Multiple light input signals to the gene network of the circadian clock

生物钟基因网络的多个光输入信号

• 批准号: BB/E015263/1
• 负责人: Andrew Millar
• 金额: $ 86.4万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE015263%2F1
• 关键词: Multiple; light; input; signals; gene

The growth of plants supports life on Earth and is vital to our economy and survival. Plant growth is important not just to farmers and foresters, and the consumers that they supply, but is also now understood to play a critical role in the global carbon cycle, and to affect the climate of our planet. Recent advances have identified the components and workings of the photosynthetic machinery in leaves and many of the genes that control the timing of plant activity, together with tools for monitoring gene activity in the laboratory. By combining these advances, we have shown that the synchronization of biological activity in plants (circadian rhythms) with external day-night cycles confers a growth and survival advantage. This result provides the first evidence of an advantage to daily plant growth arising from rhythmic behaviour; existing models of plant growth cannot account for this behaviour and are thus inadequate. Plant rhythms are synchronised to the day/night cycle, and the principles involved are very similar to the synchronisation of the human body clock that enables travellers to overcome jet lag, and that can be difficult for shift workers to achieve. Our goal now is to determine how this synchronisation works at the level of the clock genes, through a series of experiments and linked modelling studies. Previous studies in my lab and others have identified the relevant clock genes and the photoreceptor pathways involved. Both are complex. My lab has recently proposed the first mathematical models of the plant clock, which allow the many interacting parts to be simulated in a computer. The model led us to new experiments, identifying an additional part of the clock network. This was a first for plant science and is still a rare achievement in any organism, despite a wave of interest in the 'systems biology' approach that often aims to make this type of prediction. We have since developed an extended model that is even more realistic (so far as we know it's the best available anywhere) though it still simplifies or leaves out a lot of our current molecular knowledge. Fascinatingly, the new model very much resembles current models of the clocks in animal brains, despite the fact that those clocks involve connected neurones whereas our model occurs within a single plant cell. We now wish to understand how plants and animals both synchronise their clocks to the day/night cycle, despite the differences in the clock mechanisms. A major part of this proposal is based on our models, testing the effect of light on the clock genes much more carefully than before, and using these data to refine the models. We propose to use a new experimental method to get much finer data than before. This method has been proven to work but has not been extensively tested, nevertheless it is in an area of experiments that we know very well, it promises major benefits that will be useful for many other plant researchers and it will keep us ahead of our competitors. We also propose to extend the types of experiment that have proved reliable in the past. On the modelling side, we will also use new technology, part of it mathematical, part of it exploiting a very fast computer that is available to us through the Physics department in Edinburgh. If this work is successful, it will provide an example for other labs to follow, to understand other complex gene networks with multiple input signals / these are the types of network that control cancer, diabetes and other complex diseases.

植物的生长支撑着地球上的生命，对我们的经济和生存至关重要。植物的生长不仅对农民和林农以及他们供应的消费者很重要，而且现在也被认为在全球碳循环中发挥着关键作用，并影响着我们星球的气候。最近的进展已经确定了叶片光合作用机制的组成和工作原理，以及控制植物活动时间的许多基因，以及在实验室监测基因活动的工具。通过结合这些进展，我们已经表明，植物生物活性（昼夜节律）与外部昼夜周期的同步赋予了生长和生存优势。这一结果首次证明了节律性行为对植物的日常生长有利；现有的植物生长模型不能解释这种行为，因此是不充分的。植物节律与昼夜周期同步，其原理与人体生物钟同步非常相似，使旅行者能够克服时差反应，这对于轮班工人来说是很难实现的。我们现在的目标是通过一系列的实验和相关的模型研究，确定这种同步是如何在时钟基因水平上起作用的。我的实验室和其他人之前的研究已经确定了相关的时钟基因和所涉及的光感受器途径。两者都很复杂。我的实验室最近提出了植物时钟的第一个数学模型，它允许在计算机中模拟许多相互作用的部分。这个模型引导我们进行了新的实验，确定了时钟网络的一个额外部分。这是植物科学的第一次，并且在任何生物体中仍然是一项罕见的成就，尽管对“系统生物学”方法的兴趣浪潮通常旨在做出这种预测。我们已经开发了一个更现实的扩展模型（到目前为止，我们知道它是最好的），尽管它仍然简化或省略了我们目前的许多分子知识。令人着迷的是，新模型非常类似于动物大脑中的时钟模型，尽管这些时钟涉及连接的神经元，而我们的模型发生在单个植物细胞中。我们现在希望了解植物和动物是如何将它们的生物钟与昼夜周期同步的，尽管它们的生物钟机制存在差异。这个提议的主要部分是基于我们的模型，比以前更仔细地测试光对生物钟基因的影响，并使用这些数据来完善模型。我们建议使用一种新的实验方法来获得比以前更精细的数据。这种方法已被证明是有效的，但还没有经过广泛的试验，尽管如此，它是一个我们非常熟悉的实验领域，它承诺的主要好处将对许多其他植物研究人员有用，它将使我们领先于我们的竞争对手。我们还建议扩展过去已被证明可靠的实验类型。在建模方面，我们也将使用新技术，一部分是数学技术，一部分是利用爱丁堡物理系提供给我们的一台非常快的计算机。如果这项工作成功，它将为其他实验室提供一个效仿的例子，以了解其他具有多个输入信号的复杂基因网络/这些是控制癌症，糖尿病和其他复杂疾病的网络类型。

项目成果

Low-temperature-specific effects of PHYTOCHROME C on the circadian clock in Arabidopsis suggest that PHYC underlies natural variation in biological timing

PHYTOCHROME C 对拟南芥生物钟的低温特异性影响表明 PHYC 是生物计时自然变异的基础

• DOI: 10.1101/030577
• 发表时间: 2015
• 作者: Edwards K

Temporal repression of core circadian genes is mediated through EARLY FLOWERING 3 in Arabidopsis.

• DOI: 10.1016/j.cub.2010.12.013
• 发表时间: 2011-01-25
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Dixon, Laura E.;Knox, Kirsten;Kozma-Bognar, Laszlo;Southern, Megan M.;Pokhilko, Alexandra;Millar, Andrew J.
• 通讯作者: Millar, Andrew J.

Data assimilation constrains new connections and components in a complex, eukaryotic circadian clock model.

• DOI: 10.1038/msb.2010.69
• 发表时间: 2010-09-21
• 期刊: Molecular systems biology
• 影响因子: 9.9

Ubiquitin ligase switch in plant photomorphogenesis: A hypothesis.

• DOI: 10.1016/j.jtbi.2010.11.021
• 发表时间: 2011-02-07
• 期刊: JOURNAL OF THEORETICAL BIOLOGY
• 影响因子: 2
• 作者: Pokhilko, Alexandra;Ramos, Jason A.;Holtan, Hans;Maszle, Don R.;Khanna, Rajnish;Millar, Andrew J.
• 通讯作者: Millar, Andrew J.

The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops.

• DOI: 10.1038/msb.2012.6
• 发表时间: 2012-03-06
• 期刊: MOLECULAR SYSTEMS BIOLOGY
• 影响因子: 9.9
• 作者: Pokhilko, Alexandra;Fernandez, Aurora Pinas;Edwards, Kieron D.;Southern, Megan M.;Halliday, Karen J.;Millar, Andrew J.
• 通讯作者: Millar, Andrew J.