CAREER: Nature-Inspired Strategies for Protein Stabilization

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NON-TECHNICAL SUMMARYProteins and enzymes perform a wide range of functions inside cells and tissues for long periods of time, and are able to do so at body temperatures. However, most purified proteins used in scientific endeavors, or are present as vaccines or other medical treatments are extremely sensitive to temperature, and must be kept refrigerated. This need to maintain refrigeration during the storage and transportation of these materials represents a significant expense and logistical challenge for both doctors and patients. This proposal will study how different materials can be used to encapsulate such therapeutic proteins to improve their shelf life and temperature sensitivity. This work will also use this funding to create new educational opportunities for students in the lab, and help to develop science-based activities that students at the university could bring home to inspire scientific curiosity in their communities.TECHNICAL SUMMARY This proposal draws upon inspiration from nature, where liquid-liquid phase separated granules in cells are able to selectively sequester specific proteins and other biomolecules, and hold these targets in storage during times of stress. This work will use sequence-controlled polypeptide based complex coacervates as a synthetically accessible mimic for these biological condensates. The effect of charge sequence, hydrophobicity, and hydrogen bonding on the phase behavior of the resulting coacervates will be studied. Furthermore, the effect of these various parameters on the ability of complex coacervate phases to uptake different members of the caspase family of apoptotic enzymes will be evaluated, and correlated with the potential for the different coacervate environments to improve the thermal stability and shelf life of these enzymes. The goal of this effort is to enable the development of general strategies for engineering biomimetic materials for applications ranging from biosensors to thermostable vaccines. Additionally, this proposal will increase educational opportunities at the interface of biology, materials, and engineering at the undergraduate and graduate levels and engage female and minority students through outreach activities with the college's Diversity Programs Office. A new “Innovation in a Box” program will challenge undergraduate outreach leaders to develop easily translatable modules for use in the community.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.