Small Molecule Uptake and Transport in Living and Model Bacterial Membranes

活体和模型细菌膜中小分子的摄取和运输

• 批准号: 2108310
• 负责人: Tessa Calhoun
• 金额: $ 35.1万
• 依托单位: University of Tennessee Knoxville
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108310&HistoricalAwards=false
• 关键词: Small; Molecule; Uptake; Transport; Living

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Tessa Calhoun of the University of Tennessee Knoxville is studying how organization in bacterial membranes can alter their interaction with small molecules. Membranes are fundamental biological components, finely tuned via evolution to balance the protection of the living system with an ability to selectively move to the inside of cells molecular cargo essential for life. Membranes are composed of a wide range of different lipid molecules and proteins. These molecules can cluster into domains that result in multiple, unique environments within the same membrane. Using a novel light-probing and microscopy-based approach, Dr. Calhoun plans to make possible the observation of small molecules as they enter membranes and move between these domains within the membrane. Observations with membranes of living bacteria will directly inform on new directions for model membrane formation in artificial cells. Dr. Calhoun is also developing a first-year studies course to bring together women majoring in STEM (Science, Technology, Engineering and Mathematics) fields early in their career development to engage them in dialogue about the importance of diversity, implicit bias, and imposter syndrome.A deeper understanding of how the membrane interacts with exogenous molecules is integral for tailoring molecules designed to target membranes, as well as in developing model systems that facilitate controllable transport. The overall goal of the Calhoun research program is to test hypotheses regarding the functional rules that dictate the behavior of small molecules within the membrane environment of living bacterial cells using second harmonic generation spectroscopy, microscopy, and kinetic modeling. Studies will be conducted on living bacterial cells to provide specific insight on the optimization of small molecule-membrane interactions. This includes measuring dissociation constants for these small molecules and relating these to structural motifs and the presence of functional membrane micro-domain disruptors. The Calhoun group will examine small molecule behavior with model membranes designed to mimic those of bacteria with the intent of improving model membrane design by rational incorporation of membrane ingredients that facilitate transport.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）项目的支持下，田纳西大学诺克斯维尔的Tessa Calhoun正在研究细菌膜中的组织如何改变它们与小分子的相互作用。膜是基本的生物组成部分，通过进化进行微调，以平衡对生命系统的保护与选择性地将生命所必需的分子货物转移到细胞内部的能力。膜由各种不同的脂质分子和蛋白质组成。这些分子可以聚集成结构域，从而在同一膜内产生多个独特的环境。使用一种新的光探测和显微镜为基础的方法，卡尔霍恩博士计划使小分子进入膜和膜内这些域之间移动的观察成为可能。对活细菌膜的观察将直接为人工细胞中模型膜形成的新方向提供信息。卡尔霍恩博士还在开发一个第一年的研究课程，将STEM专业的女性聚集在一起。（科学，技术，工程和数学）领域在他们的职业发展早期，让他们参与对话的重要性，多样性，隐式偏见，冒名顶替者综合征。更深入地了解膜如何与外源分子相互作用是不可或缺的定制分子设计的目标膜，以及开发便于可控运输的模型系统。卡尔霍恩研究计划的总体目标是使用二次谐波发生光谱学，显微镜和动力学建模来测试关于指示活细菌细胞膜环境内小分子行为的功能规则的假设。将对活细菌细胞进行研究，以提供关于小分子-膜相互作用优化的具体见解。这包括测量这些小分子的解离常数，并将其与结构基序和功能性膜微结构域破坏剂的存在相关联。Calhoun小组将通过设计模拟细菌的模型膜来检查小分子行为，目的是通过合理地结合促进运输的膜成分来改进模型膜设计。该奖项反映了NSF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而被认为值得支持。