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Epidemiology PhD student named 2019 Vanier Scholar for research fighting antibiotic resistance

Jean-Paul Soucy is developing community-based solutions for Canada’s largest antibiotic prescribers

Epidemiology PhD student named 2019 Vanier Scholar for research fighting antibiotic resistance

When epidemiology PhD student Jean-Paul Soucy checked his email while munching on lunch with his fellow graduate students on a Monday afternoon, he fell silent.

It was the first day of what was supposed to be a usual workweek, and an email with the words “Letter of Offer’’ could have applied to a mundane range of things. He passed his laptop to a colleague. “See if it says what I think it says,” he remarked.

It said just that. He had become part of the newest selection of Canadian doctoral students to be named Vanier Scholars. The Vanier scholarship is a highly prestigious award for doctoral students that is granted by the Government of Canada.

The award will provide Soucy with $50,000 per year for three years while he works with his colleagues at the Dalla Lana School of Public Health to conduct research and develop community-based solutions to rein in the excessive prescription of antibiotics in Canada.

In particular, Soucy’s research focuses on developing “antimicrobial stewardship” programs to facilitate best practices in antibiotic prescription by family physicians. 

Why Soucy’s research field is critically important to global health

A 2014 World Health Organization (WHO) report warns that the world may be entering a “post-antibiotic era, in which common infections and minor injuries can once again kill.”

While harmful bacteria have a natural ability to develop resistance to antimicrobial drugs, the way that healthcare providers across the globe have prescribed these drugs has accelerated drug resistance.

Misuse and overuse of antibiotics facilitates the exposure of bacteria to drugs for longer than necessary to treat infection. This exposure allows microbes the conditions that foster the evolution of drug resistance.

Soucy illustrated an example of misuse with the prescription of antibiotics for the treatment of respiratory tract infections — such as the common cold and flu.

“Respiratory tract infections… are commonly caused by viruses,” said Soucy. “[But] antibiotics can’t do anything against [viruses].”

“Unfortunately, in a lot of cases, we have respiratory tract infections being treated by antibiotics.”

The consequences of the misuse and overuse of antibiotics

Such misuses of antibiotics have led to a weakened effectiveness of treatments against potentially lethal diseases.

Research reported by the WHO identifies conditions such as pneumonia and urinary tract infections as being in urgent need of new treatments, due to the advent of antibacterial resistance.

Forms of tuberculosis resistant to at least four drugs have been identified in 105 countries, while strains of gonorrhea resistant to last-resort antibiotics have been identified in 10 countries, including Canada.

In addition to accelerating the resistance of microbes to drugs, inappropriate antibiotic prescriptions can also increase the vulnerability of patients to particular infections.

“In the hospital setting, we have this nasty Clostridium difficile [bacterium],” said Soucy. “When your microbial ecosystem is disrupted by taking antibiotics, especially these broad-spectrum antibiotics that target a lot of [bacteria] at once, it creates a hole in that ecosystem that C. difficile may then enter,” he explained.

Antibiotic stewardship as a solution to excess prescription of antibiotics

Soucy’s project will revolve around antibiotic stewardship. “Antibiotic stewardship is basically the idea of making sure that we use antibiotics in a judicious way, that we’re preserving our [antibiotics’] efficacy by not giving unnecessary prescriptions, and making sure we give the right prescriptions [for microbial infections] as soon as possible,” he said.

Stewardship programs have found a footing in hospitals, but not in the community where there is a lack of comparable infrastructure. More importantly, an overwhelming majority of Canadian antibiotics — a whopping 92 per cent — is prescribed by family physicians and dentists.

The project will develop an online tool to provide “feedback to family physicians about their prescription practices,” helping them compare their own prescription practice with local guidelines and with other physicians in the area.

Soucy emphasized the importance of community-based solutions for tackling antibacterial resistance. By facilitating stewardship programs without requiring the infrastructure of a hospital, the tool will be adaptable to a wider range of less resource-intensive healthcare systems.

The path that led Soucy to epidemiology research

Soucy’s multiple interests led him to conduct research in infectious disease epidemiology. His undergraduate degree trained him in ecology, evolutionary biology, and mathematics, fostering his expertise in the mathematical modelling of infectious diseases.

