Regulation of Growth to Differentiation Transitions

项目描述（由申请人提供）：该项目的长期目标是以盘状盘基骨为模型，确定真核生物细胞分化的细胞调控机制。这个系统可以用来提供一个重要的生物学问题的全貌：单个细胞整合成具有适当形式和功能的多细胞组织。在这个系统中，控制生长到发育转变的调控网络的几个组成部分已经被表征，包括假定的受体/蛋白激酶Gdt2和Gdt9以及ABC转运体TagA和AbcGl 1。这四种调节因子是调控网络中的关键环节，控制生长，决定启动发育和初始建立特定细胞类型。将测试具体的假设，以努力确定它们在机械水平上的功能。每一种蛋白质都是新的信号通路中的关键节点，研究它们可以阐明对所有真核生物至关重要的调节系统。这些信号通路的功能将通过遗传学、分子遗传学、细胞生物学和生理学方法进行研究。这些途径的新蛋白质成分将在几个基因筛选中被发现。这些新成分的功能将通过检查突变表型，其功能和其他生理特性的直接生化测量来探索。描述复杂的生物学途径是整合许多单独成分及其相互作用的信息的结果。这在相对简单的系统中是最容易做到的，比如盘基ostelium，可以使用强大的分子工具。该结果将提高我们对真核生物细胞获取和维持分化状态的理解。因此，这项工作应该会影响我们治疗由细胞生长控制缺陷引起的人类疾病的能力，比如癌症。

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.