U of T researchers receive funding for projects on neuron regeneration, drug defense, drug discovery and metabolite sequencing

Three faculty members at the Donnelly Centre for Cellular and Biomolecular Research have secured funding through the Fall 2024 competition of the Canadian Institutes of Health Research (CIHR) Project Grant program, and a fourth faculty member secured a CIHR Catalyst Grant for the development and validation of new biomedical techniques and technologies.

The Project Grant program supports researchers across Canada whose projects have the greatest potential, according to international standards of scientific excellence, for making advancements in health. The Catalyst Grant program was launched in 2024 to address a gap in funding to advance biomedical research in Canada through technological innovation.

Collectively, Liliana Attisano, Andrew Fraser, Peter Roy and Mikko Taipale received more than $3.8M in funding for projects to be executed over the next two-to-five years.

“I extend my heartfelt congratulations to all four faculty members who have recently been granted funding from CIHR,” said Stéphane Angers, professor and director of the Donnelly Centre. “We are excited to see what comes of the Project Grant studies over the next five years, as well as the development of a new innovative tool through the Catalyst Grant that will benefit the biomedical community. This funding will support our faculty members as they work to answer important research questions in health and medicine.”

Manipulating a signalling pathway to regenerate neural axons

Liliana Attisano, professor of biochemistry, received funding for a project to study a signalling pathway known to be involved in limiting the growth of neural axons during embryonic development. The central nervous system is not able to recover from damage to axons, which are protrusions from neurons that conduct electrical impulses between neurons and other cells and are necessary for overall neural function. The Attisano lab has found that the growth of neurons—both damaged and undamaged—can be activated through drug-mediated inhibition of the signalling pathway; the new project will entail further research to determine the molecular mechanisms underlying these effects and inform the development of new methods for treating damaged neurons.

Exploring methods to mitigate the side effects of cationic amphiphilic drugs

Peter Roy, Canada Research Chair in Chemical Genetics and professor of molecular genetics and pharmacology and toxicology, received funding for a project to study how animals defend themselves from life-threatening side effects of cationic amphiphilic drugs (CADs), which encompass a wide range of drugs that include antidepressants, antipsychotics and antibiotics. Patients treated with CADs are vulnerable to phospholipidosis, where the accumulation of fats due to impaired metabolism leads to toxic effects that kill cells. Using the model nematode C. elegans, Roy lab PhD student Levon Tokmakjian discovered a pathway that responds to CADs by increasing the production of proteins that detoxify the small molecules. The new project will involve conducting a screen to find the genes responsible for activating the CAD defense system in C. elegans and another screen to identify candidate drugs for treating CAD side effects in humans.

Exploring new options in targeted protein degradation

Mikko Taipale, Canada Research Chair in Functional Proteomics and Proteostasis, Anne and Max Tanenbaum Chair in Biomedical Research and associate professor of molecular genetics, received funding for a project to study new proteins that can be used for treatments involving targeted protein degradation (TPD). TPD differs from traditional methods of targeted protein treatment in that it degrades the protein of interest instead of simply inhibiting its harmful effects, thereby increasing the precision and potency of this type of disease treatment. The Taipale lab has developed a new method to identify degrader proteins and used it to discover new E3 ligases that are more effective than ones currently in use, as well as additional proteins that could perform the same function. The new project will involve conducting screens to learn how these alternative options could be used in TPD treatments.

Searching for high-affinity sensors to bring sequencing to metabolites

Andrew Fraser, professor of molecular genetics, received funding for a project to identify new sensors for measuring metabolites. Metabolites encompass a wide variety of small molecules, including glucose, vitamins and amino acids, that are critical to human health and medicine. This level of diversity makes it very difficult to develop a tool with which they can be identified and measured. Inspired by DNA sequencing, the Fraser lab invented technology that can overcome this challenge by using aptamers to sense metabolites. The aptamer, which is a single-stranded nucleic acid, releases a unique DNA barcode upon binding to its target metabolite, allowing the barcodes to serve as a proxy for the metabolites. The new project will build on the lab’s inventory of aptamer sensors by searching for new ones that are more precise and potent than existing options found in nature.