How do vri and Pdp1 regulate cricadian rhythms?
vri 和 Pdp1 如何调节昼夜节律?
基本信息
- 批准号:6474101
- 负责人:
- 金额:$ 28.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-03-01 至 2007-02-28
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): One night of disturbed sleep is all it
takes for us to realize how essential sleep is. Our long-term objectives are to
understand the molecular signals that cause us to wake up and go to sleep. An
internal body clock regulates sleep/wake cycles and many other daily
(circadian) rhythms. We use the model system Drosophila, which has the best
molecular characterization of the molecular clock that governs circadian
rhythms.
We have found clock roles for two related transcription factors, vrille (vri)
and Pdp1 (Par domain protein 1). vri and Pdp1 expression oscillates in a
clock-dependent manner. Cycling expression of vri and Pdp1 is required for
circadian rhythmicity since flies that continuously express high levels of vri
and Pdp1 become arrhythmic. This is because vri and Pdp1 feed back to the clock
and regulate expression of the other clock genes, indicating vri and Pdp1 are
themselves clock genes that constitute a previously unidentified loop within
the central clock.
vri and Pdp1 may also connect the central clock to output pathways regulating
behavior. For vri, this may be partly by regulating levels of the Pigment
Dispersing Factor neuropeptide, which is required for rhythmicity. Other output
signals are also predicted. We will take molecular and genetic approaches to
understand the roles of vri and Pdp1 in the central clock, and a genomic
approach to ask how they may link the clock to behavior. Our specific aims are:
(1) To understand how vri and Pdp1 regulate the central oscillator. Which
central clock genes do VRT and PDP1 proteins regulate? Do VRI and PDPI proteins
form a functional complex or do they compete for binding to target gene
promoters? (2) To use a genomic approach to identify VRI and PDP1-regulated
genes. Are any of these genes expressed in pacemaker cells, and do they connect
cycling clock gene expression with rhythmic behavior? Which VRI target gene
explains how increased vri levels indirectly suppress PDF levels
post-transcriptionally.
Most of the Drosophila clock genes have related mammalian genes that function
similarly. Clock output signals we identify in Drosophila may, ultimately, be
useful in human therapy.
描述(申请者提供):一晚睡眠紊乱就够了。
让我们意识到睡眠是多么重要。我们的长期目标是
理解导致我们醒来和入睡的分子信号。一个
体内生物钟调节睡眠/醒来周期和许多其他日常活动
(昼夜节律)节律。我们使用的模型系统是果蝇,它有最好的
控制昼夜节律的分子钟的分子特征
节奏。
我们发现了两个相关转录因子vrille(Vri)的时钟作用。
Pdp1(PAR结构域蛋白1)。VRI和Pdp1的表达在
时钟依赖方式。需要VRI和Pdp1的循环表达式
自持续表达高水平VRI的苍蝇以来的昼夜节律
而Pdp1则会发生心律失常。这是因为VRI和Pdp1向时钟反馈
并调节其他时钟基因的表达,表明VRI和Pdp1是
它们自身对构成以前未知的循环的基因进行时钟控制
中央时钟。
VRI和Pdp1还可以将中央时钟连接到输出路径调节
行为。对于VRI,这可能部分是通过调节色素的水平来实现的。
分散因子神经肽,这是节律性所必需的。其他输出
信号也是可以预测的。我们将采用分子和遗传方法来
了解VRI和Pdp1在中央时钟中的作用,以及基因组
问他们如何将时钟与行为联系起来。我们的具体目标是:
(1)了解VRI和Pdp1是如何调节中枢振荡器的。哪一个
中枢时钟基因由VRT和PDP1蛋白调控吗?DO VRI和PDPI蛋白
它们形成功能复合体还是竞争与靶基因的结合
启动子?(2)使用基因组方法鉴定VRI和PDP1调节的
基因。这些基因中有没有在起搏细胞中表达,它们之间有联系吗?
自行车时钟基因表达与节律行为?VRI的哪个靶基因
解释增加的VRI水平如何间接抑制PDF水平
转录后。
大多数果蝇的时钟基因都有相关的哺乳动物基因发挥作用
同样的。我们在果蝇中识别的时钟输出信号最终可能是
在人类治疗中很有用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('JUSTIN BLAU', 18)}}的其他基金
GEF activity in circadian pacemaker neurons
昼夜节律起搏神经元中的 GEF 活性
- 批准号:
8320129 - 财政年份:2011
- 资助金额:
$ 28.22万 - 项目类别:
GEF activity in circadian pacemaker neurons
昼夜节律起搏神经元中的 GEF 活性
- 批准号:
8229061 - 财政年份:2011
- 资助金额:
$ 28.22万 - 项目类别:
How do vri and Pdp1 regulate cricadian rhythms?
vri 和 Pdp1 如何调节昼夜节律?
- 批准号:
6702228 - 财政年份:2002
- 资助金额:
$ 28.22万 - 项目类别:
How do vri and Pdp1 regulate cricadian rhythms?
vri 和 Pdp1 如何调节昼夜节律?
- 批准号:
6844875 - 财政年份:2002
- 资助金额:
$ 28.22万 - 项目类别:
How do vri and Pdp1 regulate cricadian rhythms?
vri 和 Pdp1 如何调节昼夜节律?
- 批准号:
6624357 - 财政年份:2002
- 资助金额:
$ 28.22万 - 项目类别: