ARCHIVED - National Research Council Canada

1. Name of Horizontal Initiative: Genomics R&D Initiative

2. Name of Lead Department: National Research Council Canada

3. Lead Department Program Activity: Research and Development

4. Start Date of Horizontal Initiative: April 1999

5. End Date of Horizontal Initiative: March 2011

6. Total Federal Funding Allocation (start to end date): $234.1 M

7. Description of the Horizontal Initiative (including funding agreement): The Genomics R&D Initiative was established to build and maintain capacity inside government departments to do genomics research.  As an enabling technology, genomics provides powerful tools, precise information to support operational mandates and upon which policy and regulatory decisions can be based.  Federal science-based departments and agencies (see part 10 below for listing) interact with partners, stakeholders and clients and link these enabling tools and technologies to value-added applications that enable Canada to respond to national priorities, deliver on government mandates and support the development of wealth for Canadians.

These applications range from international requirements for genomics enabled testing to support access of exported products;  interpreting and assessing genomics information submitted with product information for regulatory oversight; the development of assays and products using genomics approaches for enhancing Canadian’s lives, the environment and sustainability of human activities; socio-economic and ethical considerations related to the use and integration of genomics in health care, environmental sustainability activities and consumer and industrial products and applications; as well as facilitating Canadians’ access to accurate and understandable information concerning genome sciences.

8. Shared Outcome(s): Enhanced quality of life for Canadians in terms of health, safety, environment and social and economic development by building and maintaining genomics research capacity in support of key federal public policy objectives; in particular: a) to strengthen innovation and ensure sustainability for the benefit of all Canadians by focusing research in strategic areas of national interest from an economic and social perspective (i.e. health, environment, natural resources and energy, safety and security); b) to promote global competitiveness and expand Canada’s international influence by increasing commercialization outcomes of research activities and by improving regulatory efficiency and effectiveness; c) to grow economic opportunities through R&D by building collaborations that involve business, academia and public sectors, in Canada and internationally.

9. Governance Structure:: To ensure value for money, the Genomics R&D Initiative established a governance framework to strengthen accountability and to ensure investments deliver on making a difference in the lives of Canadians.  An interdepartmental Genomics R&D ADM Coordinating Committee was established to oversee the collective management and coordination of the Initiative.  The Committee ensures that effective priority setting mechanisms are established within departments and that investments are focused and strategic – targeting more basic and applied research in areas of strength and opportunity.

The Committee also ensures that common management principles are implemented and horizontal collaborations between organizations are pursued wherever relevant and possible.  The Committee includes members from each of the organizations receiving funding, as well as a representative from Industry Canada.

10. Federal Partners

11. Federal Partner Program Activity

12. Names of Programs for Federal Partners

13. Total Allocation (from start to end date) in $ millions

14. Planned Spending for 2007-08 in $ millions

15. Actual Spending for 2007-08 in $ millions

16. Expected Results for 2007-08

17. Results Achieved in 2007-08

Agriculture and Agri-Food Canada (AAFC)

Innovation and Renewal

Canadian Crop Genomics Initiative

see below

see below

Fisheries and Oceans Canada (DFO)

Aquaculture

Aquatic Biotechnology and Genomics R&D

see below

see below

Environment Canada (EC)

Canadians Adopt Sustainable Consumption and Production Approaches

Strategic Applications of Genomics in the Environment

see below

see below

Health Canada (HC)

Health Products

HC/PHAC Genomics Initiative

see below

see below

National Research Council (NRC)

Research and Development

Genomics and Health Initiative

see below

see below

Natural Resources Canada (NRCan)

Natural Resource and Landmass Knowledge for Canadians

NRCan-CFS Genomics R&D Initiative

see below

see below

Canadian Institutes for Health Research (CIHR)

N/A – one time allocation in 1999-00 to assist in creation of Genome Canada Secretariat

N/A

N/A

N/A

18. Comments on Variances: N/A

19. Results to be Achieved by Non-federal Partners (if applicable): N/A

20. Contact Information:
Gary Fudge, P. Eng.
Director, Life Sciences Horizontal Initiatives
National Research Council
613-949-0542

1. Commercially relevant advances in areas of genomics R&D related to human health (e.g., genetic testing, diagnostics, microbial genomic applications, treating and preventing human diseases such as cancer and cardiovascular disease and pathogen detection).

