This proposal is an administrative supplement request to grant R01GM123508. The PI requests additional funds to replace the aging analytical size exclusion chromatography (SEC) system in his lab. The original R01 award concerns the development of molecules for the delivery of hydrogen sulfide (H2S) in biological systems. Many of the proposed molecules are polymers, which are long-chain molecules. The length of the polymers (their molecular weight) is hypothesized to affect their ability to release H2S in the context of assembled polymer particles called micelles. Thus, measuring the average molecular weight of a specific polymer sample, as well as the distribution of molecular weights in the sample, is a vital component of the R01 award. This administrative supplement is submitted to request funds to replace the SEC system that is used to measure polymer molecular weights and molecular weight distributions, with the goal of preserving the impact of the R01 award. Analytical SEC, which involves a solvent pump, an autosampler, a column oven, and multiple detectors (UV-vis, refractive index, and light scattering) is the current technical standard for all polymer characterization. This request will not influence the specific aims or research design of the original award, but it will allow the methods to be implemented as discussed in the original proposal. Without a replacement instrument, the measured molecular weights and molecular weight distributions of the polymer samples will become inaccurate. This will require that samples instead be sent to outside labs for analysis. Because new polymer samples are produced nearly every day for this project, sending all samples to outside labs would adversely affect the quantity and timeliness of gathering data, which would impact project progress.
Hydrogen sulfide (H2S) is a powerful signaling gas with great therapeutic potential in a variety of diseases and conditions, but to realize the benefits of H2S therapy it must be delivered with control over the location, timing, rate, and duration of release. This project focuses on developing chemical tools for both understanding H2S biology and treating diseases with H2S, creating drug delivery vehicles that can be triggered by specific enzymes to release the gas. The results of this work will enable researchers to apply the chemical tools developed here to better understand the biological roles of H2S and to treat diseases and conditions that may benefit from H2S therapy.
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