Brenda Andrews and Cheryl Arrowsmith of the University of Toronto used functional and chemical genomic approaches to establish a comprehensive description of the biology of the budding yeast Saccharomyces cerevisiae. They used a variety of cutting-edge functional genomics approaches to define gene function and to probe the mechanistic basis for drug action and the characterization of novel, unknown and microbial proteins. They then identified the biochemical function of these proteins and made hypotheses about their cellular role in microbial cells. This new information has greatly extended fundamental knowledge about microbial biology and created an experimental basis for the development of novel anti-microbial drugs and biotechnological processes by Canadian biotech industry.
Katherine Siminovitch of The Lunenfeld-Tanenbaum Research Institute explored gene variants causing and/or modulating a number of common multigenic disorders, including Alzheimer’s, inflammatory bowel disease, cancer (breast, endometrial, prostate, ovarian, melanoma) and osteoporosis. In addition to knowledge relevant to the diagnosis and treatment of specific diseases, this program has provided new information and methods to improve technical platforms for genotyping, gene expression profiling and the computational management and statistical analyses of clinical and genetic datasets. Such tools are key to the exploitation of the human genome sequence for the purposes of disease gene discovery and, ultimately, for translation of genomic information to clinical and therapeutic applications.
One of the most important groups of bacteria in the world is also one of the least known by many people—microbes that cause the formation of nodules on the roots of many plants. Inside these nodules specialized bacteria convert atmospheric nitrogen into a chemically useful form, which is essential for plant growth and thus ultimately for life on Earth. Using complex genetic methods, Turlough Finan and Brian Golding of McMaster University created a body of knowledge about S. meliloti – a bacterium which fixes nitrogen in the roots of plants, an essential process for plant growth- by using genomic methods to study how its genes direct nitrogen fixation and other important biochemical reactions. This deeper understanding of S. meliloti growth will lead to better and more environmentally friendly methods of nitrogen fixation for the food and agricultural industries in Canada and the world.
Type 1 Diabetes (T1D) is a complex, autoimmune-mediated disease caused by multiple genetic risk factors and currently unknown environmental factors. Canada has the third highest rate of T1D in the world, costing ~$13 billion annually in T1D-related health care, disability, lost work, and premature deaths. Jayne Danska, of SickKids, led a project to identify key genes conferring T1D risk to humans, and gain insight into the biological pathways that confer early stages in disease progression. Progress made under this project was essential to the formation of an expanded $15M, 4 year T1D research effort that recently began funding with support from Genome Canada/Ontario Genomics Institute, the National Institutes of Health, Celera Diagnostics, Inc., and several European funding agencies.
In the current competitive world, agricultural and forestry industries must rely on genetic improvements to important kinds of plants to maintain an international lead. Arabidopsis is an organism which has been studied, genetically, and has many similarities to important crops such as rice, wheat, corn and canola. John Coleman, Nick Provart, and Peter McCourt of the University of Toronto created a worldwide resource for plant genomic research, setting up some of the basic tools that will enable genetic research on Arabidopsis. This will lead to a deep understanding of many aspects of plant growth that will be important for genetic improvements such as salt- and drought-tolerance, pest resistance, increased productivity, and enhanced protein content. They have made these three experimental tools available to plant researchers all over the world, speeding up research and putting Canada on the map for plant researchers everywhere to appreciate.
DNA and its close relative, RNA, carry the code of life in all of nature’s creatures, and their study enables scientists to learn a great deal about human genetic diseases, and disease-causing viruses and micro-organisms. For all of these studies, scientists need to measure very accurately the amount of nucleic acids in a sample, however, previous methods were defective, with major limitations. The goal of Alex MacKenzie, Paul Piunno and Ulrich Krull’s project was to develop a new kind of nucleic acid sensor (a “biosensor”) that is reusable, sturdy, rapid, accurate, selective, sensitive and cheap. The value of this new instrument was demonstrated by evaluating DNA associated with Spinal Muscular Atrophy, a very severe childhood genetic condition.
The Human Genome Project documents the complete DNA sequence, not only of humans, but of over 300 other organisms, with more to come. The next step is to turn this wealth of information into useful knowledge so that it can be applied to medical and biological advances. This kind of research is called “functional genomics” and it seeks to learn how genetic information coded in DNA directs all the workings of a living organism.
Jim Woodgett, of Mount Sinai Hospital, developed new techniques and measuring instruments for functional genomics, and applied them to basic research and clinical studies. The work developed better array design through the use of computational algorithms, more efficient storage and recovery of data from DNA microarray experiments, and better ways to compare our data with other researchers in the world. Additionally, one of the team’s robot designs is now sold commercially.
Peter Singer and Abdallah Daar, of the University of Toronto examined the ethical, environmental, legal and social implications of advances in biotechnology and genomics. They studied ethical questions faced by biotechnology companies and how they deal with them with the aim of encouraging companies to adopt suitable ethical policies. They also led in writing a proposal for the Canadian government to guide its strategy for development of genomics and biotechnology, and were a major contributor to the Genomics and Nanotechnology Working Group of the United Nations Science and Technology Task Force; this report was distributed all over the world.
Janet Rossant of The Hospital for Sick Children and Brenda Andrews, Jack Greenblatt, Andrew Spence of the University of Toronto led the Functional Annotation of the Mouse Genome project, which generated mouse models for human conditions such as kidney disease and osteoporosis, developed new tools to help characterize Canada’s mutant mice, and established new mouse cell lines that are in high demand by academic and industrial investigators worldwide. Their approaches now promise to provide major insights into human pathologies and highlight effective targets for therapeutic development.
While genomics/biotechnology can help address health challenges currently facing both the developed and developing world, there are growing knowledge gaps in the global community. The Canadian Program on Genomics and Global Health (CPGGH) was developed to help close some of those gaps. Peter Singer and Abdallah Daar’s program on genomics and global health has influenced federal and foreign policy decisions, increased the opportunity for Canadian genomics and biotechnology companies to internationalize in emerging and developing markets, and increased public awareness on the uses and misuses of genomics to address global health challenges. The project also published 60 papers, 22 books and monographs, 17 book chapters and contributions to collective work, and 166 invited presentations