IMMpress Magazine
Seminal Canadian Discoveries in Immunology
Exploring Indigenous knowledge of health and healing
Why anchor companies are important for Canada’s biotech sector
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IMMpress Magazine
About the Cover
This issue’s cover presents a modern and stylized interpretation of “The Jack Pine”, an iconic painting by Canadian artist Tom Thomson (1877-1917). Much like the original painting, the illustration is inspired by the boreal forests, mountains, and lakes of Northern Ontario. The hiker, bathed in sunlight, stands with a sense of hope and anticipation while gazing out at the vibrant landscape. Although absent in Thomson’s work, the addition of this figure ties the new with the old, symbolizing the continued relevance of Canadian art and the enduring connection between people and nature. The bright color palette and fluid, simplified forms echo Thomson’s influence on the Group of Seven, a collective of painters that revolutionized Canadian art in the early 20th century. Inspired by Thomson’s pioneering work, the Group of Seven sought to convey the unique spirit of our country’s wilderness through bold, expressive brushstrokes and vivid colors. This cover therefore celebrates the legacy of Thomson and the Group of Seven by honoring the beauty of the Canadian landscape. Finally, it pays tribute to the natural world that has profoundly shaped Canada’s cultural identity and continues to inspire artists and nature lovers alike.
Design notes
This issue beautifully integrates designs that reflect the Canadian landscape, using a vibrant color palette dominated by blues and greens. These colors are emblematic of vast skies, deep lakes, and lush forests that define Canada’s signature natural beauty. Several designs also incorporate bright red hues, which represent our national flag. Throughout the issue, photographs and illustrations capture the essence of the Canadian wilderness while incorporating themes of science and innovation. By combining images of nature and science, our designers have highlighted this issue’s celebration of Canada – its rich heritage, pioneering spirit, and contributions to the global scientific community.
-Jennifer Ahn-
EDITORS-IN-CHIEF
James Pollock
Karen Yeung
DESIGN DIRECTOR
Jennifer Ahn
SOCIAL MEDIA COORDINATOR
Tianning Yu
SENIOR EDITORS
Zi Yan Chen
Baweleta Isho
Tiffany Kong
James Pollock
Annie Pu
Jinny Tsang
Boyan Tsankov
Deeva Uthayakumar
Tianning Yu
DESIGN ASSISTANTS
Jennifer Ahn
Baweleta Isho
Meggie Kuypers
Annie Pu
Faizah (Numa) Sayeed
Sophie Sun
Jinny Tsang
Karen Yeung
CONTENT CONTRIBUTORS
Jennifer Ahn
Zi Yan Chen
Yinhan Dechi Castro
Beth DeConinck
Manjula Kamath
Faizah (Numa) Sayeed
Boyan Tsankov
Deeva Uthayakumar
Karen Yeung
Tianning Yu
FOUNDING EDITORS
Yuriy Baglaenko
Charles Tran
Any opinions expressed by the author(s) do not necessarily reflect the opinions, views or policies of the Department of Immunology or the University of Toronto.
Exploring Indigenous knowledge of health and healing
Why anchor companies are important for Canada’s biotech sector
The Legacy of the Canadian Society for Immunology: Advancing Canadian immunology towards scientific progress, collaboration, and inclusivity
Reconnecting with the former Chair: A Chat with Dr. Juan Carlos ZúñigaPflücker on the growth of Canadian Immunology
The Department of Immunology - 40 years and counting
Banting and Best: The discovery of insulin
Canada’s Role in the Creation of the Ebola Vaccine
Gairdner
its
and legacy
LETTER FROM THE EDITORS
Autumn has arrived, and as the maple leaves turn a vibrant red, we are thrilled to bring you this latest issue of IMMpress Magazine, dedicated to the rich and diverse landscape of Canadian immunology. Canadians from sea to sea are making significant strides in the field of immunology every day, and so in this issue, we shine a spotlight on the remarkable scientists and groundbreaking research that have positioned Canada as a leader in the global immunology community.
In this issue, we celebrate seminal Canadian achievements in immunology, including an article on the discovery of insulin led by Frederick Banting and James Best at the University of Toronto (p20). We also cover the discovery of stem cells and hematopoiesis led by James Till and Ernest McCulloch, the first identification of dendritic cells led by Ralph Steinman, and the first cloning of the TCR led by the Department of Immunology’s very own Tak Mak (p10). These remarkable scientists have not only transformed the field but have also been recognized with the prestigious Canada Gairdner International Award (p24), often referred to as the “baby Nobel prize”. We also highlight one of Canada’s recent achievements in immunology: the development of the first effective vaccine against Ebola virus (p22).
Research dissemination is a cornerstone of any thriving scientific ecosystem, and the annual conferences of the Canadian Society for Immunology (CSI) are among the most important platforms for sharing Canadian findings. We visually explore the history of the CSI with an infographic (p8) and recap the 36th CSI conference, held this year in Banff, Alberta (p26). But the journey of research and development is not without its hurdles; we discuss these in an article on the successes and challenges facing Canada’s growing biotech industry (p14).
We also take a moment to honor our department’s legacy with an article on our 40th anniversary celebration held in June (p18), and an interview with previous department chair Juan Carlos Zúñiga-Pflücker (p16). Finally, we explore valuable insights from Indigenous ways of health and healing (p12).
We extend our deepest gratitude to the student writers, editors, and designers who bring IMMpress Magazine to life. We also warmly welcome all the new students and staff who have joined the department this year. A special note of thanks goes to James Pollock, who is stepping down as Co-Editor-in-Chief, for his dedication and leadership. We are excited to welcome Meggie Kuypers, a longtime IMMpress contributor, as she takes on the role.
We hope you enjoy this issue as much as we enjoyed creating it. As always, stay safe and healthy!
In order of left to right: James Pollock (Co-Editor-in-Chief), Karen Yeung (Co-Editorin-Chief), Tianning Yu (Social Media Coordinator), and Jennifer Ahn (Design Director)
The Graduate Peer Support Network (GPSN) Mentorship Program is looking for motivated individuals to join our mentorship team as a peer mentor. Scan to fill out our recruitment form.
FROM THE CHAIR
“The best way to predict the future is to create it.” - Frederick Banting
Nobel Laureate Frederick Banting, who co-discovered insulin with Charles Best, says something that we must embrace as Canadian Scientists. In this issue of IMMpress we have lots to be proud of as Canadian Scientists. We punch above our weight class (and above our funding levels!) when it comes to scientific achievement in Canada.
But we have work to do. Here is a short list based on articles in this issue:
• We need to cultivate a culture of innovation –anchor companies in Canada are needed.
• We need leadership at all levels of science – for example Dr. JC Zuniga-Pflucker’s example as Chair.
• We need to know who we are – our roots as Canadian Scientists are not only derived from stellar academics (Drs. Tak Mak, Till, McCulloch, Steinman), but we can also be inspired by holistic approaches used by indigenous peoples.
Perhaps the secret sauce for creating our future can be found in the “Inter-generational Richness” that was on full display at the Department of Immunology 40th anniversary (I’m quoting Dr. Jayne Danska who introduced some of our speakers). On that day, we looked both backwards through the generations of scientists who built our community, and forwards to those who are creating a new era of Immunology. If you were not lucky enough to attend the reunion, you can read about it in this issue. It was a fantastic day – one for the history books. And while I write this, in a few weeks we will also celebrate the 40th anniversary of the discovery of the T cell Receptor by Drs. Tak Mak and Mark Davis.
