Betty Zou

Leah Cowen

PRiME

Faculty of Applied Science & Engineering

Chemistry

Faculty of Arts & Science

Subheadline

Federal funding will be used to strengthen talent development and health intelligence in order to respond to emerging health threats

Four research programs in the Canadian Hub for Health Intelligence and Innovation in Infectious Diseases (HI³) have received $72 million in federal funding from the Canada Biomedical Research Fund (CBRF) and Biomedical Research Infrastructure Fund (BRIF), bolstering the country’s biomanufacturing capacity and readiness to respond to emerging health threats.

Support for HI³ and the four funded research programs through the CBRF and BRIF is part of a larger investment in Canada’s Biomanufacturing and Life Sciences Strategy. The strategy aims to grow a strong, competitive domestic life sciences sector with cutting-edge biomanufacturing capabilities and to improve the country’s ability to respond to future health challenges.

HI³ – a coalition of 87 academic, hospital, research networks, industry, government, not-for-profit and community partners – was one of five national hubs established in March 2023 with CBRF funding.

Together, the four awarded programs will provide critical health intelligence data to guide the co-development of health threat surveillance platforms and next-generation precision interventions by the hub’s academic and industry partners, while building a highly skilled workforce to support Canada’s growing biomanufacturing and life sciences sector.

“Congratulations to HI³ and the collaborative teams behind these CBRF-funded programs. These four programs leverage the tremendous expertise of the ��Ƶ's researchers and our partners in academia, hospitals, industry and other sectors to develop the talent, tools and data required to be at the forefront of emerging health threats,” said Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives.

“On behalf of the ��Ƶ and HI³, I thank the government of Canada for its investment in building a strong domestic life sciences sector ready to take on the health challenges of today and tomorrow.”

One of the CBRF-funded programs is the Biomanufacturing Hub Network (BioHubNet), an immersive talent development program based at U of T and led by University Professor Molly Shoichet along with Darius Rackus, an assistant professor of chemistry and biology at Toronto Metropolitan University, and Gilbert Walker, a professor of chemistry at U of T.

“With world-leading scientists and researchers established across Canadian leading research institutions, Canada is home to a competitive and robust biomanufacturing and life sciences sector. We made a promise to Canadians that we would rebuild the domestic sector,” said François-Philippe Champagne, Canada’s minister of innovation, science and industry. “With this investment, our government is delivering on this promise by supporting the excellent innovations, collaborations and infrastructures necessary to rapidly respond to future public health threats and keep Canadians safe.”

The predicted supply of biomanufacturing workers is only enough to fill one-quarter of the positions that will be needed in the sector by 2029, according to a 2021 report from BioTalent Canada.

To address the shortage, BioHubNet will leverage its 26 industry and training partners – which include multinational and homegrown biotechnology companies, as well as five Ontario colleges and nearly $19 million in funding from CBRF – to develop a range of training programs and curricula that provide experiential, hands-on learning to graduate students, postdoctoral fellows and others who are ready to transition to industry.

The program will also outfit entrepreneurs with the skills and resources they need to commercialize their lab-based innovations, further strengthening the translational pipeline. Over the next four years, BioHubNet will produce close to 1,000 highly skilled workers through micro-credential courses, industry internships, academic exchange placements and entrepreneurial training.

A central tenet underlying all BioHubNet’s offerings is a commitment to create more equitable and inclusive participation in the biomanufacturing and life sciences sectors through intentional recruitment and active support for trainees from under-represented groups.

“Canada’s future as a leader in bio-innovation depends on having highly qualified workers, yet the sector is predicted to face severe workforce shortages in the coming years,” says Shoichet, who is the Michael E Charles Professor in Chemical Engineering at U of T and scientific director of PRiME Next-Generation Precision Medicine, a U of T institutional strategic initiative based at the Leslie Dan Faculty of Pharmacy.

“By expanding the pipeline of skilled research talent in Canada, BioHubNet will accelerate the translation of promising discoveries from bench to market and ensure that this country’s biomanufacturing sector continues to grow and attract further international investment.”

In addition to BioHubNet, three other research programs were also funded:

The Integrated Network for the Surveillance of Pathogens: Increasing Resilience and capacity in Canada’s pandemic response (INSPIRE) based at the University of Windsor. Co-led by Windsor professor Mike McKay and University of Guelph professor Lawrence Goodridge, the INSPIRE program leverages community-level wastewater surveillance data, infrastructure and expertise to monitor the arrival and spread of infectious threats. The program also received infrastructure funding from BRIF to implement technologies and processes across its network that will streamline wastewater surveillance efforts to be more rapid, agile and sensitive. Importantly, these infrastructure supports will expand wastewater monitoring capacity in northern Ontario and at the Windsor-Detroit border to strengthen supply chains.
The Prepare, React, Collect, Innovate, Share and Engage (PRECISE) Diagnostic Platform, based at Sinai Health and co-led by Jennie Johnstone and Anne-Claude Gingras – who are both faculty members in U of T’s Faculty of Medicine – will advance a comprehensive, streamlined approach for responding to emerging threats by driving the timely development of rapid diagnostic tools that will scale up testing capacity and reduce reliance on global supply chains.
The Pandemic Preparedness Engaging Primary Care and Emergency Departments (PREPARED) program, based at Unity Health Toronto and led by Andrew Pinto, who is a faculty member in the Temerty Faculty of Medicine, aims to engage primary care clinics and emergency departments across the country to enhance disease monitoring, improve patient care and health system efficiency, accelerate the development of medical countermeasures and boost recruitment to clinical trials.

All four research programs reflect the hub’s extensive network of nearly 100 partners from academia, hospital, industry, public and other sectors. The programs leverage the collective resources and expertise of this network, including U of T’s position as a global leader in artificial intelligence, data, life sciences and engineering, and the Toronto Academic Health Sciences Network’s strong track record of clinical impact and health-care innovation.

“Our goal at HI³ is to advance mission-driven, team-based science that will help Canada be more prepared, resilient and independent in the face of emerging health threats,” said Jen Gommerman, co-director of HI³ and a professor of immunology in U of T’s Temerty Faculty of Medicine.

“As we support and grow these four research programs, we will continue to work closely with our hub partners and with our counterparts across the country to ensure that we have the capacity and resources needed to respond in a co-ordinated, effective and equitable manner.”

Heart-on-a-chip model used to glean insights into COVID-19-induced heart inflammation

Christopher.Sorensen — Mon, 08 Apr 2024 19:06:23 +0000

Heart-on-a-chip model used to glean insights into COVID-19-induced heart inflammation

Christopher.Sorensen Mon, 04/08/2024 - 15:06

Cutline

Researchers worked in the Toronto High Containment Facility at U of T to examine the effects of COVID-19 on heart inflammation (photo by Lisa Lightbourn)

Topic

Institute of Biomedical Engineering

Faculty of Applied Science & Engineering

Alumni

Leslie Dan Faculty of Pharmacy

Subheadline

Researcher dedicates study to her late grandmother, who died from COVID-19-induced heart failure

Researchers at the ��Ƶ and its partner hospitals have created a unique heart-on-a-chip model that is helping untangle the causes of COVID-19-induced heart inflammation and uncover strategies to reduce its impact.

While COVID-19 is primarily a respiratory infection, clinicians and researchers are increasingly aware of the virus’s effects on other organs – including the heart. Data from the U.S. Centers for Disease Control and Prevention shows patients hospitalized with COVID-19 between March 2020 and January 2021 had 15 times higher risk for developing myocarditis, or inflammation of the heart muscle, compared to patients without COVID-19.

But the biology behind the association between SARS-CoV-2 infection and heart inflammation had remained unclear – in part because there have not been good models with which to study infection-related heart inflammation.

“Conventionally, people grow heart cells in a 2D setting and then expose it to SARS-CoV-2 to see how the virus damages the heart. But that’s not actually what happens in our body,” says Rick Lu, a PhD graduate from U of T’s Institute for Biomedical Engineering who is currently a postdoctoral researcher at U of T’s Leslie Dan Faculty of Pharmacy.

Lu is the first author of a new study published in Science Advances that describes a miniature 3D heart-on-a-chip model that more accurately captures the impact of SARS-CoV-2 infection and its associated immune response on cardiac dysfunction.

The first-of-its-kind model builds on previous work led by Milica Radisic, Lu’s PhD adviser, a senior scientist at University Health Network and a U of T professor of biomedical engineering. The approach uses a lab-made network of blood vessels surrounded by heart tissues grown from stem cells to mimic a real human heart with its tangle of vessels going in and out.

From left to right: Researchers Milica Radisic, Rick Lu and Claudia dos Santos (supplied images)

To examine the effects of COVID-19 on heart inflammation, Lu and his colleagues first had to adapt their model to work in the Toronto High Containment Facility, a specialized lab that allows researchers to study high-risk pathogens like SARS-CoV-2 in a safe and secure way.

“This work would simply not be possible without the Toronto High Containment Facility,” says Radisic, who holds the Canada Research Chair in Organ-on-a-Chip Engineering.

In the high containment lab, the researchers added live virus and immune cells to the blood vessels and allowed them to flow through their mini hearts-on-a-chip, replicating the immune response that happens after a SARS-CoV-2 infection. They found that the combination of SARS-CoV-2 and immune cells reduced the heart’s ability to contract and pump. To understand why, the researchers turned to mitochondria, the tiny energy storehouses that power the muscle’s beating movements. They showed that SARS-CoV-2 infection led to loss of mitochondria and a release of mitochondrial DNA from the heart cells into the nutrient broth used to grow the organoids.

