CELL SIGNALING IN C. ELEGANS LARVAL DEVELOPMENT
线虫幼虫发育中的细胞信号传导
基本信息
- 批准号:6520190
- 负责人:
- 金额:$ 22.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-03-01 至 2005-02-28
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (adapted from investigator's abstract): TGF Beta pathways play
important roles in human development and disease; mutations in TGF Beta
pathways cause uncontrolled cell growth and metastasis in cancers, and diseases
such as hereditary hemorrhagic telangiectasis type 2. A TGF Beta pathway in C.
elegans functions in a neuroendocrine event that controls the development of a
specialized larval form called dauer, in addition to controlling other
behaviors and phenotypes. These genes are: daf7 (a TGF Beta ligand), daf1 and
daf4 (receptor kinases), and daf8 and daf14 (Smad transcription factors). The
daf3 gene, also a Smad, mutates to a dauer defective phenotype, and genetic
analysis suggests that this gene is negatively regulated by the other five
genes.
Their aims are: 1) To study the function of the gene daf5. The dauer defective
phenotype and epistasis relationships of daf5 suggests that it, like daf3, may
be negatively regulated by the TGF Beta pathway. They will determine the
expression pattern of daf5 to identify cells in which it functions, and they
will test whether the expression or subcellular localization of daf5 is
regulated by other genes that control dauer. 2) To characterize new suppressors
of the dauer constitutive phenotype of daf7. They have 85 suppressors in hand;
analysis of a subset of these suppressors has revealed four new loci that
control dauer formation. They will determine which of the other suppressors are
also alleles of new genes, and test all of the new loci for function in the
events controlled by the TGF Beta pathway. They will determine if the new loci
control the expression or subcellular localization of daf3 and daf5. These
analyses will suggest models for the molecular mechanism by which these new
genes function. They will then select two loci for cloning, which will allow
them to study the function of these genes in dauer formation and the TGF Beta
pathway. 3) To identify cells in which the daf1 receptor kinase is expressed,
and test these cells for function by laser ablation. They will also use tissue
specific and cell type specific promoters to express daf4, daf8, daf14 and daf3
to test hypotheses for where these genes function. They will study the
biochemical relationships of the receptors and Smads in a tissue culture system
to test hypotheses for regulatory relationships. The achievement of these aims
will allow them to elucidate the function of a TGF Beta pathway in controlling
neuroendocrine mediated events in C. elegans development, and will result in
the identification new genes that participate in this pathway. The involvement
of TGFBeta and neuroendocrine signaling in important developmental processes
and diseases suggests important implications for human health.
描述(改编自研究者摘要):TGF β途径发挥作用
在人类发育和疾病中的重要作用; TGF β的突变
途径导致癌症和疾病中不受控制的细胞生长和转移,
如遗传性出血性毛细血管扩张2型。C.
线虫在神经内分泌活动中起作用,控制着一种
专门的幼虫形式称为dauer,除了控制其他
行为和表型。这些基因是:daf 7(TGF β配体)、daf 1和
daf 4(受体激酶)和daf 8和daf 14(Smad转录因子)。的
daf 3基因也是一种Smad基因,突变为dauer缺陷型,
分析表明,该基因受到其他五个基因的负调控,
基因.
目的:1)研究daf 5基因的功能。Dauer缺陷
daf 5的表型和上位性关系表明,它与daf 3一样,
受TGF β通路负调控。他们将决定
daf 5的表达模式,以确定其发挥功能的细胞,
将测试daf 5的表达或亚细胞定位是否是
由其他控制dauer的基因调控。2)为了表征新的抑制剂
DAF 7的Dauer组成型表型。他们手上有85个抑制器;
对这些抑制子的一个子集的分析揭示了四个新的基因座,
控制dauer形成。他们将决定哪些其他抑制剂是
以及新基因的等位基因,并测试所有新基因座在
由TGF β通路控制的事件。他们将确定新的基因座
控制daf 3和daf 5的表达或亚细胞定位。这些
分析将提出这些新的分子机制的模型,
基因功能然后,他们将选择两个基因座进行克隆,
他们研究这些基因在dauer形成和TGF β的功能,
通路3)为了鉴定表达daf 1受体激酶的细胞,
并通过激光消融测试这些细胞的功能。他们还将使用纸巾
表达DAF 4、DAF 8、DAF 14和DAF 3的特异性和细胞类型特异性启动子
来验证这些基因在哪里发挥作用的假设。他们将研究
组织培养系统中受体和Smads的生化关系
来检验监管关系的假设。这些目标的实现
将使他们能够阐明TGF β途径在控制中的功能
神经内分泌介导的事件。elegans的发展,并将导致
识别参与这一途径的新基因。参与
TGF β和神经内分泌信号在重要发育过程中的作用
和疾病对人类健康有重要意义。
项目成果
期刊论文数量(0)
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{{ truncateString('GARTH I PATTERSON', 18)}}的其他基金
CELL SIGNALING IN C. ELEGANS LARVAL DEVELOPMENT
线虫幼虫发育中的细胞信号传导
- 批准号:
6363344 - 财政年份:2000
- 资助金额:
$ 22.75万 - 项目类别:
CELL SIGNALING IN C. ELEGANS LARVAL DEVELOPMENT
线虫幼虫发育中的细胞信号传导
- 批准号:
6086003 - 财政年份:2000
- 资助金额:
$ 22.75万 - 项目类别:
CELL SIGNALING IN C. ELEGANS LARVAL DEVELOPMENT
线虫幼虫发育中的细胞信号传导
- 批准号:
6636409 - 财政年份:2000
- 资助金额:
$ 22.75万 - 项目类别:
CELL SIGNALING IN C. ELEGANS LARVAL DEVELOPMENT
线虫幼虫发育中的细胞信号传导
- 批准号:
6708879 - 财政年份:2000
- 资助金额:
$ 22.75万 - 项目类别:
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