Laboratory Medicine and Pathobiology

COVID-19

University Health Network

Subheadline

Post-doctoral researcher Talya Yerlici calls SARS-CoV-2 "a clever saboteur inside our cells, making sure its own needs are met while disrupting our cells’ ability to defend themselves"

Despite huge advances in our understanding of COVID-19 over the past four years, the disease is still very much among us – and there remains a lot to learn.

One thing we do know: Following infection, it’s critical that our cells make new proteins to defend against the virus.

(photo supplied)

But Talya Yerlici, a post-doctoral researcher at the 91�Թ�’s Temerty Faculty of Medicine, recently showed how SARS-CoV-2 disrupts the manufacture of proteins.

She is the first author of a paper detailing the process that was published recently in the journal Cell Reports.

Writer Jenni Bozec recently spoke with Yerlici – who is based in the lab of Professor Karim Mekhail in the department of laboratory medicine and pathobiology – about the findings.

What have you discovered about how COVID-19 uses proteins?

One way SARS-CoV-2 makes us sick is by using a strategy called “host shutoff.” This means that while the virus makes copies of itself, it also slows the production of vital components within our cells. As a result, our bodies take longer to respond to the infection.

When SARS-CoV-2 enters our cells, it disrupts the process of making proteins, which are essential for our cells to work correctly. A particular SARS-CoV-2 protein called Nsp1 has a crucial role in this process. It stops ribosomes, the machinery that makes proteins, from doing their job effectively. The virus is like a clever saboteur inside our cells, making sure its own needs are met while disrupting our cells’ ability to defend themselves.

We found that Nsp1 is good at blocking ribosomes from making new proteins, but also interferes with the production of new ribosomes. In effect, it shuts down the machinery output and the ability to make the machinery itself – a serious double hit.

It does this by blocking the maturation or processing of specialized RNA molecules needed to build ribosomes. This adds a new layer of complexity to our understanding of SARS-CoV-2's interference with the host cell.

How could this discovery impact treatment for those with COVID-19?

Building on our published research, it will be crucial to understand how Nsp1 works to stop different types of human cells, tissues and organs from making proteins when infected with different variants of SARS-CoV-2 and related coronaviruses.

Scientists have been working to find precision medicines that can counteract Nsp1 and help fight against the continually evolving SARS-CoV-2 virus. These drugs aim to help infected cells keep producing proteins and build a robust immune response when dealing with infection. Ongoing research on such drugs should now benefit from testing whether they can block Nsp1 from interfering with both the production and function of ribosomes, and this should help find more effective precision medicines.

What drew you to this line of research?

This project started because of circumstances during the COVID lockdown. We wanted to help in the fight against the pandemic. However, since I couldn't physically work in the lab, we took the opportunity to analyze next-generation sequencing datasets computationally from home.

Looking at published RNA-sequencing datasets, we realized that cells infected with SARS-CoV-2, compared to uninfected cells, may have difficulty processing the RNA molecules needed to build ribosomes. Through this analysis, together with Dr. Mekhail, we developed hypotheses and designed the project.

I had the privilege of collaborating closely with the talented members of the Mekhail lab, including Alexander Palazzo’s group from the department of biochemistry at Temerty Medicine and Brian Raught and Razqallah Hakem’s labs at the Princess Margaret Cancer Centre (University Health Network). This work wouldn't have been possible without the collective efforts of our team and collaborators, and I’m grateful for their contributions. My responsibilities included conducting numerous hands-on experiments and bioinformatics analyses, analyzing the results and preparing the paper for peer review and publication.

What were the most challenging and rewarding aspects of this project?

The most challenging part was conducting research during a global pandemic, which presented many logistical hurdles – from disrupted lab routines to limitations on collecting and using samples infected with SARS-CoV-2.

On the other hand, the opportunity to contribute to our understanding of SARS-CoV-2 viral mechanisms and shed light on potential therapeutic targets was incredibly fulfilling. Seeing our research culminate in a published paper and knowing it could inform future strategies for combating coronaviruses is deeply gratifying.

What are your longer-term goals as a scientist?

As an independent investigator in my future lab, I want to study how the complex processes of making ribosomes affect the body's natural defense against viruses. It's an area I find compelling and presents ample opportunities for further exploration. One approach I’m particularly interested in is integrating RNA-sequencing with genetic CRISPR and small-molecule chemical screens, targeting distinct stages of ribosome biogenesis across diverse infection or infection-mimicking conditions. Such integrated approaches hold promise for uncovering novel mechanisms underlying the regulation of antiviral responses and should help us find innovative and impactful ways to fight viral infections.

This research was supported by the Canadian Institutes of Health Research.

Breast milk may have protective effects against COVID-19: Researchers

Christopher.Sorensen — Mon, 29 Jan 2024 18:38:03 +0000

Breast milk may have protective effects against COVID-19: Researchers

Christopher.Sorensen Mon, 01/29/2024 - 13:38

Cutline

Samantha Ismail led a study by researchers at 91�Թ� and its partner hospitals that looked for SARS-CoV-2 antibodies in human breast milk (supplied image)

Betty Zou

Topic

Emerging and Pandemic Infections Consortium

COVID-19

Institutional Strategic Initiatives

Sinai Health

Sunnybrook Health Sciences

Vaccines

Subheadline

“COVID-19 vaccination and infection result in antibodies in human milk that have neutralizing capacity"

The COVID-19 pandemic was an especially harrowing time for pregnant people and new parents.

