Donnelly Centre for Cellular and Biomolecular Research
Other U of T Affiliations: Computer Science, Molecular Genetics
Samuel Lunenfeld Research Institute, Mt. Sinai Hospital
Where I Am From: Salt Lake City, Utah
Where I’ve Worked and Studied:
Harvard Medical School
Asst and Assoc. Professor, 2000 - 2011
Millennium Pharmaceuticals (with Dr. Chris Sander)
Scientist, 1998 - 2000
PhD in Biophysics, 1998 (with Dr. George Church)
Staff Scientist, 1990 - 1992
University of California, Berkeley
BA in Physics and Molecular & Cell Biology, 1990
My Story: Members of the next human generation will routinely read their own genomes to explore one aspect of their individuality. Humanity now has the power to read the basic DNA blueprint for any species it cares to study. Unfortunately, a genome sequence is like an encyclopedia written in an alien language, and our ability to reveal DNA sequence has greatly outpaced our ability to understand it. Only a small fraction of genes are thoroughly understood, and nearly half of our genes are a complete mystery.
Progress continues to be made through the painstaking study of model organisms— cultured human cells, worms, fruit flies, mice and baker’s yeast. The success of this strategy is due to the happy accident that all of these systems share a common ancestor. New technology is needed to accelerate our study of genes, their function, and how these functions interact to form living systems.
My research team is developing technology to accelerate discovery of gene functions, the pathways they encode, and the relationships of these genes and pathways to human disease. We are exploring new ways to adapt technology for sequencing DNA to increase the scale of functional assays. For example, in a collaboration with Brenda Andrews and Charlie Boone, we are harnessing sequencing technology to systematically map the effects of multiple genetic changes in combination across multiple environments. In a collaboration with Marc Vidal, we are applying deep sequencing technology to efficiently measure interactions between proteins, and to identify the effects of viral proteins or oncogenic kinases on the human interaction network. At the same time, we are developing new computational methods for integrating the results of diverse large-scale experiments. With Ben Blencowe and Dan Durocher, we are performing human genome sequence analysis aimed at understanding the response to DNA damage in yeast and human cells. Working with genome-wide associations of disease within the Framingham Heart Study and other cohorts, we are developing computational approaches that combine diverse large-scale datasets to prioritize candidate disease genes to better allocate limited scientific resources.
Past work has included the demonstration that DNA sequence elements regulating gene expression can be automatically discovered via large-scale expression analysis. We have also developed automated procedures to identify chemical substructures that are more likely to be bioactive. More recently, we have developed experimental methods for introducing human pathways into baker’s yeast, where they can be more efficiently studied.
We continue to focus on developing technology to more efficiently relate genes to the functioning of living systems and human disease.