All biological systems rely on protein synthesis and degradation (proteolysis). Regulation of proteolysis is needed to ensure proper signaling and growth in all cell types. For example, cells limit DNA replication to specific phases of growth by rapidly degrading factors that trigger transitions between these phases. The improper degradation of these factors results in pathological conditions like cancer. In addition, chemical or environmental shocks can generate toxic, damaged proteins that must be eliminated before they can cause harm to the cell. The buildup of these types of damaged proteins is a hallmark of many neurological diseases such as Alzheimer's and Huntington's diseases, further illustrating the importance of properly regulating protein degradation.
Protein degradation is a double-edged sword. Since protein degradation is irreversible, unregulated proteolysis would rapidly destroy all the proteins in the cell. However, the cell must have a robust way to rapidly degrade those proteins that are unwanted. Therefore, regardless of the specific organism or system, there are fundamental questions common to all proteolysis pathways. How are certain proteins targeted for destruction while other proteins are not? How does the cell regulate proteolysis to maintain normal growth while responding to environmental changes?
The general research objectives of my lab are to determine how proteolysis is regulated and the biological consequences of regulated proteolysis. We take an integrated approach to this question, using biochemical, structural, genetic and proteomic tools to address mechanistic and cellular questions. We are particularly interested in understanding how regulated protein degradation is used in bacteria. Protein degradation is crucial for bacteria development and virulence, and just as defects in proteolysis result in human disease, defects in proteolysis result in loss of bacterial fitness. This presents us with a timely opportunity to characterize specific bacterial pathways that rely on regulated proteolysis as targets for novel antibiotics that are sorely needed due to the recent alarming rise of multidrug-resistant bacteria.
Learn more at www.biochem.umass.edu/faculty/peter-chien
- PhD University of California, San Francisco
- Postdoctoral training: Massachusetts Institute of Technology