CAREER: Global analysis of in vivo protein folding efficiencies by mass spectrometry

University Of Rochester, Rochester NY

Investigators

Abstract

Proteins are initially synthesized as linear polymers and must subsequently fold into precise three-dimensional structures. Within a cell, this folding reaction is often error prone and can lead to misfolded and nonfunctional proteins. The cell contains a number of quality control mechanisms for degrading misfolded and nonfunctional proteins. In this project, Dr. Ghaemmaghami?s laboratory will develop a novel technique for measuring the fraction of proteins that successfully fold within the cell after synthesis. Using this technique, Dr. Ghaemmaghami will study variations in the folding efficiencies of several proteins. The results will elucidate relationships between physical properties of proteins and their propensity to fold successfully within a cell. On the whole, this research will establish novel techniques that will facilitate investigations of protein folding inside cells and lead to a greater understanding of factors that influence protein homeostasis. Broader impacts. Integrated educational activities of the proposal include creating an interactive, web-based teaching module that introduces students and the public to theoretical and practical aspects of modern proteomics. Additionally, a number of research opportunities will be provided to high school and undergraduate students. The multidisciplinary nature of the project (encompassing protein biochemistry, cell biology, analytical chemistry, physical chemistry and quantitative biology) will provide cross-departmental research opportunities to graduate students. The research will lead to the development of mass spectrometry related protocols and novel analysis software and will facilitate proteomic research at the University of Rochester. It will also provide a foundation for cross-departmental collaborative research. The software will be made freely available to the research community and could be widely used by researchers interested in dynamic proteomics.