How We Study Living Systems
The McManus Lab at UCSF builds scalable ways to measure and program biology, with a focus on gene regulation, immune recognition, and engineered cell-to-cell communication. Our work blends synthetic biology, functional genomics, and quantitative immunology, motivated by a recurring constraint: many of the most important phenotypes are dynamic, networked, and interaction-dependent.
Across the years our research has evolved from foundational studies of noncoding regulation to genome-scale approaches for mapping genetic networks, and now to platforms that let us observe and engineer how immune cells sense, decide, and transmit information.
Most modern medicines are "dumb"—they are injected, circulate blindly, and hope to hit the right target. Our lab is building intelligent, "living" medicines. We aim to transform immune cells into autonomous sentinels that can manufacture and deliver therapy directly where it’s needed. By merging high-content genomics with programmable RNA delivery, we are creating an "mRNA Relay" system for programmed specific delivery.
In this system, an engineered cell doesn't just deliver a drug; it senses the local environment, processes the "pathology data," responds by sending mRNA payloads to cells, and reports on its behaviors via secreted "ExoRelay" barcodes. This creates a two-way communication channel: while the mRNA payload heals cells, or even instructs neighboring cells to fight disease, the barcodes enter the circulation as a real-time status report. By reading these molecular messages in the blood, we can monitor exactly where, when, and how our engineered cells are working deep within the body’s tissues.