Add to this his interest in the social factors that cause disease to spread, and the field of infectious disease epidemiology formed the right fit. 

In parting, Soucy emphasized the role played by research mentors, friends, and the community he found through extracurriculars, which enabled him to pursue his passions. These people have helped him through “all sorts of research opportunities,” keeping him motivated and resolute throughout the challenging years of research.

When asked for advice for budding researchers, he recommended students to adamantly challenge their fears.

“The way that I get past that feeling that says, ‘You can’t do this, you can’t figure this out,’ is [that] I just commit myself to doing it,” he said. “Then I have to do it — I have to figure it out.”

Women in STEM: Madeleine Bonsma-Fisher

PhD candidate discusses challenges faced by women in physics, and what it means to be a scientist

Women in STEM: Madeleine Bonsma-Fisher

Madeleine Bonsma-Fisher is a PhD candidate in the Department of Physics in the lab of Dr. Sidhartha Goyal, specializing in biophysics. Bonsma-Fisher’s research focuses on applying physical concepts to solve biological problems. 

Unlocking science: knowledge behind closed doors

The way bacteria defend themselves against viruses is the focus of Bonsma-Fisher’s research.

“Just like us, bacteria can get sick from viruses,” wrote Bonsma-Fisher, “except that, for bacteria (which are just single cells), this often means imminent death.”

One of the ways that bacteria fight against illness is through the CRISPR-Cas system, an adaptive immune system. 

Bonsma-Fisher tries to “understand how CRISPR-Cas immune systems change the way populations look and behave” by “using mathematical tools from physics to create models of bacteria and viruses.”

An open source project she has been working on, in collaboration with over 30 colleagues internationally, is named phageParser.

As its source code is free to use and adapt for the public, Bonsma-Fisher hopes that the project “will make it easier for people to explore and use all the available information about CRISPR immune systems in known bacteria.”

“Science is largely funded by the public and should be accessible to the public,” she noted. “The problems we need science to help us solve are becoming so large and complex that not one person or group can do it alone.”

Fostering resilience through “failure” in research

A challenge highlighted by Bonsma-Fisher was accepting the inevitable delays and setbacks that happen in a research project. 

“It’s hard to look at months of work and realize it will never see daylight,” she explained, “but I try to look at slow or ‘failed’ projects as part of the process.” 

Bonsma-Fisher has since reframed these setbacks as learning experiences. “It’s like doing a homework assignment to learn something: trying something that doesn’t work or doesn’t have an obvious point is still not a waste of time.”

“I always learn things, and I think that learning to enjoy the slow process has made me a more resilient person and a better scientist,” added Bonsma-Fisher.

Subtle pressures facing women in STEM

Another challenge she has faced has been subtle forms of prejudice due to her gender.

“I have experienced many microaggressions over the years: each one by itself is hardly worth mentioning, but some people describe it as ‘death by a thousand cuts’ — eventually the never-ending low-level discomfort wears you down.”

Microaggressions are “subtle, often unintentional, [forms] of prejudice,” according to an article from Psychology Today

Examples of what she has experienced include “overhearing people saying sexist things or making sexist jokes and not being called out, having people say or imply that I experienced some aspect of my success because I’m a woman, [and] being asked on dates by male colleagues who were older or more senior than me.”

Another experience includes her repeated encounters of people who are “completely unaware” that systemic biases exist against women.

As a result of these experiences, she has felt pressured to change the way she dresses. She avoids appearing “too feminine” to blend in better with her male colleagues. 

“The feeling of not belonging is reinforced by things [that] imply that women are newcomers and outsiders in science,” she wrote, “even though this isn’t true.” 

Women who “stick it out in the face of hostility”

As she has progressed through her academic career, Bonsma-Fisher has noticed a drop in gender diversity. 

According to Bonsma-Fisher about a third of the students in her undergraduate program was comprised of women, while her graduate program only comprises about 10 per cent. 

“In terms of other underrepresented groups of ethnic, gender, and sexual identity,” she wrote, “my experience is that physics is woefully lacking.”

The issue of diversity in physics was discussed in an article by The Varsity, which noted the number of women in physics is lower than in biology or chemistry.  

A contributor to the imbalance, wrote Bonsma-Fisher, has been “a continual stream of microaggressions,” referring to a 2016 paper in Physical Review Physics Education Research.

