University of Toronto (U of T) strategic research initiatives Medicine by Design and the Data Sciences Institute (DSI) have co-awarded Catalyst Grants to two research projects that hold promise in strengthening the connection between data science innovation and regenerative medicine.
The projects are being led by Joshua Milstein, an associate professor at U of T Mississauga’s Department of Chemical and Physical Sciences, and Zhaolei Zhang, a professor at the Donnelly Centre for Cellular and Biomolecular Research and in the Department of Molecular Genetics at U of T.
“Data science is fundamental to many of our transformative regenerative medicine projects,” says Michael Sefton, Medicine by Design’s executive director and a University Professor at U of T in the Department of Chemical Engineering & Applied Chemistry and the Institute of Biomedical Engineering. “Medicine by Design’s partnership with DSI gives us the opportunity to engage new researchers and support projects that will ultimately lead to better outcomes in regenerative medicine.”
Both Medicine by Design and DSI encourage a collaborative approach that brings researchers with varying expertise together. DSI has awarded 17 grants in total to researchers as part of the Catalyst Grants program, which funds multidisciplinary research teams focused on the development of new data science methodology or the innovative use of data science to address questions of major societal importance.
“We’re pleased to partner with Medicine by Design on two of our Catalyst Grants. The global and research challenges we face today are increasingly complex,” says Lisa Strug, director of the DSI, and a senior scientist at The Hospital for Sick Children. “Regenerative medicine is one key area where data science could rapidly accelerate advancements in human health.”
Strug is also a U of T professor in the Departments of Statistical Sciences and Computer Science, and cross-appointed in the Dalla Lana School of Public Health.
Improving data derived from single cell sequencing
The collaborative team led by Zhang converges three primary research disciplines: statistics, molecular genetics and medicine. While single cell sequencing — the ability to look at cells at the individual level – has been a revolution, it has also posed challenges.
“One key challenge is that different types of sequencing approaches produce distinct data sets that don’t integrate with each other. We need robust and effective statistical tools to handle the data being measured from the thousands of cells and tens of thousands of genes in one experiment,” says Zhang.
Zhang will be working with Dehan Kong, who is an assistant Professor in the Department of Statistical Sciences and Dr. Dennis Kim, University Health Network clinician investigator and professor at Princess Margaret Cancer Centre.
Using datasets collected primarily from brain or blood cells, this research aims to refine a method that can give researchers a more complete picture of single cell data.
“Our framework will be able to integrate that data generated from different approaches in a very efficient and accurate way,” says Zhang. “Refining these methods could make managing datasets more efficient, not just in our lab but in any lab where researchers are working with multiple, large datasets.”
The strength of this team is in the unique skill set each researcher brings. Zhang is an expert in bioinformatics, specifically on gene expression, gene regulation and cancer genomics. Kong’s research focuses on statistical data science with an emphasis on complex neuroimaging and genetic and genomic data analysis. And Kim is a hematologist and clinical investigator who develops genomics-based biomarkers in leukemia, especially on monitoring response to treatment and relapse risks.
A 3D model to study therapeutic development for tumors
In a tumor, some cell populations are resistant to chemotherapy, and these cells can survive treatment and cause disease to reoccur in a person. Discovering new therapies to target these cells is a focus of many researchers.
“This model will allow labs to automate therapeutic discovery using artificial intelligence and machine learning. With this program, labs could build a model and then download a program they could use in their therapeutic discovery work,” Milstein says.
Researchers can model tumours in the lab – but often in just a single layer that doesn’t give a full picture of how different cell populations interact in a tumor. In the Milstein project, researchers are modeling a tumour microenvironment with multiple layers.
“Our project is based on a 3D model of a tumor and looks at not only how the therapy reacts to cells, but also how the cell populations regrow and what the dynamics between the cell populations are,” says Milstein. “With this model, we can study what happens when we give different types of therapeutics to a tumour.”
Milstein adds, “We think this could accelerate the important work that many researchers are doing in seeking new and improved therapeutics for tumors.”
Milstein is working with Alison McGuigan, a Medicine by Design-funded investigator and a U of T professor at the Department of Chemical Engineering & Applied Chemistry Institute of Biomedical Engineering, and Rodrigo Fernandez-Gonzalez, an associate professor at U of T’s Institute of Biomedical Engineering.
McGuigan is an internationally recognized leader in tissue engineering and disease modelling. Both Fernandez-Gonzalez and Milstein have a track record of publishing in computational biology with a focus on bioimage informatics, and will build on prior experience developing single cell analysis methods in fly and bacterial systems, respectively.
About Medicine by Design and regenerative medicine
Medicine by Design builds on decades of made-in-Canada excellence in regenerative medicine dating back to the discovery of stem cells in the early 1960s by Toronto researchers James Till and Dr. Ernest McCulloch. Regenerative medicine uses stem cells to replace diseased tissues and organs, creating therapies in which cells are the biological product. It can also mean triggering stem cells that are already present in the human body to repair damaged tissues or to modulate immune responses. Increasingly, regenerative medicine researchers are using a stem cell lens to identify critical interactions or defects that prepare the ground for disease, paving the way for new approaches to preventing disease before it starts. Medicine by Design is made possible thanks in part to a $114-million grant from the Canada First Research Excellence Fund.