Tuberculosis: Unlocking the Secrets of Immune Defense with Engineering
At the Massachusetts Institute of Technology (MIT), 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 question, believing it holds the key to developing new strategies against infectious diseases, particularly TB. "Here's a pathogen that has likely claimed more lives than any other in human history. So, the challenge is to learn how to defeat it," Bryson explains.
But here's where it gets controversial: the only TB vaccine currently available, BCG, is a weakened version of a bacterium that affects cows. While widely used in some parts of the world, it offers poor protection against pulmonary TB in adults. Despite some available treatments, TB continues to claim over a million lives annually.
"For me, improving the TB vaccine comes down to a matter of measurement. That's why my lab's mission is to develop new measurement techniques and concepts to accelerate the development of a better TB vaccine," Bryson says. He's also a member 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, an avid builder, would likely have become an engineer had educational opportunities been available to her. Bryson, the eldest of four sons, was primarily raised by his mother and grandparents, who nurtured his interest in science.
As a young child, Bryson's family moved from Worcester, Massachusetts, to Miami, Florida, where he began his engineering adventures, building robots from Styrofoam cups and light bulbs. Later, after moving to Houston, Texas, Bryson joined his school's math team in seventh grade.
In high school, Bryson was set on studying biomedical engineering in college. However, MIT, one of his top choices, didn't offer a biomedical engineering program, and biological engineering wasn't yet an undergraduate major. His family encouraged him to attend MIT and explore his academic path later.
During his first year at MIT, Bryson deliberated over his major, considering electrical engineering and computer science (EECS) and aeronautics and astronautics. He initially thought he'd study aero/astro with a minor in biomedical engineering, focusing on spacesuit design.
But during a summer internship, his mentor offered valuable advice: "You should study something that gives you a lot of options because you can't predict how the world will change." Taking this advice to heart, Bryson switched his major to mechanical engineering with a bioengineering track when he returned for his sophomore year.
A Life-Changing Lab Experience
A hallway poster caught Bryson's attention, leading him to work with Professor Linda Griffith, a biological and mechanical engineering professor. His experience in Griffith's lab, where he worked on building microfluidic devices to grow liver tissue from hepatocytes, was life-changing. He enjoyed the engineering aspects but also realized he wanted to delve deeper into the cells and understand their behavior.
Bryson stayed at MIT to earn a PhD in biological engineering, working with Professor Forest White. In White's lab, he studied cell signaling processes and how they are altered in diseases like cancer and diabetes. During his PhD, he also developed an interest in infectious diseases.
After earning his degree, Bryson worked with Professor Sarah Fortune, an immunologist at the Harvard School of Public Health. Fortune's research focused on tuberculosis, and in her lab, Bryson began investigating how Mycobacterium tuberculosis interacts with host cells. Fortune inspired Bryson to seek transformative solutions for TB, not just identifying new antibiotics but finding ways to drastically reduce the disease's incidence.
"That postdoc experience taught me to think boldly about what's possible when you're not limited by today's measurement capabilities. What are the real problems we need to solve? With TB, there are so many avenues to explore, but what's the game-changer?" Bryson reflects.
Unraveling Vaccine Targets
In the eight years since joining the MIT faculty, Bryson and his students have made significant progress in answering the question he posed during his faculty interviews: How does the immune system kill bacteria?
A crucial 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 most promising candidates for a new TB vaccine, Bryson explains.
Bryson's lab has developed methods to identify these proteins. So far, their studies have revealed that many of the 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's now working on the remaining 50% and believes that once these studies are complete, he'll have a clear idea of which proteins could be used to create a TB vaccine suitable for nearly everyone.
Once the proteins are selected, his team can design the vaccine and test it in animals, aiming to be ready for clinical trials within six years.
Despite the challenges ahead, Bryson remains optimistic, crediting his mother for instilling a positive attitude. "My mom raised all four of her children alone, and she made it look effortless. She instilled a sense of optimism and the belief that you can achieve what you set your mind to. There are always reasons to give up, but why not focus on the reasons to keep going?"
Bryson finds a similar can-do spirit at MIT. "The engineer ethos at MIT is that yes, this is possible, and our job is to find a way to make it possible. I think engineering and infectious disease are a perfect match because engineers thrive on solving complex problems, and TB is an incredibly challenging problem."
When he's not tackling tough problems, Bryson likes to take study breaks with ice cream at Simmons Hall, where he's an associate head of house. Using an ice cream machine he's had since 2009, Bryson makes gallons of ice cream for dorm residents several times a year, experimenting with non-traditional flavors like passion fruit and jalapeno strawberry. "Recently, I did some fall flavors, like cinnamon ice cream and pear sorbet. Toasted marshmallow was a huge hit, but it really took a toll on my kitchen!" Bryson shares with a laugh.
Source: MIT News
