Disruptive Innovations in Genomics (DIG) Competition

Genome Canada’s Disruptive Innovations in Genomics (DIG) competition seeks to support research projects that focus on disruptive innovations with the potential to advance the field of genomics and eventually lead to social and/or economic benefits to Canada. For the purposes of this competition, a disruptive innovation is defined as either a new genomics technology or the application of an existing technology from another field, applied to the field of genomics. These Innovations must be truly transformative in that they have the potential to either displace an existing technology, disrupt an existing market, or create a new market.

Launched on June 11, 2015, the DIG initiative exists to capture true disruptive innovation and translate it to improve human health, agriculture, and natural resources.

Funded Ontario DIG Projects

2017
On February 4, 2019, The Honourable Kirsty Duncan, Minister of Science and Sport, announced the funding recipients from Genome Canada’s Disruptive Innovations in Genomics (DIG) Phase 2 competition to improve human health, agriculture, natural resources. Ontario Genomics led five (5) of the seven (7) awarded projects – driving $4.4 million of federal funding into the province and an additional $9.5 million in investments by industry, the Ontario government and other funding partners, for a total of $13.9 million. This investment will support the development of prototypes of the disruptive innovations developed in Phase 1 of the program.

2015
On December 09, 2016, the Government of Canada announced the investment of $9.1 million in Disruptive Innovation in Genomics to improve human health, agriculture, natural resources. Ontario Genomics led twelve (12) of the awarded early-stage feasibility (Phase 1) projects:

Ontario Genomics led two (2) of the awarded prototype development (Phase 2) projects:


DIG Project Descriptions:

Phase 2 Projects

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

Project Leaders: Daniel Figeys, Alain Stintzi, University of Ottawa
Genome Centre: Ontario Genomics
Total Project Funding: $2.9 million

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.
TOP

AbSyn Technology for Identification of Synergistic Cancer Targets

Project Leaders: Jason Moffat, Charles Boone, University of Toronto
Genome Centre: Ontario Genomics
Total Project Funding: $2.7 million

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.
TOP

Beyond the Genome: Transcriptome Based Diagnostics for Rare Diseases and Cancer

Project Leaders: Adam Shlien, James Dowling, Hospital for Sick Children
Genome Centre: Ontario Genomics
Total Project Funding: $3 million

Rare genetic diseases affect more than 500,000 children in Canada, often causing severe disability and early death, while cancer is the leading cause of non-accidental death in childhood. Early diagnosis at the molecular level is essential so that the right treatment for each individual can begin as early as possible. The most advanced genetic tests, however, are able to diagnose fewer than half of all children with rare disease and cannot detect important genetic changes in tumours that are critical for successful treatment.

In the first phase of this competition, Drs. Adam Shlien and James Dowling of the Hospital for Sick Children, with co-leaders Drs. Michael Wilson and Michael Brudno, demonstrated that RNA sequencing (RNA-seq), an emerging technology that examines the activity and structure of genes, can find disease-causing genetic variants (Dowling) and detect mutations and fusions in cancer genes (Shlien). Importantly, many of these mutations are not found by current genetic testing. In this second phase, they are combining their strengths to further develop and optimize the technological elements of RNA-seq and definitively determine how well it performs as a clinical test. Their goal is to create a clinically viable, comprehensive RNA-seq–based diagnostic platform for rare diseases and cancer. This platform will be fully automated, using advanced robotics and algorithms, and will improve in accuracy for every sample it is run on.

Their work will result in the first clinical RNA-seq diagnostic test in Canada. When fully implemented, the test will significantly increase the success rate of genetic testing in children with rare genetic diseases and cancer and improve access to clinical trials. The researchers will also create a dynamic digital library to integrate RNA-seq data with a range of health information, setting the stage for true precision medicine for all Canadians.
TOP

Interactome mapping of disease-related proteins using split intein-mediated protein ligation (SIMPL)

Project Leader: Igor Stagljar, University of Toronto
Genome Centre: Ontario Genomics
Total Project Funding: $2.2 million

Every cell in the human body contains proteins, and these proteins are essential to the proper functioning of every part of our body. Proteins are not soloists, though – like an ensemble, they interact with other proteins, in a process called protein-protein interactions, or PPIs. When these interactions go awry, disease results. Because of their involvement in causing diseases, understanding how these interactions work is essential to finding targets for intervention and developing drugs that will do so.

