权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Peripheral clocks in Drosophila

果蝇的外围时钟

基本信息

批准号：
BB/P010121/1
负责人：
Charalambos Kyriacou
金额：
$ 48.16万
依托单位：
University of Leicester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FP010121%2F1
关键词：
Peripheral clocks Drosophila

项目摘要

For several decades, biorhythm researchers in the two main animal model system, the fruitfly and the mouse have believed that behavioural rhythms are determined exclusively by central brain clock neurons. These neurons act as pacemakers and can generate the 24 hour locomotor cycles that are so important for allowing the animal to interact with its environment at the optimum time of day. In the fly, the pacemaker cells are called the sLNvs and in the mouse, the SCN. In the fly, the peripheral nervous system and non-neural organs have independent clocks, whereas in the mammal, the SCN synchronises the rhythms in the periphery via a number of signalling factors. Recently we have observed that clocks in the antennae or the eyes, which lie outside the central brain of the fruitfly, can nevertheless generate behavioural rhythms even though the central clock neurons are made genetically arrhythmic. This means there are pacemaker cells in these two peripheral tissues that can mediate rhythmic behaviour, so it is not all about the sLNvs. However, the clock cells in the antennae need the central brain network to be intact, even though it is clockless, in order for these behavioural rhythms to be expressed. These results will come as something of a shock to fly clock researchers as it overturns current dogma.We shall carefully examine the antennae and identify the clock cells that act as behavioural pacemakers. We know that these cells are involved in temperature, wind and gravity sensing as well as hearing, but is it particular subsets of these or is it all of them ? The antennae as also full of smell receptors, so we shall ask whether these too can act as pacemaker cells. We shall manipulate these cells genetically in a number of ways, for example by stopping their clocks, hyperexciting these cells, or speeding them up or slowing them down to see what happens to the rhythmic behaviour. We will also examine how 'normal' these rhythms are, do they respond to light and temperature in the usual ways that clocks do, or are they abnormal? We shall also find out how the antennal pacemaker cells might connect to the central brain circuit that is required for rhythms to be expressed. We will extend our studies to the eye in a similar way and finally we shall ask whether non-neural tissue, the fly's liver called the fat body, can also drive behavioural rhythms. While this might seem unlikely, given the surprising results that we have already obtained, we take nothing for granted.

几十年来，果蝇和小鼠这两种主要动物模型系统的生物节律研究人员一直认为，行为节律完全是由中央大脑时钟神经元决定的。这些神经元充当起搏器，可以产生24小时的运动周期，这对于让动物在一天中的最佳时间与环境互动非常重要。在果蝇中，起搏细胞被称为sLNvs，在小鼠中，称为SCN。在果蝇中，外周神经系统和非神经器官具有独立的时钟，而在哺乳动物中，SCN通过许多信号因素同步外周的节律。最近，我们观察到，位于果蝇中枢大脑之外的触角或眼睛中的时钟仍然可以产生行为节奏，尽管中枢时钟神经元在遗传上是不稳定的。这意味着在这两个外周组织中存在起搏细胞，可以介导节律行为，因此这并不完全是关于sLNvs的。然而，为了表达这些行为节奏，触角中的时钟细胞需要中枢脑网络保持完整，即使它是无时钟的。这些研究结果将推翻目前的教条，让研究飞行生物钟的科学家们感到震惊。我们将仔细检查触角，并确定充当行为起搏器的生物钟细胞。我们知道这些细胞与温度、风和重力感知以及听觉有关，但它是这些细胞的特定子集还是所有细胞？触角也充满了嗅觉感受器，所以我们要问，这些感受器是否也可以作为起搏细胞。我们将以多种方式从基因上操纵这些细胞，例如通过停止它们的生物钟，使这些细胞过度兴奋，或者使它们加速或减速，以观察节奏行为发生了什么变化。我们还将研究这些节律有多“正常”，它们是像时钟一样对光线和温度做出反应，还是不正常？我们还将发现触角起搏细胞如何连接到表达节律所需的中枢脑回路。我们将以类似的方式将我们的研究扩展到眼睛，最后我们将询问非神经组织，即称为脂肪体的苍蝇肝脏，是否也可以驱动行为节奏。虽然这似乎不太可能，但鉴于我们已经获得的令人惊讶的结果，我们认为没有什么是理所当然的。