Redefining rules for global gene control in bacteria

重新定义细菌全球基因控制规则

• 批准号: BB/Y000536/1
• 负责人: David Grainger
• 金额: $ 63.47万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY000536%2F1
• 关键词: Redefining; rules; global; gene; control

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.

所有的生命形式都是由它们的DNA编码的信息的一种表现。就像任何一组指令一样，DNA代码被分成特定的部分。每一个都提供了关于给定进程的信息，在使用这些信息之前必须阅读。在细胞内，DNA的阅读是一个精心控制的过程。例如，细胞不会随意打开它们的DNA“指令手册”。相反，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个指令。这被称为“全球”对策。氧气量、食物量甚至邻近细胞数量的变化都会引起不同的全球反应。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如何相互重叠和相互作用。在我们的初步工作中，我们已经确定了DNA序列中的线索，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个问题：1。检查由DNA编码的完整指令集，以识别全球响应系统之间的联系。2.专注于个别指示的细节，以精确地计算出不同的全球反应如何相互作用。3.确定全球反应之间的相互作用如何改变细胞的行为。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Occam Biosciences Ltd.合作，他们的目标是开发可用于工业发酵的基于DNA的开关。简而言之，发酵罐内的条件必须仔细监测。然而，这样做的仪器是不完美的。相反，Occam希望修改细胞，以报告它们在发酵过程中的种群、氧气和食物水平。这可以通过全球反应系统来实现。例如，对缺氧的整体反应可以用来使细胞发出荧光。这将通知发酵罐，氧气水平应该增加。奥卡姆生物科学公司认为，这可以大大提高商业发酵程序的效率。我们将提供意见和专业知识。鉴于DNA在科学、社会和流行文化中的重要性，我们还将利用我们的工作吸引下一代科学家和公众的参与。