The project, led by Dr. Adrian West, a bioengineer and assistant professor in physiology and pathophysiology is supported through the Government of Canada’s New Frontiers in Research Fund (NFRF) – Exploration stream, a fund dedicated to investing in high-risk, high-reward research to support world-leading innovation.

The multidisciplinary research team from the Rady Faculty of Health Sciences also comprises Dr. Joseph Gordon, associate professor of nursing, and Dr. Brad Doble, associate professor of pediatrics and child health (cross-appointed in biochemistry and medical genetics), with additional support from clinical genetic collaborators specializing in rare metabolic diseases.

Support for research to improve discovery of new treatments for rare heart disease is much needed. There are 7,000 known rare diseases affecting more than 3 million Canadians, representing a significant health, economic and social burden. Adding further strain to this challenge, heart tissue samples from rare disease patients are incredibly scarce, resulting in limited understanding of the metabolic and functional changes that lead to heart failure.

To address this knowledge gap, the multidisciplinary team will work with rare heart disease patients to replicate their unique tissue and cells within 3D bioprinted structures.  This UM-led innovation will be accessible to other laboratories to create unique heart tissue structures that will support greater understanding of treatment options. While most tissue engineered heart models aim to create healthy heart muscle, this research is unique in that it will replicate the tissue and stem cells of people with rare diseases to better understand their treatment options.

“With this exploration grant, we now have the opportunity to elevate our technology to create accessible 3D bioprinted heart tissue of patients with rare metabolic diseases,” said West. “The advantage of our research is we can recreate not just the form of a patient’s heart, but also its function in both physiology and disease.”

Co-principal investigator Gordon will have a lead role in the project by overseeing adaptation of existing heart disease models to the 3D bioprinting context. He will also direct metabolic analysis of the bioprinted muscle and administer novel treatments aimed at recovering metabolic function.

“This research will address the critical need to improve the way that rare diseases are studied in order to support customized patient treatments and improve health outcomes in Canada,” said Gordon.

The project is also supported by the expertise of Doble, a stem cell biologist and the inaugural Bihler Chair in Stem Cell Research, whose lab is located on the Bannatyne campus. His extensive experience in stem cell biology will contribute significantly to the project as he will direct all aspects of stem cell culture including growing patient cells and turning them into heart cells.

“This funding will help us disseminate our knowledge across institutions and hospitals in Canada and around the world as we build upon our work at UM,” said Doble.

“We are proud to be home to this bold innovation here at UM,” said Vice President (Research and International) Dr. Mario Pinto. “This funding recognizes the incredible possibilities when researchers take risks and work together across disciplinary boundaries. Through a cutting-edge, multidisciplinary approach, this team will make significant advancements in understanding rare metabolic diseases and finding new treatments to improve patient care both at home and around the world.”

The NFRF 2022 Exploration competition is funding 128 research projects that are bringing disciplines together in novel ways to form bold, innovative perspectives. The competition is administered by the Tri-agency Institutional Programs Secretariat on behalf of Canada’s three research granting agencies: the Social Sciences and Humanities Research Council, the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council.

Dr. Adrian West, an assistant professor of physiology and pathophysiology, Max Rady College of Medicine, said it is truly an honour for his team to receive the first-ever Winnipeg Foundation Innovation Fund grant.

“The fact that The Winnipeg Foundation has the vision to invest in something like this is fantastic for our program because it really lets us develop these unusual ideas and push them forward to the national level,” he said. “High risk, high reward is always going to be difficult to fund and I think that’s the project we’re doing.”

The Winnipeg Foundation committed $1 million last year to give health sciences researchers at the UM the opportunity to work on innovative interdisciplinary research and develop projects to the point of qualifying for additional external funding.

West is collaborating on the project with Dr. Vernon Dolinsky, associate professor of pharmacology and therapeutics, Max Rady College of Medicine, and Dr. Joseph Gordon, associate professor in the College of Nursing and of human anatomy and cell science, Max Rady College of Medicine. All three are research scientists at the Children’s Hospital Research Institute of Manitoba.

The project, which was awarded close to $100,000, is looking at the origins of diabetic cardiomyopathy, a cardiovascular disease that makes it harder for the heart to pump blood throughout the body and can lead to heart failure. West said this research is important because 80 per cent of people with diabetes ultimately die of heart disease.

