Research Institute in Oncology and Hematology


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Research Institute in Oncology and Hematology
675 McDermot Ave
Winnipeg, Manitoba, Canada R3E 0V9
Phone: 204-787-2137
Fax: 204-787-2190
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Mouse Functional Genomics Centre

Introduction

The Research Institute in Oncology and Hematology is an international leader and major innovator in Functional and Cancer Genomics. With the recent completion of the human genome, the next major hurdle for the Human Genome Project will be to discover what these genes do. Given that we know there are as many as 5,000 human diseases with a genetic determinant, this new field of functional genomics will have a tremendous impact on health care and prevention. Our disease focus is clearly cancer.
The Research Institute in Oncology and Hematology has been leading the field by establishing the first Mammalian Functional Genomics Centre in Canada. The approach combines the wealth of sequence information available from the Genome Project with powerful cutting-edge genetic technologies in mice. The result is a national resource that will provide over 40,000 genetic "knock-out" mutations in mouse stem cells. Each mouse stem cell has a single gene missing as well as the capacity to actually form an intact mouse. Because mice are genetically 95% similar to humans they provide an ideal experimental model system for human disease. The mice that the Functional Genomics Centre can generate are 100% genetically identical to their mouse littermates - except for the one missing gene of interest. As such, any deficiency, defect or disease that might appear in the mutant mouse will be directly linked to the function of the single gene in question. The importance of discovering gene function in the context of the whole animal cannot be said too strongly for this is the context of disease itself - it cannot be modeled or predicted any other way. In this regard, the mutant mice themselves will not only provide insights into the genetic basis for the development of human diseases, but will also provide an experimental model to study the treatment and potential cures for human disease. On a practical note, development of the mice themselves initiates a chain of propriety that would be considered in all future discoveries as a result of the mice

Programs

The RIOH Mammalian Functional Genomics Centre, directed by Dr. Geoff Hicks, continues to provide international leadership in what is currently being dubbed as the next Human Genome Project. The centre has established a high throughput technology for the genome-wide creation of a library of transgenic knockout mice. Knockout mice are considered to be one of the most powerful approaches to discovering gene function and can be used to reveal how disease-related genes, like cancer-causing genes, work. It's a critical first piece of the puzzle towards understanding what causes diseases in humans, and more importantly, how medicine can intervene or prevent the ensuing disease processes.
Dr. Hicks' Knockout program aims to generate a knockout mouse for every single gene in the genome. The mice are freely available to the scientific community at large, thereby providing this powerful tool directly to the hands of every disease expert in the world. The impact of this project is considered to be so important that it has led to a worldwide effort to achieve the mouse resource as soon as possible, the International Mouse Knockout Project. Major funding for the centre was recently renewed by CIHR will provide the centre with an additional $2.0 M in operating funds over four years. Most notably, Dr. Hicks is also the lead investigator for a $23 Million Genome Canada application that will provide funding to support the Canadian initiatives related to the Intertional Knockout Mouse Project. This Canadian led initiative is now recognized as one of the cornerstone international programs in Mammalian Functional Genomics.

In The Future

The next step in the overall strategy is to generate and functionally analyze knockout mice. Dr. Hicks has established a leading edge Transgenics program located in both the MFGC and a state of the art transgenic mouse barrier facility located in the Faculty of Medicine's Brodie Building. The later, known as the University of Manitoba Genetic Modeling of Disease Centre (GMC, Dr. Geoff Hicks is the Scientific Director), provides both the faculty and the province with a full suite of transgenic services. GMC services are provided in a cost-recovery fee basis to ensure all members of the Institute and Faculty can have ready access to this powerful approach to study disease genes and mouse models of human disease. Services provided include the generation of mice from ES cells, cryopreservation of ES cells, germ cells, and the rederivation of mouse models brought into the faculty from around the world.
Dr. Hicks has also established the Canadian Mouse Consortium . The CMC integrates all the major mouse centres across Canada and will provide essential transgenic services to any Canadian disease-focused research program. Finally, the MFGC also provides additional key service platforms to the Institute. These include a high throughput DNA sequencing facility, a flowcytometry facility and a long term cryogenic cell storage facility. Once again, these are provided to RIOH members as cost-recovery services that significantly reduce the operating costs of RIOH research programs. As these services are used by all member of RIOH, the Institute provides support for the on-going maintenance of the key instruments.

In summary, the RIOH Mammalian Functional Genomics Centre is currently a leader in the field and creating an invaluable genetic resource. The Centre's goal is to develop this resource to its fullest potential by focusing its efforts on the functional analysis of genes that are known, or suspected to be, determinants of cancer and human disease. We are hopeful that the true impact of the project will be to discover experimental mouse models of human disease that would greatly accelerate the development of pharmaceutical therapies, or even cures, for human cancer.



RIOH gratefully acknowledges the generous support of



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