The uncertainties about how the new coronavirus could affect a pregnant person and their developing fetus – not to mention being cut off from support networks – left many expecting parents feeling isolated and anxious.

“It was a very surreal time,” says Jenny Doyle, a Toronto mom who gave birth to her first child, Elliott, in 2020 and spent hours researching how the first vaccines made available the following year might affect her and her child. “At the time, vaccines for infants were still so far away. I remember hoping that some of the protection I’d received from my vaccine would pass through to Elliott.”

Now, new findings from a study led by researchers at the 91�Թ� and its partner hospitals suggest that is the case.

Published in the American Journal of Clinical Nutrition, the study looked for antibodies against SARS-CoV-2 in breast milk from three different cohorts: individuals who contracted COVID-19 while pregnant or nursing, routine milk bank donors and individuals who received two doses of the COVID-19 vaccine while pregnant or nursing.

The researchers detected antibodies in breast milk from roughly half of the people in the COVID-19 positive cohort. That’s compared to less than 5 per cent of routine milk bank donors, who did not have any known exposures to COVID-19. In the vaccinated cohort, they found that antibodies levels were higher in people who had received the Moderna vaccine compared to those who had received the Pfizer-BioNTech vaccine. Unexpectedly, people who had shorter intervals between their first and second doses had higher antibody levels than those who waited longer between their immunizations.

“That finding definitely surprised me,” says Samantha Ismail, the study’s first author who completed her master’s degree in the lab of Deborah O’Connor, the Earle W. McHenry Professor and chair of Temerty Medicine’s department of nutritional sciences. “In [blood] serum, it’s the other way around where longer intervals between doses typically result in higher antibody levels, suggesting that something different is happening in this lactating population.”

In addition to Ismail and O’Connor, the study was led by Sharon Unger, medical director of the Roger Hixon Ontario Human Milk Bank at Sinai Health and a 91�Թ� professor of medicine and nutritional sciences, and Susan Poutanen, microbiologist and infectious disease consultant and Sinai Health and 91�Թ� associate professor of laboratory medicine and pathobiology.

The team took the study one step further by showing that some breast milk samples could prevent SARS-CoV-2 from infecting cells in a lab setting. Within the COVID-19 positive cohort, milk that contained antibodies against the virus were more likely to be neutralizing and immunization with the Moderna vaccine was associated with a stronger neutralizing capacity than the Pfizer-BioNTech vaccine.

The researchers also found a small but significant number of breast milk samples that prevented SARS-CoV-2 infection despite having undetectable levels of antibodies, suggesting that there could be other components in human milk that are active against SARS-CoV-2.

While these findings provide strong evidence to support the potential protective effects of human milk, Ismail cautions that the study alone is not enough to prove that breast milk provides tangible protection against COVID-19.

“COVID-19 vaccination and infection result in antibodies in human milk that have neutralizing capacity, but we don’t know for sure how the neutralizing capacity seen in the lab translates to protection in infants,” says Ismail, who is now a second-year medical student at 91�Թ�.

She points out that previous studies have shown a clear protective effect of antibodies in human milk against other viruses like enterovirus and rotavirus. To date, such studies have not been done with COVID-19.

Even so, the findings provide reassuring news to parents like Doyle, who breastfed her son longer than she had intended to ensure that he was still getting breast milk when she received her second COVID-19 vaccine.

“Trying to figure out how to protect this tiny being in that scary and bleak time, I was grasping at every little piece of information and whatever little piece of hope we had.”

The study was supported by the Canadian Institutes for Health Research and was a collaboration between the department of microbiology at Sinai Health System/University Health Network, the Roger Hixon Ontario Human Milk Bank at Sinai Health System and the Toronto High Containment Facility, where the live SARS-CoV-2 neutralization studies were completed.

It involved contributions from several members of the Emerging and Pandemic Infections Consortium, a 91�Թ� institutional strategic initiative. In addition to O’Connor, Poutanen and Unger, they include Scott Gray-Owen, of Temerty Medicine’s department of molecular genetics, Samira Mubareka, of Sunnybrook Health Sciences Centre and Temerty Medicine’s department of laboratory medicine and pathobiology, and Jennie Johnstone and Allison McGeer – both of Sinai Health and Temerty Medicine’s department of laboratory medicine and pathobiology.

