Researchers in UBC’s Prepare for Pandemics through Advanced Research in Evolution (PrePARE) cluster bring together complementary expertise to outwit infectious diseases.
By Sarah Anderson, PhD
The rapid development and widespread deployment of the COVID-19 vaccine was undoubtedly a triumph in infectious disease management. Not a silver bullet, its success was largely a product of its versatility: As the SARS-CoV-2 virus continued to propagate and mutate, scientists could tweak the vaccine’s mRNA sequence to target modified regions of the virus. And as new variants emerged, the public became as familiar with the Greek alphabet as they did with booking appointments for their COVID-19 boosters.
“With the pandemic, the word ‘evolution’ started to enter the public lexicon a bit more, and I think people started to appreciate that infectious diseases can evolve rapidly. It doesn't take millions of years; it can happen quickly and in a way that really impacts their health,” said Kayla King, a professor of microbiology and immunology and zoology at UBC.
Viruses, bacteria, and other pathogens undergo genetic changes as they fight to survive in new environments, evade the host immune response, and overcome neutralization by vaccines, antivirals, or antibiotics. These adaptations, in turn, influence the pathogen’s capacity to infect different species, replicate within and spread between hosts, cause severe disease and death, and circumvent treatment. As the pathogen wreaks havoc on the host, it applies its own selective pressure, pushing hosts to evolve strategies to resist infection. With so many complex factors shaping and stemming from these evolutionary dynamics, “It’s a major global challenge to be able to effectively respond to pathogens when they spill into humans or animals,” said Selena Sagan, a professor of microbiology and immunology at UBC.
Sagan and King have teamed up to help the scientific community sneak ahead in the race against looming pandemic threats. In the summer of 2023, the pair was recruited to UBC to co-direct Prepare for Pandemics through Advanced Research in Evolution (PrePARE), a collaborative and interdisciplinary research cluster based in the Faculty of Science. PrePARE focuses on leveraging new insight into pathogen evolution to tackle current and emerging infectious diseases.
Sagan, the Canada Research Chair in RNA Biology and Viral Infections, brings to the role her expertise in the molecular mechanisms governing the lifecycle of RNA viruses. “As an undergraduate, it was mind-blowing to learn that something that is so small that we can’t see it and that isn’t even considered a living organism could cause so much disease, damage, and devastation,” she said. “I’m really passionate about understanding how viruses operate and evolve and how we can develop new antivirals and strategies to control them.”
King, the Canada Excellence Research Chair in Evolutionary Dynamics of Host-Pathogen Interactions, has unique prowess in investigating infection interfaces in the context of changing environments. “Selena and I together make a perfect pairing,” King said. “It’s really valuable to have these two sets of expertise when leading a research cluster studying the role of infectious disease evolution in pandemics.”
Similarly, in building PrePARE’s core membership, Sagan and King recruited researchers with diverse and complementary skillsets, knowledge, and scientific approaches. Their work spans the arenas of antimicrobial resistance and drug discovery, immunology and vaccinology, and mathematical modelling of pathogen transmission and employs a combination of theory and computation, in vitro and in vivo experimentation, and field work. “One of the best parts of being a scientist and academic is working with others who have different perspectives and can encourage you to evaluate problems and solutions from different angles,” King said.
Drawing on her perspective as an evolutionary biologist, King utilises a technique known as experimental evolution that entails infecting animal hosts with a pathogen, letting the infection brew, extracting the pathogen, reintroducing it to hosts, and repeating the cycle. By analyzing each new pathogen population with genetic sequencing tools, her team can track its evolutionary trajectory in real time, often observing that adaptations emerge in fewer than 24 hours.
King and Sagan have launched a collaborative project to investigate how a warming climate influences the evolution of Zika, an RNA virus. As climate change makes colder regions more habitable for the mosquito disease vector, these insects are expected to carry the virus north, but it’s unclear how this shift in environment could bring about new variants. Chelsea Higgins, a joint PhD student in the King and Sagan labs, is performing experiments in which she is iteratively infecting mosquito cells with Zika virus under temperature regimes representative of its current and projected geographic range. By analyzing the virus’s evolution over several generations, she will gain insight into its potential to become more harmful and transmissible in a changing world.
While research at PrePARE has benefitted from collaboration within the cluster, the team recognizes that working to mitigate infectious diseases also requires large-scale cooperation between academia, industry, government, and healthcare. “During the COVID-19 pandemic, we realized that we couldn't all sit in our silos, that we have a lot to teach other, and that we can find solutions if we work together,” Sagan said. Researchers in Sagan’s lab developed a molecular virology course that instructed hospital personnel on how to isolate SARS-CoV-2 from clinical samples and grow and handle the virus in biosafety facilities.
To continue to break down barriers between scientific sectors, the PrePARE team has enlisted more than 20 associate members from across UBC and the greater Vancouver area, including researchers with appointments at BC Children’s Hospital, the BC Centre for Disease Control, and provincial and federal government departments. By bridging these connections, “We hope to encourage our colleagues who are directly involved in disease control to consider evolution in their endeavors. Evolution is important in considering the long-term efficacy of particular treatments or the likelihood of pathogen spillovers from animals,” King said. Her work could help to predict the genetic changes pathogens can acquire in response to different selective forces, informing new therapeutic strategies that can keep up with these adaptations. For example, researchers developing antiviral treatments may need to evaluate a combination of compounds targeting multiple mechanisms of infection in order to overcome drug resistance.
PrePARE’s core and associate membership provides the cluster’s trainees a built-in community of researchers working across the spectrum of pandemic preparedness. Through this network, graduate students and post-doctoral fellows can tap into an additional source of mentorship, become familiar with the infectious disease career landscape in British Columbia, gain exposure to employment and funding opportunities, and discover new translational applications for fundamental science. The team is planning a professional development event for trainees this fall featuring a career panel comprised of PrePARE members as well as local representatives from biotechnology and public health institutions.
As they support trainees in developing relationships throughout the cluster, the PrePARE team also strives to build connections with the communities impacted by infectious diseases. While participating in the CanHepC training program as a graduate student, Sagan had the opportunity to visit liver clinics specializing in the treatment of hepatitis C and to interact with patients and patient advocates. “I'm studying this virus in a dish, but to see how it actually affects people and learn about the social aspects and stigma associated with the disease was a really impactful experience for me,” she said.
At PrePARE, core member Jim Sun, a professor of microbiology and immunology at UBC, is engaging in real-world disease settings through his work with the Nunavut Tuberculosis Wastewater Surveillance project. By tracking the tuberculosis bacterium in wastewater in Iqaluit, Nunavut, Sun and other researchers aim to guide public health interventions to reduce the transmission of tuberculosis among the Inuit Indigenous People, who experience a disproportionate rate of infection.
“We want to make sure that the pathogens we’re studying have clear global health impacts,” Sagan said. “Hopefully, our work to better understand these pathogens will lead to new treatments and control strategies that can ultimately help patients.”