February 11, 2019 - 4:00pm
Allen 101X Cypress Auditorium
Xiaojing Gao, PhD
Programmable Protein Circuits in Living Cells: Design and Delivery
Cells use circuits of interacting molecules to sense, process, and respond to signals. In mammalian synthetic biology, we try to emulate that with synthetic molecular circuits and program new cellular functions, which holds great promise for basic research and biomedicine. Synthetic circuits have largely relied on gene regulation and especially transcriptional control. However, many natural pathways operate at the post-translational level, and synthetic protein circuits could offer advantages such as faster operation, direct coupling to more signaling pathways, and compact encoding on a single transcript. Having already engineered proteases into building blocks for protein circuits, I will continue to perfect the platform in four key directions. I will establish more sensors that transduce diverse endogenous inputs into protease activity, enhance the signal processing power of my protease circuits, develop an accompanying RNA viral vector for safe and non-mutagenic delivery where protease circuits serve as both the “driver” and the “passenger”, and validate and optimize my therapeutic circuits in more cancer-relevant models. I envision a general-purpose platform (i.e., “programming language”) for the rational design, robust implementation, and safe delivery of mammalian synthetic circuits that will facilitate both basic research and biomedical applications.
Dr. Gao received a B.S. in biology from Peking University. In grad school at Stanford University, he used and developed genetic tools for cracking neural circuits in fruit flies, in the labs of Dr. Liqun Luo and Dr. Thomas Clandinin. There he revealed new insights into innate olfactory behavior, established a reporter for permanent and noninvasive readout of neural activity, and devised a strategy to counter cas9-based gene drives. Continuing with his passion for quantitative biology and tool building, he then switched to synthetic biology in his postdoctoral studies with Dr. Michael Elowitz at Caltech. You will hear all about his postdoctoral and future research in his seminar.