CBE Seminar Series: Kate Galloway

Integrating synthetic circuitry into larger transcriptional networks to mediate predictable cellular behaviors remains a challenge within synthetic biology. In particular, the stochastic nature of transcription makes coordinating expression across multiple genetic elements difficult. Further, delivery of large genetic cargoes limits the efficiency of cellular engineering. Thus, our work is focused on the design of highly-compact genetic tools with a minimal genomic footprint. Simultaneously, we have been developing cocktails of transgenes that are capable of rapidly convert cells into neurons. The sparse and stochastic nature of reprogramming has obscured our understanding of how transcription factors drive cells to new identities. To overcome this limit, we developed a compact, portable reprogramming system that increases direct conversion of fibroblasts to motor neurons by two orders of magnitude. Low rates of direct conversion have previously limited the potential for central nervous system (CNS) applications. Using compact, optimized, polycistronic cassettes, we generate motor neurons that graft with the murine central nervous system, demonstrating the potential for in vivo therapies. In this talk, I will describe how we are building genetic controllers that can regulate transgenic cargoes and cell fate in primary cells. These genetic control systems provide an essential foundation for realizing the promise of synthetic biology in translational therapies.