Molecular Mechanisms of Crystalline Silica-Induced Phagocytosis and Cell Death

Silicosis is a chronic lung disease induced by the inhalation of crystalline silica. Some evidence suggests crystalline silica is phagocytosed via the scavenger receptor and that this uptake leads to macrophage cell death. However, it is unclear that crystalline silica is actually internalized by cells. Time-lapse imaging and fluorescence microscopy are being used to establish the molecular mechanisms by which crystalline silica is recognized and internalized by macrophages, and the relationship of uptake to cell death.

Regulation of actin cytoskeletal architecture by Fimbrin A.

The fimbrins, also known as plastins, are members of the CH superfamily of actin-binding proteins.  Fimbrin has two calcium-binding EF hand motifs at their N-terminus, followed by a tandem repeat of the F-actin-binding domain (ABD). Although fimbrin has been extensively characterized, little is known about what regulates fimbrins binding to actin filaments in the cell. In order to understand this question, we generated fluorescent fusion proteins, encoding either the entire protein or its various domains, and examined the localization of these fluorescent proteins in living cells. We have also used bacterially expressed fimbrin and its various domains to further investigate the function of the two actin-binding domains of fimbrin. This will allow us to understand fimbrin subcellular localization and what regulates its binding to F-actin filaments.