Back to Banting’s thoughts on the future, here’s some fun facts about his own history:
• He initially struggled with academic success.
• He and Charles Best discovered insulin “by accident”.
• He was an artist and an aviation enthusiast who designed “The Banting-Brown Free-Fall Parachute”.
• He sold the patent for insulin for $1 to the University of Toronto.
In short, Banting was Human, Curious, Creative, Adventurous and Generous - key ingredients that make up the Canadian Immunologist and ingredients I see in our students, post-docs, staff, faculty and alumni.
The future for Canadian Immunology is bright.
Jen Gommerman, PhD
Canada Research Chair in Tissue Specific Immunity Professor and Chair, Department of Immunology
The Legacy of the Canadian Society for Immunology
Advancing Canadian immunology towards scientific progress, collaboration, and inclusivity
1966 1987
Founding Education
The Canadian Society for Immunology (CSI) was founded in 1966 by Dr. Bernhard “Hardi” Cinader. A pioneering figure in immunological research across Canada, Dr. Cinader was inaugurated as the organization’s first president and founded the Institute of Immunology in the Department of Biochemistry at the University of Toronto in 1971, prior to the birth of the Department of Immunology in 1984. Dr. Cinader’s contributions laid the foundation for immunological research nationwide.
The CSI is dedicated to fostering immunology research and education across Canada, initiating annual spring meetings since 1987 that rotate locations nationwide. A highlight of these meetings is the Hardi Cinader award established to honor outstanding Canadian scientists in immunology, with Dr. Cinader as the first recipient. This tradition has continued for over 30 years.
The CSI has played a key international role as a founding member of the International Union of Immunological Societies (IUIS), with Dr. Cinader serving as its first president in 1969. The CSI was established to connect Canada to a global network of immunologists and to foster collaborations with international organizations such as the American Association of Immunologists, among others.
Collaboration
Dr. Hardi Cinader
Prestigious Awards
Between 2006-2012, the CSI introduced several more prestigious awards, such as the John D. Reynolds award, CSI Investigator Award, CSI New Investigator Award, and trainee travel awards. These honours were created to recognize and celebrate the achievements of individuals at every stage of their career, from young trainees to seasoned principal investigators.
Present
2006-2012 2020
In 2020, the CSI established the Equity, Diversity, and Inclusion (EDI) Committee, which became a permanent, membership-ratified committee in 2022. The EDI Committee introduced EDI workshops as a key component of the annual scientific meetings, ensuring that important topics, like eliminating gender biases, are integrated into the CSI’s ongoing activities.
Continued Excellence
To this day, CSI continues to thrive as a research community; the society has expanded to include over 500 members. The current president, Dr. S. M. Mansour Haeryfar from Western University, an expert in T-cell responses to viral and tumour antigens, has taken on the mantle of fostering scientific excellence and collaboration within CSI and beyond, with a strong commitment to EDI.
Equity, Diversity and Inclusion
Dr. Mansour Haeryfar
- Deeva Uyanakumar
Seminal Canadian Discoveries in Immunology
Despite having its statehood established relatively recently in 1867 and hosting a relatively small population of just over 40 million inhabitants, Canada has an illustrious history of major contributions to science and medicine. Perhaps most well-known among Canadian contributions to medicine is the discovery of insulin and associated methods for its purification by Frederick Banting and Charles Best at the University of Toronto in 1921. Only 29 years later in 1950, Dr. John Hopps developed the first external pacemaker, and conceptualized its insertion via venous catheters – an administration technique still in use today. During the same year, oncologist Dr. Vera Peters made the seminal discovery that Hodgkin’s disease – previously considered incurable – was highly treatable with high-dose radiation therapy. Her work in this regard guides current treatment plans for patients with cancer worldwide. Canada’s innovative research culture extends even further into all spheres of science in technology, and perhaps nowhere else is this more apparent than in the field of immunology.
1963 – Discovery
of stem cells and hematopoiesis: Drs. James Till and Ernest McCulloch
Stem cells are long-lived cells that have the unique properties to self-renew and give rise to more specialized (“differentiated”) progeny. While the theoretical concept of such cells had been hypothesized in the 19th century, there had been a lack of experimental evidence to prove their existence. Two Canadians, James Till, a biophysicist, and Ernest McCulloch, a hematologist, collaborated on pioneering experiments at the University of Toronto that examined the reconstitution of blood (i.e. hematopoietic system) in irradiated mice; work inspired by fears of worldwide nuclear disaster during the Cold War. Their experiments involved injecting bone marrow cells into mice which had lost their hematopoietic systems because of experimental irradiation. After transplantation of the bone marrow cells, Till and McCulloch noticed the appearance of nodules within the spleens of the recipient mice. These nodules contained cells of the 3 main blood cell lineages and rare cells that had the ability to self-renew. The results of their work were published in 1964, and not only provided bona fide proof of the existence of stem cells, but also of hematopoiesis - the development of functional blood cells and of the immune system. The findings of Drs. Till and McCulloch have been instrumental for the development of stem cell and bone marrow transplant therapies used today to treat certain hematological cancers.
1984 – Cloning of the TCR: Dr. Tak Wah Mak
Throughout the 1960s, immunologists began to recognize that specific cells in the blood, termed lymphocytes, were responsible for protection against infectious disease. Furthermore, during this time, there was considerable appreciation that antibodies produced by lymphocytes are important in providing protection against a myriad of different pathogens. A conundrum remained, however, that individuals with agammaglobulinemia (a disease causing an absence of antibody-producing B cells) were able to efficiently control viral infections. These observations led to the discovery of another class of lymphocytes –T cells – that can efficiently control infections even in the absence of antibodies. Whereas B cells were recognized to be the producers of antibodies that could bind fragments of foreign infectious agents, the ways in which T cells mediated clearance of infections remained unclear and was the subject of intense investigation throughout the 1970s and early 1980s. During this period, it was hypothesized that antibody-like molecules, termed the “T cell receptor (TCR)”, present on the surface of T cells formed a means for T cells to mediate clearance of infection. However, the exact genes contributing to the elusive TCR were not yet identified, which made the study of T cell function extremely difficult. This problem was termed the “holy grail of immunology” until 1983, when the laboratory of Dr. Tak Mak at the University of Toronto devised a method for screening thousands of potential candidate genes that could potentially form the human TCR. In the summer of 1983, Dr. Mak noticed gene sequences present in human T cells that resembled those of antibodies produced by B cells. Thus, the lab had successfully discovered the genetic elements encoding for the TCR. The work was confirmed in parallel by the laboratory of Dr. Mark Davis at Stanford University who had used a similar method to devise the genetic elements underlying the mouse TCR. It is hard to overstate the importance of the findings of Drs. Mak and Davis. Notably, new strategies to treat various forms of cancer involve the use of chimeric antigen receptor (CAR) T cells, which heavily rely on the findings of our Canadian discovery.
