Fundamental Studies of Protein Aggregation

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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.