Intracellular trafficking processes in disease

We are developing live cell assays which recapitulate essential features of various diseases. Novel screening approaches have allowed us to identify previously unappreciated factors bearing on Diabetes and Huntingtin aggregate degradation.

Vesicle trafficking is monitored in the L6 skeletal muscle cell line using the pH-sensitive GFP (pHluorin) coupled to VAMP2.

The formation of Huntingtin-like aggregates are observed with a reporter construct consisting of the N-terminal end of huntingtin protein, a variable polyglutamine stretch (25, 65 and 103Q), and GFP. Note: as the polyglutamine exceeds a critical length, the reporter condenses into an aggregate.