Engineering+ Health Institute Launched, Focusing on Engineering Antibodies

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From left, Chang Liu and Mohamad Abedi stand with Henry and Susan Samueli who attended the launch event for the Samueli School's Engineering+ Health Institute.

March 11, 2025 - “Antibodies are called the magic bullets of biology,” Chang Liu told the crowd that gathered in February at UC Irvine for the launch of the Engineering+ Health Institute: Rapid Antibody Engineering and Evolution.

Antibodies have special properties, explained Liu. They are the basis of medicines, immunotherapies and diagnostics, and are used in imaging, pandemic response and research to detect things that would otherwise be invisible. “This is why antibodies are important and why generating custom antibodies against antigens of interest has been an important area of biological research for many years,” said Liu, professor and Chancellor’s Fellow in biomedical engineering and director of the new institute. 

The Engineering+ Health Institute: Rapid Antibody Engineering and Evolution is the first of three e+ interdisciplinary institutes outlined in the UCI engineering school’s 2030 strategic plan – Engineering+ Environment and Engineering+ Society are the two others. The institutes are funded by a $50 million gift in 2023 from Susan and Henry Samueli.

Liu outlined his plans for the e+ Health Institute to the audience of interdisciplinary faculty, students, staff and distinguished guests including the Samuelis. With $2.5 million over five years, the institute’s main focus is to solve antibody engineering. Liu has enlisted a broad range of collaborators including researchers from Harvard Medical School, and UCI schools of medicine, physical sciences and engineering.

“Of course, antibodies are not really magic,” said Liu. The generation of specific antibodies that hit desired molecular targets has historically been a challenging bioengineering problem. The interface between antigen and antibody needs to be very specific to get the desired results.

The institute’s researchers will focus on two ways to advance engineering antibodies. One is based on a system developed in Liu’s research group called Orthogonal DNA Replication, or OrthoRep, where Liu has made cells that can selectively drive the rapid evolution of any gene. In the antibody case, they can encode antibodies onto this genetic system and force th

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Chang Liu explains researchers' approach for engineering antibodies.

em to gain the ability to specifically target the desired antigen. In previous work, they tested their approach with the SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Over six rounds, the evolved antibodies could bind and neutralize infection.

“This is a potentially great way to make antibodies, and we can do it in a test tube without relying on traditional techniques that involve animals or challenging molecular biology pipelines,” said Liu. “Another revolution occurring now is in the protein design space where AI and machine learning are being used to tackle protein engineering challenges. And this can also be applied to antibodies, in a manner synergistic with our evolution approaches. We are exploring this synergy in the institute as well.”

For example, an idea that is yielding rapid early success starts with computationally modelling antibody-antigen interactions to then computationally designing an antibody that targets a specific place on an antigen. These designs can then be evolved into highly potent antibodies. The computational design research is occurring now at the University of Washington, in the lab of David Baker, 2024 Nobel Prize winner in Chemistry.

UCI alumnus Mohamad Abedi ’14 is a postdoctoral researcher in Baker’s lab, the Institute for Protein Design. After graduating with a biomedical engineering degree from UCI in 2014, Abedi went on to earn his doctorate at Caltech. He has been working on computational protein design tools for immunotherapy and cancer treatment with Baker since 2021.

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UCI alumnus Mohamad Abedi ’14 shares his research focusing on how cells communicate with each other..

Abedi’s research looks at how cells communicate with each other, and he is specifically focused on the small signaling proteins called cytokines. "Cytokines are the 'words' immune cells use to communicate with each other. We are developing technologies to manipulate these words and use them to guide immunotherapies for cancer and autoimmune diseases," said Abedi. "That is the angle I am taking. I think a lot of the research in biomedical engineering with a health intersection is trying to figure out how can we build technologies to manipulate these biological processes." 

Ultimately, Liu says, what they’d like to do is combine computation with evolution to solve this antibody engineering problem. “On the one hand, we can design antibodies and drive them to be better through evolution. On the other hand, we can carry out evolution in a way where we generate a lot of data – a lot of different versions of an antibody that bind the antigen well – and use that data to train models for the design. By synergizing these two approaches, I think we can get to a solution to the antibody engineering problem.”

Liu says the institute plans to disseminate technology advances broadly, apply advances immediately to problems in medicine and health, and expand funding support. “The ideas of the institute will be long standing and every five years, we will take on a new problem that we have a good chance of solving,” he said. 

– Lori Brandt