The team will build heart tissue using a 3D bioprinter, which creates the tissue by combining cells, biomaterials and growth factors that imitate natural tissue. West said that 3D bioprinting allows them to create a more realistic environment for cells than in a petri dish.

“Cells aren’t flat,” West said. “Cells aren’t squished. Cells are three dimensional in nature and by creating these 3D bioprinted culture models it makes it much like it is in the body.”

They’re building the heart tissue with samples that are exposed to diabetes-like conditions during growth and development to see what underpins diabetic cardiomyopathy. Once they’ve developed a model that replicates the disease, they can test a variety of different treatments and scientists around the world can follow their model.

West said that this research will lead to building tissues with human stem cells. The idea is that they will take a cell from a patient, grow it in a dish, build a piece of their own heart and test a treatment that is personalized to them, he said. It will give them the ability to potentially test drugs and treatments on a patient’s own cells rather than just relying on the results they derive from standard cell cultures and animal models.

Dr. Peter Nickerson, vice-dean (research), Rady Faculty of Health Sciences, said that The Winnipeg Foundation Innovation Fund is unique because it can allow transformative research like West’s to take place.

“It is a bit higher risk, but if it pays off, it really will be not just a couple steps forward, but a leap forward from where we are today,” Nickerson said. “What we’re trying to achieve with The Winnipeg Foundation Innovation Fund is bringing teams together with really innovative ideas. We’ll then give them the seed money to bring that idea to life and see if they can get enough of a launch to then apply for national funding to move it to the next level.”

The Winnipeg Foundation Innovation Fund grant has already helped West’s team with future funding.

“Knowing that somebody had the confidence to fund this project, it’s already strongly advanced our other grant applications,” West said. “Just by The Winnipeg Foundation Innovation Fund grant being available has helped us apply for that grant a year, two years earlier.”

“Investments like today’s in Canada’s research infrastructure are incredibly important to the nation’s future. They give Canadian researchers the tools they need to make new discoveries that will better the lives of Canadians today and for years to come,” says federal Minister of Science Kirsty Duncan.

The investment made by the Government of Canada is part of the Canada Foundation for Innovation’s (CFI) John R. Evans Leaders Fund. This fund helps universities attract and retain the best and brightest researchers from around the world by giving them access to cutting-edge research tools.

“These investments will inspire a new generation of young explorers in the fields of science, technology, engineering and mathematics,” says federal Minister of Natural Resources Jim Carr.

“These diverse investments will support researchers in a wide range of cutting-edge scientific endeavours that will help solve problems and benefit people from this province and beyond,” says Manitoba’s Minister of Growth, Enterprise and Trade Cliff Cullen.

Canada is committed to providing strong support for new research innovation and infrastructure and University of Manitoba researchers tackle issues that matter to the lives of everyday Canadians—from spinal cord research to near real-time electromagnetic imaging that will expand the capabilities of Canada’s healthcare, agricultural, and wireless technology industries.

“This funding provides important infrastructure to allow the University’s research laboratories to be both state-of-the-art and world-class. It also enhances the educational experience for students by giving them the opportunity to work and learn from some of the best researchers in Canada and, indeed, the world,” says Digvir Jayas, Vice-President (Research and International) and Distinguished Professor at the University of Manitoba.

The funded nine

Researchers: Kristine Cowley (and Katinka Stecina), Physiology
Funded: Human Spinal Cord Injury Research Centre for Health, Balance and Motor Control

Impact: Research in the proposed Human Spinal Cord Injury Research Centre for Health, Balance and Motor Control will identify how neurons in the human spinal cord contribute to movement and how we can enhance this function after spinal cord injury (SCI). Thus a major goal of this research program is to develop novel training and rehabilitation strategies based on a better understanding of spinal cord function. Another important goal is to reduce obesity and thereby improve health after SCI. This will be achieved by developing and scientifically validating novel exercise-based strategies designed for those with impaired motor function.

Thus, “state of the art” testing facilities will be developed, including non-invasive brain stimulation, muscle recording, and a suite of specialized exercise equipment designed for use by those with reduced muscle function. This program will also train highly skilled researchers. The knowledge gained will lead to new rehabilitation guidelines and be translated to health personnel and Canadians living with SCI, ultimately reducing societal costs related to SCI: There are over 80, 000 Canadians living with SCI and the average paralyzed person requires over $1.5 million in health care because of medical issues stemming from lost basic functions like standing and walking and running.