Research challenges long-held view of early-stage Alzheimer's disease

siddiq22 — Wed, 05 Jul 2023 03:12:54 +0000

Research challenges long-held view of early-stage Alzheimer's disease

siddiq22 Tue, 07/04/2023 - 23:12

Cutline

Gerold Schmitt-Ulms, a professor in the Temerty Faculty of Medicine's department of laboratory medicine and pathology, was one of the authors of the new study (supplied image)

Eileen Hoftyzer

Topic

Tanz Centre for Research in Neurodegenerative Diseases

Medical Research

Subheadline

A new study by researchers from 91�Թ�'s Tanz Centre for Research in Neurodegenerative Diseases examines how a hormone called somatostatin influences the earliest stages of the disease

Recent research from the Tanz Centre for Research in Neurodegenerative Diseases in the 91�Թ�'s Temerty Faculty of Medicine is challenging long-held views of how a hormone called somatostatin influences the earliest stages of Alzheimer’s disease.

“Importantly, for the first time, this research indicates the extent to which somatostatin could be important in Alzheimer’s disease,” says Gerold Schmitt-Ulms, co-author of the study published in Scientific Reports.

“The answer is that somatostatin has a significant effect, but it’s not black or white. It doesn’t prevent clumping of the amyloid beta protein, but slows it down. This is important, but we don’t know what this means for treatment yet,” says Schmitt-Ulms, an investigator at the Tanz Centre and professor in 91�Թ�’s department of laboratory medicine and pathology.

The dominant hypothesis of how Alzheimer's disease begins – the amyloid cascade hypothesis – says that too much amyloid beta protein is produced, which clumps together to form oligomers (small clumps of varying numbers of amyloid beta monomeric building blocks), which then continue to accumulate to form larger plaques that damage neurons.

As early as the 1970s, researchers observed that brains of people with Alzheimer’s disease had lower levels of the hormone somatostatin than people who did not have Alzheimer’s, and that the plaques of amyloid beta that are characteristic of the disease tend to form near neurons that produce somatostatin.

These observations suggested a relationship between somatostatin and amyloid beta aggregation, but researchers did not know what it was.

Then, in the early 2000s, a team from Japan published research describing that somatostatin drives production of an enzyme called neprilysin that can degrade amyloid beta. This finding suggested that if somatostatin was decreased, the levels of neprilysin would decrease – without neprilysin to degrade amyloid beta, the plaques would continue to grow, and Alzheimer's disease would progress.

This understanding of the role of somatostatin is where the field stood for more than a decade.

An image from the study summarizing its key findings (supplied image)

Several years ago, Schmitt-Ulms and his team investigated amyloid beta in its monomer and oligomer forms, specifically looking for molecules in the brain that would bind to the toxic oligomeric forms. They found that, of all proteins in the brain, somatostatin was the smallest to bind to amyloid beta – and the most selective, as it only interacted with the oligomers.

They then observed that somatostatin blocked the formation of oligomers, with higher concentrations of somatostatin having a greater effect. This earlier study provided the first evidence that somatostatin interacts directly with the oligomeric amyloid beta that are known to be the earliest stages of Alzheimer's disease, providing an alternative perspective on the impact of somatostatin on the disease.

“We didn’t actually intend to work on somatostatin, but these results made us very curious about what would happen if somatostatin was absent in an animal model that was genetically engineered to develop amyloid beta aggregations,” Schmitt-Ulms explains.

To answer this question, the research team crossed a somatostatin-deficient mouse line with an amyloidosis mouse model.

They found that when somatostatin was absent, there were more amyloid beta aggregates, consistent with what is seen in Alzheimer’s disease in humans.

Remarkably, the result did not seem to be caused by an effect of somatostatin on neprilysin levels, as there were no differences – a contradiction to the long-held understanding of the mechanism through which somatostatin impacts Alzheimer’s disease. Instead, the data suggested that somatostatin blocks oligomer formation independent of neprilysin by interacting with amyloid beta.

“There isn’t a lot of literature that explains how the environment in the brain can promote or inhibit amyloid beta forming into oligomers, so this is a nice vignette that shows that one molecule – somatostatin – seems to influence that first small oligomeric aggregation step,” Schmitt-Ulms says.

“And if you get fewer of these oligomeric forms, then you get fewer of the small clumps, which are the next step of amyloid beta aggregation – so the process made sense, and it was a striking finding.”

While the results have challenged the conventional view of somatostatin in Alzheimer’s and prompted discussions in the scientific community, what they mean for treatment is still uncertain.

Somatostatin plays important roles in the gastrointestinal, endocrine and nervous systems, so selectively promoting its role in blocking amyloid aggregation would be challenging. Schmitt-Ulms says that it is also unclear whether augmenting somatostatin, and thereby arresting the growth of amyloid beta aggregates, is beneficial.

Still, the results have shaken up the research field.

“The evidence speaks for itself, and we stand by our conclusions, but the data can’t answer what this means for therapeutics,” Schmitt-Ulms says.

“They do, however, indicate that somatostatin – one of the first-ever molecules that were biochemically linked to Alzheimer’s disease – may play a different role in the earliest stages of the disease than expected, and that in itself is important.”

The study was supported by Alberta Innovates Bio Solutions, Ontario Centres for Excellence/MaRS Innovation and the Borden Rosiak family.

