CAREER: Synthetic mucus gels with tunable glycosylation, composition, and physical properties

职业：具有可调节糖基化、成分和物理特性的合成粘液凝胶

• 批准号: 1848054
• 负责人: Jessica Kramer
• 金额: $ 51.89万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1848054&HistoricalAwards=false
• 关键词: CAREER; Synthetic; mucus; gels; tunable

Project Non-Technical AbstractWith this award, the Biomaterials Program in the Division of Materials Research is funding Dr. Jessica R. Kramer from The University of Utah to develop polymers to mimic natural human mucus. Mucus is essential for life but remains challenging to study due to a lack of access to reproducible and homogeneous samples. This award funds development of new methods to synthesize the protein component of mucus and to study how these proteins interact with each other and with salts, DNA, and bacteria to form mucus. These materials have broad implications for probing interactions at cell-surfaces such as nutrient absorption, fertilization, and immunity and could be used in cellular models to reduce the need for animal testing. This pursuit allows undergraduate and graduate students to acquire specialized training in polymer science, microbiology, and glycobiology. This project also integrates into several outreach programs that support glycoscience education and females in the pursuit of STEM careers, and targets students from 4th grade to the graduate level. Project Technical AbstractThis research project undertakes development of a multi-block self-assembling glycopolypeptides that mimic the properties of multi-domain mucin glycoproteins. Mucins are the major protein component of mucus hydrogels that coat epithelial tissues, and are essential for life. Yet, mucins remain challenging to study due to a lack of tools to analyze and manipulate protein glycoforms. Lack of reproducible access to sufficient quantities of homogeneous mucins has hindered research in many areas of science and medicine. Mucin-mimicking multi-domain polypeptides with precise glycosylation patterns and tunable domain are chemically synthesized by sequential polymerization of amino acid N-carboxyanhydrides. The glycopolypeptides are assembled into hydrogels containing varied compositions of salts, lipids, and DNA to investigate factors responsible for mucus' bulk physical properties. The contributions of glycan-binding bacteria and galectins to the stiffness or degradation of mucus will also be explored. Overall, this study provides new materials for the study of mucus at the molecular level. This research also integrates into several outreach programs that support glycoscience education and females in the pursuit of STEM careers, and targets students from 4th grade to the graduate level.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.

项目非技术摘要 凭借该奖项，材料研究部的生物材料项目正在资助犹他大学的 Jessica R. Kramer 博士开发模拟天然人类粘液的聚合物。粘液对于生命至关重要，但由于缺乏可重复且均质的样本，研究仍然具有挑战性。该奖项资助开发合成粘液蛋白质成分的新方法，并研究这些蛋白质如何相互作用以及如何与盐、DNA 和细菌相互作用形成粘液。这些材料对于探测细胞表面的相互作用（例如营养吸收、受精和免疫）具有广泛的意义，并且可以用于细胞模型以减少动物测试的需要。这种追求使本科生和研究生能够获得聚合物科学、微生物学和糖生物学方面的专门培训。该项目还融入了多个支持糖科学教育和女性追求 STEM 职业的外展计划，目标对象是四年级到研究生水平的学生。项目技术摘要该研究项目致力于开发模拟多结构域粘蛋白糖蛋白特性的多块自组装糖多肽。粘蛋白是覆盖上皮组织的粘液水凝胶的主要蛋白质成分，对生命至关重要。然而，由于缺乏分析和操作蛋白质糖型的工具，粘蛋白的研究仍然具有挑战性。缺乏可重复获得足够数量的均质粘蛋白阻碍了许多科学和医学领域的研究。通过氨基酸 N-羧酸酐的连续聚合化学合成具有精确糖基化模式和可调结构域的模拟粘蛋白多结构域多肽。将糖多肽组装成含有不同盐、脂质和 DNA 成分的水凝胶，以研究影响粘液体积物理特性的因素。还将探讨聚糖结合细菌和半乳糖凝集素对粘液的硬度或降解的贡献。总体而言，这项研究为分子水平上的粘液研究提供了新材料。这项研究还融入了多个外展计划，支持糖科学教育和女性追求 STEM 职业，并针对四年级到研究生水平的学生。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Biomimetic Glycosylated Polythreonines by N -Carboxyanhydride Polymerization

N-羧酸酐聚合仿生糖基化聚苏氨酸

• DOI: 10.1021/acs.biomac.2c00020
• 发表时间: 2022
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: Deleray, Anna C.;Kramer, Jessica R.
• 通讯作者: Kramer, Jessica R.

Supramolecular Protein Stabilization with Zwitterionic Polypeptide–Cucurbit[7]uril Conjugates

使用两性离子多肽 – 葫芦[7]脲缀合物实现超分子蛋白质稳定性

• DOI: 10.1021/acs.biomac.2c01319
• 发表时间: 2023
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: Clauss, Zachary S.;Meudom, Rolande;Su, Bo;VandenBerg, Michael A.;Saini, Simranpreet S.;Webber, Matthew J.;Chou, Danny Hung-Chieh;Kramer, Jessica R.
• 通讯作者: Kramer, Jessica R.

Preparation and applications of artificial mucins in biomedicine

人工粘蛋白的制备及其在生物医学中的应用

• DOI: 10.1016/j.cossms.2022.101031
• 发表时间: 2022
• 期刊: Current Opinion in Solid State and Materials Science
• 影响因子: 11
• 作者: Detwiler, Rachel E.;Kramer, Jessica R.
• 通讯作者: Kramer, Jessica R.