Precision glycocalyx engineering with synthetic mucins

使用合成粘蛋白进行精密糖萼工程

• 批准号: 1807651
• 负责人: Jessica Kramer
• 金额: $ 45万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807651&HistoricalAwards=false
• 关键词: Precision; glycocalyx; engineering; synthetic; mucins

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.

凭借该奖项，化学部的生命过程化学项目正在资助犹他大学的 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）。糖萼影响多种生物事件，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萼的成分并将其展示在活细胞上。这些方法对于研究细胞表面从细胞通讯到营养吸收、受精和免疫的相互作用具有广泛的意义。这种追求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门培训。该项目还融入了多个外展计划，支持高中教育以及女本科生和研究生追求 STEM 职业。该研究项目致力于开发一种通过在活细胞上融合天然和合成蛋白质结构域来改造糖萼的方法。糖萼几乎涉及生物学的所有方面，但由于缺乏分析和操作蛋白质糖型的工具，研究仍然具有挑战性。粘蛋白 1 是糖萼的主要蛋白质成分。具有精确糖基化模式的粘蛋白 1 模拟多肽是通过 N-羧酸酐聚合化学合成的。这些多肽与活细胞表面表达的工程化截短粘蛋白 1 蛋白双正交缀合，从而可以研究特定糖型的生物效应。这项研究提供了新的化学工具和方法来询问糖萼和探测聚糖依赖性信号传导。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。