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University of Toronto professors win John C. Polanyi award

February 27, 2012

Professors Brendan Frey (ECE) & Ben Blencowe (Medicine) recognized for contributions to understanding a gene regulatory code

TORONTO, ON – The ground­break­ing research of two U of T pro­fes­sors has been rec­og­nized with the 2011 NSERC John C. Polanyi Award, which hon­ours an indi­vid­ual or team whose Cana­di­an-based research has led to a recent out­stand­ing advance in the nat­ur­al sci­ences or engi­neer­ing.

Pro­fes­sor Bren­dan Frey of The Edward S. Rogers Sr. Depart­ment of Elec­tri­cal & Com­put­er Engi­neer­ing and Pro­fes­sor Ben­jamin Blencowe of the Ter­rence Don­nel­ly Cen­tre for Cel­lu­lar and Bio­mol­e­c­u­lar Research were pre­sent­ed with the award by the Gov­er­nor Gen­er­al of Cana­da, the Right Hon­ourable David John­ston, at a cer­e­mo­ny in Ottawa’s Rideau Hall.

Pro­fes­sors Frey and Blencowe were rec­og­nized for their research that cracked the codes hid­den in DNA that allows a rel­a­tive­ly small num­ber of genes to be trans­formed into hun­dreds of thou­sands of vari­a­tions.  

After the ini­tial excite­ment sur­round­ing the sequenc­ing of the human genome near­ly 10 years ago, sci­en­tists quick­ly real­ized that unlock­ing its poten­tial would be far more com­plex than orig­i­nal­ly thought. It was assumed that humans must have more than 100,000 genes, but only 22,000 were found, rough­ly the same num­ber as the nema­tode worm. Clear­ly, humans can do much more than worms, but how?

Pro­fes­sors Frey and Blencowe, along with their research team includ­ing Yoseph Barash and John Calar­co, were able to deci­pher a genet­ic code embed­ded in vast expans­es of DNA that cells use to con­trol the rearrange­ment of gene parts in a process called “splic­ing.” It turns out that through alter­na­tive splic­ing, a sin­gle gene may do dozens or event thou­sands of dif­fer­ent things, such as con­trol when and where neur­al con­nec­tions are made in the brain for learn­ing. So far, the team has dis­cov­ered hun­dreds of bio­log­i­cal rules embed­ded in DNA that com­prise the ‘splic­ing code,’ as well as hun­dreds of exam­ples of splic­ing that are spe­cif­ic to brain, mus­cle, diges­tive and embry­on­ic tis­sues.

This break­through was enabled by tak­ing a rad­i­cal­ly new approach to this research. Pre­vi­ous­ly, sci­en­tists stud­ied one splic­ing code rule at a time and tried to deter­mine its role. Since the num­ber of pos­si­ble com­bi­na­tions of rules is larg­er than the num­ber of atoms in the uni­verse, this approach was impos­si­bly slow. Instead, Pro­fes­sors Frey and Blencowe devel­oped a machine learn­ing frame­work that can ana­lyze all the rules at the same time by mak­ing use of data for thou­sands of genes, which the researchers gen­er­at­ed using cus­tom gene chips.

“This enabled us to com­bine all the pre­vi­ous dis­cov­er­ies in the field, incor­po­rate vast amounts of new data from Pro­fes­sor Blencowe’s lab, and rapid­ly assem­ble a com­pre­hen­sive splic­ing code,” said Pro­fes­sor Frey, who is the Cana­da Research Chair in Infor­ma­tion Pro­cess­ing and Machine Learn­ing. He is cross-appoint­ed to the Don­nel­ly Cen­tre and the Depart­ment of Com­put­er Sci­ence.

“Rules pro­vid­ed by the splic­ing code are pro­vid­ing us with a fas­ci­nat­ing new per­spec­tive on how genes are reg­u­lat­ed, and this is open­ing the door to new avenues of research,” said Pro­fes­sor Blencowe, who is also appoint­ed to the Depart­ment of Mol­e­c­u­lar Genet­ics.

One of the ben­e­fits of the splic­ing code is that it can explain how DNA muta­tions, which dis­rupt the nor­mal set of rules, lead to changes in a gene that can result in dis­ease. In new research, Pro­fes­sor Frey and his team are using the splic­ing code to under­stand how muta­tions in a gene cause spinal mus­cu­lar atro­phy, a lead­ing cause of infant mor­tal­i­ty, and to pre­dict which of many poten­tial bio­mol­e­c­u­lar ther­a­pies are able to cor­rect the prob­lem. Pro­fes­sor Blencowe and his col­leagues are using the code to study the mol­e­c­u­lar basis of bio­log­i­cal dif­fer­ences between species and to dis­cov­er reg­u­la­to­ry mech­a­nisms that can be manip­u­lat­ed to improve the gen­er­a­tion of stem cells for research and ther­a­peu­tic appli­ca­tions.

An inter­view with Profs. Frey and Blencowe can be viewed here:


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