Judith Frydman is a professor in the Biology Department at Stanford University. She majored in chemistry and received her PhD from the University of Buenos Aires, Argentina. She carried out her postdoctoral training with Ulrich Hartl at the Sloan Kettering Institute in New York, where she discovered the eukaryotic chaperonin TRiC and investigated the basic principles of how proteins fold following translation in eukaryotic cells. Her research program aims to understanding the biological mechanisms controlling cellular protein folding, aggregation and quality control and the relationship of these mechanisms to the genesis of proteotoxic diseases.
The central theme of Dr. Frydmans work is to understand how molecular chaperones mediate protein folding and carry out quality control of the cellular proteome. Knowledge of how the cell achieves the correct folding of cellular proteins has important medical implications, as protein folding disfunction is linked to a growing number of human diseases, including cancer, heart disease and the so-called "amyloid" diseases, including Alzheimers', Huntington's and Parkinson's Diseases. Additionally, control of cellular protein homeostasis by cytosolic chaperones has been linked to longevity and aging.
The Frydman lab has made important contributions to our understanding of this fundamental biological problem, and uncovered basic principles of chaperone action during both de novo protein folding, i.e. when proteins are synthesized on ribosomes, as well as during quality control, i.e. when folded proteins get misfolded or damaged during normal function or during stress. Her work has recently found that chaperones play also a key role in remodeling protein assemblies, both for cellular and viral proteins. Recent work from the Frydman lab also suggests that understanding eukaryotic protein folding may lead to novel therapeutic strategies against viral infectious diseases. Additionally, the Frydman lab studies protein misfolding and protein quality control; these studies provide a framework to understand the events leading to accumulation of toxic aggregates such as those occurring in neurodegenerative diseases.
Mapping the cotranslational chaperone network in eukaryotic cells
Polypeptides exiting the ribosome must fold and assemble in the crowded environment of the cell. Chaperones and other protein homeostasis factors interact with newly translated polypeptides to facilitate their folding and correct localization. Despite the extensive efforts, little is known about the specificity of the chaperones and other factors that bind nascent polypeptides. To address this question we present an approach that systematically identifies cotranslational chaperone substrates through the mRNAs associated with ribosome-nascent chain-chaperone complexes. Our findings give us new insight into the dynamic interplay of chaperones acting on nascent chains. The strategy we use should be generally applicable to mapping the specificity, interplay and dynamics of the cotranslational protein homeostasis network.
For more information, click here.