1973 – Discovery of Dendritic Cells: Dr. Ralph Steinman
Today, dogma in immunology dictates that adaptive (T and B cell) responses to infection are orchestrated by dendritic cells (DCs). DCs take up infectious particle (bacteria, fungi, viruses) and “show” them to T and B cells so that these cells can mediate clearance of the infection. Today, immunologists appreciate DCs to have even broader roles for mediating anti-cancer immune responses as well. Much of immunologists’ understanding of these critical cells is based on the extensive work done by the late Canadian Dr. Ralph Steinman who discovered DCs in 1973 at the Rockefeller University in New York City – a discovery for which he won the Nobel Prize in Medicine or Physiology in 2011.
Despite the current acceptance of the centrality of DCs to immunity, Steinman’s initial characterization of these cells was met with skepticism from the scientific community. At the time, it was accepted that there was an “accessory cell” that was required for T and B cell-mediated immunity, and it was known that this cell would stick to microscope slides, whereas lymphocytes would not. An expert in microscopy, Steinman had set out to characterize these glass-adherent accessory cells by employing a variety of microscopy techniques. Throughout his experiments, Steinman noted a rare cell that had peculiar dendrite-like projections and organelle structures that were quite distinct from those seen from macrophages (another candidate for the “accessory” cell). Steinman coined this rare cell as the dendritic cell. Intriguingly, Steinman’s work on the characterization of DCs and their function did not come out as one singular mechanistic paper. In fact, the various functions of DCs that we now appreciate as being central to immunity were gradually unravelled one-by-one through his laboratory’s many subsequent publications. Indeed, when reading of Steinman’s resilience, creativity, and immeasurable excitement for science, we cannot help but feel inspired.
- Boyan Tsankov
“Yearsagotherewerenodrugsandweusedherbs.Inourwayoflifewedependedontraditional medicine,andwe helpedourselves…Today,modernmedicineand doctorshavetaken over.”
-StoneyCreekNationElder,BritishColumbia
Excerptfrom“TraditionalMedicineforCanada’sFirstPeoples”,RaymondObomsawin,Ph.D.
As a department immersed in biomedical research, we are conditioned to a reductionist understanding of how diseases evolve. Indeed, much of our immunology research and project proposals suggest that eliminating, blocking, or altering specific cellular or molecular offenders driving a disease phenotype would improve a person’s disease outcome. Prior to the technological advancements allowing us to delve deep into mechanistic explanations of some diseases, people have relied on instinct, trial-and-error, and spiritual meaning to treat maladies.
Many Indigenous peoples of Canada, collectively First Nations, Inuit, and Metis, traditionally view the individual as integrated within overlapping mental, social, spiritual, physical, and ecological spheres; this holistic perspective has significantly shaped the methods and practices of Indigenous medicine. Maladies are believed to arise from an imbalance between the individual, society, and the natural world. As such, holistic healing is focused on identifying and resolving internal and external factors contributing to an ailment, such as performing nature and spiritual cleanses and negative energy extraction. While herbal treatments are the most common, other therapeutic methods and practices include sweat baths and lodges, fasting, massage, special diets, and poultices
Common Plants used in Western Medicine
- medicated masses that are applied on sores or lesions. Some other common Indigenous healing practices, such as healing circles during which members sit in a circle passing around a “talking stick”, have been shown as productive, positive discussion spaces to obtain emotional support.
The responsibility of treating the sick is bestowed on the healer or the shaman of the tribe. There are strict ceremonies relating to the harvesting, preparation, and administration of these medicines that may be specific to the individual and tribal families. In some cases, healers themselves undergo purification rituals, which may include fasting or eating certain plants, that allows them to gain special energy to conduct their work.
Ethnobotanical research is the term for the discovery of plant-based medicines. Indigenous peoples have identified over 400 different species of plants, lichens, fungi, and algae with medicinal applications. Different parts of the plants have been used including: roots, bark, leaves, buds, flowers, fruit, sap, and pitch. Components of these medicinal plants and parts are known to contain different ratios of organic compounds, including alkaloids, glycosides, tannins, flavonoids, resins, and essential oils. However, instead of extracting spe-
North American Ginseng Panax quinquefolius
Part of plant: Rhizome
Preparation/Usage: Consumption alone or in combination with other plants
Treats: Colds, fevers, or stomach cramps
Isolated compound: Ginsenosides
cific compounds, in concordance to how many Indigenous peoples closely view food and medicine, they tend to be taken as food, or in combination with other plant parts. Therefore, it becomes challenging to isolate the medicinal component(s). Additionally, we should consider that there could be synergistic and/or additive effects when taken as a whole, further challenging the idea of a single magical bullet.
Nonetheless, Canadian academic researchers and pharmaceutical companies believe that a significant amount of knowledge can be obtained by learning from Indigenous medicine practices. Researchers in Cape Breton University in Nova Scotia are now working with Mi’kmaw elders to develop birch bark oil, known locally as Maskwio’mi, into a registered cosmetic through Health Canada for improving skin conditions such as rashes, eczema, and psoriasis.
However, moving forward, these collaborations should properly acknowledge this contribution is based on Indigenous knowledge that has been passed down for generations. A major hurdle to this type of collaboration is not knowing which plant component promotes the healing properties. This is not only important for passing Health Canada safety regulations and testing, but also for biomanufacturing. As of now,
Coneflower Echinacea purpurea
Part of plant: Entire plant
Preparation/Usage: Extract of aerial parts of dried plant or root
Treats: Infections and wounds
Isolated compound: Echinacosides, caffeic acid derivatives
more than 200 compounds in Maskwio’mi have been identified as potentially helpful to combat infections and inflammation, however systematic screening is required to test and validate these compounds.
Indigenous peoples’ holistic view and treatment of the human body is a reminder of how we do not live in isolation. Our physical, mental, and emotional health is influenced by our genetics, diet, exercise/ sleep habits, but it is also impacted by relationships within our community and the environment.
St. John’s Wort Hypericum perforatum
Part of plant: Entire plant
Preparation/Usage: Extract of flowering tops
Treats: Sedative, antidepressant
Isolated compound: Hypericin and hyperforin-related compounds
- Zi Yan Chen
HY are anchor companies important for Canada’s BIOTECH SECTOR?
Canada is globally renowned for its excellence in research and science, with a legacy that includes groundbreaking discoveries such as that of insulin. This strong scientific foundation attracts venture capital and private equity investors, who appreciate the reliability and proven success of Canadian science.
With world-class research and science, hundreds of biotech start-up companies and a strong global pharmaceutical presence, Canada’s biotech sector is a growing industry that has seen significant development over the past decade. Take the Canadian vaccine sector as an example: Sanofi Pasteur operates its Research & Development (R&D), biomanufacturing and artificial intelligence (AI) facilities in Toronto. In Saskatchewan, the Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) is making significant strides via developing vaccines for poultry, cattle and swine.
vectra in Prince Edward Island to expand mRNA and plasmid DNA manufacturing, enabling them to offer end-to-end manufacturing for mRNA vaccines.
Anchor companies are large, well-established companies that are uniquely positioned to support the entire chain of the regional biotech ecosystem.
