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Diverse Chemical Libraries

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Synthetic chemical libraries are a common source of drug discovery molecules. The challenge is that these libraries adhere to synthetic structures and biological activities. By contrast, naturally occurring chemicals have a vast diversity of structure, but their industrial or medical uses are limited due to the complexity and inaccessibility of these natural products.

Drs. Eiji Nambara, Peter McCourt (University of Toronto) and Dario Bonetta (University of Ontario Institute and Technology) plan to take these chemical libraries and expose them to a plethora of plant enzymes to exponentially increase the diversity of compounds with the hope of finding novel functions.

The team is using plant genomics resources to create libraries of various chemical compounds for industrial uses. In an effort to produce the advantages of these two systems, this project aims to set up an enhanced system to evaluate metabolic conversion of diverse chemical library by plant xenobiotic enzymes, which will be useful sources to identify chemicals with new functions.


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Biosensors for Healthy Plant Growth

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Plant hormones determine plant growth, and breeding programs designed around hormone action have a big impact on crop yields.

Strigolactones (SL) are plant hormones that stimulate the growth of symbiotic mycorrhizal fungi that help promote plant growth and development. However, SL also triggers the germination of parasitic plant seeds that can compete with key crop plants, especially in the developing world. To better understand how these hormones interact with their receptors in plants, Dr. Peter McCourt (University of Toronto) and his team will use synthetic biology to develop a biosensor for SL activity. With SPARK and additional support from the DOE-Joint Genomics Institute, the team will synthesize over 250 SL receptor variants that will be screened for activity within the plants. This information will be used to develop a toolbox to promote the healthy growth of agriculturally important plants, instead of the noxious plants that compete with them.


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A Genetic Toolbox for Tomato Flavour Differentiation

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Tomatoes, it is said, are the quintessence of summer in a bite. They are also responsible for more than half a billion dollars in annual farm gate sales and are Canada’s biggest fresh vegetable export. Canadian growers are facing competition due to lower production costs in other regions, leading to difficulties maintaining their market share. Canadian producers need to innovate in order to offer a differentiated product that will give them a competitive edge.

Generally, plant breeding programs focus on production traits such as yield or disease resistance. Drs. Charles Goulet (Université Laval) and David Liscombe (Vineland Research and Innovation Centre) are collaborating to ensure that new tomato varieties possess these traits, and something more important to the consumer – flavour. The team was awarded $1.8 million for this project, co-led by Genome Quebec and Ontario Genomics.


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Affordable Solutions to Clean Up Wastewater

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In response to a need for a simpler, more cost-effective and environmentally responsible solution for treatment of wastewater, Ontario Genomics provided financial support to Bishop Water Technologies (BWT) to partner with Dr. Christopher Weisener and his colleague Dr. Rao Chaganti of University of Windsor. This research project also earned an NSERC Engage Plus award, based on previous success with an NSERC Engage grant for which Ontario Genomics contributed strategy and proposal development.

Their goal? To find a solution for BWT’s product, BioCord, that would be:
  • affordable to communities
  • environmentally responsible
  • simpler to operate
  • compliant with Federal and existing provincial regulations
Towards a unique collaboration

We know that the composition of nutrients (i.e., phosphate, nitrate levels) varies across different water environments, and microorganisms accumulate different types of nutrients. Biofilm forms when a natural substance like bacteria adheres to water surfaces and creates a slimy residue. Although biofilm grows on any surface where water and nutrients are present, some natural systems only provide a limited amount of surface area for biofilm to develop.

Bishop Water Technologies (BWT) is an Ontario-based technology and engineering water company which delivers a unique and innovative suite of services and solutions for environmental challenges facing the water industry.

One of BWT’s products is BioCord, a man-made inert polymer scaffold that provides more surface area for nutrient cycling biofilm to develop, thereby improving the efficiency of (waste) water treatment at a fraction of the cost, without requiring any chemicals. BWT offers 10 types of BioCord to its clients and evaluates parameters of the water to be treated such as biological oxygen demand (BOD) and number of suspended solids in order to select the best type of BioCord.

With financial support from Ontario Genomics, as well as scientific expertise from Dr. Christopher Weisener, the team is working together to characterize the microbial ecosystem through genomic sampling. This will support future studies to identify and quantify microbes as well as determine their activities within each type of BioCord to understand nutrient removal, ultimately improving the cost and efficiency of wastewater treatment and reducing point source nutrient loads to the Great Lakes.


