Understanding and treating protein misfolding disorders

Description of projects available to graduate students:
Protein misfolding disorders are the cause of a large number of human disorders including Alzheimer's, Huntington's and Lou Gehrig's diseases. Alpha-1-antitrypsin disease is a prototypical member of this disease class and is one of the most common genetic causes of childhood liver failure and adult chronic obstructive pulmonary disease. Most patients with alpha-1-antitrypsin deficiency carry a single point mutation that results in protein misfolding and impaired translocation through the secretory pathway. We have recently developed a C. elegans model of the human liver disease component are are using this tool to identify the molecular basis of misfolded protein elimination and as a platform for high-content drug screening directed towards effective treatment of a disease that currently has no effective therapy.

Techniques graduate student will learn:
basic molecular techniques including transgene construction
high content drug screening
confocal imaging
C. elegans genetics
RNAi screens
mass spectrometry