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A genetic toolbox for tomato flavour differentiation

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Overview

Tomatoes, it is said, are the quintessence of summer in a bite. They are also responsible for more than half a billion dollars in annual farm gate sales and are Canada’s biggest fresh vegetable export. Canadian growers are facing competition due to lower production costs in other regions, leading to difficulties maintaining their market share. Canadian producers need to innovate in order to offer a differentiated product that will give them a competitive edge. Generally, plant breeding programs focus on production traits, such as yield or disease resistance. Vineland Research and Innovation Centre (Vineland) is working with Dr. Charles Goulet of Université Laval to ensure new tomato varieties possess these traits, in addition to something more important to the consumer – flavour. Flavour is a complex trait, reflecting sugar, acid and aroma, as well as texture. Because aroma is defined by more than 30 volatile chemicals and dozens of genes, genomics can greatly facilitate breeding with much greater precision than ever before. This project will use variation in aroma-related genes to develop new tomatoes with differentiated flavour. The resulting plant lines will be used to breed tasty tomatoes at Vineland, and will be made available to other tomato breeders. The first varieties should be commercially available within three years of the project’s completion. The development of locally-adapted, flavourful tomato cultivars will give Canadian greenhouse producers a clear advantage in a competitive consumer market, with total direct economic benefits estimated at more than $30 million per year.

Clinical development and translation of genomics-driven paediatric cancer diagnostics using NanoString

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Overview

Over the past decade, there have been many high-impact, genomics-driven cancer discoveries. The overriding challenge, however, lies in making the transition from the laboratory to the clinic – literally, bench to bedside. Toronto’s SickKids is a leader in the discovery and implementation of clinical diagnostics for children’s health. NanoString Technologies is a leader in providing tools to individual labs to enable laboratory-developed tests. Now, their individual strengths are being brought together to develop additional tools for diagnosing cancer in children that will deliver key information in a targeted, cost-effective and timely way. Led at Sick Kids by Dr. Cynthia Hawkins and Mr. John Racher, in partnership with NanoString Technologies, their initial work will focus on low-grade glioma (brain tumours), leukemia and soft-tissue sarcoma, for which no comprehensive tests currently exist. Further along, the tests can be expanded to adult cancers as well. Within three-to-five years, their work will result in marketable diagnostic tests for pediatric cancer. This will improve survival times and quality of life for children with cancer, reduce healthcare costs and generate licensing revenue, which will be shared between the partners. This is a market with high demand and low competition, underscoring the importance of this product.

Standardization of molecular diagnostic testing for non-small cell lung cancer

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Overview

Non-small cell lung cancer is the most common type of lung cancer, accounting for 85 per cent of cases. Specific genetic mutations in a patient’s tumour can determine which drug will work best for that patient. As new targetable genetic mutations become known, it is more important than ever to be able to carry out genetic analysis of patient samples. Dr. David Stewart, from The Ottawa Hospital and the University of Ottawa, is working with the Eastern Ontario Regional Laboratory Association (EORLA) to develop an assay that can accurately detect important genetic mutations in the very small biopsy samples that can be obtained safely from most patients with advanced lung cancer. The assays will test for multiple genetic variations at once, for a more timely result than is possible with current sequential testing strategies. Patients will benefit from the rapid availability of information that will permit them to receive the most appropriate treatment. The financial benefits are also significant. If this new assay is implemented across the country, it could result in savings of $35.9 million in testing costs and $151.4 million overall due to the elimination of ineffective treatments. The project team will assemble a national advisory board to drive national translation of its technology so that these savings can be realized.

Increasing Yield in Canola Using Genomic Solutions

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Overview

The world’s population is growing and so is demand for the crops to feed it, among them canola. The canola industry in Canada accounts for nearly a third of the gross production value of all Canadian crops, generating $19.3 billion and nearly 250,000 jobs across Canada. The industry has set a goal of increasing yield by 53 per cent in the next 10 years. Traditional breeding techniques are not sufficient to meet this goal; new technologies are needed. Dr. Peter Pauls and collaborators at the University of Guelph have identified the genetic links of traits that can be incorporated into canola. The new traits are expected to significantly enhance crop productivity by increasing photosynthetic capacity, without negatively impacting seed quality. The researchers are working with Benson Hill Biosystems (BHB), an innovative crop genetics firm, combining their strengths to produce game-changing varieties of canola for producers across Canada. The results of this project will enable commercialization of the improved plants through licensing or collaborative development agreements. Increasing the yield of the canola crop benefits growers and others across the value chain, growing industry revenues by $3-$4 billion per year. BHB will also establish a Canadian subsidiary, CanolaCo, for this project that will result in newly created jobs for Canadians.

Genomics Driven Engineering of Hosts for Bio-Nylon

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Overview

Currently, nylon is made from petroleum. While the process works well, it is not environmentally friendly or sustainable. Therefore, there is strong demand for nylon produced from renewable resources, which requires less energy and results in fewer greenhouse gas emissions. Visolis is developing processes to manufacture renewable polymer such as nylon. Dr. Radhakrishnan Mahadevan from BioZone at the University of Toronto is using a genomics-driven bioengineering approach to convert sugars derived from forestry or agricultural feedstocks into value-added industrial chemicals such as adipic acid. Adipic acid alone has a market of 2.2 million tonnes; chemicals that can be derived from it have similarly large markets. As an industrial biotechnology company, Visolis is positioned to apply the results from this research program to the development of next generation chemicals. The results of its work will benefit Canada’s economy by growing the biorefining industry and creating new manufacturing jobs, while protecting the environment through reduced greenhouse gas emissions and pollution.

