Alum Scientist Targets ‘Undruggables’ With AI

In her work in antibody design and engineering for the drug-development Absci, Rui Yin Ph.D. ’24 works to engineer better biologics that can take on stubborn targets—no small task. 

“Antibodies are little proteins, and if you unfold them, they’re like little strings of beads of amino acids. The possibilities to mix and match the beads are enormous,” she said. 

Testing even a small fraction of the possible permutations in a lab would be extremely costly and take months to complete, Yin said, but AI can quickly evaluate the real-world possibilities, tease out underlying patterns, and help design new antibodies that are specific to a target and could ultimately be turned into a drug.        

For Yin, who has contributed to antibody research for diseases ranging from cancer to coronavirus and hepatitis C, working with AI on the cutting edge of medical science is genuinely inspiring.

“I definitely have a lot of those ‘wow’ moments, seeing what AI is capable of achieving,” she said. “I firmly believe that we are on the track of deepening our understanding of the immunology of protein-protein interaction, protein design and antibody engineering with tools that weren't even an option 10 or even five years ago.”

Yin’s path to taking on disease with AI started in childhood, developing an early interest in medicine thanks to a father who was a doctor and a mother who was a nurse. While earning her B.S. in biology at the College of William & Mary in Virginia, she took classes introducing her to protein engineering and fueling her interest in the complex challenges of immunology. Intent on pursuing medical research with an emphasis on AI as a tool, Yin was accepted into the University of Maryland’s biological sciences Ph.D. program in 2019. 

“Although everybody's talking about AI now, it wasn't like that back then,” she said. “I did know that I wanted to explore machine learning because I realized I wanted to achieve a widespread impact.”

In her Ph.D. research, Yin worked with Associate Professor Brian Pierce in the Department of Cell Biology and Molecular Genetics and the Institute for Bioscience and Biotechnology Research, developing and applying computer algorithms to better understand how the body’s immune system recognizes and fights pathogens and disease.

“When I first joined his lab, I knew virtually nothing about programming, and he was able to help me expand my knowledge and master state-of-the-art techniques,” Yin said. “His lab is world-class, and being able to do research there gave me a front-row seat to observe what's happening in this field. I was very fortunate to be part of that.”                                         

In Pierce’s lab, Yin got her first exposure to the use of a type of AI known as deep learning in structural biology, working with programs like AlphaFold, the breakthrough AI system developed by Google DeepMind that predicts the 3D structure of proteins based on their amino acid sequence. Through her research, Yin developed and applied methods to predict and model immune recognition specifically studying the structures that result when molecules are targeted by antibodies and T-cell receptors. The body uses these crucial proteins to discover and interact with foreign invaders.

For Yin, who had a National Cancer Institute fellowship, it’s especially exciting to take her research from the lab to real-world applications.

“In our research, we found ways to improve antibody-antigen modeling success and were able to collaborate with amazing researchers within and outside the department to test our model in real life,” Yin said. “We were able to predict antibody-antigen interaction for COVID-19 and hepatitis C, which was super exciting.”

Pierce sees tremendous potential for Yin’s work in the future.

“In this exciting time for the field; talented scientists like Rui are poised to do amazing things that leverage AI to combat disease and improve human health,” he noted. “Rui did very impressive and impactful work while in the lab, and I’m excited to now see her on the front lines using AI to develop new and important antibody therapeutics.”

Now Yin is following what she sees as a “calling” to make an impact in medicine.

“I've always wanted to be a useful person to society, and one way I see that I'm able to do that is to help advance our understanding of a particular protein or disease on the basic research level,” she explained. “I try to apply what I've learned and translate that into drugs that can help save human lives.”