'We should be preparing': Researcher Samira Mubareka on the risks posed by bird flu

Christopher.Sorensen — Thu, 06 Apr 2023 15:27:52 +0000

'We should be preparing': Researcher Samira Mubareka on the risks posed by bird flu

Christopher.Sorensen Thu, 04/06/2023 - 11:27

Cutline

(Photo by Kevin van Paassen/Sunnybrook Health Sciences Centre)

Betty Zou

Topic

Institutional Strategic Initiatives

EPIC

Sunnybrook Health Sciences Centre

From Brampton, Ont. to sites in nearby Halton and Niagara regions, there are a growing number of reports of birds that have tested positive for highly pathogenic avian influenza (HPAI) virus, or bird flu.

While HPAI typically infects birds – more than seven million across Canada, including nearly 750,000 in Ontario, according to the Canadian Food Inspection Agency – there have also been growing reports since 2022 of mammals getting infected and dying of bird flu, which is also known as H5N1, across a large geographic area. They include small land animals like raccoons and skunks to large carnivores like bears and mountain lions, as well as marine mammals like sea lions and dolphins.

Just this week a pet dog died in Oshawa, Ont. after testing positive.

To learn more about the bird flu outbreak and what we can do to prepare, writer Betty Zou spoke to Samira Mubareka, an infectious diseases physician, medical microbiologist and scientist at Sunnybrook Research Institute. She is also an associate professor in the department of laboratory medicine and pathobiology in the 91�Թ� ’s Temerty Faculty of Medicine and a member of the 91�Թ�-based Emerging and Pandemic Infections Consortium (EPIC), an institutional strategic initiative.

Her research uses a collaborative One Health approach – looking at the interconnection between people, animals and their shared environment – to conduct surveillance in wildlife and look at the biology of emerging viruses and transmission between species, including humans.

How widespread is bird flu right now?

The level of avian influenza activity we’re seeing at the moment is unprecedented. To step back a bit, the first cases in North America were reported in late 2021 in birds in Newfoundland – and from there, it spread along the eastern seaboard into the United States along Atlantic flyways. Subsequently, there were cases reported in the west of Canada and the United States, followed by cases in Central and South America. Beyond affecting wild and farmed birds, we are seeing spillover of HPAI into mammals, many of whom die of severe neurological complications.

There has also been renewed focus on HPAI because a reported outbreak among farmed mink in Spain, with mammal-to-mammal transmission, and large die-offs of marine mammals, including sea lions. The virus also appears to be reassorting, or exchanging genetic material among H5N1 lineages. All of these represent red flags that reflect an amount of viral activity that we really haven’t seen before.

We’ve also never seen this level of bird depopulation – both from die-offs and as a control measure. This has potential to impact biodiversity, wildlife health and conservation, as well as food costs and security. There have been a significant number of outbreaks, including here in Ontario, and some of them have been fairly close to densely populated areas. Having said all this, it is important to underscore that the risk remains low for humans and that we have not had any human cases in Canada. Regardless, we need to prepare for that possibility.

H5N1 made the news in 2003 and 2014, but in both those instances the outbreaks were relatively contained. What’s changed this time that is causing it to be so widespread?

There could potentially be multiple factors. There may be some characteristics that are specific to this strain of H5N1 that are enabling this level of viral activity. One thing we do know is that bird populations are highly mobile and often exchange viruses when they’re migrating and co-mingling at migration sites, which provides an ecological context for viral reassortment and selection.

Having said that, these birds migrate every year, so why is this so different? I don’t know that we’ll get to the bottom of that without more research. People have started to look at how influenza virus pathogenesis is changing in these birds and how migration affects bird immunity, but what we don’t understand are some of the intersections between the virus and other potential exposures and ecological factors that the birds are encountering during migration or at their overwintering sites. I think there’s a lot to be learned and this is where a One Health approach could be instrumental.

How does H5N1 affect humans and what clinical interventions are available?

With people, unsurprisingly, there’s a range of clinical symptoms. Some people will experience little to no symptoms, but we don’t know exactly what proportion are asymptomatic, have mild symptoms or more severe symptoms with poor outcomes. Frequently, people have quoted mortality rates of between 40 per cent and 60 per cent for this virus, which is very high, but that could be due to biases from past events where only the most severe cases were identified.

Like with other influenza viruses, this virus could manifest as an upper respiratory tract infection or severe viral pneumonia with multi-system organ involvement and/or a severe neurological syndrome. As health-care providers, we need to be prepared for a range of symptoms. The good news is that I’m not aware of any widespread antiviral resistance. In terms of prevention, there is no vaccine specific to H5N1 available for Canadians at this moment, but we still recommend the seasonal influenza virus vaccine. Seasonal influenza vaccination reduces the burden of seasonal influenza, and it may also reduce the likelihood of H5N1 mixing with seasonal influenza viruses and potentially reassorting to become more transmissible or severe in humans.

What should individuals and health-care providers be thinking about in terms of risk factors for H5N1?

There are a few different risk factors and they’re generally related to animal exposure. One, obviously, is to have been in direct contact with animals that were known to have H5N1. People working in certain occupations like veterinary medicine and farming – particularly poultry farming – as well as anyone working directly with wild birds and other wildlife are considered at higher risk of being exposed.

