“Stay optimistic, don’t burn bridges, and most importantly, don’t overthink it!” –Dana Philpott

The Department of Immunology’s Dr. Dana Philpott was recently awarded a multi-million dollar Canada Foundation for Innovation (CFI) Leading Edge fund in collaboration with Dr. Ken Croitoru. CFI grants are awarded to institutions to bolster infrastructure and support growth. IMMpress Magazine sent a correspondent to learn more about the newly awarded CFI grant and in the process was rewarded with a glimpse into the makings and philosophy of a modern scientist.

Dr. Dana Philpott.
Dr. Dana Philpott.

The real Dana Philpott
To be awarded any major grant requires something to set the applicant apart from competitors. Luckily, Philpott has a self-proclaimed superpower: optimism.

This one word embodies Philpott’s philosophy, and in science research, now more than ever, optimism is essential to success. But there is more to Philpott than unrelenting research drive punctuated by hopeful optimism. Despite being industriously busy, she is approachable and always willing to help. Philpott also understands the importance of a work-life balance and will aim to end her work day at five to get in family time. In fact, our initial interview had to be rescheduled, as upon returning from a weekend conference in Victoria, Philpott had to take time off to stay home with her sick daughter. Nonetheless, Philpott still managed to squeeze in time for an interview and was more than happy to share her story.

The molding of a scientist
There were no epiphanies, nor life altering instances that led Philpott to a career in science. As the years passed, she enjoyed her schooling and kept pushing forward. After finishing an undergraduate degree in Calgary, Philpott entered graduate school at the University of Toronto in the Department of Microbiology. Studying enterohemorrhagic and enteropathogenic E. coli, Philpott struggled with periods of frustration throughout her graduate career. Her supervisor at the time, Dr. Philip Sherman, saw in Philpott the key ingredients of a good scientist: curiosity and perseverance. Following his advice, Philpott continued her career in science. Upon graduation, the Department of Microbiology amalgamated with the Department of Genetics and Philpott became the first microbiologist to graduate with a PhD from the Department of Molecular Genetics and Microbiology.

Philpott set her goals high and dreamed of continuing her postdoctoral studies with the “king of microbiology”, Dr. Philippe Sansonetti, at the Pasteur Institute in France. When she finally worked up the nerve to ask for a position, Sansonetti declined, citing a two-year waiting list. The scientific virtues of perseverance and optimism allowed Philpott to take the wait in stride as she completed a brief postdoctoral study at McMaster University before heading to France.

Philpott intended to spend two years as a postdoctoral fellow in France. Five years later, she was heading her own research group as an independent investigator at the Pasteur Institute. During her time in France, Philpott’s research gradually transitioned from microbiology with flavors of immunology to immunology with a microbiological garnish. Ten years after graduating from the University of Toronto, she was back with a faculty position in the Department of Immunology.

The CFI award and the groundbreaking research it will support
Philpott still dreams of microbiology and has been frustrated in trying to tackle the intricacies of the microbiome. The CFI award will allow these dreams to become reality. The CFI aims to develop research infrastructure in Canada, with the goal of pushing the boundaries of knowledge and establishing Canadian research institutes as world leaders. Money awarded by CFI comprises 40% of a larger award in partnership with investment from public, private and nonprofit sectors. These highly competitive awards allow for the purchasing of new equipment and other research infrastructure, with awards typically ranging from $100,000 to $500,000. Philpott and Croitoru were awarded $6 million from CFI, matched by $6 million from the Ontario Research Fund and $3 million as in kind contributions for a total of $15 million. Even at the current price of antibodies, for $15 million you could probably buy every common clone with every fluorochrome conjugation available!

The microbiome, or the sum of microbes that inhabit in and interact with a particular environment, represents approximately ten times the number of human cells in an average individual, and has tremendous impact on human health and disease. The CFI award will allow for the centralization of microbiome research in Toronto, with the creation of facilities unavailable elsewhere in Canada. We are currently limited by an inability to manipulate the microbiome in animal models. Furthermore, differences in microbiota between facilities can be a confounding variable that affects experimental results. These fundamental issues propelled Philpott and Croitoru to create a network between the University of Toronto and Mount Sinai Hospital that would connect basic and clinical microbiome research.

