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.

Description:

Annual Mah Lecture speaker Pablo Debenedetti of Princeton University.

Host: Randy Snurr

Title:
Evaporation Transitions of Water in Nano-Scale Confinement: Fundamentals and Biophysical Implications

Abstract:
The thermodynamic and kinetic behavior of water in nano-scale confinement plays an important role in biophysical phenomena such as hydrophobically-driven self-assembly. Using advanced sampling techniques, we investigate computationally the rate, mechanism, and energetics of evaporation transitions induced by hydrophobic confinement. We find a pronounced sensitivity of the evaporation kinetics to the substrate’s mechanical properties: a single order of magnitude reduction in the material’s modulus causes the evaporation rate to increase by nine orders of magnitude. Theoretical and numerical analysis of the underlying thermodynamics likewise suggests that it may be possible to sensitively control the relative stability of the vapor and liquid phases by tuning substrate flexibility. These findings may have implications for the function of membrane-bound protein assemblies.

Bio:
Pablo Debenedetti is the Class of 1950 Professor in Engineering and Applied Science, Professor of Chemical and Biological Engineering, and Dean for Research at Princeton University. He received his undergraduate education at the University of Buenos Aires, and his graduate education at the Massachusetts Institute of Technology, where he obtained MS (1981) and PhD (1985) degrees in Chemical Engineering. Since 1985 he has been a faculty member at Princeton University. Prior to becoming Dean for Research, he served as Chair of the Chemical Engineering department (1996-2004), and Vice Dean of the School of Engineering and Applied Science (2008-2013).

His research interests include the thermodynamics and statistical mechanics of liquids and glasses; water and aqueous solutions; protein thermodynamics; nucleation; metastability; and the origin of biological homochirality. Research in Debenedetti’s group has helped define the current state of basic knowledge on the properties of metastable liquids and glasses, and brought this vast field to the mainstream of chemical engineering thermodynamics. He is the author of one book, Metastable Liquids, and more than 260 scientific articles. Debenedetti’s professional honors include the National Science Foundation’s Presidential Young Investigator Award (1987), the Camille and Henry Dreyfus Teacher-Scholar Award (1989), a Guggenheim Memorial Foundation Fellowship (1991), the Professional Progress (1997), Walker (2008) and Institute Lecture (2013) Awards from the American Institute of Chemical Engineers, the John M. Prausnitz Award in Applied Chemical Thermodynamics (2001), the Joel Henry Hildebrand Award in the Theoretical and Experimental Chemistry of Liquids from the American Chemical Society (2008), and the Guggenheim Medal from the Institution of Chemical Engineers (2017). He received the Distinguished Teacher Award from Princeton’s School of Engineering (2008), and the President’s Award for Distinguished Teaching (2008), Princeton’s highest distinction for teaching. In 2008 Debenedetti was named one of 100 Chemical Engineers of the Modern Era by the American Institute of Chemical Engineers. He is a member of the National Academy of Engineering, the American Academy of Arts and Sciences, and the National Academy of Sciences, and is a fellow of the American Association for the Advancement of Science, the American Institute of Chemical Engineers and the American Physical Society.