Epigenetic control of nitrous oxide emission by denitrifying bacteria

最早由沃森和克里克描述的DNA结构是科学的一个标志性方面，许多人都熟悉DNA‘双螺旋’，其中包含生命的遗传信息。然而，DNA是多态的，可以采用生物功能所需的许多不同的结构，这一点鲜为人知。DNA由四个不同的被称为碱基的“构件”组成，包括腺嘌呤、鸟嘌呤、胸腺嘧啶和胞嘧啶。它们连接在一起，形成细长的链，称为聚合物，这些聚合物相互缠绕，形成一个“扭曲的梯形”螺旋结构。具体地说，富含碱基鸟嘌呤和胞嘧啶的DNA序列可以形成类似于结的替代二级结构，称为G-四链体和I-基序。在我们的基因组中，这些类型的序列广泛存在，并可能发挥各种作用，从调节基因表达到定义我们染色体的稳定性和我们细胞的寿命。科学家过去在G-四联体和I-基序方面的大部分工作都是在动物身上进行的。由于DNA编码了所有生命形式的遗传指令，可选的DNA结构也可能在细菌等微生物中读取基因的方式中发挥关键作用。这是一个很重要的研究领域，但到目前为止，与动物研究相比，这一领域受到的关注较少。我们有结合这些特殊DNA结构的化学物质，并希望确切地了解它们是如何决定DNA结构的，以及这如何影响基因的开启或关闭。特别是，我们专注于如何使用这些化学工具来阻止细菌释放导致全球变暖和气候变化的强有力的温室气体一氧化二氮。一氧化二氮更为人所知的是笑气。大约是这样。与二氧化碳相比，分子的威力是二氧化碳的300倍，在大气中稳定多年。当细菌在环境中过量生长时，会释放一氧化二氮，这通常是由于在耕种的土壤中使用氮基化肥造成的。在环境中使用化肥是维持粮食供应和维持全球人口增长所必需的，因此我们需要了解如何抵消化肥的副作用，并帮助防止温室气体的排放。我们的土地和水是密不可分的，污水处理厂的微生物也会产生一氧化二氮，它们利用从人类排泄物和农业径流中提取的氮化合物来生长。这个项目的重点是了解G-四链和I-基序DNA是如何控制细菌中破坏一氧化二氮的基因的阅读方式，以及我们如何使用针对这些替代DNA结构的化学工具来阻止细菌在富含氮营养的环境中生长时释放出强烈的破坏气候的一氧化二氮气体。我们的工作将促进我们对细菌如何利用DNA结构来确定它们的基因是如何被阅读的理解。它还将允许化学家和微生物学家控制细菌内部的这一过程，使用可以进入细胞的化合物，而不需要对生物进行基因改造。我们产生的知识可能会改变人们管理土壤肥力和处理污水的方式，以帮助减少温室气体排放、全球变暖和气候变化，这是世界各国的重要优先事项。

The structure of DNA, first described by Watson and Crick, is an iconic aspect of science and many people are familiar with the DNA 'double helix' housing the genetic information for life. However, it is less commonly known that DNA is polymorphic and can adopt many different structures necessary for biological function.DNA is composed of four different 'building blocks' called bases that include adenine, guanine, thymine and cytosine. These are joined together to form elongated chains, called polymers, that intertwine to give a 'twisted ladder' helical structure. In particular, DNA sequences rich in the bases guanine and cytosine can form alternative secondary structures that may resemble 'knots', called G-quadruplexes and i-motifs. In our genomes, these types of sequence are widespread and may play various roles from regulating gene expression to defining the stability of our chromosomes and the life span of our cells. The majority of past work by scientists on G-quadruplexes and i-motifs has been performed in animals. Since DNA encodes the genetic instructions for all forms of life, alternative DNA structures may also play a key role in how genes are read in microorganisms such as bacteria. This is an area of research which is important, but has so far received less attention than studies in animals. We have chemicals that bind these special DNA structures and wish to understand exactly how they determine the structure of DNA and how this can affect whether genes are switched on or off. In particular, we focus on how we can use these chemical tools to stop bacteria releasing the potent greenhouse gas nitrous oxide that contributes to global warming and climate change. Nitrous oxide is better known as laughing gas. It is approx. 300-times more powerful molecule for molecule compared to carbon dioxide and is stable in the atmosphere for many years. Nitrous oxide is released when the bacteria grow in an excess of nutrients in the environment, typically caused by the use of nitrogen-based fertilisers in farmed soils. Use of fertilizers in the environment is required to maintain food supply and sustain our expanding populations world-wide, so we need to understand how we can counteract the side-effects of fertilizers and help prevent release of the greenhouse gas. Our land and water are inextricably linked, and nitrous oxide is also produced by microorganisms in sewage treatment works, where they use nitrogen compounds derived from human waste and agricultural run-off to grow.The focus of this project is to understand how G-quadruplex and i-motif DNA control how genes for nitrous oxide destruction in bacteria are read, and how we can use chemical tools that target these alternative DNA structures to stop bacteria releasing the potent climate-damaging gas nitrous oxide when they grow in environments rich in nitrogen nutrients. Our work will advance our understanding about how bacteria use DNA structures to determine how their genes are read. It will also allow chemists and microbiologists to control this process inside bacteria, using compounds that can enter cells, without the need to genetically modify organisms. The knowledge we generate could change how people manage soil fertility and treat sewage, to help reduce greenhouse gas emissions, global warming and climate change, which is an important priority for countries around the world.