Main Menu
Main Menu
Menu

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

by

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.

Strain development for butanol process addition to existing biodiesel plants

by

Overview

Biodiesel production from agricultural crops generates a considerable amount of crude glycerol as a byproduct each year. The purification costs for this crude glycerol are high and market demand for refined glycerine is low, resulting in a large fraction of the crude glycerol being incinerated, adding to climate emissions and production costs. World Energy intends to commercialize the production of bio-butanol, a superior biofuel and chemical commodity, from this waste glycerol. A process has previously been developed for the conversion of glycerol to butanol using Clostridium pasteurianum, however the genetic changes that have occurred and the stability of the new strains are not well understood. The aim of this project is to improve the continuous fermentation process by gaining a better understanding of the genetic changes that have occurred in the engineered bacterial strains as well as enhance biobutanol production and fatty acid tolerance through additional genetic modifications. Process scale up is also planned. World Energy generates approximately 66,000 MT of glycerol annually that can be used for bio-butanol production. With initial goals of 30% of the carbon from waste glycerol being converted to bio-butanol, up to $3.7 million additional revenue could be incurred per facility per year.

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

by

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)

by

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

by

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

by

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

by

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.

Fast Track Diagnosis of Stress, Disease, Phenology and Growth (FastPheno)

by

Overview

The field of forest genomics has seen unprecedented advances during the past decade. A suite of genomic resources is now available for enhanced genomic selection and can be used to accelerate breeding cycles and to select genotypes that are better adapted and more resilient to future climate change and diseases. The large-scale phenotyping needed to assess adaptive traits in breeding populations with thousands of trees is now the major bottleneck hindering the rapid identification of the traits that enable trees to cope with climate change. This project will develop a drone-based precision phenotyping tool for assessing conventional and novel adaptive traits to complement the genomic selection research and operational programs of Natural Resources Canada and Ministère des Forêts, de la Faune et des Parcs du Québec. The economic impact of climate change is expected to be significant for Canada’s forest sector. The proposed technology will help the Canadian forest sector take advantage of genomic selection tools that may mitigate the impacts of climate change.

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

by

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

by

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.