Maintaining cellular protein homeostasis (proteostasis) is an essential task for all eukaryotes. Proteostasis failure worsens with aging and is considered a cause of and a therapeutic target for age-related diseases including neurodegenerative disorders. The cellular networks regulating proteostasis and the pathogenic events driving proteostasis failure in disease remain poorly understood. Protein translation machinery can be stalled by translational stress when reading the mRNA. The stalling of ribosomes results in the production of truncated polypeptides that can have deleterious effects on cells, and therefore must be eliminated. In eukaryotes, this function is carried out by a dedicated surveillance mechanism known as ribosome-associated protein quality control (RQC). Our research in this part focuses on the role of RQC in various human diseases, especially those related to aging.

Batten Disease is an umbrella term of a broad class of rare, autosomal recessive, fatal neurodegenerative disorders, also known as neuronal ceroid lipofuscinoses (NCLs). The major clinical features of Batten disease include progressive visual loss, mental and motor retardation, seizures and premature death. Most cases of Batten disease have been found to have dysfunctional lysosomal functions in patients’ cells. Lysosomes are places where cells digest large biomolecules, complexes, pathogens and cellular organelles to small components for disposal or recycling. Drosophila is an excellent model for conducting both the mechanism study and small-molecule drug screening for human neurological diseases, given its multiple advantages compared to other model systems. In this project, we will systematically analyze the Drosophila Models of Batten Disease.