UPDATE Dec. 5, 2024: The Canadian Glycomics Network, also known as GlycoNet, will give approximately $4.5 million in grants to 21 research projects, including six led by University of Alberta principal investigators and three that include U of A faculty on their research teams. Industry collaborators, health foundations and business partners are co-investing approximately $7.5 million to bring the total investment to $12 million over the next two years. The projects explore a range of human health challenges including cancer, transplant rejection and Alzheimer’s disease.
When you talk about carbohydrates, most people’s minds immediately go to the culinary world. But they’re also the central focus of a branch of science called glycomics, the study of complex carbohydrate molecules called glycans. Glycans are found in the cells of every living thing, from humans to plants and bacteria, making them an area of study with big impact.
“It’s a branch of science that affects pretty much every aspect of biology,” says Warren Wakarchuk, scientific director of the Canadian Glycomics Network (GlycoNet), the only glycomics research and commercialization hub of its kind in the country.
More than 30 U of A researchers from diverse disciplines are GlycoNet members, studying a range of glycan-related subjects involving everything from human health to food security to environmental sustainability.
“We have people who are working on animal vaccines, on small-molecule drugs for neurodegeneration, on new anti-infective strategies,” says Wakarchuk, who is also a professor in the Department of Biological Sciences at the University of Alberta. “There’s a whole bunch of really practical things coming out of the research.”
“If you think about the major classes of molecules, everybody’s heard of DNA, of RNA, protein, fat,” adds Wakarchuk, “but they haven’t necessarily heard of glycans.”
GlycoNet was one of the recipients of the Government of Canada’s inaugural Strategic Science Fund competition, awarded $24.7 million in funding over five years. GlycoNet Integrated Services also recently received $1 million in funding from Genome Canada to support infrastructure for the national network.
Here are just a few of the GlycoNet researchers at the U of A who are advancing the science of carbohydrates with the goal of improving human health and well-being.
Jason Acker: Preserving cells and tissues more effectively
When Jason Acker was trying to figure out the best ways to store and preserve cells and tissues outside the body — something that’s critical for everything from blood transfusions and organ transplantation to cell-based immune therapies — he turned his attention to nature. After all, animals like fish and frogs can survive freezing temperatures without ice forming in their bodily fluids — so if he could manufacture something that mimicked those adaptations, it would change the way researchers and medical professionals store and preserve these essential materials.
Synthetic carbohydrates that prevent ice from growing in and around cells were the answer. With professor Rob Ben from the University of Ottawa, Acker co-founded PanTHERA CryoSolutions, a spinoff company that designs and manufactures cryopreservation solutions for cells, tissues and organs. Acker himself holds 12 patents in the area of cell preservation and microfabrication, and one of PanTHERA’s involves their ice recrystallization inhibitor (IRI) technology, which offers a more effective way to preserve delicate biological materials.
GlycoNet’s involvement began when the cryoprotectants were still at the idea stage, and subsequent support fuelled the development of the first generation of IRI compounds as well as the growth and expansion of PanTHERA.
“The support that PanTHERA has received from GlycoNet has been instrumental to our success,” says Acker. “GlycoNet not only helped us develop the science and protect our platform small molecule ice recrystallization inhibitor technology, but provided important resources and contacts which have supported our growth as a company.”
“If you look at the details of the science itself, it’s really quite exciting,” says Wakarchuk. “They’ve been chasing down these compounds which are showing a lot of promise in tissue regeneration and cell therapy.”
Acker’s innovative work is one of the reasons the U of A has become an international centre of excellence for cryopreservation, says Wakarchuk: “He’s a force to be reckoned with.”
Simonetta Sipione: Getting to the roots of neurodegenerative diseases
Gangliosides — complex molecules that contain and have the properties of both carbohydrates and lipids — are abundant in the nervous system and play an important role in brain functioning and cell signalling pathways. But our understanding of these molecules is still quite limited — a knowledge gap that Simonetta Sipione is looking to address.
