Functional characterization of the chorea-acanthocytosis gene VPS13A in the yeast Saccharomyces cerevisiae

Many diseases such as cancer, atherosclerosis (narrowing and hardening of the arteries) and neurodegenerative disorders stem from problems with the uptake, transportation, storage and recycling of molecules. Proper sorting is necessary for normal cell function since many molecules are only required in specific areas or compartments of the cell. In the case of neurodegenerative disorders, defective protein sorting in nerve cells can lead to brain tissue deterioration. Disease caused by abnormal protein sorting can be studied in very simple organisms such as yeast, and the findings directly applied to human cells. Dr. Leslie Grad is researching a yeast protein, Vps13, which is very similar to a protein encoded by the human gene VPS13A. Defects in this gene can lead to chorea acanthocytosis, a neurodegenerative disorder associated with abnormal red blood cells, epilepsy, and muscle and nerve cell degradation leading to premature death. The findings could provide insight into the complicated mechanisms that regulate sorting of molecules inside cells and explain the molecular function of Vps13. Ultimately, Dr. Grad hopes to apply his findings to human cells and contribute to the development of therapies for neurological disorders caused by abnormal protein sorting.