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Caribou Genomics: A National Non-Invasive Monitoring Approach for an Iconic Model Species-At-Risk

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Overview

Caribou has been identified as a priority species for recovery by Environment and Climate Change Canada (ECCC) in consultation with provinces, territories, and Indigenous groups. Significant efforts are being made by all levels of government to gain a better understanding of the factors affecting this iconic species, including climate change, and identify the best options for monitoring the effectiveness of recovery options. The goal of this project is to build upon their established caribou genetics research program to implement a genomics platform that will enable i) long-term, non-invasive genomic monitoring of boreal caribou, ii) allow for compatibility among different data generators and, iii) house data in an open access repository that supports analytical toolkits for use by partners. Investing in the implementation of such a genomic platform will allow comparisons through space and time to monitor the recovery of caribou populations and inform conservation efforts.

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.

CLEan plAnt extractioN SEquencing Diagnostics (CLEANSED) for Clean Grapevines in Canada

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Overview

Grapevine virus disease management has been identified by the grape grower and wine industries as a top priority for long‐term sector sustainability. Losses of over $23 million per year are currently incurred by grape growers due to reduced yield of infected grapes and increased fruit rejection by wineries. To replace the currently infected acreage and meet ongoing renewal of vineyards the industry needs access to 6.7 million domestically produced, virus free vines/year. There will be two separate pathways for implementation and commercialization. To accommodate these demands, the Canadian Food Inspection Agency (CFIA) Sidney Centre for Plant Health (CPH) requires a rapid, cost effective genomic solution to replace the over 30 molecular and bioassays currently performed on , which can take up to three years to complete. By implementing a high throughput sequencing method at the CFIA the costs of analysis will be reduced and analysis time will be reduced for industry priority varieties imported into Canada as well as audit testing from certified foreign sources destined to commercial planting. Reducing the testing time to 10 days allows grape growers to rapidly improve the health of their vineyards. Domestically, the Canadian Grape Certification Network (CGCN) is commercializing high throughput sequencing through its partner Cool Climate and Oenology Viticulture Institute for the certification of propagation material in nurseries and grapevines obtained through CPH, and for monitoring of production vineyards.

Development of an Epigenomic Profiling Tool to Facilitate Precision Medicine in Early Breast Cancer

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Overview

Cancer is responsible for 30% of all deaths in Canada. Over the past two decades, what were once considered to be homogenous diseases of a tissue (e.g., breast cancer) are now known to be heterogeneous even within well-established clinical subtypes. To better understand the individual nature of breast cancer in patients, the implementation of integrated ‘omics solutions are needed to understand the combined effects of genomic and epigenomic changes in driving cancer progression and deliver on the promise of precision medicine. Emerging research in breast cancer implicates epigenomics in the regulation of multiple cancer processes including DNA repair and treatment response. The epigenomics data available across cancer driver genes from different ethnic groups, particularly from women of African descent, which further highlights the diagnostic importance of epigenomic features in patient care. This is critical in the equitable delivery of healthcare to patients, since a significant proportion of patients may not be adequately treated due to molecular processes influenced by differences in ethnicity. This project will develop and validate novel panel-based targeted approaches for the evaluation of epigenetic alterations in breast cancer to address two major needs: improved predictive and prognostic assays for all breast cancer patients and a focused study comparing methylation profiles between cancers in Black and Asian minority ethnic groups and other ethnic groups.

Cardiovascular Biomarker Translation Team 2 – Atrial Fibrillation

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Overview

The early detection and treatment of atrial fibrillation is a high priority for patients and physicians. Atrial fibrillation is the most common cardiac arrhythmia in the world, affecting over 25% of the population over age 70. Patients with atrial fibrillation are at an increased risk of a number of complications, including stroke, cognitive impairment, dementia, paralysis and heart failure. There are currently no established biomarkers to guide the clinical management of patients with atrial fibrillation. This project will develop and validate a diagnostic biomarker panel for atrial fibrillation that will enable the early detection of atrial fibrillation and predict the risk of complications. It will also improve the care of patients with this condition by predicting best treatments and outcomes. The results of the improved decision making in atrial fibrillation is expected to save over $200 million per year in health care costs in Canada alone.

YCharOS – Antibody Characterization Through Open Science – From Viruses to Human Proteins

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Overview

Commercially available antibodies are key reagents in laboratory research with global sales estimated to be $2-3 billion USD. However, despite the size of the market and the importance of the product there is no independent, state-of-the-art quality assessment body for antibodies and as a result at least half of the antibodies on the market do not perform as required – leading to billions of dollars of wasted funding and a crisis of experimental reproducibility. YCharOS has developed a standardized process that involves knockout cell lines that do not express the target protein. With these cell lines as controls, and with inventive characterization steps, antibody performance against the cognate target protein can be quantified and compared in a range of commercially relevant applications. The long-term business model involves customers such as research organizations, funding agencies or charities paying YCharOS to perform antibody studies on protein targets selected by one of the customers with a goal of attaining $9M in annual revenue by the end of the project and saving Canadian taxpayers $45M annually by enabling our scientists to order the right antibody for their experiments.