You recently received funding support from EPIC to conduct risk assessment research on highly pathogenic avian influenza. Can you tell us about that work?

Absolutely. We know that in Canada, the virus is reassorting which means it is exchanging genetic materials with other viruses. Do these new pieces of genetic material cause the virus to behave differently? Scientists at the National Centre for Foreign Animal Disease and the Public Health Agency of Canada are leading the work to try and understand that and the risks posed by these new variants. We are collaborating with them and with EPIC member Theo Moraes, who has been central to that work. Theo’s team has developed a way to take cells from inside someone’s nose and grow them in the lab. These cells serve as a model to understand how well viruses replicate and, in turn, how much of a risk they could pose to people. This work also feeds into a grant we just received from the Canadian Institutes of Health Research on using a collaborative One Health approach to zoonotic virus detection and risk assessment at the wildlife-human interface.

How worried are you about the bird flu situation right now? How should we be preparing?

I’m more worried now than I was a few months ago because there are so many reports of spillover from birds to mammals. Hearing about human cases, even sporadic ones, is another red flag. We’re sufficiently concerned that we’ve started preparatory activities like getting our sequencing protocols ready. I’m also worried about the impact on wildlife health. When you have wildlife populations that are dying off, that in and of itself should have us concerned, regardless of whether humans are getting sick.

I think every one of these events is a reminder that we should be preparing. It’s important to note that right now the risk to individuals is still low, but that can change anytime. Let’s not to wait for it to change before we start preparing. We should be more proactive in surveillance and looking at things like vaccine and antiviral development – both for poultry and for humans. Vaccinating poultry is not as straightforward as you might think because there are trade implications.

The fact that we’re seeing new HPAI viruses in Canada underscores the importance of ongoing surveillance. We also need to do a better job of communicating to frontline health-care providers, especially those working in areas where the potential for a spillover from animals to humans is high. Enhanced efforts towards surveillance, medical countermeasures, communications and research are all steps in the right direction.

Researchers discover what causes cell 'batteries' to run down

Christopher.Sorensen — Fri, 19 Aug 2022 17:58:05 +0000

Researchers discover what causes cell 'batteries' to run down

Christopher.Sorensen Fri, 08/19/2022 - 13:58

Cutline

A recent study of mitochondrial turnover by 91�Թ�'s Stephen Girardin and Samuel Killackey promises to open new avenues for research into diseases where mitochondrial stability is lost (photos supplied)

Jenni Bozec

Topic

Researchers at the 91�Թ� have discovered how mitochondrial turnover – a critical cellular function – begins.

Mitochondria are like the batteries of our bodies. They’re vital sources of energy for cells and are necessary to regulate function in almost all cell types. And, like batteries, mitochondria need to be replaced as they run down over time. If these cell batteries aren’t replaced efficiently, and don’t turn over properly, cells experience stress and can die.

Healthy mitochondria, in turn, are critical in energy-demanding organs such as the brain and muscle. When this degradation process is disrupted, vulnerable neurons can die. This type of disruption is present in many neurodegenerative diseases such as Parkinson’s.

Now, a study by Stephen Girardin, a professor of laboratory medicine and pathobiology in the Temerty Faculty of Medicine, and post-doctoral researcher Samuel Killackey shows that when certain nuclear encoded proteins aren’t brought into mitochondria, the mitochondria are removed.

“We’re proud we’ve identified the problem and made progress toward understanding and characterizing the molecular players and pathways, and how this is all integrated in a cell – in some surprising ways,” Giradin says.

Girardin studies a mitochondrial Nod-like receptor (NLR) called NLRX1. While NLRX1 has been implicated in diverse cellular processes, its underlying function remained elusive to researchers until now.

Generally, research in this area revolved around depolarization – the loss of electric potential across the inner mitochondrial membrane – as the major signal for mitochondrial removal.

Girardin and Killackey’s study also showed that depolarization is an upstream cause of restricted mitochondrial protein import.

The findings, published in Molecular Cell, open new avenues for research into diseases where mitochondrial stability is lost.

“This tells us the problem occurs when the protein import fails and the cell receives a signal from the faulty import of the mitochondrial protein, NLRX1. This is the cue to destroy the mitochondria, a process known as mitophagy,” Girardin says.

By looking at the process from a different perspective, the team demonstrated that the established science in this area didn’t show the whole picture.

“We took a step back and connected some of the dots in the literature, which helped us identify that disrupted protein import was a common denominator across many mitochondrial stressors that trigger mitophagy,” says Killackey, a Vanier Scholar who conducted the research during his PhD studies in Girardin’s lab.

The discovery paves the way for researchers to further investigate the role of mitochondrial dysfunction in disease and in metabolically active organs like the brain, heart and kidneys.

“We’ve seen a role for NLRX1-driven mitophagy in muscle function measured through endurance capacity, which could have implications for diseases that involve muscle atrophy or functional deficits. Modifying the extent and efficiency of mitochondrial protein import could also offer therapeutic benefit for neurodegenerative disease,” says Killackey.