Through Canada’s Biomanufacturing and Life Sciences Strategy, the Government of Canada has invested $2.2 billion across 38 projects to enhance the biomanufacturing ecosystem. Key investments include $39.8 million for Bio-
The challenge for Canada’s biotech sector, however, is the lack of anchor companies at the core of the biotech industry. Anchor companies are large, well-established companies that are uniquely positioned to support the entire chain of the regional biotech ecosystem. These companies typically provide financial strength to the overall economic health of an industry, offer numerous jobs to attract talent, investors and additional businesses to the region. These key anchor companies typically invest heavily in collaborative research and development initiatives with surrounding start-ups, hospitals and academic institutions. According to a white paper (a research-based summary report) published by adMare BioInnovations in June 2023, no anchor companies currently exist in the Canadian biotech industry. However, several potential anchor companies are developing in Canada, including StemCell Technologies, CellCarta, BIOVECTRA and AbCellera. An example of an anchor company in Canada’s tech sector is BlackBerry in Waterloo. During its peak years, BlackBerry’s success brought significant attention to Waterloo, attracting local and global
talents, investment, and fostering a culture of innovation. The company’s presence encouraged the growth of nu merous startups and tech companies in the region, helping to es tablish Waterloo as “Silicon Valley North”.
Today, Toronto, Montreal, and Vancouver have emerged as leading biotech innovation hubs in Canada.
To develop Canadian anchor companies in the biotech sector, adMare BioInnovations suggests in their white paper that early-stage entrepreneurs should adopt an anchor company mindset. Instead of aiming for a successful exit by selling their companies, they should consider all risk factors, from regulatory approval to market entry, to avoid significant mistakes that could undermine the company’s value. “Over the last 15 years, Canadian industry leaders have taken on major global risk to develop treatments to then sell off the final product or the company as a whole, as opposed to making a real long-term investment in the Canadian economy and taking a top spot, not only in research but in commercialization,” said Gordon McCauley, President & CEO of adMare BioInnovations, in an interview with thefutureeconomy.ca. He also pointed out in an interview with Techcouver that the emergence of an anchor company requires a vibrant innovation ecosystem: from significant basic research to an agile regulatory environment, as well as an access to a large pool of talents.
Toronto, Montreal, and Vancouver have emerged as the leading biotech innovation hubs in Canada, supported by
world-class research institutes and universities, venture capital availability and a wealth of highly educated talent. Despite these strengths, Canada’s biotech industry still significantly lags in their global impact compared to its research enterprise capabilities. A potential reason for this cap is the lack of anchor companies in the biotech sector. Given the right support and focus, a promising start-up could one day grow into a globally competitive, Canadian-based biotech anchor company.
- Tianning Yu
Dr. JUAN CARLOS
ZÚÑIGA-PFLÜCKER
Reconnecting with the former Chair, we chat about fond memories of his time as Chair and growth of Canadian immunology.
In keeping with the theme of this seasonal edition, I sat down to interview an integral member of our Canadian immunology community here at the University of Toronto (UofT). Dr. Juan Carlos Zúñiga-Pflücker was the UofT’s Department of Immunology Chair from 2012 to 2023. He has left a lasting legacy on our community, and here he recounts some of his prized memories and anecdotal wisdom along with his insight into the state of our field and the direction he sees us heading.
On the appeal of Canadian immunology
Dr. Zúñiga-Pflücker graduated with his bachelor’s degree in Zoology from the University of Maryland, and then switched gears for his PhD in Genetics and Immunology at George Washington University. Although he initially wanted to study developmental biology, he found his passion in T-cell development through working in a lab at the National Institute of Health (NIH). I asked him what brought him to Canada after spending many years of schooling in the US, to which Dr. Zúñiga-Pflücker explained that Toronto was the city where his research niche was thriving. “I applied to many places but specifically UofT because I was interested in stem cell research and developmental immunology. UofT already had an established reputation in stem cell research and was an up-and-coming force in immunology research, so it made sense to join this academic community.”
specific directions: “We created strategic plans to revisit areas in our department that needed improvement and support aspects that were thriving. The graduate student experience needed some refined streamlining, and the research capacity of our department required growth. Lastly, we pushed to expand the clinical engagement of the department.” The department needed to start tapping into the surrounding hospital power more steadily. With ready access to hospital facilities, it was time to begin integrating the clinical side of immunology into research aims and think about bridging the gaps between research at MSB and the hospitals.
Opportunities and overcoming challenges
On par with discussing the advancements made during his tenure as Chair, I brought up the question of any challenges he saw hindering our department and the field of immunology as a whole in Canada. By his reply, it was evident that the obstacles we face in Canadian immunology are luckily intertwined with ripening opportunities: “Canadian immunology still needs to make the jump from basic research to translation and commercialization.
...opportunities are present and waiting for us to take... which is the next step for Canadian immunology.
Reshaping UofT’s Department of Immunology
The Department of Immunology aligned well with his research goals and was ready to cultivate his specific aims. After two joyous decades of running his lab right here in the Medical Sciences Building (MSB), Dr. Zúñiga-Pflücker was eager for a new venture - and that involved becoming the Chair of the department. When asked about his time as Chair and the goals he had planned, he mentioned that he had “many!” but the main goal was to nudge the departmental growth in
There are many opportunities to make new therapies and biologics but we have some catching up to do compared to the States. However, the opportunities are present and waiting for us to take on this challenge, which is the next step for Canadian immunology”. He commented that this does not take away from all the amazing research being done in Canada and here at UofT but rather should propel our course towards the impacts waiting to be made in real-world applications. It is an opportunity to gift our findings back to society and simultaneously continue the drive for discoveries.
Life as an ex-Chair
Although he is no longer the Chair, Dr. Zúñiga-Pflücker has not slowed down on his endeavours to move science forward. He has since joined multiple initiatives, such as the Canadian Society for Immunology (CSI), and in particular is
participating in hosting the 2028 International Union of Immunological Societies conference in Toronto. He emphasized that this will be an important event to unite immunologists from across the globe in our tiny corner of the world, where UofT is unsurprisingly making important contributions to immunology, and help to bolster our funding and recognition to instigate even further meaningful research. When he isn’t coordinating an international event for the scientific community, he is busy at the forefront of translational immunology, pioneering his lab’s benchside discoveries into clinical applications through the company he co-founded, Notch Therapeutics. Dr. Zúñiga-Pflücker and his team made a startling discovery when he identified Notch signaling, an intracellular signaling pathway integral to T cell development, as a key factor in artificially producing therapeutic T cells. Additionally, Dr. Zúñiga-Pflücker is occupied with founding a new company, PROTGEN, that will concentrate on forming progenitor T cells from stem cells. “This is impactful for patients that lack a strong immune system such as cancer patients undergoing treatment, immunodeficient patients, and the elderly, because it helps to re-initiate T cell development.” Clearly, Dr. Zúñiga-Pflücker has found a way to link his scientific passion to the bedside. Of course, he also mentioned that in stepping down from his role as Chair, “[I] still run
my lab, and am grateful for time to engage more with my team. Ultimately, you find things to fill your time with.”
Words of wisdom for the next generation
When asked to impart advice for younger grad students looking to make a similar impact in our field, his main message was one of prudence and passion, “Ultimately, you’re in this for the science. So you should focus on your science because, at the end of the day, we are here to discover new phenomena and impact the field in this way. When you put all your efforts into your scientific research, even when it doesn’t feel productive as sometimes research is slow and presents you with hurdles and because otherwise, nothing will happen, then you will eventually find the opportunities to present your research and science in different platforms and translate your knowledge”. He emphasized that as researchers, we should follow our calling, and not get too ahead of ourselves but rather enjoy our present responsibilities and projects. He pointed out that at the same time, we should not limit our paths but rather be open-minded to new avenues to communicate and translate our research. At the beginning of our academic journeys, we will “have clear hoops to jump through, and milestones to reach such as undergraduate training and then graduate school and so on, so forth”, but these paths converge to a crossroad where the clear benchmarks end and we will “begin to set our own goals for achievement and what we wish to work towards.” Until then, this is your sign from Dr. Zúñiga-Pflücker to focus on your science and do what calls you, the rest will come.
