RUI: Sugar Probes to Track Utilization, Uptake, and Processing of Monosaccharides by Bacteria

RUI：追踪细菌对单糖的利用、吸收和加工的糖探针

• 批准号: 2247752
• 负责人: Danielle Dube
• 金额: $ 40.2万
• 依托单位: Bowdoin College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247752&HistoricalAwards=false
• 关键词: RUI; Sugar; Probes; Track; Utilization

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Professor Danielle Dube from Bowdoin College is developing sugar probes to facilitate the study of bacterial carbohydrates. Bacteria coat their cell surfaces with a dense array of complex sugars, termed glycans, that are critically important for bacteria to interact with other cells and to survive. Despite the importance of bacterial glycans in bacterial survival, their systematic study and perturbation remain challenging. The proposed experimental procedures will develop new sugar probes for tracking utilization, uptake, and processing of sugars by bacteria. Identifying which glycan structures are present on which bacterial cells could reveal fundamental insight into the role of these structures, as well as aid in antibiotic and vaccine development. Over the course of the project, undergraduate researchers will be recruited from programs at the college that serve women and historically excluded students, and they will pursue sustained research projects in a mentoring network. More broadly, the project has the potential to broaden the visibility of women and people of color in the chemical glycobiology community through a series of symposia at national meetings of the American Chemical Society. Taken together, this work could spur the next generation of students to persist and thrive in science.This research project seeks to leverage bacterial monosaccharide analogs to yield insight into optimal parameters for probe design, monosaccharide uptake, and glycan tailoring enzymes present within bacteria. Correlating monosaccharide-based reporter usage and esterase activity levels in a range of bacteria provides incisive tools for probing bacterial glycans. Developing fluorescent monosaccharide analogs to track uptake by live bacteria could allow a better understanding of the mechanisms controlling monosaccharide penetration into bacterial cells. Generating fluorogenic glycoside substrates facilitates the analysis and identification of glycan-processing enzymes in live bacterial cells and lysates. The creation of enabling tools has potential utility for glycoscientists pursuing basic and applied research in a range of bacterial systems.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.

在化学系生命过程化学（CLP）计划的支持下，来自鲍登学院的Danielle Dube教授正在开发糖探针，以促进细菌碳水化合物的研究。细菌的细胞表面覆盖着一系列密集的复合糖，称为聚糖，这对细菌与其他细胞相互作用和生存至关重要。尽管细菌聚糖在细菌存活中的重要性，但它们的系统研究和扰动仍然具有挑战性。拟议的实验程序将开发新的糖探针，用于跟踪细菌对糖的利用、吸收和加工。确定哪些聚糖结构存在于哪些细菌细胞上，可以揭示这些结构的作用的基本见解，并有助于抗生素和疫苗的开发。在该项目的过程中，本科生研究人员将从该学院为女性和历史上被排斥的学生提供服务的项目中招募，他们将在一个指导网络中进行持续的研究项目。更广泛地说，该项目有可能通过在美国化学学会全国会议上举办一系列专题讨论会，扩大妇女和有色人种在化学糖生物学界的知名度。总之，这项工作可以刺激下一代学生坚持和茁壮成长的science.This研究项目旨在利用细菌单糖类似物产生洞察探针设计的最佳参数，单糖吸收，和聚糖剪裁酶存在于细菌内。将一系列细菌中基于单糖的报告基因使用和酯酶活性水平相关联，为探测细菌聚糖提供了有力的工具。开发荧光单糖类似物来跟踪活细菌的摄取可以更好地理解控制单糖渗透到细菌细胞中的机制。产生荧光糖苷底物有助于分析和鉴定活细菌细胞和裂解物中的聚糖加工酶。该奖项反映了NSF的法定使命，并被认为值得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来支持。