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Devices for Detection and Identification of Surface Microbial Contamination in High-Risk Facilities

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Overview

Healthcare-associated infections (HAIs) are the 4th leading cause of death in Canada, predicted to move up to second place by 2050. Attention to cleanliness and disinfection of surfaces plays a large role in reducing HAIs. However, historically it has been difficult to measure cleaning effectiveness and meaningfully improve practices. There is a clear need for a system that can identify disease-causing bacteria and viruses on surfaces. Charlotte Products Ltd. (CPL), a family-owned Canadian company, has developed an environmental monitoring system and optical sensor technology, called Optisolve Pathfinder®™, to complement its innovative, award-winning cleaning products. Dr. Shana Kelley is working with the company to further enhance the OptiSolve offering to allow for recognition and identification of specific pathogen species. Dr. Kelley and her team will combine novel nanomaterials with a genomics-based approach to allow for precise identification of pathogens that cause HAIs. The resulting technology, Optisolve Insight, will allow hospitals long-term care facilities, and more to rapidly detect and identify infectious agents, such as MRSA, C. difficile, and influenza, with the resultant benefits of proactive prevention and quick interventions. The service and technology will significantly reduce HAIs while enabling environmental services and IPAC managers and to avoid taking a “worst-case scenario” approach to infection outbreaks, which can include bed closures and cancellation of procedures. The result will be improved health of patients, residents, staff, and visitors as well as healthcare savings. This first-to-market technology will contribute to economic growth and employment for highly qualified personnel.

Translating High Immune Response (HIR™) Genomics to Improve Beef Cattle Health and Welfare

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Overview

High Immune Response (HIR™) is a patented test developed by Dr. Bonnie Mallard and colleagues of the University of Guelph that identifies animals with naturally superior immunity. First used successfully in dairy cattle, the test is now being adapted to fight Bovine Respiratory Disease (BRD), the costliest disease of beef cattle raised on feedlots. BRD results in the death of some 53,000 beef cattle in Canada each year, an economic loss of more than $100 million. In North America as a whole, the estimated annual cost of BRD as high as $1 billion dollars/year. Dr. Mallard is working with the Semex Alliance and through them, the Canadian Angus Association (CAA) and the American Angus Association (AAA), to develop an HIR™ genomics test for beef cattle. The application of the test could result in a significant (20-50 per cent) reduction in deaths among calves from birth to weaning age and reduce the need for antibiotics throughout the lifetime of beef cattle. All Angus bulls marketed in Canada and the United States will have access to the HIR™-genomic test, allowing beef producers to select bulls for breeding purposes better equipped to improve animal health and welfare. The new test will demonstrate the leadership provided by Semex, the CAA and the AAA in beef cattle genomics. Integration of the HIR™ technology and selective breeding for enhanced immunity in the North American Angus population is expected to cumulatively increase BRD resistance of beef cattle over multiple generations, which if fully applied, could ultimately reduce the costs of BRD in North America by $500 million per year, $65 million of which will be in Canada. Reduced use of antibiotics will provide further benefits to consumers and retailers.

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.