Self-assembling proteins make up precisely ordered nanostructures such as filaments and capsules, each of which is promising for applications in medicine and materials.
For example, a nanoscale protein capsule could serve as a delivery vehicle for cellular and gene therapy applications.
However, such structures must be tunable for each application, and to date, the ability to predict how alterations to the protein sequence will impact self-assembly and other structural properties remains a significant challenge.
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To address this challenge, we combined comprehensive mutagenesis with high-throughput sequencing to fully characterize the assembly-competency of several self-assembling proteins, including those from a virus-like particle, a bacterial microcompartment, and a secretion system.
The resulting high-resolution fitness landscapes challenge several conventional protein design assumptions on the composition of linkers, mutability of pore-lining residues, and more. We then used the same approach but with other functional screens to design each system for enhanced performance in applications.
For example, the protein filament of the secretion system was engineered to confer >2-fold higher secretion of proteins, and the virus-like particle was engineered for improved endosomal release.
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With this talk, I will provide examples of how our sequencing-based approach is useful as a tool for uncovering the fundamental rules of self-assembly as well as for engineering new function into self-assembling systems.
About Danielle Tullman-Ercek: He is an associate professor in the Department of Chemical and Biological Engineering and director of the master’s program in biotechnology at Northwestern University.
Her research focuses on building biomolecular devices for a wide range of applications, including bioenergy, living batteries, biomaterials, biosensors, biomanufacturing in resource-limited environments, and drug delivery.
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.
Danielle 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.
In 2009, she joined the Chemical and Biomolecular Engineering faculty at the University of California Berkeley, where she held the Charles Wilke Endowed Chair of Chemical Engineering and later the Merck Chair of Biochemical Engineering. In 2016, she moved her lab to Northwestern University.
She is director of SynBREU, which is the first Synthetic Biology REU program, and is a member of the NU Center for Synthetic Biology. She is also on the steering committee of the Engineering Biology Research Consortium.
She received several awards, including the Searle Leadership Award and the NSF CAREER award for her work on the construction of bacterial organelles using protein shells.
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