REGULATION OF HETEROCYST DIFFERENTIATION BY HETR/PATA

HETR/PATA 对异形囊分化的调控

• 批准号: 6385090
• 负责人: Sean M Callahan
• 金额: $ 3.73万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6385090
• 关键词: bacterial genetics; fusion gene; gene expression; gene mutation; microorganism growth; phosphorylation; photosynthetic bacteria

The work proposed uses heterocyst formation in Anabaena 7120 as a model system for the identification and characterization of the genes and, consequently, the molecular mechanisms that organisms use to determine cell fate. Elucidation of the controls of cellular differentiation is critical to understanding the loss of cellular growth control that causes a perturbation of the differentiated state of the cell, which can lead to a diseased condition such as neoplastic cell growth and cancer in humans. Filaments of Anabaena 7120 are easily cultured, have a short generation time, are genetically manipulable, and can be induced to form a predictable pattern of two distinct cell types. Recently, several genes have been isolated that can distort this pattern. Two genes in particular, hetR and patA appear to control the differentiation and patterning of heterocysts along a filament of vegetative cells. Extra copies of hetR cause innappropriate excessive differentiation of vegetative cells to heterocysts, whereas lack of hetR prevents heterocyst formation. The molecular functions of HetR and PatA are unknown, as is control of their production. Two novel genetic selections will be used to separately isolate genes whose products act upstream and downstream of HetR/PatA, and biochemical methods will be used to elucidate the functions and the relationship between HetR and PatA. By dissecting the hetR/patA regulatory cascade, we hope to elucidate a control circuit that will be instructive for questions of cellular differentiation in both bacteria and multicellular organisms and the diseases that can result from a disturbance in the control of cell fate determination.

拟议的工作使用Anabaena 7120中的杂环形成作为模型系统，用于鉴定和表征基因的特征，因此，生物体用来确定细胞命运的分子机制。 阐明细胞分化的控制对于理解导致细胞分化状态的细胞生长控制的丧失至关重要，这可能导致患病的疾病，例如人类的肿瘤细胞生长和癌症。 Anabaena 7120的细丝很容易培养，有很短的生成时间，在遗传上可以操纵，并且可以诱导形成两种不同细胞类型的可预测模式。最近，已经孤立了几种可能扭曲这种模式的基因。 特别是两个基因，Hetr和Pata似乎控制着沿植物细胞细胞的杂环的分化和模式。 额外的HETR副本会导致营养细胞与杂环的无限分化，而缺乏HETR会阻止杂环形成。 HETR和PATA的分子功能是未知的，对其产量的控制也是如此。 两种新型遗传选择将用于分离其在Hetr/PATA上游作用的产物作用的基因，并将使用生化方法来阐明Hetr和Pata之间的功能和关系。 通过解剖HETR/PATA调节级联，我们希望阐明一个控制电路，该控制电路对细菌和多细胞生物的细胞分化问题以及可能导致细胞命运确定的扰动引起的疾病具有启发性。