Epigenetic control of nitrous oxide emission by denitrifying bacteria

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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.