High-Resolution Ion Mobility enabled LC-MS for metabolomics applications

高分辨率离子淌度 LC-MS 适用于代谢组学应用

• 批准号: BB/X019608/1
• 负责人: Thomas Wishart
• 金额: $ 72万
• 依托单位: University of Edinburgh
• 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%2FX019608%2F1
• 关键词: Resolution; Ion; Mobility; enabled; LC

This is an application to the BBSRC ALERT 2022 Mid Range Equipment call. Here we seek support for the acquisition of a Waters Select Series Cyclic Ion Mobility Q-TOF mass spectrometry system. In lay terms we need to buy a new mass spectrometer (MS) which has the ability to separate and measure metabolites not only by their accurate mass, but also of their shape.All parts of biological organisms make, change and use a group of small molecules called metabolites. Together they make up something called the "metabolome". Metabolites do lots of things in cells and also change in response various conditions such as growth, development, infectious disease etc. When we mash up some tissue (this is called homogenising) samples, people can look for them individually (one at a time) if they know what they are and where they are. Looking for them in this way is called "targeted" metabolomics. However, we can also study them with all at once by doing something called "untargeted" metabolomics. At the University of Edinburgh (UoE) we do not have instruments for doing untargeted metabolomics experiments. This new machine we propose to buy, which has a lot of novel features would let us do untargeted metabolomics to see what is in a sample and how much of it is there. This is an incredibly important ability to have. So this instrument will help us to do both targeted and untargeted metabolomics.The new machine will also help us to use a critical piece of equipment which we already have called a DART (Direct Analysis in Real Time). This machine which is dependent on being attached to an MS. The one it's on now won't work for much longer. Importantly, our DART machine is the only one in Scotland and the only one in an academic laboratory. It has broad applications for quick screening at the molecular level in biological (what is where and how much of it is there), clinical (human and veterinary medical - therapies and diseases) and forensic (historic or criminal sample) investigations. This can be in homogenised or intact samples. For example, we have used this instrument to identify contribution of diet to tissue composition (i.e. what is it made of?) and are able to distinguish captive bred from wild lion bones, and are now using it to look at blood to see if we can work out how to tell from these samples if an animal is vulnerable to a disease and things like samples from eggs to see if we can tell if its going to be a male or female. So we need a new MS machine to attach this to. The newer machines are more sensitive, so our DART will still be the only one in Scotland, but it will work faster and be able to tell us more.The new machine will also let us do other things when we detach the DART. For example, the new machine will also let us look at where these metabolites are using intact tissues. This is known as spatial omics combining information on where and how much. Like taking a molecular photograph. This would be interesting for example in the case of something a skin infection. We can take a tissue sample (for example like a piece of skin) and see exactly whereabouts on or in the skin the metabolites are. And that can tell us what is happening in there at the molecular level, and we may be able to work out what controls those aspects of the biology we are interested in like what is the virus doing as it spreads and can we use that information to work out how to stop it.These three things are critical for us: 1. being able to do both untargeted and targeted metabolomics studies, 2. Keeping DART and making it more sensitive, 3. being able to do metabolite imaging. The new piece of equipment will let us do this for our own research and to help other researchers with the same type of interests and questions spanning the range of BBSRC biological research priorities. We can contribute £291,207 and ask for £565,055.75 from the BBSRC.

这是对BBSRC ALERT 2022中程设备呼叫的应用。在此，我们寻求对沃茨Select Series Cyclic Ion Mobility Q-TOF质谱系统的支持。通俗地说，我们需要购买一台新的质谱仪（MS），它不仅能够通过代谢物的精确质量，而且能够通过代谢物的形状来分离和测量代谢物。生物有机体的所有部分都制造，改变和使用一组称为代谢物的小分子。它们共同组成了所谓的“代谢组”。代谢物在细胞中做很多事情，也会响应各种条件，如生长，发育，感染性疾病等，当我们捣碎一些组织（这称为均质化）样本时，人们可以单独寻找它们（一次一个），如果他们知道它们是什么，它们在哪里。以这种方式寻找它们被称为“靶向”代谢组学。然而，我们也可以通过一种叫做“非靶向”代谢组学的方法来同时研究它们。在爱丁堡大学（UoE），我们没有进行非靶向代谢组学实验的仪器。我们打算购买的这台新机器有很多新功能，可以让我们做非靶向代谢组学，看看样本中有什么，有多少。这是一个非常重要的能力。因此，这台仪器将帮助我们进行靶向和非靶向代谢组学研究。这台新机器还将帮助我们使用一种关键设备，我们已经称之为DART（真实的实时直接分析）。这台机器依赖于连接到一个MS。它现在的一个不会工作太久。重要的是，我们的DART机器是苏格兰唯一的一台，也是学术实验室中唯一的一台。它广泛应用于生物学（什么在哪里，有多少），临床（人类和兽医医学治疗和疾病）和法医（历史或刑事样本）调查中分子水平的快速筛选。这可以在均质化或完整样品中进行。例如，我们已经使用该仪器来确定饮食对组织组成的贡献（即，它是由什么组成的？）能够区分圈养和野生狮子的骨头，现在用它来观察血液，看看我们是否能从这些样本中分辨出一只动物是否容易感染疾病，以及从卵中的样本，看看我们是否能分辨出它是雄性还是雌性。所以我们需要一台新的MS机器来连接这个。新的机器更敏感，所以我们的DART仍然是苏格兰唯一的一台，但它会工作得更快，能够告诉我们更多。新机器还可以让我们在分离DART时做其他事情。例如，新机器还将让我们看看这些代谢物在哪里使用完整的组织。这被称为空间组学，结合了有关地点和数量的信息。就像拍分子照片一样。例如，在皮肤感染的情况下，这会很有趣。我们可以采取组织样本（例如像一块皮肤），并确切地看到代谢物在皮肤上或皮肤中的位置。这可以告诉我们在分子水平上发生了什么，我们也许能够找出是什么控制着我们感兴趣的生物学的那些方面，比如病毒在传播时做了什么，我们能否利用这些信息来研究如何阻止它。这三件事对我们来说至关重要：1。能够进行非靶向和靶向代谢组学研究，2.保持DART并使其更敏感，3。能够进行代谢物成像。新设备将使我们能够为自己的研究做这件事，并帮助其他研究人员在BBSRC生物研究优先事项的范围内具有相同类型的兴趣和问题。我们可以贡献291，207英镑，并要求BBSRC提供565，055.75英镑。