Working with Claudia dos Santos, a scientist and critical care doctor at Unity Health Toronto, associate professor of medicine and Pitts Research Chair in Acute Care and Emergency Medicine at U of T’s Temerty Faculty of Medicine, the researchers then asked whether the presence of freely circulating mitochondrial DNA is also seen in patients experiencing COVID-19-induced heart complications.

They analyzed blood samples from patients with and without COVID-19 and found nearly two-and-a-half times higher levels of mitochondrial DNA in patients who were COVID-19-positive. Their findings point to mitochondrial DNA levels as a powerful predictor of a person’s risk of experiencing cardiac problems after SARS-CoV-2 infection.

The team also showed that a new type of cell-based therapy called exosomes – little cargo vessels that bubble off cells – could reduce inflammation and mitochondria loss, as well as improve heart function, after SARS-CoV-2 infection, highlighting their potential to repair COVID-19-associated heart damage.

By integrating blood vessels and immune cells, Lu hopes that the innovative heart-on-a-chip model can help researchers and clinicians understand and identify treatment strategies for other infection-related heart conditions.

“The good thing about our system is that it’s readily adaptable to any kind of infectious disease,” says Lu. “The other benefit is that we don’t have to rely as much on animal models. Since we’re already using human-derived cells, the clinical translatability is much higher.”

As a next step, Radisic’s group plans to use the miniature organs to uncover why males are more likely than females to experience COVID-19-associated heart complications and to examine the cardiac issues commonly seen in people with long COVID-19.

Radisic says the motivation for this work was deeply personal. She dedicated the study to her late grandmother who died from COVID-19-induced heart failure after six weeks in the intensive care unit.

“The feeling of helplessness is rather profound when a loved one is dying,” she says. “As scientists, we can take small steps toward new cures so that other people do not meet the same fate. For me, this work meant overcoming the feeling of helplessness.”

The work was supported by investments from the Canada Foundation for Innovation and the creation of the U of T COVID-19 biobank and the Precision Medicine in Critical Care (PREDICT) Biobank at Unity Health Toronto – and by the contributions of patients and families that donated biological samples, making significant advances in research possible.

U of T receives $10 million from Ontario government for modernization of high containment facility

Christopher.Sorensen — Mon, 18 Mar 2024 18:15:01 +0000

U of T receives $10 million from Ontario government for modernization of high containment facility

Christopher.Sorensen Mon, 03/18/2024 - 14:15

Cutline

(photo by Julia Soudat)

Topic

Our Community

Sunnybrook Health Sciences Centre

Hospital for Sick Children

Health

Subheadline

Renewal of the 20-year-old facility, which allows researchers to study high-risk pathogens, will provide increased capacity to develop new vaccines and therapeutics

Canada’s ability to respond rapidly to emerging infectious diseases is taking a step forward with a $9.9-million investment from the Ontario government to support critical research infrastructure updates to the Toronto High Containment Facility (THCF), which houses the largest containment level 3 lab in the province.

The facility, located at the ��Ƶ, is specially equipped to allow researchers to study high-risk pathogens, such as SARS-CoV-2, HIV, tuberculosis and mpox, in a safe and secure way.

Research undertaken at the current facility has advanced our understanding of infectious diseases and strengthened our ability to respond to emerging health threats.

“The THCF strengthens Ontario’s position as a prime location for globally leading companies and top talent to discover and commercialize cutting-edge technologies, while improving our preparedness for future health challenges,” says Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives. “The updated facility will enhance Canada’s health infrastructure and health security, and ensure that Canadian researchers are trained and ready to respond to emerging infectious diseases.”

The provincial funding builds on a previous $35-million investment from the Canada Foundation for Innovation to support efforts to revitalize and expand the THCF and to transform it into the largest academic high-containment research centre in Canada.

The renewal of the 20-year-old facility will provide increased capacity to use state-of-the-art approaches supporting academic research projects as well as collaborative industry-led efforts to develop new vaccines and therapeutics for Canadians. The new provincial investment will also allow the facility to meet the growing demand from industry and public sector partners while maintaining ongoing research projects and an agile responsiveness to future outbreaks.

“The new THCF will allow our researchers to work on the most urgent infectious disease threats, provide greater opportunities to engage with government agencies and industry partners, and allow us to provide unique training opportunities for the next generation of infectious disease leaders, building a strong foundation for Canada’s response to future outbreaks,” says Scott Gray-Owen, academic director of the THCF and a professor of molecular genetics in U of T’s Temerty Faculty of Medicine.

The provincial support is part of a suite of investments through the Ontario Research Fund and the Early Researcher Awards that also include support for quantum and artificial intelligence projects at U of T. Support has also been extended to advance an infrastructure renewal of the province’s Advanced Research Computing (ARC) systems, including U of T’s Niagara ARC supercomputer, used by researchers across the country.