Production of Medium-Chain Length Polyhydroxyalkanoate (mcl-PHA) from Food Waste

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Overview

In Canada, 2.8M tonnes of plastic waste was landfilled or leaked into the environment in 2016. Banning of single-use plastics is driving demand for biodegradable plastic (bioplastic). Medium chain length polyhydroxylalkanoate (mcl-PHA) resin has ideal properties for agriculture and packaging films, showing high flexibility, processability, thermal stability and complete biodegradation into simpler, non-hazardous compounds. High production costs of existing mcl-PHA have limited the market potential and applications. Using technology to efficiently transform food waste into higher quality biodegradable resins (i.e., mcl-PHAs) would be a possible solution. This project will enable scale up and commercialization of low-carbon biodegradable medium-chain length polyhydroxyalkanoate (mcl-PHAs), through validation and enhancement of a two-stage process that consists of mixed culture dry fermentation of food waste into medium-chain length polyhydroxyalkanoates (mcl-PHA) for use as biodegradable plastics.

Lowpass Genomic Instability Characterization as a Comprehensive Cancer and Germline Diagnostic Assay

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Overview

Mutations in the mismatch repair or DNA polymerase genes lead to replication repair deficiency (RRD), a major cancer mechanism leading to genomic instability, microsatellite instability (MSI) and hypermutagenesis (high tumour mutation burden). RRD is a frequent driver of highly prevalent cancers such as colon, stomach, pancreatic, endometrial, and ovarian in adults, and brain and hematologic in children. There is a need to accurately identify patients with RRD as they are often resistant to chemotherapy but exquisitely sensitive to targeted and immuno-therapies; and have cancer predisposition syndromes so they, and their families, need surveillance. Current screening methods are time consuming, costly, and miss patients due to lack of sensitivity and specificity. This project will develop a sensitive and specific, cost-effective diagnostic tool for clinical RRD testing through a clinically validated lowpass genomic instability characterization diagnostic (LOGIC) assay. Benefits include savings to the health care system as well as potential revenue through the licence of this test to others both nationally and internationally.

Developing Novel Bioleaching Process for Ni Recovery from Pyrrhotite Streams

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Overview

Current methods for mining and processing ore and metal recovery are energy intensive. They lead to significant waste streams along with energy-related greenhouse gas emissions, exacerbating the climate crisis. In addition, electrification of the transportation sector is a key part of Canada’s climate strategy. Therefore, we need energy-efficient and environmentally friendly methods for mining and recovering critical minerals, such as nickel, that are key components in batteries and electric vehicles. The project will use genomics and bioleaching technologies to characterize and engineer microbial populations to treat pyrrhotite tailings, waste streams of current mining practices, for nickel extraction. Bioleaching technologies are already commercially used for mining, mainly extracting higher-priced metals (e.g., gold, copper) from sulfidic ores. The team will use genomic solutions to enable the widespread application of bioleaching technology, such as meeting the need for faster bioleaching kinetics, improved selectivity and monitoring methods. Metso-Outotec will work with producers/owners to implement the technology on pyrrhotite tailings from Sudbury basin mines. The extraction of nickel from pyrrhotite tailings in Canada has a potential value of $26 billion, can provide a source of critical minerals for production of electric vehicle batteries, and enable significant (>75%) reduction in waste generation from mining processes.

Biopesticide with New Modes of Action for Control of Highly Polyphagous Mite Agricultural Pests

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Overview

Pest management is a top priority for Canada’s horticulture greenhouse sector (with farm gate value of $3.9 billion), which provides Canadians with fresh produce year-round. The two-spotted spider mite (TSSM) presents a particular threat to crop security due to its well-documented resistance to pesticides. This project will develop, register and commercialize RNAi biomiticide (dsRNA biopesticides specific for mites) against the TSSM to effectively manage its outbreaks. Project researchers—the first to demonstrate that RNAi-based silencing operates in TSSM—have already developed protocols for high-throughput screening of RNAi targets, provided proof-of-principle that sprayable RNAi works against TSSM, and identified effective TSSM RNAi targets. The project benefits from Greenlight Biosciences’ experience in commercializing and producing RNAi biopesticides and the Ontario Greenhouse Vegetable Growers’ first-hand knowledge of the needs of Canada’s horticulture greenhouse growers. A potential game-changer for mite control, RNAi biomiticide will not only provide the sector with potential economic benefits of ~$600 million peryear. It will also provide growers with an alternative to synthetic chemical insecticides, thus reducing their environmental footprint.