GENETIC ANALYSIS OF CELL-CELL SIGNALING IN MYXOCOCCUS

点击翻译按钮获取中文摘要

The research will characterize cell communication in the procaryote Myxococcus xanthus, a model for multicellular behavior during development. The focus will be molecules which promote cell-cell interactions and cell- cell signaling. Research in this model will shed light in biology on factors triggering cell differentiation, factors stimulating cell proliferation, and factors guiding cell migration and attachment. Basic research could provide factors promoting differentiation in red blood cells, development factors promoting wound healing, and oncogene products controlling tumor cell behavior. A genetic approach based on the transposon tagging of genes provides a new technique for discovering factors on the cell surface which communicate messages between cells. Genetic analysis using transposon tagging will pinpoint specific cell-surface factors controlling cell motility, called "contact gliding" factors. These factors appear to be regulatory in nature and guide morphogenetic movements during development. Mutations affecting the biosynthesis of contact gliding factors will be isolated and grouped into genes using genetic complementation and genetic mapping techniques. The genes will be cloned and sequenced in order to characterize the molecular nature of these factors. The stimulation of cell motility by these factors will create a bioassay for purifying these factors and characterizing their activity in intercellular signaling. Lipopolysaccharide (LPS) on the cell surface might be the target or receptor for contact gliding factors in regulating motility mechanism. Mutants defective in either LPS or contact gliding factors will be examined for abnormal motility and aberrant multicellular behavior. Mutant abnormalities in directed cell movement and cooperative cell movement during multicellular development will be analyzed using time-lapsed videomicroscopy and scanning electron microscopy. Monoclonal antibody to map potential change in lipopolysaccharide on the cell surface during morphogenetic movements. Chemical analysis of LPS will show the normal structure of LPS and show the sugars missing in particular mutants defective in LPS. This analysis will reveal the specific sugars in LPS required for molecular contacts between cells, or between cells and intercellular signals, important in guiding morphogenetic movements during development.