Closing remarks
Lastly, from our chat, it was clear that one of Dr. Zúñiga-Pflücker’s proudest achievements is cultivating an environment where graduate students felt supported to start new initiatives and activities. From IMMPress to IMMSpire, he feels grateful to be able to vicariously enjoy the fruits of our departmental labour with respect to progressing scientific communication and reaching the younger generations. After all, the University of Toronto is a distinguished driving force of Canadian immunology, where groundbreaking discoveries like insulin, stem cells, and fundamental immunology were made, and the effects of these student-led groups help to foster this academic community, keeping us on our toes and propagating our field to new and exciting opportunities.
- Yinhan Dechi Castro
Dr. Juan Carlos Zuniga-Pflucker (photo: Doug Nicholson)
The Department of Immunology40 years and counting
The Department of Immunology at the University of Toronto celebrated its 40th anniversary with an event reflecting on its remarkable journey and the significant contributions it has made to the field of immunology since its inception in 1984. The event spanned an entire day and took place at the historical Hart House on campus grounds. The department, known for its interdisciplinary approach and excellence in research and education, has become a hub for pioneering studies that have advanced our understanding of the immune system and its role in health and disease.
The day started with opening remarks from the current Immunology departmental chair, Dr. Jen Gommerman and the interim Dean of the Temerty Faculty of Medicine, Dr. Patricia Houston. They reminded us of the rich history of the department, reminiscing on the good times spent with colleagues and friends at the department through the decades. The Great Hall at Hart House was lined with chairs full of alumni and current members of the department, eager to hear all about the discoveries and experiences of their current and former colleagues. There was a collective sense of pride in the room for the many notable accomplishments of the members that constitute the Department of Immunology.
The morning research symposium opened the dais to distinguished scientists of the likes of Drs. Akiko Iwasaki, Natalia Pikor, Lisa Wager, and Alberto Martin.
Dr. Akiko Iwasaki from Yale University, a prominent immunologist known for her work on viral infections and immune responses, presented her research on “Acute Infection Syndrome.” Dr. Iwasaki discussed the four main root causes of long COVID: viral reservoirs, autoimmunity, tissue damage, and latent virus reactivation. Her findings highlighted potential therapeutic targets and emphasized the importance of understanding the diverse mechanisms underlying long COVID to develop effective treatment strategies.
Dr. Natalia Pikor, from ETH Zurich, shared her research on the role of fibroblasts in steering antiviral immunity. She highlighted the significance of localized niche factor production by different types of fibroblasts in supporting immune cell function. Her
work demonstrated how fibroblasts maintain an activated status to support immune memory cells in tissues, with implications for enhancing immune responses and developing targeted therapies.
Dr. Lisa Wager, from UC Irvine, presented her innovative approach to predicting immunogenicity using human tonsil organoids. Her research involved creating organoids, which are three-dimensional tissue models to study organs, consisting of dissociated tonsil cells. These tonsil organoids are used to study adaptive immune cells, called B and T cells, upon stimulation. This model allows researchers to recapitulate human immune responses and investigate the factors contributing to variation in vaccine efficacy, paving the way for personalized vaccine strategies.
Dr. Alberto Martin, a current professor at the department, delved into the mechanisms of DNA mutation and repair during antibody maturation. His work focused on mechanisms that facilitate protein degradation during the maturation of the B cell receptor, that allow for antibody diversification events to proceed. Dr. Martin’s findings have significant implications for understanding immune diversity and the development of therapeutic strategies for autoimmune diseases and cancer.
Lunch was accompanied by a career panel for the students to learn more about the career opportunities in Immunology. Dr. Gayle Pulle, from Health Canada; Dr. Sara Hamilton , from Cell Reports Medicine; and Dr. Amy Berkley, from Radiant Biotherapeutics, were the three panelists for this popular segment.
The symposium also featured presentations on HIV research, highlighting the department’s contributions to understanding and combating this global health challenge. Dr. Kiera Clayton , from the University of Massachusetts, presented her work on the interactions between two immune cell players important in anti-viral responses, Natural Killer (NK) cells and CD8+ T cells, and their combined effort in targeting HIV-infected cells, like CD4+ T cells. Her research revealed how incomplete NK cell killing sensitizes surviving infected cells to subsequent CD8+ T cell-mediated killing, providing insights into potential therapeutic strategies to enhance immune clearance of HIV.
Dr. Brad Jones , from Cornell University, discussed his research on engaging cellular immunity to cure HIV. He focused on the persistence of HIV reservoirs in long-term infections and the mechanisms by which infected CD4+ T cells escape immune clearance. Dr. Jones’s work identified potential targets for therapeutic interventions to eliminate HIV reservoirs and achieve a functional cure.
Dr. Klaus Okkenhaug from the University of Cambridge explored the role of PI3Kδ, an enzyme found in immune cells, as a target for cancer immunotherapy. His research highlighted the complex and context-dependent functions of PI3Kδ in T cells, particularly in regulatory T cells. Dr. Okkenhaug’s findings underscored the potential of targeting PI3Kδ to enhance anti-tumor immunity and
improve cancer treatment outcomes.
Dr. Oscar A. Aguilar from UCSF discussed his work on Fc-receptor-mediated responses in NK cells. He highlighted species differences in CD16 signaling between humans and mice, providing insights into how these differences can inform the development of NK cell-based therapies for cancer and infectious diseases.
The event concluded in the Hart House courtyard with toasts celebrating the department’s achievements and outlining its vision for the future. Speakers, including Dr. Tak Mak , Dr. Jen Gommerman, Dr. Gillian Wu , Dr. Brian Barber, Dr. Michelle Letarte, and Dr. Tania Watts , emphasized the department’s commitment to fostering a collaborative and supportive environment for students and researchers. They highlighted the importance of mentorship, interdisciplinary research, and the development of innovative solutions to address global health challenges.
The department’s success is also attributed to its strong connections with research hospitals and its emphasis on female representation in faculty roles from its early years. As it continues to lead in the field, the Department of Immunology at the University of Toronto remains dedicated to advancing scientific knowledge and training the next generation of immunologists. Supported by sponsors such as BD, STEMCELL, and Thermo Fisher Scientific, the event was a testament to the department’s impact and its potential to drive future innovations in Immunology. Congratulations to the Department of Immunology at University of Toronto on completing 40 years!
- Manjula Kamath
Banting and Best: The Discovery of Insulin
Frederick Banting and Charles Best discovered insulin during the summer of 1921 at the University of Toronto. Since then, this seminal discovery has saved millions of diabetic patients. Before the discovery of insulin, from 1915 to 1922, physicians Frederick Madison Allen (Univ. of California) and Elliot Proctor Joslin (Harvard Medical School) promoted a strict diet with low carbohydrate intake as the main treatment for people diagnosed with diabetes.
Surgeon Frederick Banting and his assistant, the physiology and biochemistry student Charles Best, performed experiments to isolate insulin from the pancreata of dogs. They conducted these experiments in the laboratory of physiology professor John James Rickard Macleod.
