Stuart K. Kim
We are studying cell growth and cell death in the nematode C. elegans. To study cell growth, we are dissecting apart the receptor tyrosine kinase/Ras/Raf/Map kinase signaling pathway by studying how activation of this pathway causes vulval precursor cells to divide to form the vulva. First, we have used genetic screens to identify targets that act downstream of the signal transduction molecules, and identified several genes that encode transcription factors that may be phosphorylation targets of activated MAP kinase. These transcription factors may directly control cell activation, and they may explain how the MAP kinase transduction pathway can cause distinct cellular responses in different cell types. Second, we have found that the receptor tyrosine kinase (encoded by let-23) is localized to the cell junction in the vulval precursor cells (which are polarized epithelial cells), and that the receptor is poorly activated when it becomes mislocalized in cell junction mutants. Thus, cell signaling is tightly coupled to cell polarity since the proper spatial placement of the receptor tyrosine kinase to the cell junction is crucial for activation.
The genetic pathways that control programmed cell death in humans and nematodes are similar. For instance, we have shown that two human cell death genes (Bcl-2 and Fas) can also control programmed cell death in worms; human Bcl-2 prevents cell death in worms whereas human Fas causes excess cells to die. We are conducting powerful genetic screens in C. elegans to identify new genes that control programmed cell death, with the expectation that homologs of these genes will also control apoptosis in vertebrates.