2019: Top 10 Research Advances from GlycoNet Investigators

By Ali Chou

In 2019, GlycoNet researchers have made impressive discoveries, including promising inroads against diabetes and neurodegenerative diseases, uncovered new technologies to diagnose cancer or treat rare genetic disorders, as well as shedding light on improved cell therapies and organ transplantations.

As the new year approaches, here is a look back at some of the most exciting advances from GlycoNet researchers in 2019. Which one is your favorite breakthrough? Share with us on Twitter (@glyconet_nce)!

Shielding the brain from stroke damage

A series of studies has indicated that during a brain stroke, microglia—a type of immune cell in the brain—behave like double-edged sword. They can help repair damage from the loss of blood supply, or they can worsen the injury. For years, GlycoNet scientists have been looking for molecules that could control how microglia behave. Earlier this year, they found a carbohydrate-binding protein that could push microglia to their good side and prevent further damage in the brain tissue; this might provide a therapeutic solution to patients who have high risks for brain stroke. / Sachiko Sato, Université Laval

Small microbe for a big eco-impact

When bacteria degrade carbohydrates in the forest, nutrients are released and then recycled by other organisms. This facilitates carbon retention and the growth of other organisms. However, little is known about the how bacteria turnover natural biomass. This year, researchers took a closer look at a common bacterium in the forest soil and found that it could turnover multiple types of biomass (including plants and fungi). More interestingly, this bacterium demonstrated different ways to metabolize carbohydrates, depending on the type of carbon source available. Now, scientists have clearer understanding of forest bacteria within the grand ecosystem. / Harry Brumer, University of British Columbia

The assembly of virulence factors

Pili are hair-like appendages on the surface of prokaryotes. They can be repeatedly extended and retracted to help prokaryotes move and adhere to other substances. For bacterial pathogens, pili are important to establish virulence. This year, GlycoNet scientists used crystallography and cryo-electron microscopy techniques to examine how pili are assembled and disassembled. They found that the motor component (an enzyme) responsible for retracting pili has at least four different conformations, depending on what molecules are available in the surrounding environment. These dynamic changes in enzyme conformations may provide key insights into the assembly of bacterial virulence factors./ Lori Burrows, McMaster University & Lynne Howell, Sickkids Hospital

A synthetic gut microbiome

Our overall health is dependent on the gut microbiome, which consists of bacteria that digest dietary fibers, synthesize vitamins, and regulate the host immune system. The imbalance among gut bacteria can lead to digestive problems like constipation or, in more serious cases, chronic diseases, such as inflammatory bowel disease. This year, GlycoNet researchers successfully engineered a gut bacterium that expresses beneficial genes in the response to two different glycans. New abilities for the organism included the metabolism of carbohydrates it previously could not. This serves as a promising approach to introduce novel and tunable functions to the gut flora to maintain nutrient balance and intestinal health. / Wade Abbott, Agriculture & Agri-Food Canada & Douglas Inglis, Agriculture & Agri-Food Canada

A potential drug that restores vision

This year, GlycoNet scientist devised a hydrogel-based drug delivery system aiming to treat patients with retinal degeneration. The therapeutic protein, which is carried by a carbohydrate-based gel, would be injected through a fine needle to the jelly-like fluid near the retina at the back of the eye. Unlike eyedrops that are rapidly cleared by the body, the therapeutic stays around the injected site for over a week and slowly gets released from the gel to repair the retina. This discovery gives a new look at repairing visual loss caused by deterioration of the cells in the retina. / Molly Shoichet, University of Toronto

Safer hog farming

Canada is among the world’s top 10 countries for pork production. Keeping the herd healthy is a top priority for hog farmers. For decades, researchers have been trying to develop an efficient commercial vaccine to protect post-weaning pigs against infections caused by the pathogen Streptococcus suis, yet no vaccines show promise so far. This year, GlycoNet scientists produced a carbohydrate-derived molecule that could prompt the immune system to produce pathogen-killing antibodies. This discovery could help prevent S. suis infections by leading the development of novel vaccines, but also could facilitate diagnostics and treatment. / Mariela Segura, Université de Montréal

A weapon against Alzheimer’s disease

This year, GlycoNet scientists discovered the role for a glycan-binding protein (called CD33) in battling against Alzheimer’s disease. More precisely, a variant of this protein can decrease the chance of getting Alzheimer’s disease—through its complex interactions with a type of immune cells in the brain (called microglia). With more than 44 million people around the world affected by Alzheimer’s disease and other forms of dementia, this discovery not only highlights the intricate relationships between CD33 and microglia in disease control, but also opens new avenues for therapeutic strategies for neurodegenerative disorders. / Matt Macauley, University of Alberta

Designing more effective antimicrobials

One way to combat bacterial and fungal pathogens is to break their shields of protection, i.e., their cell walls or biofilms. This year, GlycoNet scientists made many major steps towards understanding the critical elements involved in cell wall architecture and biofilm construction. In one case, an enzyme isolated from a fungal species was found to be important both in building fungal biofilms and in degrading them. What’s more—this enzyme could break down biofilms in bacteria too. Now, scientists have gathered some clues to use a single enzyme as a potential therapeutic for multiple types of pathogens. / Don Sheppard, McGill University & Lynne Howell, Sickkids Hospital

Universal blood

Before a transfusion, blood types must be matched. This is to prevent antibodies in the recipient’s blood from attacking the red blood cells from the donor. In an emergency where a patient’s blood type is unknown or unclear, transfusions are typically done with universal O type blood, leading to shortages of this type. To solve the problem, GlycoNet scientists identified two efficient enzymes that work together to convert type A red blood cells to type O red blood cells. If shown to be safe, these enzymes could help increase the supply of universal O type blood and simplify blood transfusion practice in hospitals. / Stephen Withers, University of British Columbia

Circumventing antibiotic resistance

Life-threatening MRSA (methicillin-resistant Staphylococcus aureus) infections are one the hardest to tackle. The bacteria causing these infections are notorious for their resistance to many antibiotics. This year, GlycoNet scientists discovered a chemical compound with promise as a lead for a new breakthrough antibiotic. This compound is unusual in that it does not kill bacteria but has multiple disarming effects on MRSA that allows the immune system to clear the infection more effectively. When disarmed, the bacteria also became more susceptible to antibiotics. This discovery has tremendous potential to expand our existing arsenal in combating drug-resistant bacteria. / Eric Brown, McMaster University

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