Inside Job
Emily Dziedzic started to think about a career in conservation science in her late 20s. But with a degree in art history, she knew it would be a long path.
Ultimately, white-nose syndrome convinced her it was the path she had to take. First detected in upstate New York in 2006, the disease has now spread to 35 U.S. states and seven Canadian provinces, devastating populations of hibernating bats along the way.
“I had to complete years of undergraduate coursework first, but when I started working towards graduate school, it was specifically because I wanted to do something to help combat the fungus that causes white nose,” said Dziedzic, now a master’s student at Oregon State University focusing on wildlife genetics.
Co-leading the team of researchers that came up with the winning idea for the national White-nose Syndrome Challenge is definitely something. The U.S. Fish and Wildlife Service launched the scientific contest in the fall of 2019 to explore innovative and untapped ideas that could lead to long-term solutions for managing the disease.
“When this challenge came around, offering an opportunity to apply the genetics tools I’ve been developing for other wildlife applications to white-nose syndrome, it was a dream come true,” Dziedzic said.
It was also serendipitous. The team’s co-lead Jenny Urbina Gonzalez came upon the Request for Proposals for the challenge just eight weeks before the submission deadline, with less than a year left in her post-doctoral appointment at Oregon State researching white-nose syndrome in the lab of Taal Levi, an associate professor of wildlife biology.
She recognized the opportunity for their experimental work in the lab to inform a conservation response in the field. Urbina Gonzalez shared the challenge announcement with Dziedzic and Levi, and they discussed using gene editing to target the fungus. But while she and Dziedzic had complementary skillsets in the realm of wildlife biology, they recognized the need to collaborate with others.
They decided to run the idea by colleagues with more experience dealing with fungal pathogens from the Department of Botany and Plant Pathology. Beer played a key facilitation role.
“We had a meeting at a local bar, and enjoyed some beers,” recalled Urbina Gonzalez. “That’s how the idea was born.”
From those auspicious beginnings, the idea grew into something feasible thanks to contributions from collaborators in disease ecology, quantitative ecology, molecular ecology, and infectious disease epidemiology, as well as botany and plant pathology.
Running interference
So what is the idea?
In a nutshell, it’s to create an aerosol spray that genetically silences the fungus. But the proposal is more about the process than the final product, which may be years off.
Gene silencing — also known as RNA interference — is a way to target the cells of disease organisms by borrowing defensive moves from their own playbook.
If you think of DNA as the instruction manual for cell production in an organism, RNA is a messenger that copies sets of instructions (transcription), and delivers them to cells for assembly (translation).
But if a foreign RNA molecule, say from a virus, enters a cell, it sets off an alarm, triggering an enzyme that cuts the intruder into pieces. The cell’s proteins then bind the pieces of RNA to any matching RNA in the cell to prevent their instructions from being translated — effectively muting the signal. In other words, a cell suppresses a viral outbreak by silencing the virus’s genes.
“You can harness that natural mechanism to silence the RNA in the cells of Pd” — that’s shorthand for Pseudogymnoascus destructans, the fungus that causes white-nose syndrome — explained Levi.
I know what you’re thinking: if this mechanism occurs naturally, why aren’t the bats’ cells silencing the fungus on their own? The reason is hibernation — when bats are in this low-energy state, their immune system functions seem to slow down, too, though more research is needed to understand why.
That’s why the team proposes to turn the fungus on itself by creating RNA in the lab that contains the same instructions (or DNA sequence) as a gene that the fungus needs to survive.
When the researchers introduce the manufactured RNA to the fungus, the fungus will perceive it as an outside threat, despite the fact that it contains vital information. The alarm bells will go off, and the cell will mute any other RNA in the cell carrying the same message.
“The idea is that if the fungal cells can no longer produce a gene it needs, the fungus can’t grow,” Dziedzic explained.
Eventually, the goal is to use that mechanism to develop an easy-to-use product — the aforementioned aerosol spray — that scientists can apply inside hibernacula, and even to infected bats, to interrupt Pd growth in the places where it’s doing harm. Because RNA molecules are nontoxic, organic, and present in all life, they would simply pass through other organisms, only harming the target gene in Pd.
“It doesn’t even have to kill the fungus,” Levi said. “It just has to reduce its fitness enough so that it doesn’t kill bats.” That might be the best possible outcome. If the fungus is still present but weak, bats will have more time to evolve resistance to the disease it causes.
Expanding horizons
There will be multiple stages of refining and testing, and retesting, in the lab before the treatment is ready to deploy in the wild. First, there will be tests in petri dishes, using cultured Pd and mail-order RNA. Then, there will be tests on a model organism — a moth that is also susceptible to the Pd fungus when exposed in the lab.
“We want to see if we can save the lives of moths in the lab before we try it on bats,” Levi said.
But they have reason to believe they can get there. Their collaborators in plant pathology have set a precedent: RNA interference has been used successfully to inhibit fungal growth in agricultural crops.
And Urbina Gonzalez has seen evidence that they are on the right track: labeled strands of RNA that she introduced to Pd in petri dishes in the lab that successfully entered the cell, visible only through a high-powered microscope.
Even that aspect of the project required collaboration with an experienced technician. “You need to know how to organize all of the different images of the fungus, how to get to that one spore and see the strand of RNA,” Urbina Gonzalez explained. But it also expanded her horizons. “It was amazing. It’s this huge machine in a dark room that gives you this new level of clarity.”
For both Urbina Gonzalez and Dziedzic, that opportunity to see beyond one’s disciplinary limits is one of the most valuable outcomes of the challenge. Like many complex conservation issues, white-nose syndrome is too big for one discipline, one agency, or even one team to tackle.
“One of the reasons the prize was so amazing was that it enabled lots of teams to get together and really brainstorm novel techniques to combat this fungus,” Dziedzic said. The Service received 47 solutions for the White-nose Syndrome Challenge.
“We’re still in the very beginning stages, but this prize will help us take the next step,” she said.
The team will receive a $20,000 prize for their solution, which is intended to spur further collaboration with scientists, designers and engineers to potentially bring the solution to life.
Others may have that opportunity someday too. In the future, the Service may announce another challenge to motivate more innovative ideas for silencing this fungus, one way or another.
