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Assessing Freshwater Health Through Community Based Environmental DNA Metabarcoding

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Overview

With a growing economy, increasing population, and climate change, Canada faces increased pressures on its precious resource: freshwater (20% of the world’s freshwater). Current methods for monitoring the health of our watersheds remain slow, laborious, expensive and imprecise. Canada’s geographic diversity and low population density makes monitoring networks a challenge to maintain. We need more efficient, comprehensive monitoring tools to inform governments, communities and industries about the true consequences of economic development on freshwater quality, to support rapid and effective protection of vulnerable ecosystems. The WWF- Canada and Environment and Climate Change Canada (ECCC) are working with Dr. Mehrdad Hajibabaei of the University of Guelph to validate and implement a new technique called environmental DNA metabarcoding, which uses bulk environmental samples for identification of species through species specific genomic sequences (DNA ‘barcodes’) using high-throughput sequencing technologies. The project will generate biodiversity data for freshwater benthic macroinvertebrates, the small animals that live at the bottom of streams, rivers. The technique will be used to analyze bulk samples collected by community-based monitoring efforts across a wide range of Canadian watersheds. Sampling by community groups will be coordinated by WWF-Canada and its partner organizations such as Living Lakes Canada. Implementation at this scale will be a world first, supporting the wider adoption of these technologies within existing environmental monitoring and assessment applications, including ECCC’s Canadian Aquatic Biomonitoring Network (CABIN) which engages over 1,400 users, including federal, provincial and territorial government agencies, First Nations, academia, industry, NGOs and environmental consulting firms. Many of these organizations already use biomonitoring to understand and manage the impacts of resource projects such as mines, hydro dams and energy projects. By providing access to this new genomics-based technique, and by demonstrating its reliability in assessing river health, we can broaden the reach and impact of existing community-based monitoring programs, ultimately leading to better informed decisions.

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.

Targeted Next Generation Sequencing Panels for Clinical Disease Management

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Overview

Over the past 2-3 years, the Ontario Institute for Cancer Research (OICR) and Thermo Fisher Scientific (TFS) have partnered in developing genomic solutions for rapid adoption into the clinic. OICR’s collaboration with TFS resulted in the commercial launch of the Oncomine™ Comprehensive Assay (v3).  The current project is focused on developing new biomarker signatures based on combined RNA and DNA sequencing with clinical utility in well-characterized patient cohorts to develop clinical diagnostic tests in cancers for pancreatic, prostate and breast cancer patients, and provide a model for adoption in other disease settings.

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.

Systematic evaluation and optimization of immune-targeting modalities for GBM and brain metastases

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Overview

There are currently no successful therapeutic regimens for patients with recurrent/refractory glioblastoma (GBM), and brain metastases (BM). Partnering with Dr. Jason Moffat at the University of Toronto and collaborators at McMaster University, Empirica has used genomic screening technology to identify CD133 as a promising target for effective treatment in both in vitro and in vivo models using Chimeric Antigen Receptor (CAR)-T cell therapy.  The overall goal of the project is to design and validate next-generation CD133 CAR-Ts that are genetically engineered to be manufactured “off-the-shelf”- thus less costly – and are less susceptible to immune suppression.  GBM accounts for more than 50% of the approximately 22,850 cases of brain and other nervous system cancers that were diagnosed in 2015. As one of the most aggressive cancer types, with inevitable recurrence, the global GBM market was US $416.8 million in 2015 and is forecast to reach US $1.15 billion by 2024 as the global population increases. In Canada, costs of cancer care have been steadily on the rise, and this project aims to provide more effective and universal treatments for recurrent GBM that can alleviate this economic burden.

Validating and Improvement of in silico Proteome Screening and Drug Design Technologies by Experimental Drug Discovery for Neurodegenerative Diseases

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Overview

An important contributor in the decline of productivity in pharmaceutical development is the traditional focus on single target drug design, in which molecules are designed for one protein target. In practice, however, a drug is likely to interact with a number of proteins, sometimes up to 300 in the body, leading to unforeseen and adverse side effects. Cyclica intends to mitigate this problem by using their proprietary Ligand Design™ and Ligand Express® drug discovery platform. Ligand Design is a multi-targeted and multi-objective in silico drug design platform, and Ligand Express is a cloud-based and AI-augmented off-target profiling and target deconvolution platform that computationally determines polypharmacological profiles. Taken together, Ligand Design and Ligand Express offer an integrated platform to design advanced lead like molecules that minimize off-target effects, while providing insights into structural pharmacogenomics. The team at Cyclica and McQuibban Lab will seek to identify novel solutions for Parkinson’s disease, which will be commercialized jointly by Cyclica and Rosetta Therapeutics. The McQuibban Lab has established assays to substantiate the Cyclica AI predictions. It is expected that these validated platforms will assist Cyclica in further quantifying the benefits of their platforms, including the potential time and resources saved during drug development.

Optimization and Implementation of a Clinical Genome-Wide Sequencing Service for Rare Disease Diagnosis in Ontario

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Overview

Currently, more than one third of Ontarians with a rare disease lack a genetic diagnosis, despite lengthy and costly investigations. Fortunately, genome-wide sequencing (GWS), in the form of exome sequencing (ES) and genome sequencing (GS), has transformed our ability to achieve a timely diagnosis for rare disease patients. Prior to April 2021, clinical GWS for Ontario patients was only available via an exceptional access program (EAP) and completed in laboratories outside Canada. The EAP program was designed as a ‘safety net’, rather than a regular service delivery model, and presented significant challenges including lack of oversight of turnaround time, diagnostic yield and impact, timing, and outcome of exome vs. genome. To address these challenges, CHEO and The Hospital for Sick Children (SickKids), in collaboration with the Ontario Ministry of Health, developed and is delivering an optimized clinical GWS service as a two-year pilot for individuals with rare diseases that is equitable, accessible, sustainable and performed in Ontario. The pilot project will provide GWS in the form of both ES (n=325 trios) and GS (n=325 trios) to 650 families from CHEO and SickKids. This work will enable robust assessment of diagnostic utility, cost effectiveness, and timeliness of ES and GS to inform provincial and cross-provincial policy related to the long-term organization, delivery, and reimbursement of genome-based diagnostics for rare disease.

Beyond Genomics: Assessing the Improvement in Diagnosis of Rare Diseases using Clinical Epigenomics in Canada (EpiSign-CAN)

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Overview

This project will be validating a test, called EpiSign, a proprietary machine learning algorithm built on rare genetic disease datasets (EpiSign Knowledge Database) which analyzes data obtained from wholegenome methylation arrays. This approach is expected to increase diagnostic yield above that of current genetic analyses. This project will validate the conditions for maximizing patient and health system impact and assess the evidence for first-visit and reflex scenarios for adoption of genome-wide DNA methylation testing within Canada. Future clinical adaption would see EpiSign implemented as a bioinformatics service with tertiary genetic centres engaging with their patients and performing the wet lab methylation array data production locally. These centres would then utilize a secure web-based portal to have their data interpreted by the EpiSign Knowledge Database. Expected benefits to Canada include improved quality of life to patients and families who will receive a long-awaited definitive diagnosis. Providing patients with a diagnosis sooner will also have cost benefits, as many tests will be avoided in addition to reducing the reliance on out-of-country commercial laboratories.

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.

Strain development for butanol process addition to existing biodiesel plants

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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.