Coordination of replication and migration in an epithelial sheet

University Of Missouri-Kansas City, Columbia MO

Investigators

Abstract

Cell migration is a highly integrated, multistep process that underlies normal development, repair of injured tissue, and the progression of diseases such as cancers and atherosclerosis. Cells utilize key signaling proteins, notably protein kinases, to regulate changes in cell division and cell shape for proper migration. The Drosophila Tribbles protein functions to restrict cell division and promote protein turnover during the cell migration process and is related to the TRB family of proteins that includes human SKIP-1, which when mutated is associated with an aggressive form of leukemia called acute myelogenous leukemia (AML). An important, but unresolved question is whether these proteins act as kinases to attach phosphate molecules to target proteins or rather as a pseudokinases to regulate signaling indirectly. To address this, the PI's laboratory will use a powerful genetic model system to express normal and mutated versions of Tribbles and examine effects on cell structure and protein turnover. The outcome of these experiments will shed light on the molecular function of Tribbles during normal development and the work proposed will train undergraduates and graduate students in cutting edge approaches to understand the genetic basis of development with implications for human disease.