Redefining rules for global gene control in bacteria

所有生命形式都是由它们的DNA编码的信息的表现。像任何一套指令一样，DNA代码被分成几个特定的部分。每一个都提供了有关给定进程的信息，并且必须在使用该信息之前阅读。在细胞内，DNA的读取是一个精心控制的过程。例如，细胞不会随意打开它们的DNA“操作手册”。取而代之的是，单元识别在给定时刻需要读取哪些指令。这反过来又取决于细胞面临的挑战。通常，为了处理复杂的情况，单元必须同时访问多条指令。这被称为“全球”反应。氧气、食物，甚至邻近细胞数量的变化，都会引发不同的全球反应。在我们的项目中，我们希望更好地了解不同的全球响应系统是如何重叠和相互作用的。在我们的初步工作中，我们已经在DNA序列中确定了一些线索，这些线索表明全球反应以一种意想不到的方式联系在一起，这种联系一直被隐藏到现在。我们将在三个不同的尺度上研究这一点：1.检查由DNA编码的完整指令集，以确定全球响应系统之间的联系。把重点放在具体的个别指令上，以准确地计算出不同的全球反应是如何相互作用的。3.确定全球反应之间的相互作用如何改变CEL的行为。我们的工作有可能使英国经济受益。在整个项目中，我们将与奥卡姆生物科学有限公司合作。他们的目标是开发可用于工业发酵的基于DNA的开关。简单地说，发酵罐内的条件必须仔细监测。然而，实现这一目标的工具并不完美。取而代之的是，Occam希望修改细胞，以报告发酵过程中它们自己的种群、氧气和食物水平。这可以通过全球响应系统来实现。例如，全球对氧气饥饿的反应可以用来使细胞发出荧光。这将通知发酵罐应该提高氧气水平。奥卡姆生物科学公司认为，这可以极大地提高商业发酵过程的效率。我们将贡献想法和专业知识。鉴于DNA在科学、社会和流行文化中的高度知名度，我们还将利用我们的工作来吸引下一代科学家和普通公众的参与。

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.