Functional Genomics of Dictyostelium

描述（由申请人提供）：本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。该系统可用于提供一个重要的生物学问题的调控的完整画面：单个细胞整合成具有适当形式和功能的多细胞组织。几个特定的细胞系统和调控途径将在这些研究中强调，这可能阐明调控系统是所有真核生物的基础。这些信号通路在盘基骨菌中的功能将通过遗传学、生理学和基因组学的方法进行研究。随着这些途径的新蛋白质成分被发现，它们的功能将被确定，并通过检查突变表型、转录谱和其他生理指标来探索它们之间的关系。基因组中大多数基因的转录水平将在各种条件下测量所有研究的突变体和野生型细胞。基因表达的模式可以用两种方式来解释。首先，根据基因在需要的时间和地点表达的概念，功能将根据它们的转录调节来分配给基因。其次，所有基因的表达模式将被确定为所有突变菌株，研究人员将尝试根据这种转录表型分配突变基因的功能。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，这些系统可以使用强大的分子工具，比如盘基骨柱。这些描述可能会影响我们对人类疾病的理解和治疗能力。

DESCRIPTION (provided by applicant): 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.