Collaborative Research: Elucidating the Mechanism of Magnetogenetics for Remote Activation of Cell Function

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We are entering a new age of manufacturing where living cells are used to produce fuels, chemicals, and therapeutic proteins. Cell therapies offer the promise of enhancing a patient's natural immune system cells to fight cancer and other metabolic diseases. These technologies are possible because of our ability to control the metabolism of cells. Most of the currently used control methods rely on chemical signaling, but chemical signals can also interfere with normal cell metabolism. This project will develop a alternate biological control system that responds to magnetic signals. Research opportunities for undergraduates will develop a skilled STEM workforce. Outreach efforts will be multiplied through development of an 8-week summer workshop for K-12 teachers and high school students. Remote gene activation through static and alternating/oscillating magnetic fields will be evaluated for the control of protein expression in mammalian cells and cell cultures. The core hypothesis to be tested is that magnetic fields can induce the opening of ion channels upon co-expression of and mediation by ferritin tethered to the ion channel. The ferritin nanoparticles would serve as transducers, converting magnetic signals into physical ones that can activate a signal cascade. Magnetic fields offer much finer temporal and spatial control than is available using chemical signaling. The scope of the project and specific activities are threefold. First, elucidate the mechanism of static and oscillating/alternating magnetic field induced activation of ion channels. Second, tune sensitivity and responsiveness of magnetically activated ion channels by constructing genetic systems and controlling cell culture conditions to enhance ferritin properties leading to transient receptor potential (TRP) channel gating. Third, as a bioengineering application, use the genetically-encoded TRP channel-ferritin system to remotely control gene transcription and induce expression of key proteins involved in neurogenesis. The outcome of this study could be a foundation for designing methods to control cellular signaling, gene transcription, and protein expression/production for biomanufacturing applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.