As the only high containment facility of its kind in the Greater Toronto Area, the THCF is a unique asset to the life sciences ecosystem in the region, which is home to 55 per cent of Canada’s pharmaceutical companies. The modernized facility will be able to support greater engagement with industry partners to advance made-in-Ontario therapeutics such as the experimental drug paridiprubart from Markham-based Edesa Biotech, which is currently being tested in a Phase 3 clinical trial to treat acute respiratory distress syndrome, a common complication from COVID-19 or influenza infections.

In addition to industry partners, the THCF has been used by federal and provincial agencies including the Public Health Agency of Canada, Bank of Canada, Rogers Hixon Ontario Human Milk Bank and Ontario Ministry of Natural Resources and Forestry.

The THCF renewal will also be undertaken in collaboration with U of T’s hospital partners: The Hospital for Sick Children, Sinai Health, Sunnybrook Health Sciences Centre, Unity Health Toronto and University Health Network. Construction of the facility has begun but the university is seeking additional funding to complete the project.

Based at the Temerty Faculty of Medicine, the THCF is the cornerstone of the Emerging and Pandemic Infections Consortium, a U of T institutional strategic initiative that brings together the university and Toronto Academic Health Science Network (TAHSN) hospital partners to drive innovative approaches to infectious diseases and prepare for future pandemics. It is also a key infrastructure resource for the Canadian Hub for Health Intelligence and Innovation in Infectious Diseases (HI3) which was established through the Canada Biomedical Research Fund. The hub brings together over 90 partners across several sectors to bolster Canada’s biomanufacturing capacity to ensure a fast and co-ordinated response to future pandemics and infectious threats.

The revitalized THCF will also have the capacity to train more than 100 new highly qualified professionals over a five-year period with industry-relevant skills, including manufacturing practices and vaccine and therapeutics development.

At the beginning of the COVID-19 pandemic, the THCF was the first lab in Canada – and one of the first in the world – to isolate the new coronavirus in March 2020. The facility and its highly trained staff played a key role in accelerating research breakthroughs that guided the pandemic response including, for example, methods to allow safe reuse of personal protective equipment in health-care settings and to ensure safe human milk banking for premature infants.

The THCF was also a core element of EPIC’s mpox rapid research response, housing a biobank of samples from patients with mpox which are being used by researchers to better understand the dynamics of viral shedding and other important questions about the disease.

In addition to a larger physical space, the updated facility will include a state-of-the-art high containment insectary to enable research on mosquito-borne viruses like Chikungunya, dengue, Zika and yellow fever. With its modular design and enhanced safety features, the new facility will also be better positioned to respond to emerging pathogens like highly pathogenic avian influenza.

Mpox DNA can persist in the body for up to four weeks: Study

rahul.kalvapalle — Tue, 12 Mar 2024 20:04:03 +0000

Mpox DNA can persist in the body for up to four weeks: Study

rahul.kalvapalle Tue, 03/12/2024 - 16:04

Cutline

A sign containing information about monkeypox is seen in International Airport Treviso A. Canova, in Treviso, Italy, on Nov. 30, 2022 (photo by Manuel Romano/NurPhoto via Getty Images)

Topic

EPIC

Dalla Lana School of Public Health

ihpme

St. Michael's Hospital

Sunnybrook

Subheadline

The study is one of several projects supported by the mpox rapid research response launched by U of T's Emerging and Pandemic Infections Consortium (EPIC) and its hospital partners

DNA from the mpox virus can be found in different parts of the body for up to four weeks after symptom onset, according to a study led by researchers at Unity Health Toronto, the Sunnybrook Research Institute and the ��Ƶ.

The researchers analyzed samples from 64 men who contracted mpox, including participants from the Mpox Prospective Observational Cohort Study led by Darrell Tan, an infectious disease physician at St. Michael’s Hospital, part of Unity Health Toronto – where some of Toronto’s first patients with mpox were identified and cared for – and associate professor in the department of medicine and the Institute of Medical Science at U of T's Temerty Faculty of Medicine and in the Institute of Health Policy, Management and Evaluation (IHPME) at the Dalla Lana School of Public Health.

They found that persistence of mpox virus DNA varied depending on where the samples were taken from. Among the key findings was that the DNA was detectable in nearly half of genital skin swabs and one in five skin swabs from other sites a week after symptoms had resolved.

The study, which was published in Open Forum Infectious Diseases, is one of several projects supported by the mpox rapid research response launched by the Emerging and Pandemic Infections Consortium (EPIC), an institutional strategic initiative, and its hospital partners during the global outbreak of mpox – previously known as monkeypox – in 2022.

According to the World Health Organization, nearly 94,000 confirmed cases of mpox, including 179 deaths, have been reported from 117 countries since January 2022. As of September 2023, 1,515 cases have been confirmed in Canada, mostly in Ontario and Quebec.

