New Funding to Help Set the Stage for Personalized Medicine
Collaborative research receives boost from the government to build tools to predict disease risk and tailor treatment from one's genetic makeup.
An inter-disciplinary team of researchers led by University Professor and Donnelly Centre Director Brenda Andrews has been awarded funding from the Canada Foundation for Innovation (CFI) for research that may one day allow to predict with confidence a person’s risk of disease and tailor treatment based on their genetic makeup. The $2.76 million Innovation Fund grant will go towards building new technology for shedding light on how genes work together as part of a network to influence health of an organism.
“Our goal is to accelerate the important transition from basic cataloguing of genome sequences to functional characterization of genetic variation encoded within individual genomes,” says Andrews, who is also a professor in U of T’s Department of Molecular Genetics. “The wealth of information that our project will generate will impact our understanding of human cell function and disease and advance strategies for personalized medicine.”
Andrews’ team brings together U of T experts in diverse areas of genomics and from different research institutes and departments. On the team are Professors Ben Blencowe, Charlie Boone, Tim Hughes, Jason Moffat and Mikko Taipale from the Donnelly Centre and, as well as Professors Stephane Angers, of the Leslie Dan Faculty of Pharmacy and Daniel Durocher, of the Lunenfeld-Tanenbaum Research Institute at Sinai Health System in Toronto. All are also professors in the Department of Molecular Genetics. Through past collaborations, the team members have already developed technologies necessary for generating the first large-scale genetic network in human cells.
The funding was announced on October 12, 2017, at the University of Manitoba by the Kirsty Duncan, federal minister of science, as part of an investment of more than $554 million in infrastructure projects at universities, colleges and research hospitals across Canada, according to a statement from the CFI. Overall, U of T researchers received more than $100 million for projects in diverse areas, from regenerative medicine to neuroscience and astronomy.
“This funding announcement gives scientists and their students the opportunity to further their research in areas where Canada has a competitive advantage,” said Duncan. “The discoveries, innovations and skills developed in these new, state-of-the-art labs will go a long way in improving our lives, our economy and our future prosperity.”
"Our goal is to accelerate the important transition from basic cataloguing of genome sequences to functional characterization of genetic variation encoded within individual genomes" — University Professor Brenda Andrews
So far, research in human genetics has largely focused on collecting genome sequences from thousands of people in search of genetic clues of disease. But to understand how the genome impact health, it is important to study interactions between genes, which can’t be gleaned from sequence data alone.
Most diseases, such as cancer or heart disease, are caused by misspellings in dozens or even hundreds of genes, each one contributing ever so slightly to the overall risk and severity of disease. At the same time, no two genomes are the same—each person carries a unique combination of misspellings in their DNA, or genetic variants, which influence health in some way.
“The onslaught of new genome sequence information has revealed a knowledge void – while most diseases are influenced by genetic variation, we do not understand how to properly interpret personal genome sequences to predict what genetic variation is linked to disease,” says Andrews. “And we cannot embrace the idea of personalized medicine until we make a new leap in our understanding of human genetics.”
To begin to unpick how multiple genes and their variants contribute to disease, Andrews and Boone created the first map of genetic interactions for any cell. They did this by systematically removing gene pairs from yeast cells to find the genes working together to maintain the processes in the cell.
The new funding will go towards establishing a platform for doing similar studies in human cells using the gene editing tool CRISPR. Thanks to Moffat’s earlier work, a CRISPR library of “off switches” for every single human gene, is already available in the Donnelly Centre.
Medical implications of a human genetic interaction map are far-reaching. Knowing which genes work together can point to genetic variants that may fine-tune disease severity. These insights could also help develop more precise genetic tests for cancer and other common disease. And in drug discovery, distinct genetic networks of healthy and cancer cells, for example, can reveal drug targets that are unique to cancer, leading to new treatments that would not cause harm to healthy tissue.
The prospect of personalized medicine—where one’s genome spells out diseases to come and calls for the right treatment—is poised to become a reality, said Andrews.
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