During their experiments, Banting and Best treated dogs with canine pancreatic extract and observed that this treatment alleviated the symptoms of severe diabetes in dogs. In the winter of 1921, Dr. James Bertram Collip (Univ. of Alberta) aided the duo by purifying the pancreatic extract from cattle, permitting its safe testing in humans. In January 1922, a 14-year-old boy named Leonard Thompson became the first person with diabetes to be treated with insulin at Toronto General Hospital. Within 24h of insulin infusion, Thompson’s alarmingly high blood glucose levels regulated to near-normal levels. The Nobel Prize in Medicine was awarded to Banting and Macleod in 1923 for this incredible finding. They shared this award with Best and Collip, crediting this decision to their pivotal roles in the discovery of insulin.
Since 1921, insulin production has skyrocketed, and numerous variations and formulations of insulin have been developed. Eli Lilly was the first company to produce insulin on a large scale in 1923, making insulin widely available in North America. Three years later, Johns Hopkins University professor John Jacob Abel discovered a technique to crystallize insulin in small amounts in attempts to purify the insulin molecule. In the University of Toronto’s Connaught Laboratories, David Aylmen Scott worked to improve this insulin crystallization process. In 1933, with support from Arthur F. Charles and Albert M. Fisher, Scott enhanced the crystallization of insulin by adding small quantities of zinc to a buffered insulin solution so that great amounts of insulin could be purified.
To decrease the number of necessary insulin administrations, in 1946, Hans Christian Hagedorn formulated NPH (Neutral Protamine Hagedorn) insulin, whose pharmacokinetics permits slower expulsion from the body.
Additional improvements to insulin formulation continued in 1978 by David Goeddel and his coworkers at Genentech, who developed a recombinant DNA human insulin using the bacteria E. coli. This permitted the use of human insulin in place of insulin extracts from cattle and pig, which induced an allergic reaction in many patients.
This development involved insertion of the human insulin gene into bacterial DNA. Recombinant expression of human insulin by E. coli in bioreactors were collected and purified. The technique to crystallize insulin discovered by Scott was also utilized in the collection and purification of human insulin. In 1982, human insulin became available to treat patients with diabetes, substantially increasing the amount of insulin
To better control blood glucose levels, different variations of insulin that mimic the patterns of insulin secretion in the body such as basal and prandial insulin secretion were identi fied. Basal insulin refers to baseline levels of insulin when not eating and drinking, whereas prandial insulin is secreted af ter eating in response to rises in blood glucose. In 1996, insu lin analogues were developed. These synthetically derived in sulin analogues are generated by modifying the amino acids of the insulin molecule to alter its pharmacokinetics. Lispro, the first prandial insulin analogue, became available in 1996, and a basal insulin analogue glargine was accessible in 2000.
Furthermore, there have been significant technological advances in how a diabetic person manages their condition. In the 1970s, portable glucose meters became commercially available, permitting self-monitoring of blood glucose levels. In 1983, insulin pumps, which are small wearable devices that release insulin subcutaneously through a needle, became widely accessible. The pump can be programmed to deliver insulin during the day. Compared to self-administering mul tiple injections per day with numerous needles, this is a meth od of insulin administration that is both more simplistic and precise.
In 1985, insulin pens loaded with insulin became available as another way to administer insulin. Insulin pens permitted more simplistic and precise self-administration of insulin relative to the use of a syringe and vial of insulin.
To further improve self-monitoring of blood glucose lev els, the first continuous glucose monitoring (CGM) device was approved by the FDA in 1999. Modern CGMs may be paired with an insulin pump to adjust the amount of insulin released throughout the day.
Individuals with diabetes currently have the option to choose various formulations of insulin and methods to self-monitor their condition, which ultimately grants in creased autonomy over their health. Many more people with diabetes will benefit from future developments in insulin and technologies for delivering insulin and monitoring blood glu cose, as well as the potential discovery of a cure for diabetes.
- Faizah (Numa) Sayeed
Canada’s Role in the Creation of the Ebola Vaccine
Vaccines are a life-saving tool that prevent infection by training your immune system to fight against viruses and bacteria. Canada played a significant role in the creation of an Ebola vaccine.
Ebola virus (EBOV) is a deadly virus found in regions of Africa that causes hemorrhagic fever and has high mortality rates. Work on an Ebola virus vaccine spanned many decades across many countries but has important roots in Canada. Ebola was recognized for its risk of causing a global epidemic and its potential use as a bioterrorism agent. In 2001, the Public Health Agency of Canada’s National Microbiology Laboratory in Winnipeg started to create an Ebola vaccine. At this time, Dr. Heinz Feldman, working at the National Microbiology Laboratory, was
Feldman’s research group successfully created VSV-EBOV, a version of VSV that had the Ebola virus glycoprotein on its surface.
Then Dr. Feldman and his team wanted to see if the VSV-EBOV could act like a vaccine and protect mice from the Ebola virus. They injected mice with the VSV-EBOV and then infected the mice with the Ebola virus. The results were striking; the unvaccinated mice who were infected with Ebola virus died, whereas all the vaccinated mice who then received the Ebola virus survived. This protection was likely due to an immune response against the Ebola virus glycoprotein and was a major breakthrough that led to further research for generating the VSV-based Ebola virus vaccine.
The next step was to test the safety and efficacy of the VSV-EBOV vaccine in non-human primates. A study published in 2005 showed the VSV-EBOV vaccine was safe and effective in preventing infection and death from the Ebola virus in monkeys. However, the progress to create a human vaccine was slow and funding for the Ebola vaccine research was hard to secure in Canada, with other pressing public health needs taking priority. Finally, a switch in funding leadership combined with the promising results in monkeys and strong advocacy from researchers allowed the Canadian scientists to secure half the funding for vaccine development. The scientists in Winnipeg partnered with the company IDT Biologika GmbH in Germany to produce the vaccine on a larger scale. The new vaccine products were once again tested in animals with promising results, so IDT scaled up production of the Ebola vaccine.
In 2013 a large and deadly epidemic of Ebola virus disease started in Guinea and rapidly spread through West Africa. From 2013-2016 the Ebola virus disease killed more than 11,000 people in 30,000 cases. This epidemic revealed the pressing need for human clinical trials of the Eb -
Phase 1 Study (Halifax,
ola vaccine. Many scientists around the world raced to validate the safety and effectiveness of the VSV-EBOV vaccine in humans. One of the first phase 1 studies of the VSV-EBOV vaccine occurred in Halifax, Canada at the Canadian Center for Vaccinology, where healthy adults were vaccinated with either the VSV-EBOV vaccine or a placebo (a saline injection that does not contain any virus). Then they were monitored for adverse reactions and for anti-Ebola antibodies in the blood. The trial successfully showed that the Ebola vaccine was safe and produced an antibody response against the Ebola virus glycoprotein. In addition to Canada’s contribution of creating and testing the Ebola vaccine, the Government of Canada offered 1000 doses of the Ebola vaccine to the World Health Organization (WHO) to test in clinical trials in Africa, and Canada provided more than $100 million in funding to the WHO to support Ebola countermeasures.
