Regulation of Growth to Differentiation Transitions

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DESCRIPTION (provided by applicant): The long-term objectives of this 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 a significant biological problem: the integration of individual cells into a multicellular tissue with the proper form and function. Several components of the regulatory network that govern the growth to development transition in this system have been characterized, including the putative receptor/protein kinases Gdt2 and Gdt9 and the ABC transporters TagA and AbcGl 1. These four regulators are critical links in the regulatory network that controls growth, the decision to initiate development and initial establishment of specific cell types. Specific hypotheses will be tested in an effort to determine their functions at a mechanistic level. Each of the proteins are critical nodes within new signaling pathways and studying them may illuminate regulatory systems that are fundamental to all eukaryotes. The function of these signaling pathways will be studied by genetic, molecular genetic, cell biological and physiological methods. New protein components of these pathways will be uncovered in several genetic screens. The function of these new components will be explored by examining mutant phenotypes, direct biochemical measurements of their function and other physiological properties. 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 such as Dictyostelium that afford the use of powerful molecular tools. The results will improve our understanding of the cellular acquisition and maintenance of the differentiated state in eukaryotes. Thus, this work should impact our ability to treat human diseases caused by defects in cellular growth control, such as cancer.