“Even though we’ve known about mpox for over 70 years, it was new to us because we hadn’t seen it outside the endemic regions,” said Robert Kozak, one of the study’s authors and a clinical microbiologist at Sunnybrook Research Institute and assistant professor in the department of laboratory medicine and pathobiology at Temerty Medicine. “There was still a lot about the virus and disease that we didn’t know,”

To answer key questions about viral shedding, Kozak teamed up with Tan and Sharmistha Mishra, an infectious disease physician at St. Michael’s Hospital and associate professor in the Temerty Faculty of Medicine’s department of medicine and Institute of Medical Science and IHPME.

(L-R) Robert Kozak, Sharmistha Mishra and Darrell Tan (supplied images)

The researchers used a technique called quantitative polymerase chain reaction (qPCR) to determine the persistence of mpox virus DNA. Samples were taken from six different sites on the body — genital region, nasal cavity, semen, skin, throat and urine — and over an extended period of time.

On average, mpox DNA was detected in skin swabs from the genital and perianal region and from other skin sites at 30 and 22 days after symptom onset, respectively. These findings are consistent with the sexually transmitted nature of mpox during the recent global epidemic, which primarily affected gay, bisexual and men who have sex with men.

The researchers were unable to detect viral DNA in a large proportion of semen samples and nasal cavity swabs taken when individuals first presented with symptoms, whereas in urine and throat swab samples, mpox DNA persisted for roughly two weeks after symptom onset.

Interestingly, the researchers did not observe a difference in the length of viral DNA persistence between people who received the antiviral drug tecovirimat and those who did not. Tan noted that while study participants were not randomly assigned to receive the drug, these results underscore the uncertainty around tecovirimat’s effectiveness in treating mpox infections.

He added the study provides several key learnings for his clinical colleagues. “First, we’ve documented the breadth of clinical samples in which mpox DNA can be identified and therefore can be used to confirm a diagnosis. Our findings also reinforce that it’s worthwhile for clinicians to collect such samples in individuals where an mpox diagnosis is being considered, even after symptoms of feeling unwell are gone," Tan said.

The researchers caution that just because mpox DNA can be detected up to four weeks after symptom onset, it doesn’t mean that individuals are infectious for that long.

“We don’t know for sure whether the presence of detectable viral DNA necessarily means that the virus is transmissible to other people, so more research definitely needs to be done to determine definitively the period of infectiousness,” Tan said.

To that end, Jacklyn Hurst, a postdoctoral fellow in Kozak’s lab, recently started work in the Toronto High Containment Facility to look for live virus in the same samples from which mpox DNA was detected. The researchers are also using the facility’s biobank of mpox patient samples to identify biomarkers that could predict whether a person will have a mild or severe infection.

“Without the Toronto High Containment Facility, we wouldn’t be able to do any of this. Having that facility will help us answer a lot of questions about this virus and how to stop it,” said Kozak.

He acknowledged the immense contributions of the patient community to this work. “A huge thank you to all the study participants. We wouldn’t be able to do this work without their sacrifice and commitment.”

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 U of T and its partner hospitals that looked for SARS-CoV-2 antibodies in human breast milk (supplied image)

Topic

COVID-19

Sunnybrook Health Sciences

Laboratory Medicine and Pathobiology

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 ��Ƶ 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 U of T professor of medicine and nutritional sciences, and Susan Poutanen, microbiologist and infectious disease consultant and Sinai Health and U of T 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 U of T.

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 U of T 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.

U of T PhD student uses synthetic biology to create low-cost diagnostic tools

Christopher.Sorensen — Wed, 25 Oct 2023 14:55:23 +0000

U of T PhD student uses synthetic biology to create low-cost diagnostic tools

Christopher.Sorensen Wed, 10/25/2023 - 10:55

Cutline

Justin Vigar, pictured here in a lab in South America, is developing paper-based diagnostics like the paper chip shown on the right, where each dot represents a different test (supplied image)

Topic

Our Community

Leslie Dan Faculty of Pharmacy

Graduate Students

Subheadline

Justin Vigar and his colleagues are creating a customizable, paper-based platform to rapidly screen for COVID-19 and other infectious diseases

“Synthetic biology” might sound like a contradiction in terms, but ��Ƶ graduate student Justin Vigar believes it can improve the health and lives of people around the world.

A relatively new field of research, synthetic biology applies engineering principles to recreate fully functional biological systems. In Vigar’s case, he’s using the approach to develop rapid, low-cost diagnostic tools to combat infectious diseases as the recipient of a doctoral award from the Emerging and Pandemic Infections Consortium (EPIC) – one of several U of T institutional strategic initiatives.

