The interior of cells contains high concentrations of protein. Cells have complex systems to prevent these proteins from aggregating. However, recent evidence has shown that the aggregation of specific proteins is used to regulate various important cellular functions. In this research project, the investigators will use a combination of genetic, biochemical and computer modeling techniques to develop improved methods to predict this particular protein aggregation, and to examine how such aggregates are used to regulate cellular functions. This project will offer diverse interdisciplinary training to junior scientists. A portion of the research will be conducted in the context of a novel laboratory course, which is designed to be a hybrid of independent research and traditional laboratory classes. This course will allow students to generate new, publishable research, but in a sufficiently structured setting to allow for training of a large number of students. Additionally, the PI will continue to expand his "Biochemistry is Elementary" outreach program. This program introduces elementary school students to the scientific process and to basic concepts in biochemistry using exciting, hands-on activities.
Despite the growing realization of the importance of prions and prion-like aggregation in normal cellular physiology, the exact basis for and regulation of these aggregation events are poorly understood. In this project, the investigators will utilize a combination of genetic, biochemical and computer modeling techniques to develop improved methods to predict prion-like aggregation and to examine how prion-like aggregation of RNA binding proteins affects the formation of cytoplasmic RNA-protein granules. The first goal is to develop better tools to predict prion aggregation and to predict how protein modifications affect prion activity. These studies will generate new resources to facilitate searches for new prion-like elements, and will provide key insight into the regulation of prion-like aggregation. The second goal of the project is to examine the role of prion-like domains in the formation of cytoplasmic RNA-proteins granules. These studies will provide a framework for studying functional protein aggregation, while offering insight into the role of prion-like aggregation in post-transcriptional regulation of gene expression.