Broad-range disease resistance in greenhouse vegetables

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Overview

Canada’s greenhouse vegetable industry generates more than $1 billion from retail sales and exports. Its top three crops are tomatoes, peppers and cucumbers, produced mainly in Ontario, British Columbia and Quebec. In an extremely competitive environment, plant diseases are an enormous burden on growers, causing up to 20 per cent crop loss. There is a strong demand for genomics-based technologies to mitigate these losses. Drs. David Guttman, Darrell Desveaux, and Adam Mott of the University of Toronto have discovered a previously uncharacterized family of genes that allow plants to show broad-range disease resistance against bacteria and fungi. Further, it is extremely difficult for pathogens to overcome the resistance linked to these genes. Now Dr. Guttman and team are working with the Vineland Research and Innovation Centre and its reverse genetics platform (developed with earlier Genome Canada funding) to further develop these Broad Range Resistance genes, as they are known, to protect against multiple pathogens, reduce losses and increase yield. The result will be new varieties of vegetables that give Canadian growers a competitive advantage. Vineland will take this gene technology from its translation through to the commercial release of new plant varieties with improved disease resistance, within five years of the end of this project. Annual benefits of around $26 million will start to accrue to the Canadian greenhouse industry within the same timeframe. The enhanced competitiveness of Canadian growers will lead to sustained growth, expansion of operations and further job creation. Additional benefits will be seen as Vineland re-invests its licensing revenue from the new vegetable varieties into further research, driving innovation throughout the entire horticultural sector.

NanoString nCounter Vantage 3D platform-based complementary diagnostic tests for precision medicine in pediatric cancers

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Overview

DNA-based next generation sequencing provides important information about DNA alterations however, most oncology drugs are designed against defined molecular targets at the protein level. There is a pressing need for novel diagnostics that interrogate all levels of cellular information, protein, RNA and DNA, in order to best guide therapeutic choices.  This project aims to amalgamate proteomic data with genomic and transcriptomic information to develop laboratory developed (LDT)-complementary diagnostics for the most common pediatric cancers.  Furthermore, the partnership between NanoString Technologies and the SickKids Department of Paediatric Laboratory Medicine will leverage their combined technological, clinical and business expertise.

Field Validation of Technologies for Anaerobic Benzene and Alkylbenzene Bioremediation

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Overview

There are thousands of sites in Canada contaminated with benzene, and the alkylbenzenes toluene, ethylbenzene, and xylenes (collectively known as BTEX), negatively impacting soil and groundwater resources. Current BTEX remediation technologies are often too costly and not applicable at the many sites with prevailing anoxic conditions. Building on previous research that developed, characterized and scaled-up a single methanogenic benzene-degrading culture, this GAPP project’s goal is to demonstrate the efficacy of a broader set of novel and specialized anaerobic bioaugmentation cultures in pilot trials at three different benzene contaminated sites. The team will use metagenome-enabled analysis, groundwater modeling, and tracking of the microbial populations and functional genes associated with anaerobic BTEX biodegradation in the subsurface to improve overall remediation outcomes and to restore ecosystem health.

Targeting fungal stress responses to provide first-in-class treatment for drug resistant fungal pathogens

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Overview

The impact of fungal infections on human health in Canada is profound, with recent epidemiological reports of approximately 3,000 invasive fungal infections annually, resulting in approximately 1,000 deaths, with immunocompromised individuals being the most vulnerable. Only three major classes of antifungal drugs are currently available and resistance to each class is increasing at an alarming rate.
This team has established that fungal stress responses are critical for fungal drug resistance and virulence traits and has identified potential antifungal inhibitors of the molecular chaperone and stress response regulator Hsp90. This project couples Schrödinger’s computational drug discovery expertise with the Cowen lab’s expertise in fungal genomics and Hsp90 to enable Bright Angel Therapeutics to rapidly translate existing data supporting the benefit of targeting fungal Hsp90 into an IND-ready drug candidate. The project will pursue a 3-task development approach based on computational design, targeted medicinal chemistry, and biological verification/validation. The project gives Canada a chance to be a global leader in antifungal research. The drug coming to market would be expected to reduce morbidity and mortality due to fungal infections and provide significant savings to the Canadian health care system, which currently spends $345 million on invasive fungal infections.

Stopping Enteric Illnesses Early (Sentinel)

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Overview

In Canada, consumption of contaminated food causes 4 million illnesses, 14,150 hospitalizations and 323 deaths each year, with an estimated annual economic burden of approximately $4 billion, and a major impediment to the identification of contaminated food is that current surveillance methods rely on sick people to seek medical help. The Public Health Agency of Canada (PHAC), in partnership with the University of Guelph and Université Laval, aims to develop a novel, integrated approach to improved foodborne outbreak detection, beginning with metagenomic detection of foodborne pathogens in raw sewage within geographically localized monitoring sites (Quebec City, Guelph, Winnipeg), and monitoring of social media for keywords associated with enteric illness. The tools, methods and datasets generated through this project will be translated for downstream operational use into the network of Canadian foodborne surveillance programs through collaborations between PHAC and its federal/provincial/territorial partners. Implementation is expected to result in a reduction in the amount of illnesses and hospitalizations and economic savings due to a reduction in food recalls through faster detection of outbreaks. A key advantage of this flexible ‘omics and social media surveillance approach is that it can be scaled for rapid detection of other pathogens, and will be immediately utilized to monitor levels of SARS-CoV-2 (the COVID-19 virus) in wastewater, as an early indicator of changing case numbers prior to clinical presentation.