The findings are the culmination of 15 years of research, marking a milestone for Girardin.

“I love fundamental questions,” he says. “What happens next with the knowledge is a question of physiology, translational medicine or drug development. So, now it’s time to pass the baton to others, or to partner with enthusiastic collaborators.”

From happiness to health care, undergraduate summer program inspires future data scientists

Christopher.Sorensen — Thu, 18 Aug 2022 13:13:32 +0000

From happiness to health care, undergraduate summer program inspires future data scientists

Christopher.Sorensen Thu, 08/18/2022 - 09:13

Cutline

Victoria College's Anthony McCanny is exploring whether gross domestic product (GDP) is a good measure of economic and societal success as part of a Data Sciences Institute summer research program (photo courtesy of the Data Sciences Institute)

Chris Sasaki

Topic

Institutional Strategic Initiatives

Data Sciences Institute

Dalla Lana School of Public Health

Artificial Intelligence

Computer Science

Earth Sciences

Faculty of Arts & Science

Innis College

Psychology

St. Michael's College

Victoria College

What causes glacial periods to end? Can machine learning help make medical decisions? Can money buy happiness?

These were among the questions studied during the 2022 Summer Undergraduate Data Science (SUDS) Research Program run by the 91�Թ�’s hub for data science research: the Data Sciences Institute (DSI), based in the Faculty of Arts & Science.

The program pairs faculty members with undergraduate students from universities across Canada who are interested in data science careers.

“The DSI SUDS program is about inspiring the next generation of data scientists and giving undergraduate students an opportunity to explore data science as a career opportunity,” says Laura Rosella, the institute’s associate director of education and training and an associate professor at the Dalla Lana School of Public Health and in the Faculty of Medicine’s department of laboratory medicine and pathobiology.

“In addition to their research projects, these students are provided with a full set of data science networking, academic and professional development opportunities. And we couldn’t be more thrilled to have the chance to inspire them and hopefully kickstart their careers in this exciting field. They are truly an exceptional bunch.”

The variety of projects tackled in the program reflects the growing number of disciplines that are increasingly reliant on data skills and expertise. Three projects involving Faculty of Arts & Science faculty members and students addressed questions in psychology, Earth sciences and the intersection of machine learning and health care.

Students presented their research during the SUDS Research Day in August (photo courtesy of the Data Sciences Institute)

What causes ice ages to end?

Innis College student Tina Tsan is working with Ulrich Wortmann, an associate professor in the department of Earth sciences on an analysis of why the last ice age came to a sudden end.

During glacial periods, ocean levels dropped as water was taken up in glaciers. This exposed the continental shelf, triggering a chemical reaction that released large amounts of carbon dioxide into the atmosphere. Tsan and Ulrich’s analysis supports the idea that this CO2 may have warmed the atmosphere enough to end the last ice age.

“The work I'm doing in SUDS is an extension of my previous undergraduate research into changes in ocean chemistry,” says Tsan. “By exploring the data science side of this work, I now have a better understanding of my research and this gives me a solid foundation for the fall when I start my master’s degree in Earth sciences.

“For me, the biggest reward from the SUDS program has been how it’s broadened my perspective and understanding of what data science is and how it's used in different fields.”

Wortmann praised the program.

“The SUDS program is fantastic – especially for students who are not embedded in a large research group or who are working in a field where few of their peers have an interest in data science,” he said.

Can machine learning help make medical decisions?

A member of St. Michael’s College, Yingke Wang is working with Rahul Krishnan, an assistant professor in the department of computer science and the department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine.

Krishnan’s research exists at the intersection of machine learning and health care. Among his lab’s projects: redesigning patient risk scores, which are metrics used in hospitals to predict aspects of a patient’s care and inform clinical decisions such as who should receive an organ transplant.

One of the ways such scores are evaluated is with a population simulator called LivSim, which simulates how a group of people might be affected by a specific choice of risk score.

“Yingke will be working to help optimize LivSim,” says Krishnan. “His work will get it operational and running efficiently, so we can evaluate the efficacy of some of the novel risk scores designed in the lab.

“It's been wonderful to see the support that SUDS provides to young scholars like Yingke. Introducing students to research early is an important step for them to see the opportunities that graduate study can provide."

Wang, similarily, says he has reaped significant rewards from the program.

“Thanks to SUDS, I’m learning how to combine machine learning algorithms in the health-care industry as well as explore survival analysis,” says Wang. “Plus, the self-learning skills I gain will be essential to me for approaching graduate study.”

Can money buy happiness?

Anthony McCanny, a member of Victoria College where he was a Northrop Frye Centre Undergraduate Fellow, is interested in whether gross domestic product (GDP) is a good measure of economic and societal success –and what type of government spending improves the lives of citizens.

He is working with Felix Cheung, an assistant professor in the department of psychology who studies the determinants and consequences of subjective well-being across diverse populations – including the question of whether economic growth translates into personal happiness.

“During SUDS, Anthony and I will study an age-old question: whether money buys happiness,” says Cheung. “We examine this question at a policy level by testing how governments can allocate their expenditures to best benefit citizens' well-being.

