NIST only participates in the February and August reviews.
Modern medicine is increasingly using biologics to treat disease. However, these proteins and nucleic acids are fragile and to work effectively, they need to be appropriately formulated, or packaged. Polymers, lipids, and other excipients are playing a more important role in this packaging, but the nanoscale "handshake" between the polymer and the biologics are poorly understood. This research opportunity centers on advancing experimental measurement methods to quantify the structure formed between poly(organophosphazene) polyelectrolytes and therapeutics biologics (proteins). Modern polymerization methods are used to develop polymers bearing a phosphazene main chain with organic-substituent pendant groups through post-polymerization modification with a variety of functionality (anionic, zwitterionic, hydrophobic, hydrophilic). These substituents lead to different modalities of interactions with proteins and immunoadjuvant characteristics. These polymers are under active clinical investigation and provide a platform for both fundamental science and application-directed study. This research opportunity will emphasize advancing characterization and data analysis aspects of these multi-component soft matter therapeutic formulations. The binding between polyphosphazenes and proteins are visualized by cryogenic electron microscopy (cryoEM), therefore providing a strong basis for developing structure-function relationships and enhancing indirect studies by scattering techniques [1,2]. Additionally, interactions, protein structure and stability are accessed through analytical techniques including fluorescence, circular dichroism, and assays (ELISA). Experience and/or interest in performing experimental investigation in these formulation with the following methods are of interest: polymer synthesis, high-throughput size-exclusion chromatography multi-angle light scattering, small-angle X-ray scattering, small-angle neutron scattering, and cryoEM to characterize the relationships between polyorganophosphazenes (block ratio, charge fraction, degradability), proteins, and resulting solution properties. This unique opportunity includes world class facilities at NIST and the Institute for Bioscience and Biotechnology, University of Maryland.
[1] R Hlushko, VM Prabhu, AK Andrianov, Cyclic Macromolecular Chains Visualized by Cryo-EM and AFM Reveal a Ring Expansion Polymerization Mechanism in a Classical Synthetic Pathway to Polyphosphazene, ACS Macro Lett. 14, 1476 (2025)
[2] R Hlushko, VM Prabhu, AK Andrianov, Directly visualizing individual polyorganophosphazenes and their single-chain complexes with proteins. Commun. Mater. 5, 36 (2024).
polyelectrolytes; protein; complex coacervation; polymer physics; polymer solutions; polymer gel;
level
Open to Postdoctoral applicants