Today, the gold standard for diagnosing many infectious diseases is a technique called real-time reverse transcription-quantitative PCR (RT-qPCR), which is both sensitive and specific enough to detect small amounts of a particular microbe in a patient sample. However, the process is complex, requires expensive equipment and materials, and must be carried out by highly trained personnel.

“We talk a lot about South America and other countries in the Global South but in most areas in Canada, including rural Alberta where I grew up, there’s no access to RT-qPCR,” says Vigar, a fourth-year PhD student who is working with Keith Pardee, an associate professor in the Leslie Dan Faculty of Pharmacy.

The lack of access to RT-qPCR testing was especially apparent during the COVID-19 pandemic when many low- and middle-income countries struggled to track the spread of SARS-CoV-2 within their borders because they did not have the infrastructure, expertise and resources to conduct timely RT-qPCR tests for their citizens. Rapid antigen tests helped fill the void, but they aren’t as sensitive and cannot be scaled up easily to process hundreds of samples at once.

“We wanted to fill that gap by building really accessible tools that could do rapid screening for COVID-19 and other infections – something that would be a midway between a rapid antigen test and RT-qPCR,” says Vigar.

To that end, he and his lab colleagues are creating a customizable, paper-based platform that uses pocket-sized slips of paper with embedded genetic circuits. The circuitry is built by freeze-drying proteins and other molecular components, which function as amplifiers and sensors, directly onto the paper. Patient samples are minimally processed to extract the genetic material and applied directly to the paper. If the patient sample contains genetic materials from the pathogen of interest, it will trigger the circuitry to switch on and produce a colour change on the paper, which can be spotted by the naked eye.

Pardee’s team has already proven the effectiveness of their paper-based diagnostic tool in enhancing disease surveillance during Brazil’s 2015-2016 Zika virus outbreak and, more recently, during the COVID-19 pandemic. Now Vigar is working with collaborators in other Latin American countries and India to expand use of the diagnostic tool to monitor other infectious diseases such as dengue fever and leishmaniasis, which is caused by the Leishmania parasite.

“We have the system working very well in Toronto and a couple of our collaborating countries but the challenge now is sourcing the materials to embed onto the paper and scaling up in other countries,” Vigar says.

While it’s easy for Vigar to get the components and build the paper devices in Toronto and ship them to collaborators around the world, his ultimate goal is to empower them to manufacture and distribute the tools locally.

“We need to work with researchers in other countries to build a network that will give them access to these reagents and materials so they aren’t relying on us to ship it to them. Then they’ll be able to build their own pipelines to detect the pathogens and diseases that they’re interested in.”

Vigar was in Chile for two weeks this past summer to help local researchers to test the reproducibility of their own paper tests. Pardee’s lab also recently hosted two visiting students from Universidad de Los Andes in Columbia to learn the process for building the low-cost devices.

Beyond monitoring infectious diseases in humans, Vigar says the paper-based platforms are being used to answer other important questions – for example, tracking the spread of an agricultural pest or the movements of an endangered species.

Vigar’s passion for synthetic biology and ensuring equitable access to new biotechnologies extends beyond the lab.

He is an active delegate to the United Nations Convention on Biodiversity (UNCBD), which includes two international agreements on biosafety and profit sharing related to synthetic biology and biotechnology. As an attendee at the UNCBD Conference of the Parties (COP) in Sharm El-Sheikh, Egypt in 2018 and in Montreal in 2022, he educated attendees about synthetic biology and shared his perspective on how low-cost diagnostics can improve the lives of people around the world.

“These technologies are so powerful but they’re limited in where and how they’re used. We want to make it more accessible – and if we work collaboratively toward that goal, it’s going to benefit so many more people.”

Study uncovers how the gut's microbiome boosts immune system development

Christopher.Sorensen — Wed, 11 Oct 2023 17:02:48 +0000

Study uncovers how the gut's microbiome boosts immune system development

Christopher.Sorensen Wed, 10/11/2023 - 13:02

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Arthur Mortha, left, and Pailin Chiaranunt led research that revealed new insights about how gut microbes influence immune system development (photo by Mark Bennett)

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“The gut is probably one of the most dynamic ecosystems in the body because you essentially have the outside environment inside of you”

A study is shedding new light on how the gut’s microbial communities contribute to a well-functioning immune system and defend against harmful pathogens.

The findings, published in the journal Science Immunology, include important insights on how monocytes, a type of white blood cell, transform into macrophages, which play a key role in eliminating foreign microbes and initiating an immune response.

Lead author Pailin Chiaranunt, a PhD student in the department of immunology at ��Ƶ’s Temerty Faculty of Medicine, says she first learned about the microbiome as an undergraduate student and then fell in love with immunology as a research technician.

“The fact that there are these vast ecosystems of bacteria, fungi, viruses and other microbes living inside us really reshaped the way I see the human body,” Chiaranunt says.

