Chemical Engineering Seminar

Abstract: Self-assembling proteins make up precisely ordered nanostructures from filaments and capsules to pumps, each of which is promising for applications ranging from biomanufacturing to medicine to materials. For example, a nanoscale protein-based container could serve as a vaccine scaffold or as a delivery vehicle for cellular or gene therapy. However, such structures must be tunable for each application, and despite great leaps in our ability to predict how amino acid sequences will fold into a soluble protein, it remains a significant challenge to predict how proteins come together to form the assemblies and machines that are ubiquitous to life. To address this challenge, and inspired by advances in next-generation DNA synthesis and sequencing, we developed a workflow to fully characterize the assembly competency of all possible single mutations in several model systems, including those from a virus-like particle, a bacterial organelle, and a secretion system. The resulting high-resolution datasets challenge several conventional protein design assumptions on the composition of linkers, mutability of pores, and more. We then used the same approach but screened for desired functions to enhance the performance of each system in its target application space. For example, a protein filament of a secretion system was engineered to confer >2-fold higher production of a target product, a virus-like particle was engineered to target delivery to specific cell types, and a bacterial microcompartment was engineered to produce biochemicals in a sustainable manner. With this talk, I will provide examples of how our sequencing-based approach is useful as a tool for uncovering the fundamental rules of protein self-assembly as well as for engineering new function into self-assembling systems, highlighting how such approaches may be used to generate nanoscale precision design in next-generation materials.

Bio: Danielle Tullman-Ercek is the James N. and Nancy J. Farley Professor in Manufacturing and Entrepreneurship, and Professor of Chemical and Biological Engineering at Northwestern University, Co-Director of the NU Center for Synthetic Biology, and Director of the Master of Science in Biotechnology Program. She also served as the inaugural Director of SynBREU, which is the first and longest-running NSF-funded Synthetic Biology undergraduate research program. Outside of Northwestern, she was also a founding council member of the Engineering Biology Research Consortium, served as an Editor for mSystems, and is Chair-Elect for the American Chemical Society Biochemical Technology Division. She is also co-founder of a company, Opera Bioscience, which is built on her research innovations related to biomanufacturing. She received her B.S. in Chemical Engineering at Illinois Institute of Technology in Chicago, and her Ph.D. in Chemical Engineering from the University of Texas at Austin. She carried out postdoctoral research at the University of California San Francisco and the Joint Bioenergy Institute, while part of the Lawrence Berkeley National Laboratory. Tullman-Ercek's research focuses on building biomolecular devices for a wide range of applications, including energy, materials, manufacturing, and medicine. She is particularly interested in engineering multi-protein complexes, such as virus capsids and the machines that transport proteins and small molecules across cellular membranes. She received several awards for this work, including the Searle Leadership Award, an NSF CAREER award, and the Biochemical Engineering Journal Young Investigator award, and she was inducted as a Fellow of the American Institute of Medical and Biological Engineering in 2023.