Tuberculosis: Unlocking the Secrets of Immune Defense with Engineering
At the Massachusetts Institute of Technology, Associate Professor Bryan Bryson '07, PhD '13, is on a mission to tackle one of humanity's oldest and deadliest foes: tuberculosis (TB). Bryson's journey began with a simple yet profound question: How do immune cells, our body's natural defenders, kill bacteria?
Since establishing his lab in 2018, Bryson has dedicated his scientific career to finding answers to this critical question. He believes that understanding the immune response to TB is the key to developing new treatments and vaccines, potentially saving millions of lives.
"Tuberculosis has been a relentless killer throughout human history. If we can learn how to defeat it, we can unlock a whole new era of therapies and vaccines," Bryson explains.
The current BCG vaccine, a weakened version of a cow TB bacterium, offers limited protection against pulmonary TB in adults. Despite some available treatments, TB continues to claim over a million lives annually. Bryson and his team are determined to change this.
"Creating a better TB vaccine is all about measurement. Our lab's mission is to develop innovative measurement tools and concepts to accelerate the development of an effective vaccine," Bryson says. His work is part of the Ragon Institute, a collaborative effort between Mass General Brigham, MIT, and Harvard.
Engineering and Immunology: A Family Legacy
Engineering runs deep in Bryson's family. His great-grandfather was an engineer who worked on the Panama Canal, and his grandmother, a natural builder, would likely have followed in his footsteps if educational opportunities had been more accessible.
Raised primarily by his mother and grandparents, Bryson's interest in science was encouraged from a young age. He began tinkering with engineering at three, building robots from Styrofoam cups and light bulbs. Later, after moving to Houston, he joined his school's math team.
As a high school student, Bryson was set on studying biomedical engineering. However, MIT, his top choice, lacked a biomedical engineering program at the undergraduate level. His family's encouragement led him to MIT, where he initially deliberated between electrical engineering and computer science (EECS) and aeronautics and astronautics.
A valuable piece of advice from a mentor during an internship changed his trajectory. "Study something that gives you options; you never know how the world will change," he was told.
Bryson switched to mechanical engineering with a bioengineering track and began undergraduate research. A chance encounter with a poster led him to work with Professor Linda Griffith, a biological and mechanical engineering expert. This experience, Bryson says, "changed the trajectory of my life."
In Griffith's lab, Bryson worked on microfluidic devices for growing liver tissue from hepatocytes. He enjoyed the engineering aspects but also wanted to understand the cells' behavior. He stayed at MIT to earn a PhD in biological engineering, working with Professor Forest White.
In White's lab, Bryson studied cell signaling processes and their alterations in diseases like cancer and diabetes. He also developed an interest in infectious diseases, which led him to work with immunology professor Sarah Fortune at the Harvard School of Public Health.
Fortune's research on tuberculosis inspired Bryson to seek transformative solutions. He realized that finding a new antibiotic was not enough; the goal was to dramatically reduce TB incidence through vaccination. To achieve this, he needed to understand how immune cells respond to the disease.
"My postdoc with Fortune taught me to think boldly about the possibilities beyond today's measurements. What are the real problems we need to solve? With TB, it's not just about identifying new antibiotics; it's about changing history," Bryson reflects.
Identifying Vaccine Targets
Since joining the MIT faculty eight years ago, Bryson and his students have made significant progress in answering the question that drove him into research. How does the immune system kill bacteria?
A critical step is for immune cells to recognize bacterial proteins displayed on the surfaces of infected cells. Mycobacterium tuberculosis produces over 4,000 proteins, but only a small subset is displayed by infected cells. These proteins are the ideal candidates for a new TB vaccine, according to Bryson.
His lab has developed methods to identify these proteins. Their studies have revealed that many TB antigens presented to the immune system belong to a class known as type 7 secretion system substrates. Mycobacterium tuberculosis expresses about 100 of these proteins, but which ones are displayed by infected cells varies from person to person, depending on their genetic background.
By studying blood samples from people with different genetic backgrounds, Bryson's lab has identified the TB proteins displayed by infected cells in about 50% of the human population. He is now working on the remaining 50% and believes that once these studies are complete, they will have a clear idea of which proteins could be used to create a TB vaccine effective for nearly everyone.
Once the proteins are identified, his team can design and test the vaccine in animals, with the hope of being ready for clinical trials within six years.
Despite the challenges, Bryson remains optimistic. He credits his mother for instilling a positive attitude. "My mom raised four children on her own, and she made it look effortless. She taught me that I could do anything I set my mind to and instilled a sense of optimism. There are always reasons to continue, even when faced with potential failures."
Bryson finds a similar can-do attitude at MIT. "The engineer ethos here is that everything is possible, and our job is to find ways to make it happen. Engineering and infectious disease are a perfect match because engineers love a challenge, and TB is one of the hardest problems out there."
When not immersed in research, Bryson enjoys lightening the mood with ice cream study breaks at Simmons Hall, where he is an associate head of house. Using his trusty ice cream machine, he treats dorm residents to unique flavors like passion fruit and jalapeno strawberry several times a year. "Recently, I did a fall-themed ice cream with cinnamon and a pear sorbet. Toasted marshmallow was a hit, but it really took its toll on my kitchen!" Bryson laughs.
Bryson's work at MIT is a testament to the power of engineering in tackling global health challenges. His journey, from a curious young engineer to a leading immunology researcher, showcases the impact of a can-do attitude and a relentless pursuit of scientific discovery.