In the study, the researchers turned their attention to macrophages, key immune cells whose job is to gobble up cellular debris and foreign microbes and kick start the immune response.

They found that the transformation of monocytes, a type of white blood cell, into macrophages in the gut requires both a diverse microbiome and a host factor called CSF2. Then, in a series of experiments, Chiaranunt and her colleagues identified the microbial factor driving macrophage development as ATP, a molecule that is used as energy currency across all forms of life.

Their work also uncovered how microbial and host factors work together to support a robust immune environment in the gut: ATP produced by resident bacteria in the gut activates immune cells within a network of small, lymph node-like structures across the intestinal tract. These cells then produce the host factor CSF2 which spurs monocytes in the structures to become response-ready macrophages.

The researchers further showed that the macrophages born from this pathway have high metabolisms and as a result, produce a lot of antimicrobial chemicals called reactive oxygen species. The abundance of these chemicals, in turn, contribute to the immune system’s ability to ward off microbial intruders in the gut.

“That was a really cool finding because it suggests a new way in which microbial metabolism can directly impact immune cell metabolism,” says Chiaranunt, who recently defended her PhD thesis and is preparing to start a postdoctoral fellowship at the University of California, San Francisco.

The collection of microorganisms that live in and on our bodies plays a critical role in health and disease. Certain microbiome features – for example, whether there is more of one species or less of another – have been linked to a variety of health outcomes, from autoimmune and mood disorders to cancer risk and treatment response.

Chiaranunt says her interest in how the microbiome and immune system interact with each other, particularly in the gut, led her to U of T to pursue a PhD with Arthur Mortha, an associate professor of immunology in the Temerty Faculty of Medicine who studies the crosstalk between the immune system and gut microbiome.

“The gut is probably one of the most dynamic ecosystems in the body because you essentially have the outside environment inside of you,” Chiaranunt says. “There’s a lot of work the immune system must do to maintain a balance between tolerating helpful microbes, food and other outside factors, and being able to mount an effective defence against pathogens like salmonella that might show up.”

In addition to other members of Mortha’s lab, the study also included collaborators Slava Epelman, a scientist at the Toronto General Research Institute, University Health Network and clinician scientist in U of T’s department of medicine in the Temerty Faculty of Medicine, and Thierry Mallevaey, an associate professor of immunology in the Temerty Faculty of Medicine. Mortha, Epelman and Mallevaey are all members of the Emerging and Pandemic Infections Consortium, a U of T Institutional Strategic Initiative focused on developing innovative responses to infectious threats.

While other studies have also found a link between the microbiome and macrophage development, the researchers’ recent paper is one of the first to uncover how gut bacteria trigger white blood cells to become macrophages. The identification of CSF2 as a key contributor to that process also highlights the potential of CSF2-targeting treatments to modulate the immune response in people with autoimmune disorders and inflammatory bowel disease.

“Our results bring us a big step closer to understanding the biochemical language spoken by the microbiota,” says Mortha. “Assembling a comprehensive dictionary for this language will help us to interpret when and why friendly and offensive messages are used by gut microbes to communicate with our immune system.”

Research may explain why men are more likely to experience severe cases of COVID-19

Christopher.Sorensen — Tue, 03 Oct 2023 15:11:29 +0000

Research may explain why men are more likely to experience severe cases of COVID-19

Christopher.Sorensen Tue, 10/03/2023 - 11:11

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Haibo Zhang, a researcher at Unity Health Toronto and U of T, led pre-clinical research that suggests why males are more likely to experience worse outcomes from COVID-19, opening the door to potential new treatments (photo by Julia Soudat)

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Sunnybrook Health Sciences

Hospital for Sick Children

Graduate Students

St. Michael's Hospital

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Pre-clinical study points to ACE2 protein as a key contributor to the differences in COVID-19 outcomes between males and females

A new study by a team of researchers at the ��Ƶ’s Emerging and Pandemic Infections Consortium (EPIC) has uncovered biological reasons underlying sex differences in COVID-19 outcomes, offering a promising new strategy to prevent illness.

The pre-clinical research, published in the journal iScience, has yet to be replicated in humans, but points to the ACE2 protein as a key contributor to differences in COVID-19 outcomes between males and females.

During the early days of the pandemic, clinicians noticed that males were more likely than females to be hospitalized or admitted to the ICU or to die from COVID-19 despite having similar infection rates.

This pattern held true across all age groups and in countries around the world.

“COVID-19 severity and mortality are much higher in males than in females, but the reasons for this remain poorly understood,” says study senior author Haibo Zhang, a staff scientist in the Keenan Research Centre for Biomedical Science at St. Michael’s Hospital, Unity Health Toronto, and a professor of anesthesiology and pain medicine, and physiology in U of T’s Temerty Faculty of Medicine.

“That was the driving force for our work.”