“Anthony is using a cutting-edge method to test this long-standing research question with the largest dataset on global happiness. The results hold promise to inform governmental expenditure, an extremely timely topic as many countries around the world are reprioritizing their spending given recent events such as the invasion of Ukraine.”

McCanny, for his part, says the program brought “learning, fun, joy and community” to his summer.

“I’ve been very lucky in Professor Cheung’s lab to have the freedom to conduct my own research, paired with great guidance,” he says. “It’s hard not to feel like this summer has redefined my path in life, filling me with enthusiasm for a career in research, and connecting me with people that I hope I get to keep working with.”

With the support of profs, Mitch De Snoo finds a way to balance PhD research and pro lacrosse

Christopher.Sorensen — Mon, 08 Aug 2022 13:56:11 +0000

With the support of profs, Mitch De Snoo finds a way to balance PhD research and pro lacrosse

Christopher.Sorensen Mon, 08/08/2022 - 09:56

Cutline

(Photo by Ryan McCullough)

Erin Howe

Topic

Hospital for Sick Children

Institute of Medical Science

Sports

Mitch De Snoo is not only completing his MD/PhD studies at the 91�Թ�’s Temerty Faculty of Medicine – he has successful career as a professional lacrosse player, too.

De Snoo, who studies the basic mechanisms involved in memory formation, just completed the second year of his PhD studies at the Institute of Medical Science (IMS) in the lab of Professor Paul Frankland, who has appointments with IMS and physiology at Temerty Medicine and is a senior scientist at SickKids Research Institute.

De Snoo also plays defense for the Toronto Rock, and last month he was named Defensive Player of the Year by the National Lacrosse League (NLL), the world’s largest professional lacrosse organization.

He recently spoke with writer Erin Howe about how he balances science and sport.

What is the focus of your research?

I’m part of Professor Paul Frankland’s neurobiology lab at SickKids. Working with mouse models, we look at basic science factors that affect the saliency and longevity of memory. My project specifically uses a technique called calcium imaging to track the activity of neurons in the hippocampus, an essential structure for memory formation, while mice are engaged in learning tasks. Calcium imaging allows me to track the same neurons over extended periods of time so I can compare how their hippocampal representations of the task evolve with time. I also study how neurogenesis – the birth of new neurons during adulthood, and a process that is unique to the hippocampus – affects these memories.

What sparked your interest in this area?

I’m interested in neurodegenerative diseases and, in particular, Parkinson's disease. My father had Parkinson’s and was diagnosed when he was quite young, which influenced me to do research and pursue studies in medicine.

When I was doing my master’s degree in laboratory medicine and pathobiology in [Associate] Professor Suneil Kalia’s lab, I explored the cell biology involved in some of the pathways known to cause genetic forms of Parkinson’s disease.

Difficulties related to memory and cognition are among the most concerning symptoms in Parkinson’s and other neurological diseases. My goal is to better understand the fundamental science underlying memory so that I can eventually apply the concepts and techniques that I am learning in my PhD to study the pathophysiology and treatment of disease in my own research program in the future.

What drew you to lacrosse?

I'm very lucky things have worked out as they have.

I played lacrosse and hockey while I was growing up in Oshawa and never imagined that playing sports would become more than a pastime – it just sort of happened.

I was older than many players are when I began to play competitively. Some of the other people I played with were recruited for scholarship opportunities at universities in the United States. When I realized that could be a possibility for me, it was exciting. I was recruited to study at and play for Drexel University in Philadelphia. Each summer, I returned home to Canada to play in the competitive leagues here.

At some point, I was ranked on an NLL draft board and people were talking to me about prospects and playing professionally – I was surprised! Then, when I finished my undergraduate degree in 2015, I was drafted to the Calgary Roughnecks. While I initially made the team out of training camp, I was traded to play for the Buffalo Bandits in New York State before the season began. I played my first five seasons in Buffalo.

When did you join the Toronto Rock?

I was traded to the Toronto Rock early in 2020, a few weeks after our league announced a shutdown due the COVID-19 pandemic. With public health precautions remaining in place, this past 2021-22 season was the first time I got to play with the team. It was a tremendous experience to be able to play for the hometown team that I watched when I was a kid. Once it was safe for friends and family to begin coming to see our games toward the end of the year, it was great.

What was your reaction to learning you’d been named Defensive Player of the Year?

It was pretty shocking. Even though it all worked out in the end, I never thought it would be possible to have a career in the NLL. I was just focused on doing my best and becoming a better player each year.

How do you balance the demands of academic life with the rigours of professional sport?

I’ve been fortunate to work with supportive faculty members like Professors Frankland and Kalia and to do the kind of research that allows me to manage my own time. And although the NLL is a professional league, we only play games during weekends. Our team practices are also capped to once a week and I do other workouts during the week around my research schedule. When I’m on the road, I also find time to work at my computer, whether I’m on a plane or fitting in time during the afternoon between our morning shootaround and gametime in the evening.

