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July 10, 2020

A Revolutionary Way to Study the Immune System

Peter Linsley, PhD, hit a career crossroads in 2012: After years in the private sector, he wanted to get back into research that would move medicine forward.

“I called BRI because I saw an opportunity to study autoimmunity in a whole new way,” he says.

BRI’s then-president, Jerry Nepom, MD, PhD, knew Dr. Linsley was pioneering a “systems” approach that examines how myriad factors conspire to cause disease. Dr. Nepom also knew that Dr. Linsley’s research helped lead to breakthrough cancer treatments.

Dr. Nepom wanted to make similar progress against autoimmune disease, and was intrigued by making BRI one of the first to embrace the systems approach. So he offered Dr. Linsley a job.

Eight years later, BRI is home to a Center for Systems Immunology that is helping us investigate the immune system’s deepest mysteries and the riddles of COVID-19.

“Our systems immunology team has become indispensable to understanding these complicated diseases and in guiding us to develop better treatments,” explains BRI’s current President, Jane Buckner, MD.

Featured BRI Bioinformatics Team 2020
The Bioinformatics Team

A Broader Perspective

Immunology researchers traditionally focus on something narrow — such as a type of cell or a pathway within that cell — and learning everything possible about it. The systems immunology team examines how those elements interact with dozens of other factors, including things like age and gender.

“The traditional approach is like looking for your keys under a streetlamp,” Dr. Linsley explains. “Systems immunology takes you out wider to see what’s in the shadows.”

Combining these approaches has led BRI to key insights. For example, Dr. Linsley and his colleagues have collaborated with Alice Long, PhD, to identify potential new approaches to treating type 1 diabetes (T1D).

“There are so many complex factors that contribute to T1D,” Dr. Long says. “The systems immunology team helps us identify which ones are important and which ones to ignore.”

Seeing the Big Picture Through Big Data

A study can involve a vast amount of information culled from blood and tissue samples. The Systems Immunology team of bioinformaticians and data specialists use the latest cloud computing tools to organize, analyze and visualize that data.

“A lot of that analysis comes down to finding patterns — this cell type in combination with that clinical data is associated with this outcome,” says Charlie Quinn, who is director of the Research Information Systems team. “Finding patterns across millions of data points is tremendously complicated, but that’s kind of our superpower.”

Having this team in-house means it can join forces with people like Dr. Long early in the research process, to be sure everyone knows which patterns to look for. This helps researchers understand autoimmune responses and investigate how to correct them.

Investigating COVID-19

Now Dr. Linsley and his colleagues are helping us unravel COVID-19. Hamid Bolouri, PhD, has been using systems immunology tools to wade through huge COVID-19 data sets since mid-March. In June, Systems Immunology faculty including Peter Linsley, Scott Presnell, PhD, and Matt Dufort, PhD, started additional COVID-19 projects.

One goal is to find markers that identify why some people with the virus don’t have symptoms while others get fatally ill. The sickest patients tend to have multiple health issues, which makes it hard to pinpoint the factors related to COVID-19.

“That is precisely why systems immunology is necessary — we can find meaningful patterns in a sea of noise and coincidence,” Dr. Bolouri says. “Once we know what the markers are, we can use them to look at the different ways the virus affects people, identify what goes wrong in their immune processes, and tailor treatments for individual patients.”

BRI’s ability to comprehensively study COVID-19 achieves the vision that Dr. Nepom and Dr. Linsley hatched back in 2012.

“We have the pieces in place to jump into action and make discoveries that can help,” Dr. Linsley says. “That’s exactly what you hope for as a scientist.”

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