Making Connections: Comparative Innovations in the Sciences

Looking into the Crystallin Ball: Elucidating the Role of aB-crystallin in Inflammasone Activation in Retinal Epithelial Cells Dr. Merideth Krevosky, Dr. Jeffery Bowen Inhibitors of apoptosis are upregulated in cancer, conferring cellular survival, and are downregulated in neurodegenerative and inflammatory diseases such as age-related macular-degeneration (AMD) which are characterized by increased cell death. The small heat shock protein, αB-crystallin inhibits apoptosis by disrupting activation of an enzyme critical for cell destruction. Previous work demonstrated αB-crystallin cleavage and inactivation is coincident with destructive endophthalmitis and loss of retinal function, supporting αB-crystallin’s cytoprotective role in the retina. Research implicates inflammation in retinal destruction during AMD which involves a protein complex known as the inflammasome. Studies are underway to address whether αB-crystallin interacts with inflammasome complex proteins. Our current studies support that αB-crystallin is localized to and cleaved within cellular lysosomes during inflammasome activation, supporting that loss of αB-crystallin correlates with retinal cell destruction. Since few therapeutic interventions exist for AMD, modulation of αB-crystallin expression may promote retinal cell viability and prevent vision loss. Rapid Fooling Around in the Presence of Competitors Favors Breakups Dr. Thayaparan Paramanathan The title makes common sense with human behavior, but is this true for the breaking apart of non-covalent complexes in biological systems? The formation and breaking apart of these non-covalent complexes is a key determinant of functions in molecular biology and pharmacology. Dissociation rates of complexes are conventionally assumed to depend only on the interactions between the molecules forming the complex, and not on the presence of competitors. We use a single-molecule technique, where we label the molecules with fluorescent dyes of different colors and shine them with the appropriate laser color to watch them individually. Our results suggest that, indeed, the competitor accelerates dissociation of a non-covalently bound molecular complex by occluding the rapid rebinding of binding partners. The results show that an acceleration of ligand dissociation rate with increasing competitor concentration is a natural feature of a molecular competition that can occur in biologically relevant ranges of competitor concentration