In phase 1 of this competition, Dr. Igor Stagljar of the University of Toronto and his team developed a new method for studying PPI interactions, called Split Intein-Mediated Protein Ligation (SIMPL), which outperforms current methods for studying PPIs. They now propose to further develop SIMPL as a groundbreaking assay for biomedical research by combining it with mass spectrometry to extend its capabilities and facilitate a more powerful and convenient platform. The team will also use SIMPL to globally map PPIs involved in disease, particularly cancer development. Finally, they will use SIMPL as a drug-screening platform to identify chemicals that can interfere in PPIs implicated in cancer development.

SIMPL will be a transformative technology for studying functional genomics. It will displace current methods of studying PPIs, accelerate our understanding of cell physiology and disease development and identify new therapies for some diseases. SIMPL will be commercialized through a newly founded Canadian company, ProteinNetwork Tx, ensuring both economic and health benefits for Canada.
TOP

Development of a digital microfluidic platform to identify and target single cells from a heterogeneous cell population for lysis in an ultra-low volume for non-invasive prenatal diagnosis

Project Leaders: Aaron Wheeler, University of Toronto; Elena Kolomietz and David Chitayat, Sinai Health Systems
Genome Centre: Ontario Genomics
Total Project Funding: $3 million

Currently prenatal diagnosis, by amniocentesis or chorionic villi sampling, is costly, is being done only by specialists in a small number of centers and carries a risk of miscarriage. Amniocentesis is done later in pregnancy, with results often not known until 17 weeks gestation. To reduce the cost, these prenatal diagnostic tests are usually offered only after an earlier prenatal screening test result or fetal ultrasound shows an increased risk for chromosomal abnormality. A safe, non- invasive and less expensive procedure, which can be done by a variety of health care professionals, would allow testing of all pregnant women for fetal chromosome abnormalities, rather than only those at an increased risk, as well as testing for single gene disorders of pregnancies at risk. This will relieve parental anxiety while reducing healthcare costs, substantially.

Experts at Mount Sinai Hospital have developed a method to collect fetal cells non-invasively, using a technique similar to a PAP smear. In the first phase of this project, Dr. David Chitayat and Dr. Elena Kolomietz from Mount Sinai worked with Dr. Aaron Wheeler and his team at the University of Toronto to develop a way to isolate and analyze these cells using microfluidics and genomic analysis. The team built a proof-of-principle digital microfluidic platform that it will now further develop for beta testing and validation for accuracy, precision, sensitivity and specificity in a clinical laboratory, culminating in a 550-patient clinical trial.

This new technique could transform prenatal diagnosis, providing a safe, non-invasive and inexpensive diagnostic test that can be performed as early as six weeks of pregnancy. With no other test like it available, it will compete in the multi-million dollar global market and save the healthcare system hundreds of millions of dollars. The technique will be commercialized through a start-up company that will attract investment and create job opportunities in Canada’s burgeoning high-tech/biotech sector.
TOP

Phase 1 Projects

AbSyn Technology for identification of synergistic cancer therapeutics

Project Leaders: Charles Boone, Jason Moffat
Institution: University of Toronto
Total Project Funding: $249,389

