2 Minutes with Brendan Frey and Benjamin Blencowe
January 13, 2014
As elated as scientists were with the sequencing of the human genome in 2003, they soon recognized that it was only one important piece of a much more complex puzzle. Expecting to find at least 100,000 genes, they instead found just 22,000—too few to account for the remarkable complexity of human cells. What else was happening?
Brendan Frey and Benjamin Blencowe of the University of Toronto set out to solve the mystery of how humans can do so much with so few genes. What they found has revolutionized our understanding of how our bodies work and earned them the 2011 NSERC John C. Polanyi Award.
So everybody knows that genes are important. Everybody knows that the genes stored in our DNA are what makes us who we are. But the really interesting question is how does this work? So scientists used to think that each gene did one thing and one thing only. But in the past seven years or so, scientists have come to realize that each of our genes can actually do many different things, depending on circumstances. And, in fact, over 90 percent of our genes do this. And so, together, what we did is we assembled what we call a splicing code, which is a set of instructions that are embedded in DNA that control this process that enables individual genes to do many different things in different cells.
A good analogy for RNA splicing is film editing, where you have raw footage that has to be cut and ... cut and spliced together to generate a coherent message and film. And RNA splicing is similar in that our genetic messages contain important pieces of information in segments that have to be joined together in a very precise fashion. And this occurs by a complex cellular machinery that does the editing and cutting, the cutting and the joining process.
A nice example is the set of three genes that control how you learn. These are called neurexin genes, and there's three genes and yet over 20,000 different effects can be constructed from these three genes using this process of splicing. Now there's two kinds of expertise that are involved in this discovery. The first one came from Ben's lab where they were able to measure what different genes were doing in different cell types such as brain tissue, heart tissue and other kinds of tissues. And his group was able to do that for thousands of examples. The second contribution came from my group, which consists of expertise in putting together codes, if you like, or inferring codes based on large-scale data sets. So my group developed a mathematical and computational framework that allows to infer this instruction set, if you like, that resides in DNA and controls how these genes act differently in different cell types.
So one application of the type of research we're doing is to understand the controls by which cells in the body — somatic cells — can be reprogrammed to generate stem cells, and that's a very promising area for future therapeutic applications.