Redefining rules for global gene control in bacteria

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All lifeforms are a manifestation of information encoded by their DNA. Like any set of instructions, the DNA code is divided into specific sections. Each provides information about a given process and must be read before the information can be used. Inside cells, reading of DNA is a carefully controlled process. For instance, cells do not open their DNA "instruction manual" at random. Instead, cells identify which instructions need to be read at a given moment in time. This in turn depends on the challenges facing the cell. Often, to deal with complex situations, the cell must access multiple instructions simultaneously. This is referred to as a "global" response. Changes in amounts of oxygen, food, and even numbers of neighbouring cells, provoke different global responses. In our project, we want to better understand how the different global response systems overlap and interact with each other. In our preliminary work, we have identified clues in the DNA sequence that suggest global responses are linked, in an unexpected way, that has been hidden until now. We will study this at three different scales:1. EXAMINE THE COMPLETE SET OF INSTRUCTIONS encoded by DNA to identify links between the global response systems.2. FOCUS ON INDIVIDUAL INSTRUCTIONS in fine detail to work out precisely how the different global responses interact. 3. Determine how interactions between global responses alter BEHAVIOUR OF THE CELL.Our work has potential to benefit the UK economy. Throughout the project, we will engage with Occam Biosciences Ltd. Their goal, is to develop DNA based switches that can be used during industrial fermentation. In simple terms, conditions inside fermenters have to be carefully monitored. However, instrumentation for doing this is imperfect. Instead, Occam hope to modify cells to report their own population, oxygen and food levels during fermentation. This could be done using global response systems. For instance, the global response to oxygen starvation could be used to make cells fluoresce. This would inform the fermenter that oxygen levels should be increased. Occam Biosciences believe this could dramatically improve efficiency of commercial fermentation procedures. We will contribute ideas and expertise. Given the high profile of DNA in science, society, and popular culture, we will also use our work to engage the next generation of scientists, and the public in general.