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

有了这个奖项，材料研究部的生物材料项目资助了犹他大学的Jessica R. Kramer博士开发模拟天然人体粘液的聚合物。黏液对生命至关重要，但由于缺乏可重复和均匀的样本，研究仍然具有挑战性。该奖项资助开发合成黏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黏液。这些材料在探测细胞表面的相互作用（如营养吸收、受精和免疫）方面具有广泛的意义，并可用于细胞模型，以减少对动物试验的需求。这种追求使本科生和研究生能够获得高分子科学、微生物学和糖生物学方面的专门训练。该项目还整合了几个支持糖科学教育和女性追求STEM职业的外展项目，目标学生从四年级到研究生水平。项目技术摘要：本课题旨在开发一种模拟多结构域粘蛋白糖蛋白特性的多嵌段自组装糖共肽。粘蛋白是覆盖上皮组织的黏液水凝胶的主要蛋白质成分，是生命所必需的。然而，由于缺乏分析和操纵蛋白糖型的工具，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的途径阻碍了许多科学和医学领域的研究。通过氨基酸n-羧基氢化物的顺序聚合，合成了具有精确糖基化模式和可调结构域的模拟黏液蛋白的多结构域多肽。这些甘共肽被组装成水凝胶，其中含有不同的盐、脂质和DNA组成，以研究导致黏液体积物理性质的因素。甘聚糖结合细菌和凝集素对黏液硬度或降解的贡献也将被探讨。总之，本研究为在分子水平上研究黏液提供了新的材料。这项研究还整合到几个支持糖科学教育和女性追求STEM职业的外展项目中，目标学生从四年级到研究生水平。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.