1.1 Researchers discovered a new family of antibodies that can play a role in preventing tumour invasion by blocking the function of secreted Clusterin, a glycoprotein associated with human cancers that play a role in cell survival or death.  By inhibiting gene function in cancer cells, it is possible to enhance the effects and efficiency of cell reaction and sensitivity to chemotherapy and other drug mediated therapeutics.  A Canadian biotech company, Alethia Biotherapeutics, entered into a licensing agreement with NRC in 2007-08 for the worldwide therapeutic and diagnostic rights to Clusterin-specific antibodies.

1.2 NRC is developing portable and efficient “all-in-one” diagnostic devices to detect human pathogens.  The objective is to create low-cost diagnostic tools that can be produced industrially for commercial applications that will rapidly identify human pathogens and provide instant read-outs eliminating conventional lengthy lab procedures.  In a first step towards this goal, in 2007-08 researchers developed a ‘personal microarray spotter’ – a powerful miniature device used to spot and analyze many protein samples simultaneously.  With further development, personal microarray spotters may revolutionize genomic/proteomic research in the laboratory and play a larger role in how researchers and clinicians understand, diagnose and treat a vast array of diseases or pathogens - from pesky allergens to pathogens such as Salmonella and E-Coli.

2. Improvements in crop value in cereals, soybean and canola through quality improvements in areas related to plant adaptation to biotic and abiotic stresses (e.g., resistance to disease, tolerance to drought and cold), as well as seed development and metabolism (e.g., related to oil content for biofuels and nutraceutical applications).

2.1 A functional analysis of Brassica (e.g., canola) seed development and metabolic processes was undertaken to improve Brassica seed quality traits.  NRC researchers discovered a gene that can boost productivity and resilience of canola; DNA sequences suggest that the gene, which produces a hydroxysteroid dehydrogenase (HSD) protein, is involved in steroid metabolism and has a profound impact plant growth.  Researchers over-expressed the gene to create "transgenic" plants that produce higher levels of the HSD protein than typically found in normal plants.  The experiment resulted in taller, stronger and more durable plants with increased seed production and an average oil yield that exceeded regular control plants by roughly 23%.  This has the potential to help Canadian canola growers produce more oil for food applications, as well as increase oil production to meet the growing demand for biodiesel fuel.

2.2 Wheat is the largest crop in Canada with approximately 9 million hectares.  Leaf rust, caused by Puccinia triticina, results in yield losses of 5-20% annually and is the most common disease of wheat worldwide.  AAFC has an outstanding reputation as a world leader on the genetic control of leaf rust with 30 of the 59 leaf rust resistance genes discovered by AAFC researchers.  To analyze genetically avirulence P. triticina mapping populations, linkage groups containing avirulence genes and molecular markers were developed by AAFC CCGI researchers.  During 2007, simple sequence repeat (SSR) markers were incorporated into these linkage maps.  The process of somatic fusion in P. triticina was also investigated for the first time using a combination of bright field and flourescence microscopy.  This pioneering work is helping to explain how the important process of asexual recombination physically takes place.  The P. triticina population in Canada during 2007 and in previous years was assayed for virulence and the recently developed SSR markers to determine the relationships among the virulence phenotypes and track the development and origin of new and emerging races.  These data will help to explain the population structure of this important wheat pathogen and give clues to the evolution of the various North American virulence phenotypes.

2.3 In 2007-08, AAFC researchers identified a key gene, Lhk1 that enables legumes to host nitrogen-fixing bacteria.  Using this discovery AAFC researchers plan to develop a way to transfer nitrogen-fixing ability to non-legume crops.  This breakthrough could lead to the development of ecological and cost effective alternatives to certain industrial fertilizers, which could bring enormous environmental and financial benefits to Canada.  Nitrogen makes up more than 80% of the earth's atmosphere and is essential to the growth of all living organisms.  However, atmospheric nitrogen cannot be directly accessed by most plants or animals until it is incorporated into organic compounds by biological nitrogen fixation or other natural processes.  As a result, today's farming practices require the annual application of approximately 90 million tons of nitrogen based fertilizer to agricultural land.  Although inorganic fertilizers provide crops with essential nutrients, such practices come at an enormous cost, primarily due to the immense amount of energy required for the production of fertilizers and their propensity to run off, which contributes to pollution of the environment.  Biological nitrogen fixation provides more than twice the amount of industrially produced nitrogen to natural and agricultural ecosystems in a manner that is both sustainable and environmentally friendly.  If the ability to host nitrogen-fixing bacteria could be extended to even one lucrative crop, such as corn or rice, the results would constitute a second 'green revolution' with clear benefits to producers and the environment.

