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AbSyn Technology for Identification of Synergistic Cancer Targets

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Overview

Diagnosing disease has been revolutionized by our ability to decipher the genetic changes that lead to cancer; our treatment abilities have not kept up and most patients still receive decades-old treatments that do not target the individual genetic nuances of each individual’s tumour and are highly toxic as well. The development of antibody-based drugs, such as Herceptin for breast cancer and Humira for rheumatoid arthritis, has changed the treatment landscape and had a tremendous impact on patient survival in these areas. But the success of antibodies is limited by our lack of ability to develop and apply efficacious new antibodies to kill target cells, particularly because of the complexity of diseases such as cancer.

Drs. Jason Moffat and Charles Boone of the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research, with previous funding from Genome Canada, have invented AbSyn, a disruptive technology that combines expertise in the production of antibodies (Ab) and the deciphering of genetic networks to produce combination or synergistic (Syn) treatments for cancer. In the first phase of this competition, the researchers confirmed AbSyn’s potential to be a robust drug discovery pipeline. Now, in phase 2, their goal is to promote the development of AbSyn into a platform that is attractive to the pharmaceutical industry. With the support of Celgene, a global leader in biopharmaceuticals, they will undertake large-scale screening to further demonstrate AbSyn’s potential. The technology will ultimately be incorporated into Bridge Genomics, a Canadian start-up company, where it will enhance their mission of searching for disease-specific interactions that can be targets for drug development.

AbSyn presents an opportunity for Canada to attract the biotechnology investment needed to create a vibrant biotech sector in Ontario and attract and retain talented, highly trained researchers and have far-reaching economic benefits in terms of intellectual property and revenues. It will also highlight Canada’s growing influence in the field of precision medicine.

RapidAIM: A technology to rapidly assess the effects of compounds on individual microbiomes

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Overview

Human microbiomes – the microbial colonies that exist in our guts –play a key role in disease development, progression, and therapeutic response. While global changes in the microbiome have been correlated to a disease or response to therapies, we lack methods to rapidly assess the impact of drugs and compounds on individual microbiomes. The development of a rapid screening platform would provide a groundbreaking and effective tool to screen novel and existing drugs and compounds for their effect on individual microbiomes. This would allow the screening of compounds for drug development to induce the desired changes in the microbiome.

Dr. Daniel Figeys and his team, in the first phase of this competition, demonstrated the proof-of-principle of RapidAIM, an assay that measures functional changes in individual microbiomes following exposure to drugs or compounds. The team is currently developing commercial applications, which include a fully automated, high-throughput prototype of the RapidAIM platform, together with a bioinformatics analysis platform, MetaLab. The Companion software developed for RapidAIM, METAMCI, will rapidly assess the effects of drugs/compounds in individual microbiomes. The team will also create a drug-microbiome interaction database of FDA approved and novel compounds to test RapidAIM and METAMCI , in collaboration with their industrial partners Biotagenics and Filament BioSolutions.

The development and commercialization of RapidAIM will provide significant economic benefit. The product will enable identification of new drugs/compounds that target the microbiome, facilitate more rapid clinical development of drug candidates, prevent unwanted negative effects on the microbiome of new therapeutics, and achieve a better understanding of the impact of currently used therapeutics on the microbiome. The technology can also be used to select the most effective treatment for individuals, based on their microbiome’s differing responses to drugs, improving health and reducing healthcare costs by targeting treatments to those who will benefit most.

Canadian Data Integration Centre

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Overview

The Canadian Data Integration Centre (CDIC) is an international leader in genomics, bioinformatics and translational research, supporting some of the world’s largest programs in genomic data analysis, genomic and clinical data hosting, cancer data analyses and access and the development of algorithms for advanced sequencing technology. The CDIC’s services range from small, bespoke data integration solutions to comprehensive large-scale genomic analyses and include the ability to handle difficult and small-volume biosamples, enabling investigators to maximize the utility of scant or rare clinical tissues. Its informatics and bio-computing core is the largest academic cancer informatics program in Canada and it is the only site in Canada to offer 3rd generation bioinformatics tools for researchers in genomics and functional and clinical genomics. In its first five years, CDIC has generated $87 millions in grants and $14 million in service revenue.

Over the next five years, CDIC will develop new technologies and methodologies for long-read sequencing, for research and clinical application; roll out translational biomarkers of therapeutics response and prognosis for clinical applications and services; and develop already-identified pan-cancer biomarkers for biopsy diagnoses to make them clinic- and industry-ready.

Network Biology Collaborative Centre

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Overview

The Network Biology Collaborative Centre (NBCC) at the Lunenfeld-Tanenbaum Research Institute was founded in 2014 to assist scientists with coupling the vast understanding of genomic and phenotypic variation in health and disease with a functional understanding of how gene products convey biological information and how their alterations drive disease.

The NBCC is built on one of Canada’s first proteomics mass spectrometry facilities and one of the first academic screening centres, which date back to 1999. Since that time, the Centre and its precursors have provided critical support for high-impact research and the translation of that research into an understanding of disease mechanisms, increased economic activity and potential new treatments and improved health outcomes.

The NBCC currently operates through multiple complementary nodes: proteomics, high-throughput screening including next-generation sequencing, and high-content to high-resolution imaging. The NBCC provides not only its extensive expertise in the design and application of sophisticated screening strategies through these nodes, but also its ability to integrate these screens with each other to drive biological insights.

