Michael J. Ragusa

To maintain cellular homeostasis long-lived and toxic cellular components must be degraded. Due to their size, large protein aggregates and long-lived organelles are completely inaccessible to the proteasome, the major protein degradation machinery in the cell. As such, cells have evolved autophagy, a process in which double membrane vesicles engulf cytoplasmic material and target it to the vacuole or lysosome for degradation. The sequestering of autophagic cargo was predominantly thought of as a non-selective process. However, it is now clear that the selection of certain autophagic cargo including mitochondria, peroxisomes, lipid droplets, large protein aggregates and intracellular pathogens can occur through a separate process termed selective autophagy. Defective selective autophagy has been correlated with tumorigenesis, chronic infection and neurodegenerative disease. We are using protein crystallography, small angle X-ray scattering and biochemistry to dissect the molecular mechanisms governing this essential pathway. Gaining an understanding of the molecular mechanisms of selective autophagy will allow for the development of novel therapeutics for the treatment of cancer, neurodegeneration, and infectious diseases.