2.4 The soilborne fungus Sclerotinia sclerotiorum causes white mould on a broad range of crops, including soybean and canola.  In order to aid in the identification of genes that are critical for pathogenicity and fungal survival, researchers at AAFC developed an efficient method for Agrobacterium tumefaciens-mediated gene disruption in S. sclerotiorum.  It is anticipated that the application of this tool to molecular genetic studies of S. sclerotiorum will contribute to an improved understanding of the molecular factors that control pathogenesis and survival structure development and could be targeted for disease management.

2.5 The soil borne pathogen Phytophthora sojae causes root rot and damping off of soybean.  Race-cultivar compatibility between the pathogen and its host is controlled by discrete genes.  Thus, P. sojae avirulence (Avr) genes can restrict the pathogen and determine which cultivars of soybean are resistant or susceptible to disease.  In 2007-08 AAFC researchers identified at least three different P. sojae Avr genes; Avr1a, Avr3a  and Avr3c.  The discovery of Avr genes will lead to a more rational approach to breeding, diagnostics and cultivar deployment and help in the control of P. sojae in the field.  It will also lead to a better mechanistic understanding of disease and how it may be managed.

2.6 Seed is perhaps the most important end product of plant agriculture.  Improvement of seed quality requires thorough understanding of how seeds develop, particularly the seed maturation phase.  Seed storage proteins are hall markers of seed maturation.  AAFC’s efforts have been focused on identification of genetic repressors of storage protein genes.  Researchers at AAFC identified six genes as repressors of seed storage protein genes in vegetative organs.  These works provide new insight into the control of seed maturation genes.  Knowledge gained from this work will contribute to the manipulation of seed quality traits and will be useful for developing seeds as a molecular farming system for producing proteins of high value.

2.7 Fusarium graminearum, a fungal plant pathogen that causes head blight of wheat and barley and ear rot of maize, not only reduces grain yield and quality, but also contaminates the grain with toxic metabolites that are a threat to human and animal health.  Efforts in 2007-08 by AAFC researchers resulted in the development of a large collection of genes expressed by Fusarium graminearum in a range of growth conditions and especially during host invasion.  One of the unexpected and striking findings is the presence within the genome of highly variable and gene-rich regions harbouring genes potentially associated with pathogenicity.

3. Sustainable management of aquatic resources through the use of genomics tools to: manage fishery openings; generate increased understanding of population genetics and structure; further understanding of behavioural, physiological and immunological responses to the environment; and through the management of aquatic animal diseases.

3.1 To better manage fishery openings and understand the changing behaviour of fish stocks due to climate change and pollution, genomics tools including gene expression profiling are used by DFO to determine physiological changes along the migration route to natal streams that is associated with early entry, a behavioural shift in late run Fraser River sockeye salmon.  Results to date indicate that osmoregulatory readiness was not used to cue the timing of river entry but may be important to successful migration within the river.  It has been shown that there is a strong physiological association of gill expression with fate in the river.  As well, biomarkers were identified that are associated with gross somatic energy reserves, maturation processes, navigation strategies and cueing systems, osmoregulatory preparedness and temperature response.  A tremendous breadth of new knowledge on salmon migration physiology was gained.  Predictive biomarkers are being developed for monitoring relevant genes to enable pre-season prediction of migration behaviour and fish survival for fishery managers.

3.2 Research to efficiently and effectively identify genetic differences between two morphologically similar mussel species Mytilus edulis and M. trossulus and determine the relative distribution of these species within Nova Scotia is being undertaken by DFO, with support from industry and the province of Nova Scotia.  Genetic markers have been tested and optimized for higher throughput lower cost species identification in mussels.  Results in 2007-08 indicate that there are very different species compositions at locations that are adjacent to each other and have identified sites suitable for mussel seed collection for use in aquaculture in Nova Scotia, thereby helping to overcome the impacts from the restriction of movement of species from areas with aquatic invasive species.

3.3 Infectious diseases present a significant economic burden to finfish aquaculture industries and there is concern that diseases may also negatively impact wild fish populations.  Genomic approaches are being used by DFO to better understand the diversity of viral hemorrhagic septicemia virus (VHSV) and to relate this diversity to host responses to infection, disease development and recovery or resistance to, clinical disease.  Multiple isolations of VHSV from marine waters off the coast of New Brunswick, Nova Scotia and British Columbia have been genetically analyzed and this information has been used to develop a database for use in rapid identification and analysis of isolates. Recently, VHSV has been detected in the Great Lakes region; this strain is most closely related to isolates from New Brunswick and Nova Scotia, suggesting introduction from an eastern reservoir.  Characterization of VHSV types has yielded information that is necessary for policy development and regulation to help prevent the spread of new virus types in to an area.  Research is continuing to better understand the genetic basis of virulence among strains identified in Canadian waters.

