CAREER: Elucidating Surfactin Modus Operandi with 2D IR Spectroscopy

通过这项由化学结构、动力学和机制B项目(CSDM-B)资助的NSF职业奖项，科罗拉多州立大学的Amber T.Krammel教授将利用二维红外(2D IR)光谱确定一种小的成孔毒素表面素将与模型类脂膜相互作用的方法。已知表面活性蛋白具有抗菌、抗病毒和抗肿瘤活性，但在生物膜形成过程中，表面活性蛋白也与细胞信号活动有关。该项目将确定在这些不同的活动中，表面活性物质的作用方式的不同。二维红外光谱提供的结构敏感性将被用来定量表面素膜插入和脂膜破坏过程中表面素脂相互作用的分子细节。预形成毒素是由包括人类免疫系统在内的许多生物体合成的蛋白质。这些蛋白质插入细胞膜，以允许小分子进入细胞，导致细胞渗漏，或破坏细胞的完整性，从而导致细胞死亡。在这项工作中，先进的光学光谱技术将被用来监测具有结构敏感性的蛋白质-脂质相互作用。这些研究结果将使人们对一种小孔形成毒素--表面蛋白--如何自组装并与脂质相互作用，以驱动细胞信号传递过程和脂膜的破坏有一个新的理解。在这个项目的过程中，本科生研究人员和研究生研究人员将接受高级光学光谱学技术、化学建模和数据分析方面的培训。用于培训参与该项目的学生研究人员的方法也将被纳入科罗拉多州立大学化学专业的本科课程。因此，这个项目将对一个重要的化学系统产生新的见解，并将产生新的方法来培训科罗拉多州立大学下一代化学专业的学生。

Through this NSF CAREER award, funded by the Chemical Structure, Dynamics, and Mechanisms B Program (CSDM-B), Professor Amber T. Krummel from Colorado State University will identify the means by which a small pore-forming toxin, surfactin, will interact with model lipid membranes using two-dimensional infrared (2D IR) spectroscopy. Surfactin is known to have antibacterial, antiviral, and antitumor activity, but surfactin has also been implicated in cell-signaling activities during biofilm formation. This project will identify the differences in the mode of action by surfactin during these different activities. The structural sensitivity offered by 2D IR spectroscopy will be utilized to quantify the molecular details of the surfactin-lipid interaction during the surfactin insertion and lipid membrane disruption processes.Pore-forming toxins are proteins that are synthesized by many organisms, including the human immune system. These proteins insert into cell membranes in order to allow small molecules to move into cells, cause cell leakage, or to disrupt the integrity of cells such that cell death occurs. In this work, advanced optical spectroscopy techniques will be used to monitor the protein-lipid interaction with structural sensitivity. The results from these investigations will lead to a new understanding of how a small pore-forming toxin, surfactin, self-assembles and interacts with lipids in order to drive cell signaling processes and the disruption of lipid membranes. During the course of this project, undergraduate researchers and graduate student researchers will be trained in advanced optical spectroscopy techniques, chemical modeling, and data analysis. The approaches used to train the student researchers involved with this project will also be incorporated into the undergraduate curriculum for Chemistry Majors at Colorado State University. Thus, this project will generate new insights into an important chemical system and it will generate new approaches to training the next generation of Chemistry majors at Colorado State University.