From watermelons to forest fires, 91�Թ� graduate students unpack research in three-minute thesis competition

Christopher.Sorensen — Wed, 27 Apr 2022 15:49:17 +0000

From watermelons to forest fires, 91�Թ� graduate students unpack research in three-minute thesis competition

Christopher.Sorensen Wed, 04/27/2022 - 11:49

Cutline

Atefeh Mohammadi took home the top prize in this year's Three Minute Thesis contest for presenting research on using a compound found in watermelons to treat a common long disease in premature babies (photo courtesy of Atefeh Mohammadi)

Gayatri Kumar

Topic

John H. Daniels Faculty of Architecture

Faculty of Dentistry

Forestry

Graduate Students

School of Graduate Studies

As an undergraduate student, Atefeh Mohammadi used to attend the Three Minute Thesis (3MT) competition with a friend – “for funsies,” she says with a laugh – and watch in awe as the competing graduate students tried to present their research in just three minutes.

“I thought it was so fun and so cool,” she says. “And, of course, so challenging.”

It was a challenge Mohammadi met head on. Earlier this month, the second-year master’s student from the Temerty Faculty of Medicine’s department of laboratory medicine and pathobiology placed first in the 3MT final, taking home the top prize at the annual competition for her presentation on neonatal lung disease.

“It’s every grad student’s dream to get a platform to talk about what you do,” she says about her decision to enter this year’s competition. “And the other thing is that I love science communication. I believe very strongly that everyone should make their research accessible to the public.

“What’s the point of doing what you’re doing and arriving at your findings if you’re not going to communicate that to the people who can use them?”

Mohammadi was one of nine finalists in this year’s competition, which challenges participants to present the complexities of their research to a generalist audience in just three minutes, using only one static slide. The global higher-education event has been one of the signature programs of the Centre for Graduate Professional Development since 2013 and encourages graduate-student researchers to develop their public engagement skills.

Judges assess the presentations for clarity, comprehension and engagement, rather than the quality of the research. The winner of the 91�Թ� final receives a $1000 prize, as well as the opportunity to compete in the Ontario-wide final featuring winners from other universities.

This year’s winners also included: Shivam Sharma, of the Faculty of Dentistry, who won both second place and the People’s Choice Award for his presentation on wound-healing in diabetes patients; and Melanie Wheatley, of the Institute of Forestry and Conservation in the John H. Daniels Faculty of Architecture, Landscape, and Design, who won third place for her presentation on fighting forest fires from the sky.

As for Mohammadi, her presentation focused on how citrulline, a compound occurring naturally in watermelons, can help treat bronchopulmonary dysplasia (BPD) – a common lung disease in premature babies that causes tissue damage in the grape-like alveoli (air sacs) of the lungs. Existing courses of treatment for BPD produce inconsistent results and have many side effects. But if Atefeh can confirm that the substance does indeed help alveolar cells (specifically, the type 1 cells) fight off inflammation, her findings may pave the way forward to a safe and inexpensive treatment.

As with her research protocol, Mohammadi says the most difficult element of the competition was figuring out where to start. During the competition’s first round, she says she worried that offering too many details about her work would scare off her audience. But the feedback she received after each round encouraged her to include more details of her research and learn to trust her material.

Finding the balance between scientific sophistication and accessible communication is something Mohammadi considers a lot in the course of her work. For the past three years, she has been a show host as well as the social media and promotions lead for the Raw Talk Podcast, a student-led project from the Institute of Medical Science that aims to bring medical science innovation to the general public in an accessible, engaging format. (Now in its sixth season, Raw Talk has tackled a variety of topics, ranging from underrepresentation in STEM to refugee health care in Canada and the science and ethics of organ donation.) Next year, Atefeh will move into a new role as one of the podcast’s executive producers.

Mohammadi says she often feels like there’s a wall with scientists on one side and the public on the other. “Especially now with the pandemic happening and the spread of misinformation, there’s a real need to break down that barrier between scientists and the general public,” she says. “Building that trust has become so important. And social media is where it all happens.”

She’s also glad to note that senior academics and faculty members are beginning to recognize the importance of non-traditional methods for disseminating student research. “For some people, it’s a complete shift. In the past, they might have thought it a waste of time – ‘You could be doing research instead, or publishing’ – but that attitude is changing.”

As for other graduate students who might be considering the competition, Mohammadi encourages them to sign up. “I can’t think of a reason why you shouldn’t do it,” she says. “3MT will help you understand for yourself the most important aspects of your work, and also what aspects need to be translatable to make its value known. I went into it with no pressure on myself, which I would recommend to everyone.

“It’s the perfect challenge for graduate students.”

Unearthing the truth: Michael Pollanen on the role of forensic pathology in war zones

geoff.vendeville — Tue, 19 Apr 2022 16:18:04 +0000

Unearthing the truth: Michael Pollanen on the role of forensic pathology in war zones

geoff.vendeville Tue, 04/19/2022 - 12:18

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Michael Pollanen is a professor in the department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine and Ontario's chief forensic pathologist (photo by Andrew Francis Wallace/Toronto Star via Getty Images)

Temerty Faculty of Medicine staff

Topic

Global Lens