Genome sequencing has revolutionized our understanding of the genetic changes that lead to cancer. Unfortunately, treatment still remains in the relative Dark Ages, with decades-old treatments that can be highly toxic and that don’t consider the subtle genetic differences among each patient’s disease. Dr. Charles Boone and his team at the University of Toronto are developing AbSyn, a new technology that will identify combination therapies tailored to individual cancers. AbSyn stands for the development of antibodies (Ab), whose promise for treating cancer has been hugely under-realized, and synergistic (Syn) therapies for cancer based on these antibodies. AbSyn will change the way we prioritize and discover new cancer drugs, building a new bridge between the gap of biological understanding and the commercial drug discovery process.
TOP

RNA-seq in patient derived ex-vivo models: Genetic diagnostics beyond whole exomes

Project Leaders: James Dowling, Michael Brudno
Institution: The Hospital for Sick Children
Total Project Funding: $250,000

There are more than 6,000 rare diseases caused by mutations in a single gene; together they affect more than 500,000 Canadian children. Exactly what gene is causing a disease is unknown in more than half the cases. RNAseq may provide a strategy for discovering novel genetic mutations that cause rare diseases – but can’t be used without obtaining the specific tissues in which the disease is present. Drs. James Dowling and Michael Brudno, of The Hospital for Sick Children will use ex vivo disease models created at Sick Kids in place of tissue biopsies to perform RNAseq for gene mutation discovery. By combining recent advances in cell biology, genomics and bioinformatics, the lab will develop a new diagnostic methodology, fundamentally transforming the clinical diagnostics process.
TOP

Massively parallel single molecule protein sequencing in-situ

Project Leader: Andrew Emili
Institution: University of Toronto
Total Project Funding: $250,000

Proteins in cells are responsible for virtually every biological process. When they don’t work properly, the result can be human diseases such as cancer, Alzheimer’s, diabetes and heart disease. Dr. Andrew Emili of the University of Toronto will develop a revolutionary new sub-microscopic imaging technology that will allow researchers to identify and quantify each and every one of the many millions of different protein molecules present in human cells and tissues at an unprecedented level of detail. The proprietary chemical probes and tool “kits” he and his team develop will be applicable to a wide diversity of biomedical specimens, displacing existing technologies and ultimately changing the study of human cell biology and medicine.
TOP

RapidAIM: A high-throughput assay of individual microbiome

Project Leaders: Daniel Figeys, Alain Stintzi
Institution: University of Ottawa
Total Project Funding: $250,000

The more than 1,000 different species of bacteria that colonize our gastrointestinal tract are collectively known as our microbiome. Dr. Daniel Figeys and Dr. Alain Stintzi of the University of Ottawa are developing RapidAIM to gain information on how drugs affect the microbiome and vice versa. The team will also develop a computational program that will combine and analyze these results, to better predict drug efficacy and clinical outcomes. RapidAIM could allow rapid screening of candidate or current drugs for potential adverse microbiome effects. The economic benefits will come in the form of a commercializable assay and computational platform for the screening of human microbiomes.
TOP

Development of advanced genetic toolbox for Sinorhizobium meliloti to enable genome scale engineering

Project Leader: Turlough Finan
Institution: McMaster University
Total Project Funding: $250,000

Genetic engineering seeks to improve agricultural outcomes by enhancing traits such as disease resistance, drought tolerance or superior levels of production. Conducting this engineering, however, requires a host where genes can be implanted and researchers perform genetic manipulations – a process known as synthetic biology. Drs. Turlough Finan, Bogumil Karas and Trevor Charles are developing a bacterial surrogate host system (Sinorhizobium meliloti) that allows replication and engineering of large DNA fragments before reintroducing them back to the original organism. In addition to its general application for genome engineering, the S. meliloti surrogate host-system technology can be used in short-term technology developments, including the generation of large DNA libraries for bioprospecting.
TOP

Cell biosensors for rapid screening of insect attractants

Project Leaders: Peter J. Krell, Daniel Doucet
Institution: University of Guelph, Natural Resources Canada
Total Project Funding: $233,901