3.4 In 2007-08, novel vaccine types continued to be explored by DFO.  Three different approaches are being targeted and based on the indirect but more powerful stimulation of the immune system via the activation of antigen presenting cells (APC) through heat-shock proteins (HSP)-antigen complexes.  Atlantic cod and the pathogen nodavirus is the model for several reasons.  Cod farming is nearing the commercial stage in eastern Canada and is a promising substitute to an almost inexistent fishery.  Nodavirus is a serious pathogen of concern for cod farming, with several outbreaks reported in juvenile fish in the past 4 years.  The immune system of Atlantic cod seem to possess unique characteristics, although cods can be immunized, a specific immunoglobulin response cannot be detected, so it is believed that cellular and non-specific immune responses are likely to be more important for this species.  HSP-peptide vaccines are considered excellent candidates since discovering that HSP-peptide complexes are potent stimulators of a variety of immune responses, but to our knowledge, assays for fish vaccines have not been performed yet.

4. Positioning the Canadian regulatory system for health to enable innovation while minimizing the risks to Canadians through a focused genomics R&D program aimed at strengthening capacity in priority areas such as genetic information, biotechnology products, human genomics and microbial genomics, on human, animal and environmental health.

4.1 In 2007-08, genomics research within the Health Portfolio (HC and PHAC) continued to focus on the development and application of "omics" tools to reduce exposure to foodborne pathogens.  Current research is providing insight into the cellular changes associated with dietary exposure to different classes of naturally occurring carcinogens that contaminate foods.  The results of this research will further our understanding of events involved in tumour induction and will provide a mechanistic framework for regulatory decision-making.

4.2 Health Portfolio projects continued to build on existing research initiative focusing on the Evaluation of Environmental Toxicogenomics.  Toxicogenomics is the application of genetic methods to the study of toxicology.  The results from a project in 2007-08 have provided insights specific to gene expression changes, driven by exposure to toxic substances.  These gene expression changes are critical pieces of knowledge to acquire and apply to gene expression profiling studies, for eventual application to regulatory decision making.  Another research project was successful in characterizing cardio-pulmonary responses to cigarette smoke in the laboratory, which resulted in the identification of potential candidate biomarkers to predict the health outcome of cigarette smoking.

4.3 In 2007-08 research continued in the generation of pharmacogenomic and biotherapeutics data, specifically facilitating new knowledge of the potential health risks related to the toxicogenomics and proteomics of biotherapeutics.  Health Canada increasingly recognizes the significant role that such data will play in future drug submissions and that this data holds the possibility to influence human drug approvals in Canada.  Results revealed differential patterns of host responses following various regimes of biotherapies, which could help future exploratory studies aimed at identification of specific biomarkers suggestive of adverse reactions associated with biotherapeutics.  This increased understanding helps position HC to meet the regulatory challenges of analyzing such data in order to issue sound, science-based decisions.

4.4 Federal scientists, together with local, national and international collaborators, continued their focus on genomics, including a wide range of public health genomics research.  Research completed in 2007-08 at the Public Health Agency of Canada led to the development of a large-scale RNA interference library targeting most of the human genome for its ability to identify host cellular genes that have a role in supporting virus and transmissible spongiform encephalopathy (prion) pathogenesis.  Prion diseases of humans include classic Creutzfeldt-Jakob disease. Further funding from national and international partners and commercial partners was secured to continue towards the development of a commercially available pre-clinical test.  These results are likely to prove effective in the rapid detection, surveillance and risk assessment of prion contamination and other subtypes of organisms with the greatest public health risk.

5. Increased knowledge for forest generation and protection methods and for addressing environmental impact considerations, through a focused genomics R&D effort on species and traits that are of economic importance to Canada.

5.1 A genome scan by NRCan scientists in 2007-08, revealed that gene islands underlying growth and adaptation in spruce allowed the rapid selection of candidate gene to support linkage and association mapping experiments.  Budset related genes were the target of newly synthesized libraries and ongoing expression profiling experiments.  The NRCan Canadian Forest Service (CFS) developed a Single Nucleotide Polymorphism discovery Laboratory Information Management System and Database to track family members, expression data, PCR primers, amplification success and re-sequencing efforts.  A white spruce consensus genetic map was assembled and major quantitative trait loci were identified for the control of bud set and annual height increment.  In collaboration with Arborea II, a large-scale forest genomics project funded by Genome Canada (led from U. Laval); several hundred candidate genes have been identified for wood formation in white spruce.  In collaboration with Treenomix, the other large-scale forest genomics project funded by Genome Canada (led from UBC); the CFS was able to localize the expression and induction profile of defence related genes, leading to improved understanding of insect resistance mechanisms in spruce and poplar.  Recent progress in 2007-08 also demonstrated that a previously identified candidate gene in white pine is an important factor for plant defence response against pathogen invasion as well as for plant development.  The CFS identified Douglas-fir disease resistance genes.

