We Don’t Understand Life… But We’re Trying

While human life is massively complex, we can gain all sorts of insights at the genetic level by studying, of all things, yeast cells.

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Genes are the blueprint for life, and they drive how cells behave in health and disease. But the complexity of life and the interactions between different components of the cell mean that when things go wrong, it can be hard to pinpoint why.

Molecular geneticist Charles Boone, CIFAR senior fellow and professor at the University of Toronto, studies yeast cells as a model for human cells, probing how genetic mutations interact.

“The reality is we don’t understand how life works, and so we’re trying to figure out fundamental things about life so that we can understand it, and manipulate it, if things go wrong like disease states,” says Boone.

Boone believes that understanding the inner workings of the cell is a crucial step to treating genetic diseases.

Internationally, the yeast community used a method called CRISPR to selectively edit genes, creating a library of yeast that each have a mutation, covering every single gene that yeast carry. In total, 6,000 different genes in just as many mutants.

Now Boone is taking this library and using automation to cross all the mutants together to make a library of every possible double mutant. There are 18 million double mutants, and they will help the community understand how genes interact.

This work helps group genes into clusters that influence the same molecular pathways, building a framework of functional connections and interactions. Building out from there, similar tests can be done on more complex human cells, building a map for human health.

“The exploration is what drives a lot of science because we’re moving into the unknown and it is sort of moving into an exponential phase,” says Boone. “We walk in, it’s so exciting because you never know what’s around that corner and what’s going to happen next, and you just have to be prepared.”

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Charlie Boone joined the Banting and Best Department of Medical Research at the University of Toronto in July 2000. His lab is now situated in the Donnelly Centre for Cellular and Biomolecular Research, a multidisciplinary research institute involving several different faculties within the University of Toronto. His open concept lab that is shared with researchers Brenda Andrews and Tim Hughes, who collaborate on a number of projects, including global mapping of genetic interactions in yeast. Robotics and methods developed by the Boone group are used to manipulate high density yeast arrays and automate yeast genetic analysis.