with the “mountain of paperwork” required for the R01 funding mechanism.
“All of the people in the Office of Research have been so fantastic, accommodating all of our crazy schedules, helping us make good decisions on the budget, and working with people from around the UT campus to capture the resources needed to succeed,” he said. “For example, requirements seem to constantly change for something as simple as a biosketch. Their insights were invaluable in helping us be compliant and aware of all of the necessary details. These proposals turn out to be around one hundred pages, so it’s easy to miss something.”
Reynolds advises fellow researchers to reach out to ORE early in the process and to “follow their advice and get things in on time; be polite—they’re trying to help you; and don’t expect a 24-hour turnaround for your proposal. They are tremendously effective, but they need time to do their work.”