5.2 In 2007-08, the CFS made significant advances in the development of DNA diagnostic and monitoring tools for the early identification and tracking of pathogens.  The Canadian Food Inspection Agency (CFIA) and the United States Department of Agriculture Animal and Plant Health Inspection service (USDA-APHIS) have adopted operationally the DNA-based diagnostic assays developed for sudden oak death by the CFS for their survey, certification and quarantine applications.  The CFS is currently generating large databases to identify genes that are involved in important disease processes (pathogenicity, infection, toxin production, host defence compound detoxification and host recognition) for use in diagnostic tools.

5.3 The interaction between viruses and the natural host is a culmination of co-evolutionary events that lead to successful viral infection and the survival of the host.  CFS work in this area in 2007-08 has demonstrated the dynamic relationship existing in any given populations of insect viruses and their host.  Microarray studies have shown precise gene expression profiles following infection.  The CFS also found through these studies that certain viruses produce proteins that have a down regulating effect on host genes involved in the immunity of larvae to parasites.  This is a promising avenue to generate effective biological control agents against Lepidoptera and pest beetles such as the mountain pine beetle.  The CFS fully sequenced and annotated the genome of the whitemarked tussock moth nucleopolyhedrovirus.  The sequencing of viral genomes has resulted in a proposal for a new classification of the family Baculoviridae and CFS work was a significant contribution to the state of the art understanding of the evolution of baculoviruses and their adaptation to their insect hosts.  The CFS developed molecular tools for the detection of microsporidia, a group of unicellular insect pathogens, in outbreak populations of forest defoliators.  These tools were used to track the prevalence of microsporidia during an outbreak cycle of the jack pine budworm and eastern spruce budworm to elucidate their role in outbreak dynamics and study their transmission in insect populations.

6. Development of genome-science applications to support regulatory and enforcement activities in key areas such as environmental risk assessment and management; enforcement and compliance; pollution detection, monitoring and prevention; conservation biology and wildlife genetics; technology forecasting and assessment; and the responsible and sustainable development and use of bio-based products and industrial processes.

6.1 Environmental genomics-based approaches were used in 2007-08 by EC to:

• Investigate molecular-level effects of environmental contaminants on wild species to improve environmental risk assessment/monitoring;
• Conduct molecular characterization of communities of microbes in contaminated soil so as to enhance bioremediation;
• Detect pathogenic micro-organisms in water and wastewater to assess the quality of water/wastewater and the effectiveness of treatment systems;
• Detect pathogenic micro-organisms in soil in support of regulatory and enforcement needs;
• Improve decision making regarding management and conservation of several species of concern (e.g., polar bears; various bird populations);
• Develop and validate a lobster eco-toxicogenomic array - correlation of gene expression profiles with traditional toxicological end-points for contaminant exposure, histological effects and behavioural changes;
• Determine the environmental impacts of transgenic crops and commercial bacterial consortia to aquatic invertebrates;
• Apply genomics to support the development of Aquatic nanotoxicology issues in fish; validate the gene expression responses in terms of physiological effects at the biochemical and cellular levels;
• Apply genomics to microbial source tracking: Identification of genetic markers specific for animal fecal pollution in aquatic environments;
• Validate genomics tools for the prediction of environmental effects: response of fish to contaminated sediments;
• Investigate environmental effects of genetically modified organisms and biotechnology microbes on functional microbial communities to improve risk assessment/monitoring; and
• Develop and validate sampling methods and molecular analysis techniques for rapid detection of virulent emerging infectious diseases in Canadian native amphibian species for wildlife disease surveillance and for wildlife conservation biology.

6.2 In 2007-08 investments continued in environmental genomics foresight, knowledge development, instrumentation, infrastructure and outreach (e.g., periodic comparative analysis of international environmental genomics activities via bilateral with US EPA).  EC is also working closely with The Organization for Economic Co-operation and Development (OECD) and the International Programme on Chemical Safety (IPCS) of the World Health Organization (WHO) in developing strategies and work-plans on several fronts to lead and co-ordinate international efforts to attempt to see how toxicogenomic methods and approaches might be applied within in a regulatory context.  Strengthening of partnerships and joint-projects between Federal Departments continues (i.e. Environment Canada and Fisheries and Oceans Canada).