During the West African epidemic in 2014 the pharmaceutical company Merck acquired the rights to the VSV-EBOV vaccine to produce it on a larger scale for clinical trials. The next big milestone was a large, randomized control trial in Guinea during the epidemic to test the efficacy of the VSV-EBOV vaccine in the field. This trial was led by the WHO and Norway but had Canadian funding and components. The Guinea trial had a unique and effective strategy called “ring vaccination”: people who had a clinical case of Ebola virus disease were identified by the Ebola response team and all contacts of the infected person and their contacts were identified and randomized 1:1 to either receive the VSV-EBOV vaccine immediately or to receive the vaccine 21 days later (as a control group). The trial enrolled nearly 4,000 people. Remarkably, in people who received the vaccine immediately, zero cases of Ebola virus disease were reported 10 days after vaccination. In contrast, in the delayed vaccine group, 16 individuals had confirmed Ebola virus disease. The vaccine was 100% effective in preventing Ebola virus disease in this clinical trial, paving the way for the vaccine to be li-
censed and approved. This trial might have also helped preventing community infections in Guinea.
In 2019 the WHO gave pre-authorization to the VSV-EBOV vaccine, which allowed it to be used to fight outbreaks in the Democratic Republic of Congo and Guinea in 2020 and 2021, respectively. The VSV-EBOV vaccine was approved by the FDA in the United States in 2019 and was also authorized for use in Canada. However, the vaccine is not part of the regular immunization recommendations for Canadians because Ebola virus disease is very rare in Canada. Rather it can be used to treat someone immediately after they have been exposed to the Ebola virus, such as a health care worker treating a patient with the Ebola virus disease. Worldwide, more evidence has recently accumulated from clinical trials that the Ebola vaccine is safe and effective in creating antibody responses against the Ebola virus. The Ebola vaccine developed in a Canadian lab now can save lives in emerging outbreaks of the Ebola virus disease globally.
- Beth DeConinck
Vaccine discovery (Winnipeg, Canada)
Canada)
Merck & Co. (New Jersey, USA)
IDT Biologika GmbH (Germany)
Clinical trial (Guinea)
The Canada Gairdner Award: its conception, prestige, and legacy
James Arthur Gairdner was not a scientist – rather, he was a World War I veteran who had served in the Canadian Expeditionary Forces, a track-and- field athlete, landscape painter, and chairman of profitable businesses. Although not formally trained in the sciences, Gairdner recognized the value of biomedi- cal research, and sought to celebrate and encourage continual breakthroughs in science, medicine, and global health. His personal battle with severe arthritis further fueled his motivation to support scientific research. Consequently in 1957, Gairdner contributed $500,000 (CAD) to establish a foundation in his family name and two years later, he began what is now regarded as Canada’s most prestigious award in biomedical science.
In 1959, the inaugural Canada Gairdner International Award was granted to six physicians. They included cardiologists, Alfred Blalock and Wilfred Bigelow, who pioneered innovative techniques in cardiac surgery. Of note, Wilfred Bigelow was a Canadian surgeon who introduced the technique of lowering the patient’s body temperature to enable open-heart surgeries and played a pivotal role in inventing the first electronic pacemaker. British pharmacologists, Eleanor Zaimis and William Paton, were also recognized for developing treatments for high blood pressure. Finally, Charles Ragan and Harry Rose received the award for creating a diagnostic test for rheumatoid arthritis, an autoimmune disorder which had been poorly understood prior to their work.
During the years following 1959, the Gairdner Foundation awarded numerous investigators around the world for breaking new ground in cellular and molecular biology, chemistry, surgery, neuroscience, and more. Given its 65-year-long history and thus extensive list of awardees, this article will discuss several immunologists who received the Canada Gairdner International Award – hereafter termed Gairdner Award – and highlight the most recent winners of 2024.
In 1966, the Gairdner Foundation awarded the French-Australian immunologist, Jacques Miller, for discovering the role of the thymus – an organ dedicated to producing immune cells. Specifically, Miller had shown that surgically removing the thymus from neonatal mice stunts the development of a proper immune system. After receiving the award, Miller continued to establish key foundations for immunological research. For instance, he demonstrated that the thymus produces a specific type of immune cell (named “T cell”) that enters the bloodstream to fight infections and interacts with a different, bone marrow-derived immune cell (later named “B cell”) to support antibody production.
Subsequently in 1969, Canadian scientists, James Till and Ernest McCullough, received the prestigious award for developing a technique that was instrumental to the discovery of stem cells. Remarkably, stem cells can generate diverse cell types in the body while sustaining their own population by making copies of itself. Till and McCullough’s seminal work showed that stem cells in the bone marrow can establish a complete cellular repertoire of the blood by giving rise to red and white blood cells as well as platelets.
During the 1970s and 80s, multiple immunologists received the Gairdner Award. In 1973, Kimishige and Teruko Ishizaka were recognized for their discovery of a specific antibody type, called IgE, that triggers allergic reactions. In 1986, Peter Doherty and Rolf Zinkernagel won the award for identifying the immunological mechanism required for recognizing and killing virus-infected cells. Specifically, they had found that immune cells must simultaneously detect both viral and certain “self” (host-derived) molecules to trigger a specified immune response that does not attack against healthy, uninfected cells. Also, along with Mark Davis, Canadian scientist Tak Mak was awarded in 1989 for his joint discovery of genes encoding the T cell receptor. This receptor is a defining feature of T cells that allows them to discern “self” molecules – which are indicative of healthy cells – from foreign counterparts derived from cancerous or infected cells.
Out of 418 recipients of the Gairdner Award thus far, 98 have progressed to become Nobel laureates. For example in 1996, Doherty and Zinkernagel won the Nobel Prize in Physiology or Medicine for their previously described contributions. Additionally, Jules Hoffman received the Gairdner Award for his collaborative discovery of Toll-like Receptors, molecules that allow the immune system to detect invasive microorganisms and initiate an immediate response. Coincidentally, Jules Hoffman won the Nobel Prize that same year in 2011. Similarly, James Allison – recipient of the 2014 Gairdner Award – earned the Nobel Prize in 2018 for his work on cancer immunotherapy. Finally, Katalin Karíko and Drew Weissman won the Gairdner Award and Nobel Prize in 2022 and 2023, respectively, for their research on mRNA vaccines that was critical for resolving the global COVID-19 pandemic.
Flash forward to 2024, the Gairdner Foundation continues to uphold its superior standards in commending outstanding researchers. This year, the Gairdner Award was granted to Shankar Balasubramanian, David Klenerman, and Pascal Mayer for their contributions to creating large-scale, affordable genomic sequencing technologies. Their work has made it possible to analyze the entire genetic makeup of organisms at precedented scale and speed. Zelig Eshhar and Michel Sadelein also received the award for their work on developing Chimeric Antigen Receptor (CAR) T cell therapy, a revolutionary approach that involves engineering the patient’s own T cells to identify and destroy cancer cells.
It is worth noting that aside from the Canada Gairdner International Award, there are two other accolades offered by the foundation. The John Dirks Canada Gairdner Global Health Award recognizes researchers in public health who engage in policy intervention and address health inequities. Additionally, the Canada Gairdner Momentum Award is presented to mid-career investigators who work in Canada and whose scholarly contributions show potential for continued impact on human health.
Altogether, five Canada Gairdner International Awards, one John Dirks Global Health Award, and two Momentum Awards are presented each year. Along with esteem, the laureates earn $100,000 (CAD) and acclaim from the global, scientific community in form of a gala. By commemorating scientific achievements this way, the Gairdner Foundation not only pays tribute to the history of researchers past but also propels the current generation to continue and expand the growing scientific legacy.
