Description:

Laura Segatori of Rice University.

Host: Danielle Tullman-Ercek

Title: 
Engineering synthetic regulatory systems to reprogram mammalian cells

Abstract:
The chemical and energetic properties specified by a protein’s amino acid sequence and encoded by our genome, while determining the protein folding energy landscape, are only part of what shapes how proteins evolve their function. A sophisticated network of macromolecular assistants is needed to control protein synthesis and folding, and mediate degradation of aberrant proteins – functions achieved through completely different and independent mechanisms balanced extrinsically by chemical feedback agents. We seek to develop novel biotechnologies to manipulate these mechanisms for applications ranging from systems-level investigations of protein function to development of therapeutic approaches for restoring cellular homeostasis. We employ synthetic biology tools to develop genetic circuits that interface with pathways that mediate protein folding and degradation (e.g., the Ubiquitin-Proteasome System and the Unfolded Protein Response) with the ultimate goal to monitor and manipulate cellular protein levels with high specificity, sensitivity, and dynamic resolution. We recently developed a technology for degrading a target protein with high specificity and selectivity that provides dynamic control over protein accumulation and that can be customized to target any cellular protein and post-translational modifications (ACS Synth Biol. 2018 Feb 16;7(2):540-552). We have deployed this technology to improve the design of synthetic gene circuits through stimulus-dependent, targeted depletion of the circuit reporter and, ultimately, develop a universal platform for monitoring changes in gene expression with high sensitivity and dynamic resolution. I will discuss the use these tunable cell-based platforms not only to monitor and engineer cellular protein degradation but also to generate novel tool for the mammalian synthetic biology community.

Biography:
Laura Segatori is an Assistant Professor of Bioengineering at Rice University with joint appointments in the departments of Chemical & Biomolecular Engineering and Biosciences. She received a Laurea in Industrial Biotechnology from the University of Bologna in Italy in 2000 and a PhD in Chemical Engineering from the University of Texas at Austin in 2005. She completed her postdoctoral work at The Scripps Research Institute in La Jolla California and joined the faculty at Rice University in 2007. She is the recipient of the NSF CAREER Award. Her research group is highly interdisciplinary and combines principles and tools from engineering and science to decipher and manipulate cellular quality control mechanisms that underlie the development of human diseases. Current research interests include the design of synthetic biology tools and nanotechnology-based approaches to engineer protein degradation pathways in the complex environment of mammalian cells.