About a quarter to a third of all the cell proteins formed in the cell pass through the cell excretory system that begins in the stage of the transition from the cytosol into the endoplasmic reticulum (ER) where the proteins undergo changes after translation and fold into the desired structure. Unsuccessful entrance to ER constitutes protein stress for the cell, as the proteins that remain in the cytosol do not have a correct spatial structure and they are therefore designated for degradation by the ubiquitin-proteasome system. Damage to the mechanism for removing these proteins, which are mislocalized in the cell, is a major reason for the formation of various pathological conditions. Therefore, it is very important to understand in depth the systems that recognize and control these processes.
In the laboratory for researching proteolysis, we have discovered a number of components that are involved in processes of removing proteins that have not entered the ER. By using molecular methods and genetic models in CRISPR technology in cell cultures and model organisms, we demonstrate the functions of these systems in maintaining normal homeostasis in the cell. The laboratory focuses on discovering and understanding the various components involved in removal of mislocalized proteins.
Dr. Ariel Stanhill is hosted in the laboratory of Prof. Ami Navon of the Department of Biological Regulation, the Weizmann Institute of Science.