Award Abstract # 2339330
CAREER: atomistic characterization of protein-polymer conjugates
| NSF Org: | DMR Division Of Materials Research |
| Recipient: | |
| Initial Amendment Date: | January 5, 2024 |
| Latest Amendment Date: | January 5, 2024 |
| Award Number: | 2339330 |
| Award Instrument: | Continuing Grant |
| Program Manager: | Nitsa Rosenzweig nirosenz@nsf.gov (703)292-7256 DMR Division Of Materials Research MPS Direct For Mathematical & Physical Scien |
| Start Date: | May 1, 2024 |
| End Date: | April 30, 2029(Estimated) |
| Total Intended Award Amount: | $642,952.00 |
| Total Awarded Amount to Date: | $118,658.00 |
| Funds Obligated to Date: | |
| History of Investigator: |
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| Recipient Sponsored Research Office: | 1523 UNION RD RM 207 GAINESVILLE FL US 32611-1941 (352)392-3516 |
| Sponsor Congressional District: | |
| Primary Place of Performance: | 1523 UNION RD RM 207 GAINESVILLE FL US 32611-1941 |
| Primary Place of Performance Congressional District: | |
| Unique Entity Identifier (UEI): | |
| Parent UEI: | |
| NSF Program(s): | BIOMATERIALS PROGRAM |
| Primary Program Source: | |
| Program Reference Code(s): | |
| Program Element Code(s): | |
| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.049 |
ABSTRACT Technical description 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.
Non-technical description
Protein-based materials have unique potential in both industrial and medical applications because they can be precisely tailored for specific tasks. However, the ability to fine-tune protein materials also makes them vulnerable to quickly falling apart and becoming useless. While proteins hold the promise to be powerful biological sensors or potent drugs able to treat a range of diseases, they often do not survive in the human body. The most promising method for making proteins more robust is to attach a polymer to them. This creates protein-polymer molecules that are joined together, where the polymer can shield the protein without changing its beneficial properties. This approach has led to several important drugs for treating inflammation and cancer. However, unlocking the potential to create many more biological materials or drugs made from protein-polymer conjugates has been very difficult. There are many different ways to build protein-polymer conjugates, with some being useful while others are not, and there is no guide for how they should be put together. The goal of this research is to advance the understanding of what makes some protein-polymer conjugates more robust and create rules so that they can be intentionally designed, which is crucial to unleashing their full potential as medicines, biological sensors, and new biological materials. The proposed research is integrated with an educational program that aims to provide an introduction and training on scientific techniques used to visualize proteins at the microscopic level as well as closely related scientific methods used to image the human body. The principle investigator will lead several hands-on workshops created for visits of high school and undergraduate students in partnership with the university precollegiate education and training center.
While protein-polymer conjugates are widely valued in materials research, their development is mostly empirical due to the lack of accurate molecular-level depictions of conjugates. The goal of this research is to experimentally provide atomistic descriptions of protein-polymer interactions that enhance the stability of conjugated proteins in biological materials. Conjugates are classified between two types based on their overall conformation and the degree to which the protein and polymer interact: ?dumbbell?-like structures that are loosely connected or ?shroud?-like structures that are more interwoven and show more persistent protein-polymer interactions. Macromolecular properties of the conjugated protein, including resistance to thermal and chemical denaturation, are expected to correlate with the three-dimensional conformation of the conjugate. It is hypothesized that the equilibrium between these two forms is determined by specific interactions between protein side chains and conjugated polymer. Conjugates exhibiting shroud-like interactions appear to possess unique and advantageous properties. The use of NMR will enable determination of the factors contributing to formation of shroud-like interactions and establish a set of quantitative principles for the design of protein-polymer conjugates with predictable properties. A deeper understanding of how polymers effectively stabilize proteins against thermal or chemical denaturation, will enable exploration of novel phenomena, such as leveraging polymer conjugation to rescue partially misfolded proteins and stabilize intractable proteins. Visualizing protein-polymer interactions at the atomistic level is crucial in unlocking the full potential of new polymer synthesis approaches and conjugation strategies, which are essential for utilizing biological materials in demanding environments.
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