Area 15C Plenary Award to
Danielle Tullman-Ercek
Designing with nanoscale building blocks: How protein engineering enables new solutions for medicine, sustainability, and materials
Self-assembling proteins make up precisely ordered nanostructures from filaments to capsids to transporters, each of which is promising for applications ranging from biomanufacturing to medicine to materials. For example, a nanoscale protein-based virus-like particle 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 next used these datasets to enhance the performance of each system in its target application space. For example, bacterial microcompartment shell proteins were engineered to form distinct geometries for materials applications while a virus-like particle was engineered for encapsulation of protein cargo and display of targeting ligands. Our work shows the power of uncovering the fundamental rules of self-assembly as well as the utility of such data sets engineering new function into self-assembling systems, highlighting how such approaches may be used to generate nanoscale precision design in next-generation materials.
Dr. Danielle Tullman-Ercek is the James N. and Nancy J. Farley Professor in Manufacturing and Entrepreneurship, and Professor of Chemical & Biological Engineering at Northwestern University, where she also serves as Director of the Master of Science in Biotechnology Program. She earned her B.S. in Chemical Engineering from the Illinois Institute of Technology and went on to receive her Ph.D. in Chemical Engineering from the University of Texas at Austin. Her research centers on engineering highly organized self-assembling protein systems—such as virus-like particles, bacterial microcompartments, and membrane protein machines—with applications spanning therapeutics, biomanufacturing, and sustainable materials. Dr. Tullman-Ercek is also Co-Director of Northwestern’s Center for Synthetic Biology and leads the SynBREU program for undergraduate synthetic biology research.