Researcher: Rebecca Davis, Chemistry
Funded: Laboratory for Asymmetric Organocatalysis 

Impact: Living organisms are comprised of chiral molecules including amino acids, proteins, and sugars. These molecules are typically present in only one three-dimensional form (enantiomer), and as a result, biological organisms can respond differently to the two enantiomeric forms of a compound. In terms of drug development, this means that the two enantiomers of a single compound can have vastly different activities and side effects. It is an ongoing challenge and requirement to develop robust and reliable catalytic processes that produce a single enantiomer of a compound. With the state of the art equipment requested in this proposal, Dr. Davis proposes to overcome this challenge through the development of novel methods for converting cheap, abundant organic substrates into industrially relevant, single enantiomer compounds. The results of this work will serve to expand the toolbox of enantioselective organic reactions, providing the foundational knowledge and techniques necessary for the efficient production of a wide range of pharmaceuticals and agrochemicals.

Researcher: Chuang Deng, Mechanical Engineering
Funded: In-situ Nano-mechanical and Nano-electrical Characterization of Low-dimensional Nanomaterials

A CRUMPLED GRAPHENE SHEET ON A SILICON WAFER // IMAGE: KONSTANTIN NOVOSELOV

Impact: The requested equipment will be used to perform state-of-the-art mechanical and electrical characterization of 1D and 2D nanomaterials. When materials are reduced to nanoscale, many novel properties emerge. As an example, 1D metal nanowires and nanotubes have the potential to exhibit strength up to 1000X than that of conventional bulk metals. Many novel electronic or photonic properties also emerge in nanowires or nanotubes, which make them ideal for constructing “miniature” devices like nanosensors, nanorobots, and nanogenerators. Nanogenerators, for example, could potentially exploit human body movement to power wearable electronics. Graphene, which is 2D sheet made of a single layer of carbon atoms, holds great promise in the design of flexible batteries that charge faster and last longer than conventional batteries. There is an urgent need to understand how the structures of these materials define their properties, but their small size makes them hard to handle and characterize.

The work enabled by the requested instrumentation will reveal the mechanisms that lead to an extraordinary mechanical and electrical properties of nanomaterials. This will make it possible to optimize their physical properties so that they can be used as building blocks for nano-devices like sensors, transistors for superfast computers, and high efficiency solar cells and battery systems. This will have a direct impact on Canada’s emerging nanotechnology industry.

Researcher: Joseph Gordon, Nursing/CHRIM
Funded: Comprehensive in Vivo and Culture-based Exercise and Metabolic Analysis Platform

Impact: Exposure to maternal diabetes during development is now recognized as a risk factor for early-onset type 2 diabetes in youth. However, the reasons why this occurs are not completely understood. The new equipment will allow research on: 1) how exposure to maternal diabetes causes insulin resistance in developing muscle by changing fetal metabolism; 2) the mechanisms responsible for the higher cardiovascular risk associated with exposure to maternal diabetes during development; and 3) development of several new treatments to prevent youth-onset insulin resistance and cardiovascular disease associated with type 2 diabetes.

This research will improve cardiovascular health and quality of life for youth with type 2 diabetes and benefit the Canadian economy and health care system.

Researcher: Ian Jeffrey, Electrical & Computer Engineering
Funded: Near Real-time Electromagnetic Imaging

Impact: This research concerns three applications of electromagnetic imaging: low-cost and safe microwave imaging for frequent breast cancer screening and monitoring, radio-frequency monitoring of stored grain to prevent spoilage losses, and source reconstruction methods for faster and cheaper testing of new antennas. Electromagnetic imaging algorithms involve huge amounts of computation, and can take hours to produce an image even with powerful and expensive distributed, high-performance computing hardware. This is not cost effective, and because computer systems like this are large and cannot be directly integrated with imaging hardware, electromagnetic imaging is not currently commercially viable.

Gordon’s research will develop entirely new high-order fast algorithms that are compatible with co-processor (graphics card) acceleration. This will result in state-of-the-art software that can produce accurate, 3D images in near realtime (i.e. minutes) on relatively inexpensive, 64-core computers with high end graphics cards that can be fully integrated with imaging system hardware. Gordon and his research team at the University of Manitoba’s Electromagnetic Imaging Lab have over a decade of experience developing tools of this type. New, state-of-the-art imaging algorithms will make electromagnetic imaging technology commercially attractive and unlock its potential to expand the capabilities of Canada’s healthcare, agricultural, and wireless technology industries.

