Dr. Yuzhong Liu Awarded Michelson Prize for Proposal to Strengthen Vaccines Using Natural Compounds
Like many people, Dr. Yuzhong Liu draws inspiration from nature—not just for its beauty but for its vast repertoire of bioactive compounds with clinical potential. Trained as a synthetic chemist, she is leveraging nature’s chemistry to develop novel vaccine adjuvants. The Michelson Medical Research Foundation and the Human Immunome Project have awarded Liu one of the 2024 Michelson Prizes: Next Generation Grants to biosynthesize vaccine adjuvants based on natural products.
Despite recent advancements in cancer vaccines, researchers still face a fundamental challenge that antigens alone often fail to elicit a lasting immune response. Adjuvants—compounds that enhance immune stimulation—are critical for improving vaccine efficacy. One of the most promising adjuvants is QS-21, a sugar-based extract from the Chilean soap bark tree (Quillaja Saponaria). This molecule is currently being tested as part of a glioblastoma vaccine in clinical trials and has already been used in vaccines against shingles, malaria, and COVID-19.
Although QS-21 induces a strong immune response, it has several limitations. Its supply is restricted to Q. saponaria, making large-scale production unsustainable. Additionally, its complex structure makes it difficult to chemically synthesize at scale, and it can cause toxicity in high doses, especially to immunocompromised people such as cancer patients.
But Liu sees this as a challenge. “I'm always curious about the unknown,” Liu says. “Whenever people say, ‘You can't do this. It's too difficult,’ I take that as a challenge.” She's been tackling challenging chemical problems since she was a chemistry student at the University of Michigan, where she worked on small molecules that modulate protein misfolding in Alzheimer's disease. As a graduate student at the University of California Berkeley, she developed elastic materials from woven molecular threads, laying the groundwork that allowed her to dissect the structures of complex compounds like QS-21.
To address toxicity and sustainability challenges of QS-21, Liu turned to synthetic biology. Since growing a 15-meter-tall tree in the lab is impractical, she copied the genes encoding the enzymes Q. saponaria uses to biosynthesize the compound and inserted them into brewer’s yeast, enabling it to produce QS-21. “Instead of chaining our graduate students to the chemical hood 24/7, we let yeast do the work. We just shake them over the weekend, and on Monday, the molecules are ready,” she explains.
As a postdoc at UC Berkeley and Lawrence Berkeley National Laboratory, Liu successfully biosynthesized QS-21. Now, she is turning her attention to the numerous sugar molecules that cells attach to the compound through a process called glycosylation, as sugars play a central role in glycosides’ abilities as adjuvants—and its toxicity. Indeed, removing just one sugar can dramatically alter the toxicity profile of one molecule. “I've never really seen anything quite like that,” she says. “The more we study sugars, the more we realize their profound impact on biology.”
The Michelson Prizes grant will allow Liu to continue working on glycosylated molecules with enhanced adjuvant properties. By modifying the biosynthetic enzymes, she hopes to generate novel variants of QS-21 and other natural glycosides, optimizing their immune-stimulating effects while reducing toxicity.
Her work also paves the way for sustainable biomanufacturing of next-generation vaccine adjuvants. “These trees didn't evolve over billions of years to treat our human diseases—often, the natural molecules are not the most potent derivatives,” she says. “By creating new adjuvants through synthetic biology, we can reduce our dependence on tree harvesting and develop better vaccines for the future.”
