Invited resubmission: the Drosophila circadian clock under simulated natural conditions

受邀重新提交：模拟自然条件下的果蝇生物钟

• 批准号: BB/J005169/1
• 负责人: Charalambos Kyriacou
• 金额: $ 47万
• 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: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ005169%2F1
• 关键词: Invited; resubmission; Drosophila; circadian; clock

Like humans, the fruitfly, Drosophila melanogaster, has an internal 24 hour clock that times its behaviour and physiology. The genetic basis for this clock is practically the same for both organisms, which also have dedicated neurons in the brain in which these clock genes are expressed. These neurons generate rhythmic signals that are transmitted to other regions of the brain and serve to generate rhythmic behaviour. These similarities between humans and flies means that the latter serve as a cheap and convenient model system for studying the molecular neurobiology of clocks. As clocks are important for human health and well-being (consider chronic shift workers, who have higher levels of health-related problems than the general population), clock research in flies has significant medical relevance. Much of what we know about the fly clock has been collected in artificial laboratory environments at constant warm temperatures, usually in 12 hours of light followed by 12 hours of darkness, or in constant light or constant dark. While it is necessary to simplify the complex natural environment, we also run the risk of misunderstanding how clocks might work in nature. We have spent more than three years studying fly locomotor rhythms in the wild, and our results suggest that some of our cherished concepts about the fly clock, might need some serious revision. However, we cannot expect our colleagues to go through the pain of studying fly behaviour in the wild, as it is very inconvenient, difficult, and unpredictable in terms of the elements, which have us at their mercy. Thus, we need to simulate natural conditions in the laboratory, and this is what our proposal is about. We have amassed an enormous amount of field data on fly behaviour, for different fly strains, clock mutants, as well as associated meteorological observations, but we need to realistically mimic any kind of day, hot, cold, bright, overcast, with moonlight, without, in any season. In order to do this, we have developed a simulated programmable light-source which can mimic the natural light cycle in almost any environmental situation, including moonlight, twilights, and the daily changes in the spectrum. This is placed in a programmable incubator that can similarly simulate any environmental temperature cycle. In preliminary studies we have shown that we can routinely replicate almost all of the unexpected findings we have recorded in the wild, so we know our simulations are realistic. We now have an unique opportunity to study a complex behaviour in a quasi-natural setting and we can now attempt to systematically dissect and manipulate the clock, behaviourally, genetically, and neurobiologically, using the sophisticated fly-specific tools we have at our disposal, and understand more completely how natural environmental signals tune up biological rhythms. Natural circadian entrainment has been a fundamental feature of the evolution of life and has guided the rhythmic behaviour and physiology of higher organisms. In recent centuries, natural entrainment in humans has been replaced by artificial entrainment, with ample evidence for maladaptive physiological and psychological responses. By assessing which behavioural, molecular and neurobiological features are disturbed by manipulating these external signals, our results will be of considerable interest to the scientific and lay community.

像人类一样，果蝇（Drosophila melanogaster）也有一个内部的24小时生物钟，可以控制其行为和生理。这种生物钟的遗传基础对于两种生物体来说几乎是相同的，它们在大脑中也有专门的神经元，这些生物钟基因在其中表达。这些神经元产生有节奏的信号，这些信号被传输到大脑的其他区域，并用于产生有节奏的行为。人类和苍蝇之间的这些相似之处意味着后者可以作为研究时钟分子神经生物学的廉价且方便的模型系统。由于时钟对人类健康和福祉很重要（考虑到长期轮班工人，他们比普通人群有更高水平的健康相关问题），苍蝇的时钟研究具有重要的医学意义。我们所知道的关于苍蝇时钟的大部分信息都是在恒定的温暖温度下的人工实验室环境中收集的，通常是在12小时光照后12小时黑暗中，或者在恒定的光照或恒定的黑暗中。虽然有必要简化复杂的自然环境，但我们也有可能误解时钟在自然界中的工作方式。我们花了三年多的时间在野外研究苍蝇的运动节奏，我们的结果表明，我们所珍视的一些关于苍蝇时钟的概念可能需要一些认真的修正。然而，我们不能期望我们的同事经历在野外研究苍蝇行为的痛苦，因为这是非常不方便的，困难的，并且在元素方面不可预测，这让我们受到他们的摆布。因此，我们需要在实验室中模拟自然条件，这就是我们的建议。我们已经积累了大量关于苍蝇行为的实地数据，对于不同的苍蝇品系，时钟突变体，以及相关的气象观测，但我们需要逼真地模拟任何一种天气，热，冷，明亮，阴天，有月光，没有，在任何季节。为了做到这一点，我们开发了一种模拟的可编程光源，它可以在几乎任何环境条件下模拟自然光周期，包括月光，黄昏和光谱的日常变化。将其置于可编程培养箱中，该培养箱可以类似地模拟任何环境温度循环。在初步研究中，我们已经证明，我们可以常规地复制我们在野外记录的几乎所有意外发现，因此我们知道我们的模拟是真实的。我们现在有一个独特的机会在准自然环境中研究复杂的行为，我们现在可以尝试系统地解剖和操纵生物钟，行为，遗传学和神经生物学，使用我们掌握的复杂的苍蝇专用工具，更全面地了解自然环境信号如何调节生物节律。自然的昼夜节律是生命进化的一个基本特征，并指导了高等生物的节律行为和生理。近几个世纪以来，人类的自然夹带已被人工夹带所取代，有充分的证据表明存在适应不良的生理和心理反应。通过评估哪些行为，分子和神经生物学特征受到操纵这些外部信号的干扰，我们的研究结果将引起科学界和非专业人士的极大兴趣。

项目成果

Glutathione peroxidase activity is neuroprotective in models of Huntington's disease.

• DOI: 10.1038/ng.2732
• 发表时间: 2013-10
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Mason, Robert P.;Casu, Massimiliano;Butler, Nicola;Breda, Carlo;Campesan, Susanna;Clapp, Jannine;Green, Edward W.;Dhulkhed, Devyani;Kyriacou, Charalambos P.;Giorgini, Flaviano
• 通讯作者: Giorgini, Flaviano

An electromagnetic field disrupts negative geotaxis in Drosophila via a CRY-dependent pathway.

电磁场通过哭泣的依赖性途径破坏了果蝇中的负岩石。

• DOI: 10.1038/ncomms5391
• 发表时间: 2014-07-14
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Fedele, Giorgio;Green, Edward W.;Rosato, Ezio;Kyriacou, Charalambos P.
• 通讯作者: Kyriacou, Charalambos P.

Genetic analysis of circadian responses to low frequency electromagnetic fields in Drosophila melanogaster.

• DOI: 10.1371/journal.pgen.1004804
• 发表时间: 2014-12
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Fedele G;Edwards MD;Bhutani S;Hares JM;Murbach M;Green EW;Dissel S;Hastings MH;Rosato E;Kyriacou CP
• 通讯作者: Kyriacou CP