U of T researchers receive funding for projects on gene regulation and evolution

Two faculty members at the Donnelly Centre for Cellular and Biomolecular Research have successfully secured funding through the Spring 2024 competition of the Canadian Institutes of Health Research (CIHR) Project Grant program.

The program supports researchers across Canada whose projects have the greatest potential, according to international standards of scientific excellence, for making advancements in health. Collectively, Benjamin Blencowe and Henry Krause received more than $3.5M in funding for projects to be executed over the next five years.

Harnessing alternative splicing as a tool for treating disease

Benjamin Blencowe, professor of molecular genetics, Canada Research Chair in RNA Biology and Genomics and Banbury Chair in Medical Research at the University of Toronto, received funding for a project to develop a CRISPR-based strategy for targeted control of alternative splicing events impacting human physiology and disease. Alternative splicing is a process in which the protein-coding segments of genetic material, called exons, are spliced in different ways to diversify the instructions for protein production – such that a single gene can produce multiple, functionally distinct protein products. This process is widespread, occurring across the vast majority of human genes, and is often dysregulated in human diseases and disorders. Through collaboration with Mikko Taipale, associate professor of molecular genetics, and Anne-Claude Gringas, Director of the Lunenfeld-Tanenbaum Research Institute, Vice-President of Research at Sinai Health and professor molecular genetics, the new strategy will be used to screen for factors that regulate alternative splicing and to probe functions of the myriad of uncharacterized exons linked to cell growth, development and disease.

Mapping RNA distribution throughout the cell

Henry Krause, professor of molecular genetics, received funding to complete a project on the localization and movement of all RNAs encoded by the fruit fly genome within the cells of developing embryonic and larval tissues. The Krause lab developed technologies to study the previously unrecognized role that RNA molecules play in determining where protein-coding RNAs are translated into proteins in the cell. The lab found that RNAs, including those that code for proteins and those that do not, are directed to specific locations in the cell. The additional funding from CIHR will help the lab expand its existing database of around 10,000 mapped RNAs. The database could potentially inform disease treatment by improving our understanding of gene regulation.

Exploring the evolutionary role of lncRNA found in the testes

Henry Krause also received funding, along with Julie Brill, Senior Scientist at The Hospital for Sick Children Research Institute and professor of molecular genetics, for a project on the role of long non-coding RNA genes on organism evolution and diversity. Earlier this year, the Krause lab published a study on their discovery of much higher levels of lncRNA genes in the testes than expected, dispelling the long-standing assumption that lncRNAs do not play a significant role in gene regulation simply due to their non-protein-coding nature. The project team will conduct a genome-wide study on lncRNA genes in the testes.

"Benjamin Blencowe and Henry Krause are well-established members of the Donnelly Centre community, each having contributed many breakthroughs in biomedical research throughout their time here," said Stéphane Angers, professor and director of the Donnelly Centre. "Both faculty members are tackling gene regulation, but from different angles. Their funded projects will pave the way for understanding the role of alternative splicing in disease and identifying new roles performed by RNA."