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

在化学系生命过程化学（CLP）项目的支持下，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。细菌在细胞表面包裹一层密集的复杂糖，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生存中的重要性，它们的系统研究和扰动仍然具有挑战性。提出的实验程序将开发新的糖探针，用于跟踪细菌对糖的利用、摄取和加工。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基本作用，并有助于抗生素和疫苗的开发。在项目进行的过程中，将从学院为女性和历来被排斥的学生服务的项目中招募本科生研究人员，他们将在一个指导网络中从事持续的研究项目。更广泛地说，通过在美国化学会的全国会议上举行一系列专题讨论会，该项目有可能扩大女性和有色人种在化学糖生物学界的知名度。总的来说，这项工作可以激励下一代学生坚持并在科学中茁壮成长。该研究项目旨在利用细菌单糖类似物来深入了解探针设计，单糖摄取和细菌内存在的聚糖裁剪酶的最佳参数。将一系列细菌中基于单糖的报告蛋白使用和酯酶活性水平相关联，为探测细菌聚糖提供了敏锐的工具。开发荧光单糖类似物来跟踪活菌的摄取，可以更好地了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。对于糖科学家在一系列细菌系统中进行基础和应用研究来说，这些工具的创造具有潜在的效用。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。

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.