The long-term objectives of this program project are to define the cellular regulatory mechanisms that govern cell differentiation in eukaryotes using Dictyostelium discoideum as a model. This system can be used to provide a complete picture of the regulation of a significant biological problem: the integration of individual cells into a multicellular tissue with the proper form and function. Several specific cellular systems and regulatory pathways will be highlighted in these studies which may illuminate regulatory systems that are fundamental to all eukaryotes. The function of these signaling pathways in Dictyostelium will be studied by genetic, physiological, and genomic methods. As new protein components of these pathways are uncovered, their functions will be determined, and the relationships among them explored, by examining mutant phenotypes, transcriptional profiles, and other physiological measures. Transcription levels of most genes in the genome will be measured for all mutants studied and for wild-type cells under various conditions. The pattern of gene expression will be interpreted in two ways. First, function will be assigned to genes based on their transcriptional regulation, according to the notion that a gene is expressed when and where it is needed. Second, the pattern of expression of all the genes will be determined for all the mutant strains, and the investigators will attempt to assign function to the mutated genes based on this transcriptional phenotype. Describing complex biological pathways is the result of integrating information on many individual components and on their interactions. This is most easily done in relatively simple systems that afford the use of powerful molecular tools, such as Dictyostelium. These descriptions will likely impact our understanding of, and ability to treat, human disease. ? ? ?
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