The availability of complete eukaryotic genome sequences promises to accelerate research into fundamental mechanisms of cell and developmental biology. Before one can fully exploit this information and study the biology of an organism from the context of its entire genome one must be able to: (1) identify the relevant information within the genome, (2) understand how the information is translated into function, and (3) integrate these data into a comprehensive biological picture. The investigators' are developing tools, both experimental and theoretical, that will facilitate these goals for the study of all organisms. They intend to test these tools by analyzing the soil amoebae Dictyostelium discoideum, and by comparing there findings to those found in the analyses of other genomes. The project will combine technology development and genetic resource acquisition with genome-based approaches to functional analysis. Recent published reports provide ample evidence that microarray data can be used effectively for genetic analysis (phenotyping, epistasis tests, etc.). The investigators' basic idea is that the transcriptional state of a cell can be used as a high-resolution phenotype with the necessary discriminating power to place all of the genes in Diclyostelium within a framework regulatory network, from which, the appropriate experiments to test molecular mechanisms can be planned. The investigators' will examine the expression of all genes during the growth and development of Diclyostelium within each of about 5,000 knockout mutants. This data, when combined with the fitness data from parallel phenotyping and other traditional phenotyping, will allow us to make testable predictions of gene function and to propose regulatory networks. The unique value of functional genomics lies in the power of large databases to provide a broad, and presumably less-biased, view of biological systems. This approach will open the exploration of development to a broader viewpoint. It will re-emphasize the entire organism as the fundamental biological unit and reveal relationships between signaling pathways and cell-types that could not be appreciated from the analyses of small groups of genes. The investigators' are interested in those aspects of Dictyostelium biology that are common to all eukaryotic organisms, and that will be informative for defining both the function of individual genes and the organization of regulatory hierarchies that operate in development. The relative simplicity and genetic tractability of organisms such as Dictyostelium will lead the way in the genomic analyses of multicellular development over the next five years.
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