Yeast study reveals how multiple genes interact to influence a surprising cellular outcome | 10/17/2017 | Staff
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Most diseases are complex—caused by faults in multiple genes—but studying how combinations of different genetic variants affect cellular traits is challenging. A new study from Frederick Roth's team, out today in the journal Cell Systems, uses baker's yeast as a model system to demonstrate a new approach to understand how genes can interact in unexpected ways.

Previous research in yeast cells by Donnelly Centre teams revealed how genes interact in pairs and in combinations of threes, taking into account almost all 6,000 genes in the yeast genome.

Roth - Professor - Genetics - Computer - Science

Now Roth, a professor of molecular genetics and computer science in the Donnelly Centre for Cellular and Biomolecular Research and a senior scientist at the Lunenfeld-Tanenbaum Research Institute at Sinai Health System in Toronto, wanted to take this further and investigate how larger groups of genes work together.

He decided to focus on a group of 16 genes which encode proteins known as ABC transporters that pump out toxins and waste from cells. ABC transporters are found on the cell's surface and are implicated in drug resistance.

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"ABC transporters are a key way to pump small molecules out of the cell," says Roth. "They are a major source of resistance to cancer drugs, and also of antibiotic resistance in bacteria and fungi."

Roth's team developed a general strategy, X-gene Genetic Analysis, or XGA, for understanding the impact of perturbing many different gene combinations. To demonstrate the approach, they engineered more than 5000 yeast strains, each lacking a random subset of 16 ABC transporter genes, and tested the ability of each strain to grow when exposed to a panel of 16 different drugs.

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ABC transporters are each capable of ridding cells from a specific subset of harmful molecules. For any given drug, it was therefore expected that knocking out ABC transporters would either do nothing or make the yeast more...
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