Forestry and agriculture together contribute close to eight per cent of GDP in Canada, but insect pests pose a continual threat. Functional genomics has long promised to bring new solutions to recurrent and new pest problems. Dr. Peter J. Krell of the University of Guelph, in collaboration with Drs. Daniel Doucet and Jeremy Allison (NRCan), is creating highly sensitive surveillance and mitigation systems targeting insects, using a family of insect genes known as odorant receptors (ORs). This innovation should not only disrupt the discipline of functional genomics, but also the field of insect pest management, making surveillance and mitigation more feasible and faster, while helping preserve Canada’s position as a leading exporter of forest and agricultural products.
TOP

Economical high throughput de novo whole genome assembly

Project Leaders: Stephen Scherer, Si Lok
Institution: The Hospital for Sick Children
Total Project Funding: $241,467

“De novo” sequencing, or constructing an individual’s genome from his or her own data alone (as opposed to comparing it to a reference genome), is a formidable task, akin to assembling a jigsaw puzzle comprising hundreds of millions of small blank pieces. Drs. Si Lok, Stephen Scherer, and their colleagues from The Hospital for Sick Children are developing a new “mate-pair” technology that would overcome the financial and logistical barriers to de novo sequencing by linking sequences to one or more other reads in precisely known orientations and distances. Mate-pair technology would create a high-resolution backbone to enable de novo sequencing to be carried out in a single simple step. This new adaptation of mate-pair sequencing is a disruptive technology that could supersede all current methods of de novo sequencing, thereby representing a leap forward in many areas of research and, ultimately, in healthcare.
TOP

Development of SIMPL, a novel protein-protein interaction assay based on split intein for biomedical research

Project Leader: Igor Stagljar
Institution: University of Toronto
Total Project Funding: $250,000

Proteins control every function of every cell in our body. Proteins, however, never act alone; rather, they interact with many other proteins in what are called protein-protein interactions (PPIs). Gain or loss of PPIs can be the driving force behind disease development. Dr. Igor Stagljar of the University of Toronto is leading a team to develop and implement a novel disruptive genomics technology that can detect and monitor PPIs in human cells. This technology can be used to identify novel proteins as components of many essential cellular processes, leading to greater understanding of the role of specific proteins in our cells. Furthermore, the technology also has the potential to identify drugs that disrupt a defined set of PPIs when the PPIs cause disease.
TOP

Solid-state nanopore-based quantification of low-abundance biomarkers

Project Leader: Vincent Tabard-Cossa
Institution: University of Ottawa
Total Project Funding: $250,000

Many illnesses, such as cancer or cardiovascular disease, leave physical evidence in our bodies, called biomarkers. Spotting these biomarkers early would make it possible to begin treatment with personalized, targeted therapy, or even prevent disease entirely. Solid-state nanopore-based devices can do this, but are too expensive for widespread use. Dr. Tabard-Cossa’s laboratory has pioneered a technique to fabricate nanopore devices more rapidly and at substantially lower cost than present-day technology. They are integrating the devices into a disposable cartridge within compact platforms offering comprehensive sample-in, answer-out capability. The lab is positioned to develop a point-of-care prototype that can be used in the lab and the clinic, resulting in significant economic and health benefits for Canada.
TOP

Functional genomics in human cells for drivers of lethal metastatic human cancers

Project Leaders: Michael Taylor, Rama Khokha
Institutions: The Hospital for Sick Children, Princess Margaret Cancer Centre
Total Project Funding: $250,000

Often in cancer it’s the spread of the cancer to other areas of the body, a process called metastasis, that kills. This is particularly the case with two highly lethal types of cancer, medulloblastoma (MB), the most common malignant brain tumour in children, and pancreatic adenocarcinoma, the fourth leading cause of cancer deaths in Canadians. Recent results from the lab of Dr. Michael Taylor of The Hospital for Sick Children have shown that the biology of the metastases is extremely different from the primary tumour, making it unlikely that treatments developed to treat the primary tumour will work on the metastases. Dr. Taylor has teamed with Dr. Rama Khokha (Princess Margaret Cancer Centre) to develop and deploy unique tools to discover the drivers of metastasis, helping to improve survival rates of Canadians with these deadly human cancers.
TOP

