The human genome can be thought of as a computer program that controls the generation of biological complexity and the activities within living cells. While the text comprising the genome was revealed 10 years ago when the genome was ‘sequenced’, deciphering the genetic code hidden within the genome has been difficult. Recently, Drs. Frey and Blencowe at the University of Toronto have developed a method that enabled them to identify the instructions comprising a ‘splicing code’ within the genome. This pilot project was successful and led to 1) the development of a $1 million proposal to scale up the approach to fully support medical research, 2) a collaboration between the University of Toronto, Cold Spring Harbor to investigate the causes and therapeutic treatment of spinal muscular atrophy, the leading cause of infant mortality, and 3) the training of graduate students and postdoctoral fellows who are now working to scale up the methodology to support medical research. The exploratory research enabled by this project has opened the door to a new major direction of research in the Canadian genomics community.
Our work in the health sector:
MedSavant
June 5, 2011Using the Ontario Genomic’s SPARK award, Dr Budno and Mr Fiume of the University of Toronto have been developing MedSavant, a high-performance software platform for the analysis of DNA data that helps researchers pinpoint the causes of genetic diseases. The platform serves as a repository and search engine for huge volumes of genomic mutations that are being gathered through genome sequencing. It harnesses the information collected from many patients and studies, and provides a flexible interface for organizing data, performing sophisticated analyses, and generating reports.
Automated pronuclear microinjection
June 5, 2011Pronuclear microinjection is a technique for creating transgenic mice, an important tool in genetics/genomics and developmental biology research. Drs. Yu Sun and Zhe Lu at the University of Toronto are developing key technologies to automate pronuclear microinjection capable of 3D orienting individual mouse embryos, demonstrating feasibility of injection via computer mouse clicking.
The Canadian Pediatric Cancer Genome Consortium
July 1, 2010Cancer is the most common cause of non-accidental death in children from infancy to young adulthood. A group of Canadian researchers and clinicians have joined forces to use one of the most powerful gene sequencing technologies ever developed, to probe the genomes of four of the most challenging childhood cancers known. The ultimate aim of this project is to use the newly discovered genetic information about these cancers to gain insight into targets and new therapies that may be developed. This project also provides the opportunity to study the ethical issues that arise in deciding when and how best to provide the results from genetic studies on childhood cancers back to the patients and their families. This multi-disciplinary, cross-Canada national study will redefine the genetic basis of aggressive childhood cancers, and the results will lead to improved survival and reduced long-term consequences for children with cancer.
Finding of Rare Disease Genes in Canada (FORGE Canada)
July 1, 2010Genetic disorders of children are individually rare but collectively frequent, causing medical problems including birth defects, intellectual disability, and organ failure. Most genes that cause these conditions have not yet been found, mainly because gene-discovery studies are difficult to perform when DNA from only a small number of affected children is available. Recently a new technology (called Next Generation Sequencing) has been developed which allows a person’s entire genetic code to be analyzed within a few days at reasonable cost. Through this national collaboration between Canadian doctors and scientists, many genes responsible for genetic disorders that affect children will be able to be rapidly identified.
Nuclear hormone receptor screening system
June 5, 2010InDanio, an early-stage drug discovery and development company, has developed a novel and unique screening system for the complete human nuclear hormone receptor (NR) family. The company uses fluorescent tags attached to copies of human genes in living zebrafish embryos to identify and localize functioning individual NRs. The screening system can be used to both characterize certain receptors as potential targets for drug discovery, and to identify and refine potential new drugs that target NR proteins.
Predicting age-related macular degeneration
June 5, 2010ArcticDx, Inc, a Toronto-based company, has developed a genetic test, Macula Risk®, to determine one’s inherited risk for age-related macular degeneration (AMD). AMD is the most common form of acquired blindness in the developed world, affecting over 10 percent of individuals. ArcticDx will use an Ontario Genomics’ PBDF investment to undertake studies in support of a planned filing for Food and Drug Administration (FDA) approval for Macula Risk.
In vivo models for human disease & drug discovery
June 5, 2010Identification of the genes associated with human disease is essential to the development of new prognostic, diagnostic, and treatment options. This project, the recipient of a $10.9 million LSARP award, is made up of Canadian and UK scientists who aim to study the developmental problems and diseases that occur in mouse models. Their work will add to the global effort to understand the function of every gene. The knowledge generated and new discoveries made will enable the development of new drugs and new therapies by Canadian researchers in academia and the biopharmaceutical industry.
Targeting pediatric medulloblastoma
June 5, 2010Brain cancer is the leading cause of pediatric cancer deaths. With $4.8 Million from Genome Canada’s LSARP program, Michael Taylor, David Malkin, Marco Marra from the Hospital for Sick Children are studying medulloblastomas, the most common form of childhood brain cancer, to develop markers to more accurately classify tumors for treatment. As they unravel the genetic basis of brain cancer, the research team is also working with families to determine what additional risks they are willing to assume in reducing therapy to improve quality of life. It is anticipated that the results of this research will lead to new ways to treat childhood brain cancers more effectively and to enhance the quality of life of children struck by this devastating disease
Synthetic antibody program
June 5, 2010The Donnelly Centre at the University of Toronto has established the Toronto Recombinant Antibody Centre (TRAC), a state-of-the-art antibody platform that can be applied to the generation of therapeutic grade antibodies against hundreds of antigens in a high-throughput pipeline. In turn, the TRAC has partnered with the Centre for Drug Research and Development (CDRD) to leverage additional expertise in therapeutic antibody development. They have compiled a panel of cancer related proteins that are high-value targets for next-generation cancer therapeutics. In a three-year framework, the team under Sachdev Sidhu and Charles Boone will generate and validate hundreds of antibodies against a host of cancer-associated targets. These antibodies will be powerful tools for discovery research and a significant subset will be candidates for new therapeutic entities.