Researcher: Sachin Katyal, Pharmacology/RIOH-CCMB
Funded: Identification of Novel Therapeutics to Modulate DNA Damage Repair in the Treatment of Cancer

DNA

Impact: Malignant glioma (MG) is one of the most devastating forms of brain cancer. This deadly disease has a dismal survival rate of approximately one year after diagnosis. Treatment includes surgery followed by radiotherapy and chemotherapy. Unfortunately, the chemotherapy of choice only enhances patient survival by 3 months, mainly due the tumour cell becoming resistant, tumour recurrence and metastasis. Despite advances in drug delivery, there is a lack of effective anti-MG therapies and patient treatment ultimately becomes palliative. Furthermore, MG treatment regimens are very taxing on the Canadian public and its health care system.

CFI-sponsored infrastructure will enable Katyal to study the over-activity of the brain tumour’s cellular DNA repair mechanisms using methods that allows analysis of each individual cell’s DNA repair activity. Through these studies, Katyal will be able to discover how these tumours are able to resist chemotherapy. Katyal will also identify new drugs that can combat both the initial brain tumour and subsequent brain tumours that recurs due to resistance to commonly used anti-cancer chemotherapies.

Researcher: Peter Pelka, Microbiology
Funded: Studies of Cellular Reprogramming by Adenovirus

Impact: Adenoviruses are a family of small DNA viruses that cause a variety of diseases in humans, and, importantly, were shown to cause cancer in animals. One of the genes responsible for these properties of the virus is the E1A gene, which is the first gene expressed after cells are infected with the virus.

Pelka will exploit this property of E1A to investigate how E1A modulates the activities of cellular hub regulators, proteins that frequently are involved in cancer and carcinogenesis. The proposed work aims at identifying novel modulators of the cell cycle and differentiation, processes deregulated in cancer. Understanding these processes on a fundamental level, which the proposed experiments enable us to do, is crucial to developing new cancer therapies.

Researcher: Qiuyan Yuan, Civil Engineering
Funded: Infrastructures for Zero Waste Research Program

Photo: Alan Levin, Flickr

Impact: Solid waste in Canada represents both a growing problem as well as an opportunity for economic growth. Solid waste is traditionally disposed of in large landfills. Approximately 24 million tonnes of municipal solid waste are sent to landfills annually. The decomposition of the material being sent to these sites is posing environmental challenges in terms of toxic compounds leaching into and contaminating groundwater, and the production of greenhouse gases like methane, which exacerbate the progression of climate change. In fact, about 20 per cent of Canada’s methane emission comes from landfill. 

CFI has invested in infrastructure to establish a Zero Waste Research Laboratory at the University of Manitoba. This will support the development of new techniques that would allow diversion of the waste materials away from landfills and into processing streams that can produce commercially valuable end products like compost and biogas. As a result, this program will 1) benefit the environment by decreasing the greenhouse emissions from the landfill, 2) promote solid waste industry growth; and 3) advance the technology and training of more high qualified personnel in the solid waste treatment.

Researcher: Adrian West, physiology
Funded: A Tissue Engineering Platform for Fibrotic and Developmental Diseases

Impact: Asthma is a major concern for child health. Severe asthma is difficult to treat because irreversible structural changes in the lung significantly change the way that lung cells function. The effects of these structural changes are difficult to study, because traditional cell culture experiments use stiff plastic substrates that do not accurately replicate the in vivo environment in health or disease.

Three dimensional (3D) bioprinting is an exciting new technology that allows us to build better experimental models of structurally remodelled lung tissue. CFI’s latest investment will allow West to purchase a 3D bioprinter to produce rings of airway smooth muscle, a tissue comprised of cells that are important in the development of asthma. Making these rings softer or stiffer better represents the structural differences between healthy and diseased lungs. The rings will then be tested using a powerful new analysis system to determine why airway smooth muscle behaves differently in asthma.

West will then use the 3D bioprinter to develop disease models of other structurally remodelled tissues including blood vessels, skeletal and heart muscles. These new bioprinted models will allow us to better study how cells behave in healthy and diseased tissue, which will increase our understanding of how changes in organ structure affect cell function. This is an important step towards developing new treatments that improve the health of patients.