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Novel Cancer Immunotherapy with Genomics

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Nearly all (96 percent) people aged 65 or older diagnosed with acute myeloid leukemia (AML) die within five years, as do two-thirds of younger patients. Because it primarily affects older people, the incidence of this aggressive cancer is expected to rise in the coming years as the population ages. Chemotherapy regimens for AML have remained essentially unchanged since the 1970s. With standard treatment, many patients can achieve remission, but most will relapse; following relapse two-thirds of patients will die within three years.

One of the reasons for the high rate of relapse in AML is that standard chemotherapy does not kill leukemia stem cells, leaving them to grow and mature into new leukemia cells. Leukemia stem cells express high levels of a protein called CD47. This protein sends a “do not eat” signal that stops white blood cells of the immune system called macrophages from surrounding and “eating” cancer cells.

With previous support from Genome Canada and Trillium Therapeutics Inc. (TTI), a publicly traded biotech company in Toronto, Canada, Dr. Jean Wang and team at the Princess Margaret Cancer Centre, University Health Network, and Dr. Jayne Danska and team at SickKids have developed SIRPaFc, a novel therapeutic that blocks the “do not eat” signal, freeing the immune system to attack leukemia stem cells. With new funding of $3.4M, Drs. Wang and Danska and TTI are again collaborating to complete formal preclinical studies and to carry out clinical trials aimed at demonstrating SIRPaFc’s safety and efficacy. This will help realize the commercial potential of this promising discovery.


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New Genomics Analysis Methods with Micro Laser Beams

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Not all cells in our bodies are created equal. Scientists around the world are working hard to understand the differences. The work has been difficult, because even seemingly uniform tissues like skin can consist of a diverse population of cells, usually in many different states. The differences between cells are important because, for example, they can lead cells to respond in surprisingly different ways to the same drug treatments. Progress has been slowed by the lack of good tools for accurately tagging individual cells in intact tissues for careful study. Researchers in Ontario are developing innovative technologies to address that need.

Drs. Matthew Bjerknes and Hazel Cheng (University of Toronto) aim to develop new methods for measuring the genomic status of single cells in intact tissues. Collaborating with scientists at the University of Georgia, the research team will validate and optimize efficient methods using micro laser beams to attach unique barcodes to cells. This will make single cell genomics more accessible to labs with limited resources and provide researchers with an effective, low-cost, and easy to use methodology for tagging individual cells in intact tissues for genomic analysis.


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Preclinical Development of Drugs for Intracerebral Hemorrhage (ICH)

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Intracerebral hemorrhage (ICH) is a form of brain hemorrhage responsible for 10 percent of all strokes. It affects about 90,000 people in North America each year, more than half of whom either die or are disabled. Anywhere from one-quarter to 44 percent of those who survive have recurring ICH. The annual economic burden of ICH is estimated at $300 million to Canada and $6 billion to the United States. Apart from treating hypertension, which is one of the causes of ICH, there is currently no way to prevent recurrent ICH.

Dr. Xiao-Yan Wen, director of the Zebrafish Centre for Advanced Drug Discovery (ZCADD) and his team at St. Michael’s Hospital, used genomics-driven research tools to identify several existing drugs that are already approved by the US Food and Drug Administration (FDA) that have shown the ability to prevent ICH in zebrafish models. Edge Therapeutics partnered with Dr. Wen in this project, to perform preclinical studies on the most potent anti-ICH molecules known as EZF-0100 for treatment of ICH and brain microhemorrhages (BMH). The project was awarded $5.9 million.


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Genomics to Create Biopolymers from Tree Biomass

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In a world that is requiring increasingly biological-based solutions to meet a growing need for sustainable materials, tree biomass remains one of the most abundant resources on earth. Ontario researchers are applying genomics technologies to create materials from underutilized tree biomass to replace those made from fossil fuels used in everyday products — such as resins, adhesives and food packaging. These innovations will create higher value bioproducts, reduce our carbon footprint, and develop new tools for effluent treatment and energy recovery.

While there is general appreciation of the potential of microbial enzymes in expanding the range of products made from tree biomass to date, biotechnology development has focused largely on the deconstruction of renewable biomass into sugars that can then be converted through fermentation to biofuels.

Drs. Emma Master of the University of Toronto and Harry Brumer of UBC are leading a team looking in the other direction. Their project SYNBIOMICS is distinguished from other projects by focusing on biocatalysts that upgrade (rather than degrade) tree biomass to create and replace materials made from fossil fuels used in everyday products, from adhesives to packaging. By upgrading biomass, Synbiomics aims to leverage the unique qualities of Canadian bioresources, which can open new opportunities for the Canadian forestry sector.

The project will also foster small and medium-sized enterprises that will work together synergistically with nearby pulp mills, creating lasting knowledge-based economic opportunities for Canada’s forestry sector and breathing new life into rural communities across Ontario.

