Investigating metabolite-RNase communication.

在活细胞内，为了提供细胞维持生命所需的能量，会发生一系列的化学反应。这一系列的反应统称为细胞的新陈代谢。了解细胞内的新陈代谢是如何控制的是非常重要的，并且直接适用于医学、环境和生物技术的进步。目前，人们对代谢控制的某些方面已经有所了解，但我们最近发现了一种全新的至关重要的控制机制。我们已经知道，细胞内的信使分子（RNA）在控制代谢中起作用，反过来，细胞内的破坏者分子（RNA降解者）控制RNA分子的数量。我们的研究已经确定了一种参与代谢的化学物质，被称为代谢物，与RNA降解物相互作用并影响其破坏RNA的能力。因此，我们的工作表明，细胞内存在一个完整的反馈系统，代谢物改变RNA降解物破坏RNA的能力，进而影响细胞代谢，进而影响代谢物，代谢物随后与RNA降解物相互作用，如此循环下去。这项工作的目的是详细研究新发现的代谢和rna降解物之间的相互作用。具体来说，我们的目标是回答一些关键问题。当这种机制发生时，细胞内信使分子的数量发生了什么变化？是否有些信使分子比其他信使分子更早被靶向？通过监测信使分子的数量，可以看到当RNA降解物与其他RNA降解物形成更大的复杂结构时，这种机制是否会发生变化？如果我们特别改变rna降解体上的代谢识别位点，信使分子的数量会发生什么变化，这能告诉我们什么机制？从简单的细菌到复杂的动物细胞，所有类型的细胞都存在这种代谢和rna降解物之间的通讯机制吗？为了回答这些问题，我们的研究将使用经过验证的实用和计算生物学研究技术的综合最先进的工具集。了解新陈代谢和rna降解物之间交流的这些额外细节，使我们能够采取下一步行动，实现我们最近发现的全部影响。从长远来看，这些知识可以让科学家人为地控制活细胞内的新陈代谢。例如，简单的细菌细胞在许多工业应用中发挥着重要作用，这种人工代谢控制可以优化它们的使用。这可能会通过降低能源成本、增加产量和减少原料需求来潜在地提高效率，所有这些都具有经济和环境价值。例子包括制药工业（如更有效的药物生产），食品工业（如改善食品生产），特别是与环境问题有关的开发（如帮助生物燃料生产和生物修复项目）。以类似的方式，在动物细胞内的代谢的人工控制有可能提供深远的治疗效益。

Within living cells a whole series of chemical reactions occur in order to provide the energy the cell needs to sustain life. This series of reactions is collectively known as a cell's metabolism. Understanding how metabolism is controlled within a cell is fundamentally important and is directly applicable to medical, environmental and biotechnological advances. At the present time, some aspects of how metabolism is controlled are understood, but we have recently discovered a whole new control mechanism of key importance.It is already known that messenger molecules (RNA) within a cell play a role in controlling metabolism and that in turn, destroyer molecules (RNA degraders) in the cell keep the number of RNA molecules in check. Our studies have identified that one of the chemicals involved in metabolism, known as a metabolite, interacts with an RNA degrader and affects its ability to destroy RNA. Our work therefore indicates that a full feedback system exists within a cell, with metabolites altering the ability of RNA degraders to destroy RNA, which in turn affects cellular metabolism, which impacts metabolites, which then interact with RNA degraders and so the loop continues.The aim of the proposed work is to investigate the newly identified interactions between metabolism and RNA-degraders in detail. Specifically, our objectives are to answer a number of key questions. What changes occur to the population of messenger molecules within the cell when this mechanism takes place and are some messenger molecules targeted earlier than others? By monitoring the population of messenger molecules can it be seen whether the mechanism changes once the RNA-degraders form larger complex structures with other RNA degraders? If we specifically change the metabolite-recognition site on the RNA-degrader, what happens to the population of messenger molecules and what can this tell us about the mechanism? Is this mechanism of communication between metabolism and RNA-degraders found in all types of cells from simple bacteria to complex animal cells? To answer these questions our research will use a comprehensive state-of-the-art toolset of proven practical and computational biological research techniques. Understanding these additional details about the communication between metabolism and RNA-degraders allows us to take the next step towards realising the full impact of our recent discovery. In the longer term, such knowledge could allow scientists to artificially control metabolism within living cells. For example, simple bacterial cells play an important role in many industrial applications and this artificial metabolic control could optimise their use. This may potentially increase efficiency by reducing energy costs, increasing yields and reducing starting material requirements, all of economic and environmental value. Examples include exploitation within the pharmaceutical industry (e.g. more efficient drug production), the food industry (e.g. improvements in food production) and particularly in relation to environmental concerns (e.g. aiding biofuel production and bioremediation projects). In a similar manner, the artificial control of metabolism within animal cells has the potential to offer far reaching therapeutic benefits.