Redefining the rules - widespread bidirectional transcription from prokaryotic promoters

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All lifeforms embody the information encoded by their DNA. Like any set of instructions, the DNA code is divided into specific sections. Each section provides information about a given process and must be read before the information can be used. Inside cells, reading of the DNA is a carefully controlled. For instance, cells do not open their DNA "instruction manual" at random. Instead, cells identify the start of each section before reading of the DNA code commences. This is possible because the DNA code contains "signposts" to direct DNA reading events. These signposts were discovered in the 1960s and have always been assumed to direct reading of the DNA in one direction; it would seem illogical to read backwards. Our recent work has shown that the signposts are often symmetrical in nature. As such, when the cell recognises the signpost, the direction in which to read is ambiguous. Whilst counterintuitive, we have found that this occurs in many different lifeforms. In this proposal, we wish to understand the phenomenon and its impact. Our preliminary work suggests cells can turn this "bidirectional" reading of the DNA to their advantage. Our experimental aims are as follows: 1. Understand how symmetrical DNA signposts work.2. Understand the consequences of bidirectional reading of DNA in cells.3. Understand symmetrical DNA signposts in distantly related lifeforms.Given the high profile of DNA in science, society, and popular culture, our work has substantial potential for socio-economic impact. Of particular benefit to the UK economy is the potential to develop technologies that allow more precise control of DNA reading events. To this end, we will collaborate with Robin Dickinson, CEO Aruru Molecular LTD, a biotechnology company, to identify opportunities to exploit the results of our research commercially. The wider societal benefits of our work will be realised by engaging the next generation of scientists, and the public in general. Our socio-economic impact aims are as follows:1. Work with Aruru Molecular LTD to identify opportunities for commercialisation.2. Offer laboratory experience to young people interested in science to help them take the next step.3. Use the media to engage the wider public to raise awareness of our research and science in general.