UC Santa Cruz

Understanding the operating principles of life requires complete characterization of cellular biology at the molecular level. While genomic analysis illuminates the blueprints used by organisms to store and propagate information, proteins are the principal active ingredients in the recipe of life. Thus, our ability to perceive biological processes hinges on describing the structure and function of proteomes--robust methods to identify and characterize proteins are vital to this effort. The primary focus of this dissertation is to develop a new method of protein analysis by coupling a protein unfoldase to a nanopore sensor. In this system, intact protein strands are interrogated as they are enzymatically translocated through the sensitive nanopore lumen. This process results in a series of ionic current blockades that are diagnostic of protein structure at the single-molecule level. This work represents the first steps towards developing the principles of this technology as a general platform for protein identification. This analytical approach is aimed at achieving the resolution required to fully grasp the complexities of the proteome.