Sipione, a professor in the Department of Pharmacology, studies the role of gangliosides in neurodegenerative diseases like Huntington’s and Parkinson’s. Her research, and work by others, has shown that people with these disorders typically have reduced levels of gangliosides. Understanding how this anomaly affects disease onset and progression is key to developing potential treatments that can stop or slow down neurodegeneration, rather than just the symptoms, and requires a deeper understanding of ganglioside function at a molecular level.
“Her research program has been focused on some of the subtleties around these glycolipids, which are really important in the brain,” says Wakarchuk. “For any sort of neurodegenerative process, you can be pretty sure that a glycolipid has some role to play there.”
Sipione has shown that providing certain gangliosides to animal models of Huntington’s can block disease progression and symptoms. “We are uncovering exciting novel roles for gangliosides in the nervous system that might explain their neuroprotective activity,” says Sipione. “For example, some gangliosides increase the ability of brain cells to dispose of toxic proteins that cause neurodegeneration. They can also decrease brain inflammation, which aggravates many neurodegenerative diseases.”
Huntington’s affects about 4,700 Canadians, and the number of those affected by Parkinson’s and Alzheimer’s, two common neurodegenerative diseases, is even higher at over 100,000 and 750,000, respectively. Though each disease has its own characteristics and complexities, any insight about these important molecules that affect how the brain functions gets researchers a few steps closer to potential treatments.
Chris Cairo: Demystifying molecular mechanisms
To better understand inflammation and the immune system, we have to examine cells at a molecular level, which is precisely what Chris Cairo’s work is about. Cairo, a professor in the Department of Chemistry, studies a group of enzymes called neuraminidases that modify glycans and may help immune cells get to sites of inflammation in the body.
Many molecules within the immune system are glycosylated, which means they have some type of carbohydrate attached to them. The role of neuraminidases is to trim certain carbohydrate residues from proteins and lipids, changing the function of receptors on the surface of immune cells. Cairo’s lab designs compounds and molecules that selectively target these enzymes.
“The kinds of molecules that he has been making have shown efficacy in a few different clinical models and have a broad range of applicability,” says Wakarchuk, who also highlights a longtime collaboration Cairo has with Alexey Pshezhetsky, a researcher in Montreal whose lab has animal models that are used to test the compounds Cairo’s lab creates. “That’s how drug discovery happens,” notes Wakarchuk.
Anne Halpin: Creating a better ABO antibody test
Anne Halpin’s first interactions with GlycoNet were as a trainee, but the researcher is no stranger to the laboratory, having spent more than 15 years working as a laboratory scientist before beginning her doctoral studies. Her PhD focus was on a trio of antibodies in children who have had heart transplants, and now she is an associate professor in the Department of Laboratory Medicine and Pathology. In addition to her work in histocompatibility for transplantation compatibility testing, she studies ABO histo-blood group antibodies and antigens that affect organ transplantation.
A transplant patient's ABO blood group test is one of the first steps in the organ donation and transplantation process. But ABO-O and ABO-B patients wait longer to be transplanted so sometimes crossing the ABO barrier is considered to provide more transplant options. To do this, the ABO antibodies need to be measured to see if this is a safe option for a given patient. Halpin’s expertise is in finding ways to make the test more precise and accurate.
Alongside researcher Lori West, who directs the U of A’s Heart Transplant Research Program, Halpin is working to set up a spinoff company and commercialize the technology she’s developed for testing ABO blood antigens. The goal is a more effective test that improves outcomes for transplantation, something Halpin is passionate about as a living kidney donor herself.
“This idea that you could revolutionize ABO histocompatibility testing for clinical labs globally is a fantastic opportunity,” says Wakarchuk. “Being exposed to the depth of science we have within the network has, I believe, helped them think about how to take the combination of carbohydrate chemistry and modern clinical practice for ABO antibody testing and take the test out into the world where it’ll be far more useful than the current one.”