Development of a digital microfluidic platform to identify and target single cells from a heterogeneous cell population for lyses in an ultra-low volume

Project Leaders: Aaron Wheeler, Elena Kolomietz
Institutions: University of Toronto, Mount Sinai Hospital
Total Project Funding: $250,000

Genetic abnormalities are a leading cause of death among Canadian newborns and infants. Less invasive, less expensive prenatal diagnostic techniques that are able to provide relevant information at earlier stages of pregnancy are needed. Scientists and physicians at Toronto’s Mount Sinai Hospital have developed a method to collect and isolate fetal cells non-invasively, using a technique similar to a PAP smear. Now Dr. Aaron Wheeler’s research group at the University of Toronto is developing techniques to isolate and analyze these cells for prenatal diagnosis of genetic abnormalities. If successful, these techniques could transform the way prenatal diagnosis is delivered, resulting in higher coverage of the population, reduced patient anxiety, increased medical options for at-risk pregnancies and significant reductions in healthcare costs.
TOP

SANGRE-seq (systematic analysis of blood gene regulation by sequencing): Bringing RNA-seq to clinical diagnostics

Project Leaders: Michael Wilson, Adam Shlien
Institution: The Hospital for Sick Children
Total Project Funding: $249,934

Diagnostic tests based on blood samples are mainstays of the healthcare system. Adding RNA sequencing (RNA-seq) can extract more information from blood samples, including a snapshot of all the genes active in a patient’s blood cells. Such a snapshot can tell us about the current condition of the patient’s immune system, whether there are cancer cells in the blood and/or whether blood cells are fighting an infection. Drs. Michael Wilson and Adam Shlien of The Hospital for Sick Children are developing an RNA-based clinical test called SANGRE (systematic analysis of blood gene regulation in blood) that will provide unprecedented power to use RNA expression as a routine and affordable test that can better diagnose disease, disrupting clinical practice and improving the health of Canadians.
TOP

Phase 2 Projects

Synthetic inhibitors of ubiquitin-binding cancer targets

Project Leader: Sachdev Sidhu
Institution: University of Toronto
Total Project Funding: $3,009,018

Our cells remove damaged or nonfunctional proteins through a small protein called ubiquitin, which attaches to target proteins and signals their destruction. In many diseases, ubiquitin does not work as it should. Dr. Sachdev Sidhu of the University of Toronto is using an innovative high-throughput molecular genetics engineering platform, which is unique in the world and has attracted intense interest from industry and academia, to enable the rapid and cost-effective development of highly specific and potent ubiquitin-like molecules. These molecules attach to key, cancer-associated enzymes of the ubiquitin system, to block or enhance their function. The project will enable the discovery of new drug targets, speed up drug development and generate effective anti-cancer drugs with fewer side effects, all of which should be of great socio-economic benefit to Canadians.
TOP

The Mammalian Membrane Two-Hybrid (MaMTH) assay: Advanced proteomics technology for biomedical research

Project Leader: Igor Stagljar
Institution: University of Toronto
Total Project Funding: $3,000,000

Integral membrane proteins have roles in many human diseases, but are notoriously difficult to study due to their unique biochemical features. Dr. Igor Stagljar and his team at the University of Toronto recently developed a powerful new technology, the Mammalian Membrane Two-Hybrid (MaMTH) assay, which can map protein-to-protein interactions (PPIs) of integral membrane proteins directly in the natural context of the cell. They now propose to further develop MaMTH technology by converting it into a platform that can map these PPIs on an extremely large scale. This work will allow researchers to develop better-targeted therapies for human disease more rapidly. The technology will be the foundation for an Ontario-based company called Protein Network Sciences that will offer easy access to this novel disruptive MaMTH technology, advancing biomedical research and therapeutic discovery while benefiting Canadian social and economic infrastructure.
TOP