Quick facts:
  • As part of this project, the research team is coordinating an iterative bioproducts development cycle with end-users to ensure sustainability.
  • The team is also developing economic ecosystem models for small and medium enterprises in the forestry sector.
  • Additionally, the project includes a research component to develop predictive tools for effluent treatment and energy recovery, thereby reducing both economic and environmental burdens for Ontario.

For more information about the SYNBIOMICS projects, please visit http://www.synbiomics.ca/.


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Reducing Sulphur Contamination in Mining Wastewaters

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Sulfur-contaminated wastewater is the largest global mining-related environmental liability, with a legacy cost of trillions of dollars. Ontario researchers are applying genomics technologies to develop innovative monitoring, management and treatment tools. These innovations will safeguard the quality in receiving waters, better monitor, manage and reduce toxicity, and generate new tools to support cost-benefit decision-making.

The Canadian mining sector is a cross-country presence, with mines in every province and territory contributing more than $57 billion to the economy (3 percent of Canada’s GDP) and employing over 375,000 people. As pressures on Canada’s freshwater water supplies grow, the sector as a whole, is seeking to develop the most sustainable approaches to mining possible. Mining wastewaters contain sulphur compounds, which can cause acidification and toxicity in receiving waters if not properly managed. Currently the industry lacks effective monitoring tools and innovative biological solutions to better control these contaminants.

Dr. Lesley A. Warren of the University of Toronto, along with Dr. Jillian Banfield of University of California, Berkeley, is leading a project that will apply genomics, geochemistry and modeling to mining wastewaters to develop innovative biological monitoring, management and treatment tools. The integration of genomics will provide understanding of bacterial opportunities in these wastewaters for new flexible management and treatment options to safeguard the quality of wastewater.

Lesley Warren, McMaster University, and Stephanie Marshall, Glencore, discuss how their collaboration can help better understand the role of microbes and how genomics information can be used to meet the goals of environmental stewardship, efficiency and sustainability in the mining industry.

Quick Facts
  • This project — the first of its kind in Canada and possibly the world — involves three mining and two environmental consulting companies, provincial and national sector industry associations and government.
  • Project collaborators are focused on ensuring the project’s findings are applied to lowering costs, decreasing risk of environmental damage, reducing liabilities for the industry and developing better safeguards for Canada’s vital freshwater supplies.
  • The project includes a research component to develop a Risk and Options Assessment for Decision-making. This process will enable translation of the team’s scientific knowledge into a nested set of decisions to help guide mining operational practices, corporate strategic planning and policy development.


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Competitive Dairy Production

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Demand for aged cheddar is increasing, requiring Canadian producers to increase their manufacturing capacity in order to remain globally competitive. To achieve this goal, researchers at the University of Guelph are implementing genomics-based tools to improve manufacturing processes and controls, significantly increasing the production capacity of high-quality aged cheese, and generating higher revenues for dairy farmers.

Trade deals — such as CETA — make it more urgent for Canadian dairy producers to gain efficiency and protect their market share.

Led by Dr. Gisele LaPointe, a team at the University of Guelph has partnered with Parmalat Canada to better understand the microbiota of cheese and increase its manufacturing capacity. The microbial components of cheese play a key role in its physical, chemical and organoleptic properties, such as taste, sight, smell, and texture. By validating and implementing genomic-based tools, this project will improve manufacturing processes and controls to overcome current bottlenecks and significantly increase the production capacity of high-quality, competitive aged cheddar cheese.

With over 120 years of brand heritage in the Canadian dairy industry, Parmalat Canada is committed to the health and wellness of Canadians and markets a variety of high-quality food products that help them keep balance in their lives. Parmalat Canada produces milk and dairy products, fruit juices, cultured products, cheese products and table spreads, employing more than 3,000 people, with five operating facilities in Ontario and eleven more across the country.

This project will bring the Canadian knowledge base related to cheese making processes into a new era. With increased production of high-quality cheese, Parmalat will contribute even more to the Canadian economy. At the same time, our dairy farmers will benefit significantly from the increased demand for and utilization of Canadian milk and increased revenues for dairy farmers estimated at approximately $28 million a year.

Quick Facts
  • Cheddar is the most popular cheese around the world.
  • Parmalat Canada’s commitment to quality and innovation has helped them become one of the largest food group companies in Canada, and the largest dairy company in Ontario.
  • Parmalat is the top producer of premium-quality, award-winning aged cheddar (winner of the 2016 world cheese championship – see http://baldersoncheese.ca/about-us/awards/).


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