Fundamental Studies of Protein Aggregation

在化学部生命过程化学奖中，来自蒙大拿州立大学的Mary Cloninger博士将研究可用于聚集蛋白质的多价相互作用。树枝状大分子、超支化聚合物和含有低亲和力和高亲和力配体的线形聚合物将被合成和研究。为了充分彻底地评估蛋白质/聚合物聚集体，以便能够实现关于形成蛋白质簇的指导原则，将进行一系列不同的实验。分析将包括酶联免疫吸附分析、电子顺磁共振/层析分析、动态光散射实验、透射电子显微镜成像、荧光寿命波形光谱和尺寸排除色谱-多角度光散射实验。这项研究的目的是提高对合成多价体系如何将蛋白质聚集成特定聚集体的基本理解。目前，还没有好的方法来控制离散的蛋白质/聚合物聚集体的形成，这些聚集体可以用于研究和中介多价生物识别过程。这项研究应该能够开发新的方法来控制蛋白质在合成多价大分子和聚合物上的显示。这项提案还将为来自蒙大拿州农村地区的学生和在学年期间就读保留高中和部落大学并参加蒙大拿州立大学暑期项目的美国原住民学生提供丰富的培训场所。此外，这项研究的显微照片和其他结果将用于向当地中学生进行演示。在Cloninger博士在学校进行初步介绍后，一小群中学生将能够参加蒙大拿州立大学的实地考察活动，以观看仪器设备并进行聚合物实验。

In this award from the Chemistry of Life Processes in the Chemistry Division, Dr. Mary Cloninger, from Montana State University, will study multivalent interactions that can be used to cluster proteins. Dendrimers, hyperbranched polymers, and linear polymers bearing low and high affinity ligands will be synthesized and studied. In order to evaluate the protein/polymer aggregates thoroughly enough that guiding principles regarding formation of protein clusters can be enabled, a diverse set of experiments will be performed. Assays will include enzyme linked immunosorbent assays, electron paramagnetic resonance/chromatography assays, dynamic light scattering experiments, transmission electron microscopy imaging, fluorescence lifetime waveform spectroscopy, and size exclusion chromatography-multiangle light scattering experiments. The goal of this research is to improve the fundamental understanding of how synthetic multivalent systems can cluster proteins into defined aggregates.Currently, good methods for controlled formation of discrete protein/polymer aggregates that can be used to study and to mediate multivalent biological recognition processes are not available. This research should enable the development of new methods for controlling the display of proteins on synthetic multivalent macromolecules and polymers. This proposal will also serve as a rich training ground for students from rural Montana and for Native American students who attend reservation high schools and tribal colleges during the school year and participate in summer programs at Montana State University. In addition, the micrographs and other results from this study will be used in presentations with local middle school students. After initial presentations by Dr. Cloninger at the school, small groups of middle school students will be able to participate in field trips to Montana State University in order to see the instrumentation and to perform experiments with polymers.