The study was a collaborative effort through EPIC, a U of T institutional strategic initiative that involves five hospital research partners – the Hospital for Sick Children (SickKids) Research Institute, Lunenfeld-Tanenbaum Research Institute at Sinai Health, Sunnybrook Research Institute, Unity Health Toronto and the University Health Network (UHN) – to facilitate an integrated and innovative response to high-risk, high-burden infectious diseases.

From left: PhD student Jady Liang, co-lead author of the study and Professor Haibo Zhang (photos supplied)

Located on the cell’s outer surface, ACE2 plays an important role in controlling blood pressure and inflammation and protecting organs from damage caused by excess inflammation. During a SARS-CoV-2 infection, the coronavirus spike protein locks on to ACE2 to enter the cell.

The gene encoding the ACE2 protein is located on the X chromosome, which means that females have two copies of the gene and males only have one.

In times of health, the extra copy of the gene for ACE2 doesn’t appear to make a difference – Zhang and his team found similar levels of ACE2 protein in healthy males and females.

Following a SARS-CoV-2 infection, however, they observed a dramatic decrease in ACE2 in males while levels remained consistent in females, suggesting that the additional copy of the ACE2 gene on the X chromosome is helping to compensate and maintain high protein levels in females.

The changes in ACE2 levels were also correlated with a drop in estrogen hormone signalling in males, which could also contribute to the sex-specific differences in COVID-19 outcomes.

To test whether low levels of ACE2 were responsible for the more severe outcomes seen in males with COVID-19, the researchers devised a therapeutic approach using an inhaler to deliver lab-made ACE2 proteins directly into the lungs. Males who received a daily puff of ACE2 after SARS-CoV-2 infection had less virus in their lungs, less lung injury and higher levels of estrogen signalling.

Together, these results paint a clearer picture of how the extra copy of the ACE2 gene and higher estrogen levels in females work together to protect them from experiencing more severe COVID-19.

“A common misconception is that an increased presence of ACE2 receptors would result in a higher infection rate,” says Zhang.

“However, the enhanced activation of ACE2 in females actually serves as a compensatory mechanism during infection that’s aimed at safeguarding the lungs and other vital organs from potential damage.”

In males who lack the second copy of the gene, much of the existing ACE2 gets co-opted by SARS-CoV-2 during an infection. As a result, there is not enough of the protein to fulfil its usual functions of tamping down inflammation and preventing organ damage.

The extra dose of ACE2 delivered by inhaler serves as a decoy to glom onto the coronavirus, thereby preventing it from entering cells while also keeping the native ACE2 proteins free to exert protective effects.

Beyond the thrill of discovery, Zhang says he is excited by the potential implications of these findings, which are the first to demonstrate the effectiveness of inhaling ACE2, on preventing and treating COVID-19 in humans.

He imagines a scenario where people who are entering high-risk situations – boarding an airplane or attending a large in-person conference, for example – might take a puff of ACE2 to protect their lungs from the virus. Similarly, the treatment could also be given to people after infection to reduce the risk of hospitalization and death.

“By using the inhaler, ACE2 remains in the lungs at a sustained, low concentration over an extended period, where it can neutralize the virus even before it enters into our cells. We anticipate that our research will motivate individuals to contemplate this faster and more efficacious strategy for both prevention and treatment of COVID-19 in humans,” says Zhang.

Zhang worked with fellow researchers Samira Mubareka (Sunnybrook, Temerty Faculty of Medicine), Theo Moraes (SickKids, Temerty Faculty of Medicine) and Mingyao Liu (UHN, Temerty Faculty of Medicine). Much of their work took place in the Toronto High Containment Facility (THCF), which is the only containment level 3 research lab in the Greater Toronto Area and the largest in the province.

Having access to the THCF allowed Zhang and his team to pivot quickly during the early months of the pandemic and apply their expertise in lung physiology and disease to answering rapidly emerging questions about COVID-19.

Jady Liang, the co-lead author of the new study, had just started her PhD with Zhang when the pandemic started. She recalls the stress and intensity of training and working in the THCF during that time but credits EPIC staff and other THCF users with helping her become comfortable with the processes and protocols.

“It was a lot of hard work from everyone on the team during the pandemic, especially during the first wave,” says Liang, who is now a fourth-year PhD student in the department of physiology.

“We need a lot of people with expertise in different fields to work together so that we can advance and be prepared for the next pandemic.”

The study received support from the Canadian Institutes of Health Research, among others.

Research shows how boosting immune memory could help develop improved flu vaccine

siddiq22 — Thu, 11 May 2023 20:33:55 +0000

Research shows how boosting immune memory could help develop improved flu vaccine

siddiq22 Thu, 05/11/2023 - 16:33

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PhD student Karen Yeung is one of the recipients of the inaugural EPIC Doctoral Awards for her work on boosting immune memory to enhance protection against influenza (supplied photo)

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EPIC