By continually innovating, improving and implementing new technology, NBCC continues to offer the highest-calibre services. Over the next five years, the Centre will extend its proteomics and functional genomics screening into more sophisticated systems that will better model health and disease states, and continue to integrate data management and analytics across all of its nodes. Through its work, it will help to ensure that future scientists remain internationally competitive and drive their science to realize the greatest benefits for Canada.

The Centre for Phenogenomics

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Overview

Discovering and understanding the function of genes and abnormalities in genes (“mutations”) that cause disease in children and adults remains a major challenge. Researchers use mouse models to evaluate the impact of these mutations, but need access to state-of-the-art services to enable their research. Since 2007, The Centre for Phenogenomics (TCP) has been providing these services, designing and producing customized mouse models, determining the functional consequences of genetic abnormalities, validating a phenotype (”observable characteristics that result from a mutation”) comparable to the human disorder, and investigating the underlying molecular pathways. It also supports translational services to reverse the effect of the mutations through genetic or pharmaceutical approaches. In the past five years, TCP has provided more than 40,000 services to 615 clients, generating nearly $13 million in revenue. A Canada Foundation for Innovation review panel called TCP “the best facility of its kind in Canada and … among the top five in the world.” TCP brings together a unique Canadian critical mass of infrastructure, expertise, interaction and technology. Over the coming five years, it will expand its research services to infectious diseases and inflammatory conditions, both of which are common and major health and economic burdens to Canada. To support Canadian scientists’ efforts to understand gene function and the genetic changes that cause disease, TCP will provide Canadian scientists with unparalleled access to leading-edge genomic services in disease model production and evaluation. TCP will also continue to develop new technologies and enhance existing ones to deliver state-of-the-art services, thereby maintaining its competitiveness and that of its users.

The Centre for Applied Genomics

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Overview

The Centre for Applied Genomics (TCAG), founded in 1998, has been a Genome Canada Science and Technology Platform since 2001. TCAG provides genomics support and analysis to more than 800 Principal Investigator labs per year, a total of more than 2,000 over its lifetime, spanning 45 countries, 317 academic institutions, 150 companies and 46 government agencies and non-governmental organizations. Through its work, TCAG has catalyzed many significant scientific advances. TCAG developed and hosts the Database of Genomic Variants and the Ontario Population Genomics Platform repository, leads the “MSSNG” autism genome sequencing project and the Canadian Personal Genome Project, and is the Toronto node of Canada’s Genomics Enterprise (CGEn), a national network of whole genome sequencing centres.

With additional funding from Genome Canada, TCAG will continue to actively develop novel methodologies for whole genome sequencing, genome assembly and statistical analysis of genome-wide data. These activities will complement the development and implementation of additional pipelines and methods for generating and analyzing genomic data. TCAG will continue to work with national and international partners to advance the utilization of genomics to address many facets of multidisciplinary science, including a strong focus on human diseases and neurodevelopmental disorders.

Pathway and network visualization for personal genomes

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Overview

Cancer is a disease caused by the accumulation of multiple genetic mutations. Highly specific drugs that target mutated proteins in cancer cells are currently being used to treat the disease. However, since cancer patients have different mutation profiles, a drug that is effective in one may not have the same result in another. Personalized medicine based on genomic data would allow doctors to determine the best targeted therapy for each patient.

Dr. Lincoln Stein and his team aim to develop software that will improve the treatment of cancer patients by enabling physicians to study and visualize the genomic aberrations of individual patients. It will help identify genes related to cancers and other disease.

Leveraging meta-transcriptomics for functional interrogation of microbiomes

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Overview

Bacteria do not live in isolation but tend to form parts of microbial communities (called “microbiomes”), displaying complex inter-dependencies between themselves and their environments. The composition of these communities is increasingly viewed as having a significant impact on human health and disease.

To understand more about how bacteria function within their communities, whole-microbiome gene expression profiling has emerged as a powerful tool to study their influence on their environment. However, few methods and tools to fully understand the data resulting from this profiling have been developed.

Dr. John Parkinson and team aim to bridge this gap by developing new software that enable the identification of genes and pathways that have critical roles within the microbiome. Such genes and pathways represent potential targets for new treatments that help maintain healthy microbiomes and reduce the risk of diseases such as Type 1 diabetes, irritable bowel disease and rheumatoid arthritis.

Large data sets and novel tools for plant biology for use in international consolidation-tier data repositories and portals

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Overview

New technologies allow plant biologists to identify important DNA sequences in an organism’s genome. Among other things, these advances have helped gain insight into the expression level of genes in many different parts of plants under different conditions, the interactions between the proteins present in organism and the 3D structures of these proteins. However, researchers still find it difficult to draw meaningful conclusions from the huge amounts of data that confront them.

The research team led by Drs. Nicholas Provart and Stephen Wright aims to develop data visualization tools and applications to accelerate advances in plant biology. Their contribution to making vast amounts of data easier to interpret will increase our understanding of plant biology, which is important for feeding, housing, clothing and providing energy to the world’s growing population.

Development of a unified Canadian clinical genomic database as a community resource for standardizing and sharing genetic interpretations

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Overview

Canadian scientists have made exciting discoveries about the complex relationship between genetic mutations and disease. However, much of this information is spread across dozens of databases in widely differing formats. In order to use this information to improve patient outcomes, researchers and clinicians need a more widely-accessible resource designed for sharing and collaboration.

Drs. Jordan Lerner-Ellis, Matthew Lebo and their team aim to address this issue by creating a shared, open-source genetic database that will amalgamate the work of participating clinical and research laboratories across Canada and internationally. This resource will provide sophisticated new tools for the diagnosis and management of common and rare diseases, while improving the effectiveness of healthcare delivery.