Center for Advanced Proteomics
Department of Cell Biology & Neuroscience
174 Frelinghuysen Rd.
Piscataway, NJ 08854
Structural biology of neurodegenerative diseases by cryo-electron tomography
Huntington's disease: structure and organization of protein aggregates; 3D architecture of the diseased cells under misfolded protein aggregation stress
Huntington's disease (HD) is an inherited neurodegenerative disease characterized by progressive motor, cognitive, and psychiatric deterioration. In HD neurons, the formation, abundance and persistence of mutant huntingtin (mHTT) aggregation species are correlated with neurodegeneration, however, the identity of toxic species and the structural basis for mHTT toxicity are not clear. Multiple cellular pathways have been implicated in the pathogenesis of HD, including protein homeostasis, calcium signaling, mitochondrial dysfunction, and vesicular transport and recycling. Using cryoET to directly visualize mHTT and cellular components involved in these cellular pathways will provide insights to HD pathogenesis and potential therapeutic targets.
Structural biology of phage/virus maturation
Using the new phase contrast technology, we have visualized multiple assembly intermediates of cyanobacterial phages inside the host at different stages of maturation. Current studies focus on further unraveling the details of capsid accessory protein assembly and genome packaging.