Nicholas Harden

Molecular Biology & Biochemistry


We are interested in the Rho subfamily of Ras-related small GTPases and their involvement in embryonic development. The Rho subfamily GTPases are a group of closely related proteins that act as molecular switches, cycling between a GTP-bound “on” state and a GDP-bound “off” state. As molecular switches, the Rho subfamily proteins are components of signal transduction cascades and have been implicated in the regulation of a wide range of cellular events including cytoskeletal organization, membrane trafficking, transcription, and cell growth. Much of what is presently known about the Rho subfamily has been derived from studies on cultured mammalian cells. We wish to move beyond studies at the cellular level to looking at these proteins in the context of a multicellular organism. The regulation of the actin cytoskeleton by the Rho subfamily controls the shape and motility of cells. As cell shape change and cell movement are essential processes in the formation of a multicellular organism, the Rho subfamily is likely to play a significant role in development, and this is supported by preliminary studies in various model organisms, including Drosophila.

We have been characterizing the roles of Rho subfamily signaling in Drosophila embryonic development through the study of mutants and by expression of dominantly acting transgenes. We are using confocal microscopy to build up a detailed picture of how this signaling regulates the complex morphological changes of embryogenesis. We are particularly interested in Rho subfamily participation in dorsal closure of the Drosophila embryo, a morphogenesis of the epidermis that has emerged as an excellent system for studying signal transduction during development.