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

项目非技术摘要有了这个奖项，生物材料计划在材料研究部是资助博士杰西卡R。犹他州大学的克雷默开发了模拟天然人类粘液的聚合物。粘液是生命所必需的，但由于缺乏可重复和均匀的样品，研究仍然具有挑战性。该奖项资助开发新的方法来合成粘液的蛋白质成分，并研究这些蛋白质如何相互作用，以及与盐，DNA和细菌形成粘液。这些材料对探测细胞表面的相互作用具有广泛的意义，如营养吸收，受精和免疫，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聚合物科学，微生物学和糖生物学的专业培训。该项目还融入了几个支持糖科学教育和女性追求STEM职业的推广计划，目标是从四年级到研究生水平的学生。项目技术摘要本研究项目致力于开发一种模拟多结构域粘蛋白糖蛋白性质的多嵌段自组装糖多肽。粘蛋白是覆盖上皮组织的粘液水凝胶的主要蛋白质组分，并且是生命所必需的。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同质粘蛋白阻碍了许多科学和医学领域的研究。通过连续聚合氨基酸N-羧基氰脲酸，化学合成具有精确糖基化模式和可调结构域的粘蛋白模拟多结构域多肽。将糖多肽组装成含有不同组成的盐、脂质和DNA的水凝胶，以研究负责粘液的整体物理性质的因素。聚糖结合细菌和半乳糖凝集素的粘液的硬度或降解的贡献也将进行探讨。总体而言，本研究为粘液在分子水平上的研究提供了新的材料。该研究还融入了支持糖科学教育和女性追求STEM职业的几个外展计划，目标是从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。

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.