Building The Code
Rutgers–Camden Professor Trains Next Generation of Computer Simulation Experts
Grace Brannigan has always liked solving puzzles. In fact, the Rutgers University–Camden researcher said puzzles and their solutions are what science is all about. “I find it very satisfying to organize my understanding of a certain problem and use the power of science to solve it,” said Brannigan, associate professor of physics and director of the Center for Computational and Integrative Biology (CCIB) in the Camden College of Arts and Sciences.
With Brannigan’s boundless curiosity and love of science, she can turn seemingly routine experiences into inquisitive case studies. Taking medicine or a vaccine, for instance, becomes a moment to contemplate the drug’s journey through her body until it gets to the site where it acts on proteins. And doing dishes? That’s a chance to visualize the tiny aggregates that soap molecules create. “It’s the same principle that forms the membranes of cells or the envelope of a virus,” she exclaimed. “It all comes naturally. Most kids are born with a sense of curiosity, but scientists are people who have kept that part of their inner child alive.”
Brannigan is now putting her natural curiosity and puzzle-solving skills to the test to bridge the diverging fields of biological information (DNA) and biological function (proteins). She currently leads Codes4Life (C4L), an innovative program that uses software engineering and artificial intelligence to reconnect the fields, supported by a $2 million National Science Foundation Research Traineeship (NRT) grant.
The C4L research team comprises nine scientists trained in computational genomics, evolutionary genomics, computational biophysics, and computational chemistry, who are collaborating on projects focused on the interface between genetics and proteins. Brannigan explained that there is a traditional lack of communication between scientists in these two fields, worsened by the shortcomings of currently available software.
“Even though DNA and proteins are closely linked within cells, these two communities of scientists don’t communicate very often,” said Brannigan, who serves as principal investigator on the project. “They have both produced an exciting but overwhelming amount of vital data. Software is a powerful method for sharing that data and bridging disciplinary divides.”
A principal component of C4L—and a primary reason for the NRT grant, Brannigan explained— is the program’s use of innovative and systematic approaches to develop a diverse group of 25 Ph.D. students over the course of the project, with an additional 15 Ph.D. and 15 master’s degree students expected, in uncommonly high proficiencies in software engineering and artificial intelligence.
This past fall, C4L welcomed the first 11 graduate students to the program, each with their own research project underway. Brannigan is excited to get to work. “It’s amazing to work with my colleagues who are as focused on training the students as developing software,” Brannigan said.
Just as importantly, Brannigan said, graduate students already have that same strong love of science and curiosity that she has, and it’s her job to help them discipline their thinking and scientific approach, without abandoning their curious inner child.
“They are learning to shift the way they think dramatically, but we don’t want them to change the way they feel about science,” Brannigan said. “I will do what I can to help protect their love of science from the challenges they face.”
Inaugural C4L class of students
Inaugural C4L class of students
Inaugural C4L class of students
Inaugural C4L class of students
Inaugural C4L class of students
Inaugural C4L class of students
Brannigan’s own love of science, she recalled, took root at an early age. In fact, her mother was a scientist who studied plant diseases for the U.S. Department of Agriculture. Brannigan, however, was drawn to physics for its dependence on order and consistency. While other sciences required a lot of memorization, she only had to remember several fundamental principles from which everything else followed. “No matter how chaotic my life was outside of the physics classroom, the science we learned inside the classroom was organized and consistent,” she said.
Brannigan also got her first taste of computers in the late 1980s when her father brought one home – a Macintosh 512K – and she made sure that it wound up in her bedroom. The computer soon became a companion, a video game console, a diary, an easel, and a continual source of puzzles. “What’s not to enjoy?” she asked. “My computer did what I told it to do, which felt really powerful as a kid.”
As Brannigan grew older, she thought about becoming a computer programmer, a writer, or a psychologist. She also dabbled in theater and considered becoming an actor. Then it dawned on her: A scientist can do all of those things.
Brannigan would then have a seminal moment during her high school years. She began taking antidepressants and was alarmed and frustrated to find that, although they are widely prescribed, scientists don’t really know how they work. She felt that if people had a better understanding of how the drugs act on proteins in the body, it would be easier to predict which antidepressants would work best for different people. She decided that it was just the right job for physics and its powerful, orderly approach.
“Physics isn’t just the study of black holes or high-energy particles. It’s a set of laws that all of nature has to obey, and that includes proteins,” Brannigan said. “When there is something confusing about proteins—or any other aspect of biology—physics can come to the rescue.”
Brannigan pursued a bachelor’s degree in physics at Reed College in Portland, Ore., with plans to enter a research career. With burgeoning interests in biological systems and physics, she discovered that biophysics—physics applied to biological systems—was a natural fit. Her undergraduate mentor thought she might enjoy studying proteins using computers and arranged an internship at the University of California–San Diego for Brannigan to do just that. “I guess he was right,” she said with a laugh.
Brannigan ran her first computer tests using simulated proteins and never looked back. She recalled that the tests were attempts to simulate the folding process of a certain protein. She watched in awe as the simulation with the protein started out as just a disordered string and folded into helices and other structures – all based on the laws of physics. “It felt very powerful,” she said.
Brannigan subsequently earned a Ph.D. in physics at the University of California–Santa Barbara and did postdoctoral work at the University of Pennsylvania. There, she worked closely with the anesthesiology department on a National Institutes of Health grant to study the side effects of anesthetics. The goal, she explained, was to understand how anesthetics work and to limit side effects. There are still drugs in development today that are informed in part by simulations Brannigan ran.
As her career has progressed, Brannigan has relished the advances in computer technology that have allowed for more complex simulations. Although computer programming is key to her research, she said, she still gets to fulfill her other aspirations—writing and presenting scientific stories; learning the psychology of how people learn, make decisions, and form habits in order to convince her colleagues and students; and standing up in front of a room to connect with a live audience, which is where her theater training comes into play.
Brannigan has never tired of solving puzzles and seeking new collaborations, including one that began where she least expected it: at home. She recalled that she and her husband, a genomicist, began sharing research during the height of the pandemic lockdown.
“We began to talk about our work; in a way, we had to. After all, he was the colleague in my house,” Brannigan said. “I recognized then that exciting collaborations were possible and knew the CCIB was the ideal center to further that engagement.”
The couple ended up partnering on a research project that centers on the connection between gene mutations in protein structures and diseases. Brannigan explained that mutations tend to occur within the body’s oily regions of proteins, which is typical of Mendelian diseases such as Alzheimer’s, Parkinson’s disease, and epilepsy. She and her team sequenced data to predict specific patterns in large strains of proteins in order to identify certain “suspects” of diseases. The researchers published their findings in a recent paper published in the Proceedings of the National Academy of Sciences.
Brannigan likewise never tires of training the next generation of puzzle solvers. “For me, the lightbulb went off at an early age, but I see it in my students too,” she said. “It can be pretty enthralling work and, just like me, it’s not hard to get bitten by the bug.”
Creative Design: Douglas Shelton
Photography: Ron Downes Jr.
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