Sherry Gao Receives NIH MIRA Award to Advance Precision Genome Engineering

From life-saving antibiotics to powerful anticancer drugs, some of the most important medicines in modern history trace back to an unexpected source: fungi. These organisms are master chemists, capable of producing a vast array of complex molecules with potent biological effects. Yet scientists have only scratched the surface of this chemical diversity, and genomic studies suggest that most of the compounds fungi can make remain hidden and unexplored. Unlocking this untapped potential could reveal entirely new classes of therapeutics and transform how we discover and manufacture drugs.

Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering, has received a Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS) to support her research on precision genome engineering and the discovery of novel products from natural fungi.

“Fungi are remarkable producers of chemically diverse molecules, many of which have already led to important medicines such as antibiotics, anticancer agents and immunosuppressants,” says Gao. “But they can produce far more than we’ve been able to observe so far. Our work aims to unlock this untapped chemical space by using advanced genome editing tools to activate these silent pathways, with the goal of discovering new bioactive compounds and expanding the chemical diversity available for research and drug discovery.”

The MIRA program provides long-term support for investigators pursuing innovative and fundamental research questions. Gao’s lab is investigating a largely unexplored class of molecules in fungi called RiPPs — small peptides that cells chemically modify into more complex, bioactive compounds — which, like past fungal-derived drugs such as penicillin and other antibiotics, could lead to new therapies while also revealing natural strategies for efficiently building complex molecules.

“This award enables us to both build the tools needed to study fungi more effectively and to apply those tools to discover entirely new classes of molecules,” says Gao. “By expanding our understanding of how these compounds are made, we hope to uncover new opportunities for therapeutic development.”

This work builds on the Gao Lab’s broader efforts to develop advanced genome-editing technologies and synthetic biology approaches that uncover and engineer biologically active molecules from microbes, with the goal of enabling new therapeutics and biotechnology applications.

The project involves undergraduate, graduate and postdoctoral researchers in the Gao Lab and includes collaborations with experts in structural biology, molecular biology, chemistry and computational science. Learn more here.