CBE Seminar: “Harnessing Biological Asymmetry: Engineered Protein Sensors for Scalable Isomer Analysis” (Simon d’Oelsnitz, Harvard Medical School) [FACULTY CANDIDATE]
February 18 at 3:30 PM - 4:30 PM
Abstract:
Biological systems are inherently asymmetric, arising from chemical isomer specificity that propagates from metabolite chirality to higher-order structure and function, with profound consequences for the development of pharmaceuticals, fragrances, and agrochemicals. Yet, modern isomer analysis relies on slow and resource-intensive chromatography, limiting the deep characterization of biochemical systems. In this seminar, I will present a biology-driven alternative in which bacterial regulatory proteins are repurposed as genetically-encoded biosensors for precise, scalable measurement of chemical isomers. Through directed evolution of malleable protein scaffolds, we generate sensors selective for diverse compounds, including terpenes, polyphenols, alkaloids, and synthetic pharmaceuticals. I will also describe computational strategies that leverage large biological datasets to systematically identify biosensors and engineer enzymes for therapeutic compounds. Finally, I will introduce growth-coupled assays combined with massively parallel sequencing that enable the simultaneous measurement of over 900,000 protein–chemical interactions, generating quantitative data to guide predictive protein engineering. Together, programmable genetic sensors provide a scalable platform for studying and engineering asymmetric biochemical systems with applications spanning diagnostics, biocatalyst development, and drug discovery.
Simon d'Oelsnitz
Postdoctoral Fellow
Simon is a postdoctoral Synthetic Biology Fellow at Harvard Medical School and the Wyss Institute. His current work focuses on using genetically-encoded biosensors to generate massive-scale methods for enzymology, as well as portable diagnostics for PFAS contamination. Previously, Simon worked at the National Institute of Standards and Technology where he engineered biosensors to measure enzyme enantioselectivity and developed computational methods for biosensor design. He completed his PhD in Molecular Biology at the University of Texas at Austin, where he used growth and emulsion-based selections to engineer enzymes for therapeutic plant metabolites, protein transporters for solvent tolerance, and aminoacyl-tRNA synthetases for noncanonical amino acid incorporation. Simon has an undergraduate degree in Pharmacology. His research integrates genetic circuit design, protein engineering, and computational biology with applications in chemical analysis and manufacturing.