In the average human cell, ~2-4 million membrane proteins are produced every minute. Each of these nascent proteins must be accurately synthesized, targeted to the correct cellular compartment, inserted into the membrane, and assembled into functional macromolecular complexes. These steps must happen in tight coordination with quality control machinery to recognize nascent polypeptides that fail at any step of the maturation process. The balance between biogenesis and quality control is critical for cellular proteostasis, and varies dramatically between cell types and under different environmental stimuli.
Our goal is to dissect the molecular details of this fundamental process, to delineate the logic used to establish and maintain unique protein compositions within cellular compartments. We are particularly interested in identifying new factors and pathways that regulate protein biogenesis and quality control in human cells. To do this we use an integrated approach that combines functional genomics, cell biology, biochemistry, and structural techniques. A detailed understanding of the rules governing protein sorting and localization will provide the insight for manipulating protein flux, first in cells, then in organisms, and finally as a strategy to treat human disease.