Shedding light on microsporidia—the tiniest eukaryotes

MoGen faculty member Dr. Aaron Reinke received the Early Researcher Award, winning $150,000. The provincial government issues these awards to newly established faculty members and principal investigators who started their careers at publicly funded Ontario research institutions in the last five years. The Reinke lab, housed at MaRS, will use the award to fund research projects aiming to characterize host immunity and screen molecules that can prevent infection by a type of parasite called microsporidia. When asked about choosing microsporidia as a research area compared to more well-known pathogens, Dr. Reinke notes that we know little about the biology of microsporidia—and as a result, there are numerous areas for his lab to investigate and unearth. 

Microsporidia is a group of parasitic fungi that grows and reproduces only inside their host cells. These parasites infect and afflict a range of different hosts, including agriculturally important species such as pigs, fish, shrimp, silkworms and honeybees. They also cause diseases such as microsporidiosis in humans, causing millions of infections annually and proving deadly to immunocompromised patients. Combating microsporidia infections in humans and other animals is challenging due to the limited treatment options. What's fascinating from an evolutionary standpoint is that microsporidia hold the record of the smallest eukaryotic genomes, making them the model for the minimum genes needed to make a functional eukaryote. Currently, researchers have discovered around 1400 species—as catalogued by undergrads in the Reinke lab—with far more to be uncovered in the future. Indeed, one of the tasks of the Reinke lab is collecting environmental samples containing worms and screening them to discover new microsporidia species to shed light on their evolution. 

One challenge in microsporidia research is that individual species grow only in their designated host and lack of widely used model systems or organisms. To address this, the Reinke group utilizes the popular model organism Caenorhabditis elegans (C. elegans), a type of microscopic worm, to study microsporidia more in-depth. In addition to the many genetic tools available for this organism, other advantages of C. elegans include being able to research, test, and screen large populations feasibly and ethically and its established use as a model system for humans and other animals. The group plans to shed light on the host immune response against microsporidia and screen potential pharmaceuticals with this worm and its microsporidian pathogen Nematocida parisii.  

With the funding from the Early Research Award, the Reinke group plans to investigate further the molecular mechanisms behind the host immune response, especially how microsporidia infect cells. Recent publications from the Reinke lab that delve into this include discovering how microsporidia take advantage of a C. elegans antibacterial protein to promote host invasion and how parent worms infected with the parasite pass on immunity to their offspring, demonstrating inherited or intergenerational immunity. The scientists have also performed drug screens for small molecules that inhibit infection and plan to carry out genetic screens on C. elegans to identify microsporidia resistant to inhibitors and, ultimately, the targets of these compounds. Other future routes of investigation include looking into bacterial chemical compounds with anti-microsporidia activity and identifying genetic variants within a population that impact disease susceptibility, such as mutations that modify resistance against infection.  

For outreach, the Reinke lab hopes to utilize part of the funding to teach young audiences about their lab work at future Science Rendezvous events. “We plan to have a booth that will teach children about what we do with the worms and what happens when they’re infected, as it’s an easy and safe system to teach others about the principles of infectious diseases since the microsporidia that infect C. elegans doesn’t infect or harm humans,” said Dr. Reinke. Similar to what they do in the lab to discover new species, the group will develop kits that can screen worms in Petri dishes for microsporidia, allowing participants to engage in citizen science.  

Congratulations to Dr. Reinke on his award and thank you for his contributions to this piece! Readers can inquire more about the award on the Government of Ontario website and its data catalogue.