Systematic small molecule analysis using GC-MS

使用 GC-MS 进行系统性小分子分析

• 批准号: BB/E013155/1
• 负责人: Simon Turner
• 金额: $ 18.14万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE013155%2F1
• 关键词: Systematic; small; molecule; analysis; using

Every cell contains very large numbers of small molecules known as metabolites. These metabolites are the essential currency of the cell; they can be used to make larger molecules, generate energy and can be used as signalling compounds. There may be many hundreds, or even thousands, of metabolites within a single cell. Generally the composition of the metabolites reflects the status of the cells, for example if the cell is highly specialised it may make a large amount of one particular metabolite, or a range of other specific metabolites. Traditionally scientists have tended to examine small numbers of metabolites at a time, but we are now in a position to measure several hundred metabolites simultaneously. This information can be used as a fingerprint to give information about that cell, is it busy or resting for example. The information can also be used to see what happens if we alter the cell in some way, by, for example, adding a drug and seeing how the metabolites change. The metabolites in a cell are all interconnected by different pathways that are analogous to a map of the London underground in which the metabolites are represented by stations. By measuring all the metabolites simultaneously and seeing how they change over time we are better able to understand how individual metabolites (the stations) are interconnected. It also gives an excellent snapshot of the current status of the cell. This proposal is to buy equipment that will be used to measure a large number of metabolites simultaneously. This is a difficult process as many metabolites are structurally very similar even though they may have very different functions. The proposal is to use Gas Chromatography coupled with Mass Spectrometry. Essentially this separates molecules based upon their chemical properties and their size. It also gives information on how abundant different metabolites are. It is a specialised process that generates a very large amount of data. In order to handle such a large amount of data and to analyse a large number of samples much of the process is automated or handled by a computer. This same equipment can also be used to study any small molecules including pollutants, soil nutrients and complex volatile mixtures. We will use the equipment to address a range of problems in diverse areas of research including: 1. Study the relationship between metabolites in the single yeast cells and extrapolate from this relatively simple system to help understand how all cells work in complex multicellular organisms such as people or plants. 2. Stem cells offer the potential to cure many diseases that are currently untreatable, but in order to be able to generate enough of these cells much more needs to be known about how they behave and what regulates their unique properties. 3. Measuring metabolite changes in insulin-producing cells under different conditions will help us to understand the onset of diabetes and may help us to design better drugs to treat the condition. 4. Many new drugs are produced by growing cells in culture and in order to maximise production it is important to understand how producing these drugs affects the behaviour of the cultures. 5. Plant cell walls offer a huge resource that could potentially be harvested for use as a renewable source of energy and novel materials. To optimise production, more information is needed on how the compounds in the cell wall are made. 6. Nutrient availability and pollutants both limit plant productivity - by measuring these factors accurately it offers the potential to boost production. 7. The binding properties of olfactory receptors remain a mystery; we will be able to identify the natural ligands of single olfactory receptor neurons that express a single kind of olfactory receptor. This will have far-reaching implications for neurobiology and for the development of pest control strategies.

每个细胞都包含大量的小分子，称为代谢产物。这些代谢物是细胞的基本货币。它们可用于制造较大的分子，产生能量，并可以用作信号化合物。单个细胞中可能有数百甚至数千种代谢物。通常，代谢产物的组成反映了细胞的状态，例如，如果细胞高度专业化，则可能会产生大量的一种特定代谢物或一系列其他特定代谢物。传统上，科学家倾向于一次检查少量的代谢产物，但我们现在可以同时测量数百个代谢产物。例如，该信息可以用作提供有关该单元格的信息的指纹，例如忙还是休息。这些信息也可以用来查看如果我们以某种方式改变细胞，例如添加药物并查看代谢产物的变化会发生什么。细胞中的代谢产物都与不同的途径相互联系，这些途径类似于伦敦地下的地图，在该图中，代谢物由车站代表。通过同时测量所有代谢产物，并了解它们如何随着时间的流逝而变化，我们就能更好地了解单个代谢物（站点）如何相互联系。它还提供了细胞当前状态的出色快照。该建议是购买将同时测量大量代谢物的设备。这是一个困难的过程，因为许多代谢物在结构上非常相似，即使它们的功能可能非常不同。该建议是使用气相色谱和质谱法。从本质上讲，这将根据分子的化学特性和大小分离。它还提供了有关不同代谢物的丰富代谢物的信息。这是一个专门的过程，可以生成大量数据。为了处理如此大量的数据，并分析大量流程是由计算机自动化或处理的。该设备也可以用于研究任何小分子，包括污染物，土壤养分和复杂的挥发性混合物。我们将使用该设备来解决不同研究领域的一系列问题，包括：1。研究单酵母细胞中的代谢产物之间的关系，并从该相对简单的系统外推外，以帮助了解所有细胞在复杂的多细胞生物（例如人或植物）中如何工作。 2.干细胞提供了治愈许多目前无法治疗的疾病的潜力，但是为了能够生成足够多的这些细胞，需要更多地了解它们的行为以及如何调节其独特特性。 3。在不同条件下测量产生胰岛素细胞的代谢产物变化将有助于我们了解糖尿病的发作，并可能有助于我们设计更好的药物来治疗这种情况。 4。许多新药是由培养细胞增长而产生的，为了最大程度地生产，重要的是要了解产生这些药物如何影响培养物的行为。 5。植物细胞壁提供了一种巨大的资源，可以将其作为可再生能源和新颖材料的可再生能源。为了优化生产，需要更多有关如何制作细胞壁中化合物的信息。 6。养分的可用性和污染物都限制了植物生产力 - 通过准确测量这些因素，它提供了增强生产的潜力。 7。嗅觉受体的结合特性仍然是一个谜。我们将能够鉴定出表达单一嗅觉受体的单个嗅觉受体神经元的天然配体。这将对神经生物学和制定害虫控制策略具有深远的影响。