The University of Toronto Host-Microbiome Research Network
Philpott intends to create a two node research program called the University of Toronto Host-Microbiome Research Network (HMRN). The University of Toronto will house the larger, basic science node with $10 million in support and Mount Sinai will be home to the clinical science node. Philpott envisions these nodes to serve as centers of excellence; researchers can utilize either node for immediate access to the expertise and advanced equipment needed to tackle microbiome research.

At the clinical node, a large patient database will be established with extensive, longitudinal specimen libraries. New equipment will be purchased, including a research-dedicated MRI. The focus at Mount Sinai will initially be inflammatory bowel disease (IBD) and diabetes with room for expansion.

The basic research node will be equally ambitious. In order to study the microbiome in animals, it is important to accurately identify and manipulate its composition. There are very few research institutes worldwide capable of such studies. Still, knowing the microbiome composition is not sufficient to predict how it will affect the host. To keep microbial composition consistent, the CFI grant will support a germ-free animal facility located in the Medical Sciences Building. On top of this, there will be a completely new culturing facility, with anaerobic capability, to allow for the direct isolation, culturing, and eventual re-population of specific bacteria.

To complement these facilities, the CFI award will also fund the acquisition of high resolution confocal microscopes with intravital imaging capacity, and a next-generation, time-of-flight mass spectrometer (CyTOF). CyTOF uses mass spectrometry in combination with antibodies conjugated to metal isotopes for analysis of cell data and allows for the simultaneous acquisition of over 50 parameters, without requiring compensation.

Sustainable science
Awards for infrastructure are often complicated by sustainability issues. With expensive equipment, come maintenance costs and technician salaries. These factors are often neglected and can lead to intricate pieces of equipment being underused. In applying for CFI funding, one must provide a plan for the sustainability of the infrastructure to be funded. The HMRN was designed with a portion of the funds to be allocated towards upkeep and personnel. In addition, the basic research and clinical nodes will operate on a cost-recovery basis, with user fees recuperating the cost of upkeep and maintenance.

A microbiology renaissance
A defining moment in the history of the Department of Immunology came when it refused to assimilate all of the collapsing Department of Microbiology. The Department of Immunology Chair at the time preferred to have a departmental focus on molecular and developmental immunology. This narrow focus certainly had its strengths but the scope of immunological research has expanded rapidly. With a plethora of recent publications stressing the importance of the microbiome in shaping the immune response, immunologists can no longer deny the importance of understanding host-microbe interactions. These observations have brought about a change in the philosophy of immunology, with those in the field realizing that “they need to take into account all this bacteria, which was just called LPS for so many years”. It appears we are seeing the rebirth of microbiology, now inseparable from immunology.

The role of multi-investigator awards
Large and ambitious CFI awards support the compelling argument that modern science will no longer be sustainable under the single-group research model. Philpott, however, is adamant that individual operating grants are here to stay. “You need to harness the interest of the individual to drive success in science. Pushing team grants only works if the group functions well together to answer a common question.” Philpott stressed that in the current economic climate, short term projects are being funded over open-ended projects. This trend seems to favor translational medicine over basic research: “Pushing translational medicine, exclusively, could be a mistake. We’re forgetting that basic science drives the ideas that create translational research.” So why is basic research falling behind? Philpott is of the opinion that public support is not present due to a lack of understanding of basic research. Perhaps science, with an ever increasing complexity, is becoming increasingly inaccessible to the public. In the future, communicating findings to the public may well be a necessary requirement to ensure continued support of basic science research.

Philpott and Croitoru’s CFI grant opens up many roads and avenues for continued microbiome research. The state of the art equipment and facilities funded by the grant will enable researchers to address many outstanding questions on the microbiome. Under Philpott and Croitoru, the HMRN will advance our understanding of host-microbiome interactions and provide us with unparalleled insight into the underlying microbial processes impacting human diseases.

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Eric Gracey

Contributing Editor
Eric is a PhD student with the Department of Immunology at the University of Toronto. He did his undergraduate degree at the University of Auckland, New Zealand where he investigated the effects of diet on gout. He currently studies the role of the immune system in arthritis, specifically an arthritis of the spine called ankylosing spondylitis. When not in the lab, Eric likes to run and has taken up backcountry canoeing.

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