Main Menu
Main Menu
Menu

Targeted Next Generation Sequencing Panels for Clinical Disease Management

by

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

by

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

by

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

by

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

by

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)

by

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

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.