Small Molecule Uptake and Transport in Living and Model Bacterial Membranes

在化学系生命过程化学(CLP)计划的支持下，田纳西诺克斯维尔大学的Tessa Calhoun正在研究细菌膜的组织如何改变它们与小分子的相互作用。膜是基本的生物成分，通过进化进行微调，以平衡对生命系统的保护和选择性地移动到细胞内对生命至关重要的分子货物的能力。膜由多种不同的脂质分子和蛋白质组成。这些分子可以聚集成区域，从而在同一膜内产生多个独特的环境。卡尔霍恩博士计划使用一种新的光探测和基于显微镜的方法，使观察小分子进入膜并在膜内的这些区域之间移动成为可能。对活细菌膜的观察将直接为人工细胞中模型膜的形成提供新的方向。卡尔霍恩博士还在开发一门一年级的研究课程，让主修STEM(科学、技术、工程和数学)领域的女性在职业发展早期聚集在一起，让她们参与关于多样性、隐性偏见和冒名顶替症的重要性的对话。更深入地了解膜与外源分子的相互作用对于定制针对膜的分子以及开发促进可控运输的模型系统是不可或缺的。卡尔霍恩研究计划的总体目标是使用二次谐波产生光谱、显微镜和动力学模型来测试有关功能规则的假设，这些规则决定了活细菌细胞膜环境中小分子的行为。将对活的细菌细胞进行研究，以提供对小分子-膜相互作用的优化的具体见解。这包括测量这些小分子的离解常数，并将其与结构基序和功能膜微域干扰物的存在联系起来。卡尔霍恩小组将用模拟细菌的模型膜来研究小分子行为，目的是通过合理地加入便于运输的膜成分来改进模型膜的设计。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 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.