Slick Software, Slow Hardware: Balancing Biophysical Tradeoffs Drives Cellular Reprogramming

12/10/2018 - 2:30pm
Katie Galloway, Ph.D., Postdoctoral Research Fellow, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California
Communicore, C1-7

Integrating synthetic circuitry into larger transcriptional networks to mediate predictable cellular behaviors remains a challenge within synthetic biology. While significant efforts have been devoted to the design of enhanced synthetic circuitry, less is understood regarding how cellular hardware may impose fundamental performance limitations on integrated circuits. Within the mammalian context, cellular reprogramming continues to generate new cell types, increasingly expanding our perspective of cellular plasticity. Despite improved genetic tools and epigenetic modulations, reprogramming remains a rare cellular event. In this talk, I will describe how I identified epigenetic roadblocks in reprogramming that arise from tradeoffs between transcription and proliferation rates. My discovery highlights how topological stress impacts the function of gene networks (e.g. native or synthetic circuits) and constrains cellular transitions. This finding opens completely new questions about how the structure of the genome stabilizes cellular identity and suggests strategies to improve the design of synthetic gene circuits.


Katie Galloway earned her B.S. in Chemical Engineering from UC Berkeley and Ph.D. in Chemical Engineering (minor in Biology) from the California Institute of Technology. As a chemical engineer working in molecular systems biology, her research focuses on elucidating the fundamental principles of integrating synthetic circuitry to drive cellular behaviors. While a graduate student in Christina Smolke’s laboratory at Caltech, she designed, constructed, and tuned wrap-around genetic control systems capable of dynamically programming cell fate in yeast. As a postdoc training in stem cell biology and neuroscience in Justin Ichida’s laboratory at USC Stem Cell, Katie utilized a systems-level approach to identify previously unrecognized roadblocks in reprogramming. Identifying these roadblocks illuminated strategies to enhance cellular reprogramming efficiency by two orders of magnitude and improve cellular maturity. Her research has been featured in Science and she has won multiple fellowships and awards including the NIH F32 and Caltech’s Everhart Award. 

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