- Jennifer Ahn
James. A. Gairdner
CANADIAN SOCIETY FOR IMMUNOLOGY 2024
36th Annual Meeting
For this issue of IMMpress Magazine on Canadian Immunology, we take our readers to April 2024 when immunologists across Canada gathered at scenic Banff, Alberta for the annual spring conference hosted by the Canadian Society for Immunology (CSI). Home to nine CSI spring conferences since 1997, the snow-capped Rockies were the backdrop for four days of scientific and social events.
KEYNOTE
CSI 2024 opened with a keynote address from Professor Dame Fiona Powrie (Univ. of Oxford). She emphasized the use of novel technology in therapeutic discovery, discussed in the context of inflammatory bowel disease (IBD). Powrie and her group leverages a novel technique known as NICHEseq on regulatory T cells (Tregs) in a mouse model of intestinal colitis. This technique labels photoactivatable T cells upon excitation with near-infrared light. Spatial locations of cells can then be inferred based upon their photoactivation status. Using NICHE-seq, Powrie identified the disruption of Treg compartmentalization during colitis induction, thereby implicating several molecular pathways in the development of IBD pathology in their mouse model. Powrie argues that such novel techniques can provided the needed resolution in heterogenous diseases such as IBD. The proper stratification of large spectra of pathologies permits the identification of underlying molecular drivers to create targeted treatments for IBD.
IMMUNE MECHANISMS IN TISSUE
The first series of talks discussed how local environment influences immune responses. Dr. Adrian Liston (Churchill College Cambridge) proposed a “pan-tissue” model to describe the development of transient tissue-resident Tregs. In this model, circulating Tregs that enter tissue express genes associated with general tissue residency but remain capable of rehoming to most other tissue sites. Dr. Lisa Osborne (Univ. of British Columbia) shared how intestinal helminth colonization improves disease outcomes in a mouse model of multiple sclerosis through intestinal induction and mobilization of protective type 2 immune responses to the brain. Dr. Gretchen Diehl (Memorial Sloan Kettering Cancer Center) demonstrated that microbiota exposure in early life supports the development of anti-microbial effector T cells that cross-react against other gut microbes in adulthood. Dr. Markus Geuking (Univ. of Calgary) unified concepts from Drs. Liston and Diehl’s talks by showing that microbiota-specific intestinal Tregs that develop in early life can protect against a chemically induced mouse model of colitis. Finally, Dr. Sebastien Talbot (Queen’s University) dipped into the realm of cancer immuvveillance to examine how sensory neurons that detect pain releases neurochemicals that restrain the anti-tumour function of CD8+ T cells and dendritic cells.
CELL DEATH
The second day of the conference began bright and early with Dr. Douglas Green Green (St. Jude Children’s Research Hospital) explaining how sleep interruption can render a sublethal lipopolysaccharide challenge fatal in otherwise healthy mice because of increased wakefulness. This wakefulness causes neuronal activity that pathologically activates macrophages in the brain. Next, Dr. Kim Newton (Genentech) described to us how the interferon regulator factor members IRF1 and IRF2 modulate inflammation and pyroptotic cell death by influencing chromatin remodeling. Dr. Barbara Porto (Univ. of Manitoba) introduced necroptosis as an alternate flavour of cell death that can exacerbate lung pathology after respiratory viral infection through an autocrine tumour necrosis factor axis. Dr. Shawn Beug (Univ. of Ottawa) brought a translational perspective using a family of drugs called SMAC mimetics that inhibit apoptosis proteins and showed how they can enhance multiple aspects of the anti-tumour immune response. Lastly, Dr. Simona Stäger (Institut national de la recherche scientifique) described how chronic human immunodeficiency virus (HIV) infection sensitizes CD4+ T cells to multiple routes of apoptosis through a TLR7-IRF5 axis.
T cells after treatment with immune checkpoint blockade. Dr. Israt Alam (Stanford University) expanded on Dr. Truillet’s talk by giving examples of T cell PET tracers in current clinical trials and additional PET tracer candidates for cancer immunotherapy monitoring. The final talk of the conference was given by Dr. John Ronald (Western University), who spoke about incorporation of PET imaging reporters into chimeric antigen receptor-based cell therapies to help accelerate preclinical development and allow a better understanding of how these engineered cells behave once given to patients.
AWARDS AND ACKNOWLEDGEMENTS
This year, the prestigious Bernhard Cinader Award was bestowed to Dr. Fumio Takei (Univ. of British Columbia, Terry Fox Laboratory). Dr. Takei discussed his career working on innate lymphoid cells (ILCs), from his initial discovery of the first known natural killer (NK) cell receptor family Ly49, to his current interest on ILC2s. Although lacking in antigen-specificity, lung ILC2s exhibit a lymphocyte-like activation response involving an expansion and contraction phase. Like lymphocytes, these primed ILC2s develop a memory-like capacity with enhanced effector function upon reactivation. Activated lung ILC2s may also migrate to other tissue sites such as the liver and play a protective role in a model of liver fibrosis. Aside from his scientific accomplishments, Dr. Takei also shared with us the importance of collaboration and perseverance, citing Nobel laureates and giants in the field of biochemistry Drs. Cesar Milstein and Frederick Sanger as major figures in helping to shape his academic career. Dr. Takei emphasized the advocation of your own work; he recalled with great humour the rejection of Dr. Sanger’s pioneering work in DNA sequencing by the journal Nature as “[a technique of] no biological significance”, which later won Dr. Sanger the 1980 Nobel Prize in Chemistry.
This was a phenomenal year for the local immunology community at the University of Toronto as we offer our warmest congratulations to Dr. David Brooks and Dr. Sarah Crome, recipients of the Investigator Award and New Investigator Award, respectively, as well as all travel and poster award winners.
The final symposium focused on visualization of immune cells to complement existing clinical therapies. Dr. Charles Truillet (Univ. Paris-Saclay) discussed the use of radioisotope-labelled antibodies combined with positron emission tomography (PET) imaging to optimize cancer treatments. One example would be to track infiltration of anti-tumour CD8+
The annual CSI meeting is an enormous undertaking that is only made possible by the tremendous efforts of the local organizing committee, trainee engagement committee, staff, and generous support from sponsors. A big thank you to the local organizing committee from the Univ. of Alberta and Univ. of Calgary: Drs. Troy Baldwin (Chair), Colin Anderson, Xavier Clemente-Casares, Markus Geuking, Kathy McCoy, and Sue Tsai; and to this year’s CSI sponsors: BioLegend, Miltenyi Biotec, Beckman Coulter, Cytek Biosciences, Li Ka Shing Institute of Virology (University of Alberta), Olink, the International Microbiome Centre (University of Calgary), Mucosal Immunology, BD Biosciences, Sony, CIHR – Institute of Infection and Immunity, University of Toronto, CIHR – Institute of Gender and Health, and Pathogens and Immunity.
Congratulations on another successful conference and we look forward to seeing everyone again next year in Gatineau, Quebec for the 37th CSI meeting!
- Karen Yeung
Department of Immunology
University of Toronto
1 King’s College Circle
Toronto, ON M5S 1A8
Canada
Credits: University of Toronto Archives.
McCaul’s Pond, present site of Hart House (1880)
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