(l-r) Kathryn Rozen-Gagnon, Haissi Cui, Bowen Li, Jun Liu
July 23, 2024
By Betty Zou
Two new cross-disciplinary collaborations are getting off the ground thanks to New Connections Grants from the Emerging and Pandemic Infections Consortium.
The grants, worth $100,000 each over two years, aim to support innovative projects led by joint lead researchers with clearly distinct expertise from different institutions and/or university divisions, and who are coming together for their first significant research collaboration.
“One of our primary goals at EPIC is to help foster new collaborations among our research community,” says Scott Gray-Owen, academic director of EPIC and a professor of molecular genetics at the University of Toronto’s Temerty Faculty of Medicine.
“By bringing together diverse ideas, perspectives and expertise, we can advance leading-edge solutions to tackle some of the most pressing infectious challenges facing the world today.”
The two projects that received funding from the 2024 New Connections Grants competition focus on RNA. One explores the role of RNA in the biology of viral infection, while the other aims to develop an RNA-based vaccine against infectious diseases.
Untangling the role of RNAs in chikungunya virus infection
Transmitted by mosquitoes, the chikungunya virus often leads to debilitating symptoms such as joint and muscle pain, headache, nausea, fatigue and fever. Historically, chikungunya outbreaks were mainly seen in Africa and Asia. But with climate change and human activity expanding the range of virus-carrying mosquitoes and viral adaptations making it more transmissible, chikungunya cases have now been identified in over 110 countries in Africa, Asia, Europe and the Americas.
Like many other RNA viruses, the chikungunya virus relies on the cellular machinery of its host to complete its life cycle, which makes these interactions a potential target for much-needed therapies for this disease.
EPIC New Connections Grant recipients Kathryn Rozen-Gagnon, an assistant professor in the department of molecular genetics at Temerty Medicine, and Haissi Cui, an assistant professor in the department of chemistry at Faculty of Arts & Science, are teaming up to uncover how the virus hijacks different host RNA molecules and pathways to survive and how mosquito and human cells fight back. The collaborative project combines Rozen-Gagnon’s expertise in mosquito-borne viruses and computational and RNA biology with Cui’s experience studying how a type of RNA molecule called tRNA contributes to human disease.
“As early career researchers, the support to build collaborations and to combine our expertise is extremely precious and will allow us to pursue new research directions together,” says Cui.
“By obtaining a better understanding of the molecular underpinnings and identifying weak spots, we hope to contribute to finding new therapeutic targets and strategies to combat viral infections.”
Importantly, this project will also leverage unique infrastructure resources at U of T, including a mosquito facility in the Rozen-Gagnon lab and the Toronto High Containment Facility, where studies of the chikungunya virus can be undertaken safely and securely.
Developing an intranasal mRNA vaccine against tuberculosis
According to the World Health Organization, tuberculosis (TB) is the second leading infectious killer after COVID-19 worldwide. The disease is caused by the bacteria Mycobacterium tuberculosis and affected an estimated 10.6 million people in 2022.
Currently the Bacillus Calmette-Guérin (BCG) vaccine is the only approved vaccine against TB, but it offers limited protection in teens and adults against pulmonary TB, the most common form of disease that affects the lungs. It also does not prevent re-activation of the disease in people who have a latent infection.
With the support of an EPIC New Connections Grant, Bowen Li, an assistant professor in the Leslie Dan Faculty of Pharmacy, and Jun Liu, a professor of molecular genetics at Temerty Medicine, are joining forces to develop a new generation of mRNA vaccines specifically designed to combat TB.
These new vaccines will improve on the same Nobel Prize-winning lipid nanoparticle and mRNA technology used to develop the COVID-19 vaccines. Notably, the researchers will optimize the vaccine so that it can be delivered through the nose and generate a protective immune response in the airway that can prevent bacterial entry. This is important because infection typically occurs when a person breathes in the TB-causing bacteria.
“Despite major efforts, a more effective TB vaccine has not yet been developed and the century-old BCG vaccine remains as the only TB vaccine used today. The situation calls for new technologies,” says Liu.
“The extraordinary success of the mRNA COVID-19 vaccines has kindled great interest in using mRNA as a platform for TB vaccine development. Our teams, with complementary expertise, are positioned to carry out such projects. We are thrilled to receive the New Connections Grant, which will facilitate and spearhead our efforts.”
The collaborative project leverages Li’s expertise in lipid nanoparticle technologies and RNA-based vaccines and therapeutics as well as Liu’s extensive experience in TB vaccine research. It also takes advantage of the world-class capabilities of the Toronto High Containment Facility to test the safety and effectiveness of new TB vaccine candidates.