“In a recent study, 74% of surveyed women undergraduate physics students had experienced sexual harassment in a physics context,” she further noted. “Faced with that kind of environment, why would anyone want to stick around?”

“These kinds of systemic biases are almost invisible to any individual woman in, say, a physics undergraduate program,” wrote Bonsma-Fisher, “but it can be very sobering (and it was for me) to learn that the system is subtly stacked against you, mostly in ways that will never be obvious to you.” 

Advice for students pursuing a career in STEM

When asked for advice for other students pursuing a career in STEM, she wrote that it’s difficult to give general guidance, as “what helps one person is often specific to their situation and might not help another.”

“But I think some things apply in general: the system does suck in a lot of ways, but there’s no one right way to do science and be successful.”

Rather than feeling out of place, she encourages students to remind themselves that “[their] perspective and unique experience is important and makes science better, and it’s okay to be yourself AND be a scientist.”

“I wish I knew then that there is no one kind of person who is meant to be a scientist, and also that “academic success” isn’t the only, or even best way to contribute to science.”

“I saw only a narrow path forward at that time that was basically just get good grades, go to a prestigious grad school, and write good papers. I would tell a younger me, ‘you belong in science,’” wrote Bonsma-Fisher.

Tooth decay may result from immune response, not just bacterial plaque

U of T researchers find evidence for maverick theory first published in 1970

Tooth decay may result from immune response, not just bacterial plaque

Cavities in teeth may result from an immune system response, not just bacteria, according to a recent U of T study. This counters decades of established thinking in dental research.

In 1970, Dr. John Gabrovsek of the Cleveland Clinic published research in the Journal of Dental Research that found that our immune system may contribute to dental cavities. But during the almost 50 years since it was published, most dental researchers have not taken Gabrovsek’s theory seriously — until U of T’s findings were published in April.

The research was spearheaded by Dr. Yoav Finer and Dr. Michael Glogauer, both professors at the U of T Faculty of Dentistry.

“Glogauer approached me a few years ago, [and] told me that these immune system cells have the same enzymes and more enzymes than bacteria have, so why not check them?” Finer explained to The Varsity.

The research team began by examining immune cells called neutrophils. Neutrophils are a type of white blood cell routinely found in the mouth, and they act as the first line of defense against harmful bacteria.

However, as these immune cells fight against harmful pathogens that can damage teeth, they can also cause collateral damage to what they are originally trying to protect — our teeth.

While bacteria still cause most of the damage that results in tooth decay, Finer explained that the research team has found evidence that these immune cells also contribute to cavity formation.

How the research team arrived at the discovery

Through years of study, the team created samples from extracted teeth and then used acid to remove minerals from them.

The application of acid mimicked the effect that harmful bacteria have on teeth, as the acid they release causes tooth decay.

The researchers then isolated neutrophils from human volunteers and kept them at a warm temperature with the extracted teeth.

“That was a daily procedure because you can’t culture these cells — neutrophils — unlike bacteria,” said Finer. “You need to get these cells isolated from the blood donors on a daily basis or every other day.”

The team found that while these immune cells help protect teeth from damage caused by bacteria, they can also remove minerals from tooth dentin, as well as break down white-coloured tooth fillings.

A possible explanation for why neutrophils can degrade teeth, according to Finer, is their enzymes — biological molecules that speed up chemical reactions. However, it remains unclear which type of enzyme could be responsible for contributing to dental decay.

Applications of the research findings

Protecting our teeth is important, as dental diseases can affect not just our mouths, but our overall health. For example, bacteria that cause gum disease can lead to infections of our lungs and increased risk of blockage in arteries that can damage our hearts.

Glogauer’s research team has been developing a mouth rinse that could prevent some of the degradation caused by these immune cells to apply the findings to clinical dentistry.

Finer’s research team has also been developing a dental varnish that contains anti-degradative factors to help counteract the effect of both bacteria and neutrophils on teeth.

However, preventing tooth decay ultimately comes down to maintaining good oral hygiene.

“With a recommended toothpaste and toothbrush, keeping good oral hygiene is the key,” explained Finer. “It’s our first line of defense and can eliminate a lot of problems… the immediate thing is making sure you keep your sugar consumption under control.”