Precision glycocalyx engineering with synthetic mucins

通过这一奖项，化学部生命过程化学计划资助犹他大学的Jessica R.Kramer博士开发化学工具来研究细胞表面的碳水化合物，统称为糖萼。糖萼会影响不同的生物事件，但由于缺乏分析和操纵碳水化合物的工具，研究仍然具有挑战性。该奖项资助开发新的化学方法来制造糖基化的成分并将它们展示在活细胞上。这些方法对研究从细胞通讯到营养吸收、受精和免疫的细胞-表面相互作用具有广泛的意义。这一专业使本科生和研究生能够获得碳水化合物化学、聚合物科学和细胞生物学方面的专业培训。该项目还纳入了几个支持高中教育和女性本科生和研究生从事STEM职业的外联方案。本研究项目致力于开发一种通过在活细胞上融合天然和人工合成的蛋白质结构域来设计糖基化的方法。糖萼几乎涉及生物学的所有方面，但由于缺乏分析和操纵蛋白质糖形式的工具，研究仍然具有挑战性。粘蛋白1是糖萼的主要蛋白质成分。通过N-羧酸酐的聚合，化学合成了具有精确糖基化模式的粘蛋白1模拟多肽。这些多肽与表达在活细胞表面的工程截短粘蛋白1蛋白双正交连接，这使得研究特定糖形式的生物效应成为可能。这项研究提供了新的化学工具和方法来审问糖基化和探测糖依赖的信号。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Jessica R. Kramer from The University of Utah to develop chemical tools to study the carbohydrates on cell surfaces, collectively termed the glycocalyx. The glycocalyx influences diverse biological events, but remains challenging to study due to a lack of tools to analyze and manipulate the carbohydrates. This award funds development of new chemical methods to make the components of the glycocalyx and display them on live cells. These methods have broad implications for investigating interactions at the cell-surface from cellular communication to nutrient absorption, fertilization, and immunity. This pursuit allows undergraduate and graduate students to acquire specialized training in carbohydrate chemistry, polymer science, and cell biology. This project also integrates into several outreach programs that support high school education and female undergraduate and graduate students in the pursuit of STEM careers. This research project undertakes development of a method to engineer the glycocalyx by fusing natural and synthesized protein domains on live cells. The glycocalyx is involved in nearly all aspects of biology, yet remains challenging to study due to a lack of tools to analyze and manipulate protein glycoforms. Mucin 1 is a major protein component of the glycocalyx. Mucin 1 mimic polypeptides with precise glycosylation patterns are chemically synthesized by polymerization of N-carboxyanhydrides. The polypeptides are biorthogonally conjugated to an engineered truncated mucin 1 protein expressed on live cell surfaces, which allows the study of biological effects of specific glycoforms. This study provides new chemical tools and methods to interrogate the glycocalyx and probe glycan-dependent signaling.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.