Anti-inflammatory Drug Discovery Using DictyoSuitelium

As critical components of cell-mediated immunity, chemokine and chemokine receptors play pivotal roleukocyte migration and cell adhesion. A long term objective is to discover and develop small molecucan block the binding of chemokine to its receptor or the downstream signaling pathways, and therebyan essential step in the inflammation process. DictyoSuitelium is a simple eukaryote that exhibits wresponses remarkably similar to that in leukocytes. The genetics and cell biology of DictyoSuiteliumsystem for reconstituting chemokine receptor-mediated signal transduction component and for developiscreening assay. The primary goal of this Phase I proposal is to test the feasibility of coupling ina model chemokine receptor, to the signal transduction cascade in DictyoSuitelium. Specifically, theIL8R-B will be expressed on cell surface of DictyoSuitelium; the mammalian Gai will be co-expressedbinding activity to IL8R will be determined; and the functional linkage between IL8R and adenylyl cyDictyoSuitelium will be tested.