South SFV Today

Stanford researchers have introduced a new synthetic receptor that expands the possibilities for controlling cellular activities. Detailed in a paper published on December 4 in Nature, this innovation is called "Programmable Antigen-gated G protein-coupled Engineered Receptors" (PAGER). It utilizes G protein-coupled receptors, which are responsible for turning on molecular switches inside cells to manage vital functions.

Alice Ting, a professor of genetics at the School of Medicine and biology at the School of Humanities and Sciences, commented on the potential impact of PAGER. She stated, “I think PAGER has potential for impact, both in the G protein coupled receptor biology field, and in synthetic circuits or cell-based therapies.”

Previously, researchers faced challenges with customizing G-protein coupled receptors due to the need for specific small molecules to activate them. Nicholas Kalogriopoulos, a postdoctoral fellow and co-lead author of the paper, explained their approach: “Essentially, what we did is fuse something that blocks that pocket, and it only opens up when it binds something you’ve chosen.”

The team demonstrated PAGER's capabilities by controlling neuronal activity, triggering immune responses, and delivering therapeutic treatments during lab experiments. Collaborations with Ivan Soltesz from Stanford Medicine and Yulong Li from Peking University were instrumental in these experiments.

Reika Tei, another postdoctoral fellow involved in the study said: “The very collaborative environment of Stanford expedited the study. I think it really led to the success of the experiment and the project.” Ting expressed satisfaction with PAGER's performance across various applications: “We didn’t expect all four applications to work right away, but they did.”

The research was supported by several initiatives including Stanford's Wu Tsai Neurosciences Institute and Knight Initiative for Brain Resilience. Future plans involve exploring more applications for PAGER while simplifying its structure.

Kalogriopoulos emphasized collaboration moving forward: “We need people who actually study the biology of a specific disease or cellular function because they know the proper inputs and outputs."

This research received funding from multiple sources such as Chan Zuckerberg Biohub–San Francisco and St. Jude Children’s Research Hospital Collaborative Research Consortium on G protein-coupled receptors.

A provisional patent application related to this work has been filed by Kalogriopoulos, Ting, Ravalin, and Tei. Ting also serves as a scientific advisor to Third Rock Ventures and Nereid Therapeutics.

For further information contact Taylor Kubota at Stanford University via tkubota@stanford.edu.