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

这是BBSRC ALERT 2022中程设备呼叫的应用程序。在这里，我们寻求获得Waters Select系列循环离子迁移率Q-TOF质谱系统的支持。通俗地说，我们需要买一台新的质谱仪（MS），它不仅能根据代谢物的精确质量，而且能根据它们的形状分离和测量代谢物。生物有机体的所有部分都制造、改变和使用一组被称为代谢物的小分子。它们共同构成了所谓的“代谢组”。代谢物在细胞中做很多事情，也会在不同的条件下发生变化，比如生长，发育，传染病等。当我们捣碎一些组织（这被称为均质化）样本时，如果人们知道它们是什么，在哪里，他们可以单独（一次一个）寻找它们。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，它有很多新颖的功能，可以让我们做非靶向代谢组学，看看样本中有什么，有多少。这是一种非常重要的能力。所以这个仪器将帮助我们做靶向和非靶向代谢组学。新机器还将帮助我们使用我们已经称为DART（实时直接分析）的关键设备。这台机器需要连接到电脑上，而现在的那台机器很快就不能工作了。重要的是，我们的DART机器是苏格兰唯一的，也是学术实验室唯一的。它在生物（在什么地方和有多少）、临床（人类和兽医医学-治疗和疾病）和法医（历史或犯罪样本）调查方面的分子水平快速筛选方面具有广泛的应用。这可以是均质或完整的样品。例如,我们使用这个乐器识别组织贡献的饮食成分(即它是什么做的?),能够区分人工养殖和野生狮子骨骼、血液,现在用它来看看,看看我们可以如何从这些样本告诉如果一个动物是容易受到疾病和类似鸡蛋样本,看看我们可以告诉如果一个男性或女性。所以我们需要一台新的MS机器来连接它。新的机器更灵敏，所以我们的DART仍然是苏格兰唯一的，但它会更快地工作，并能告诉我们更多。当我们分离DART时，新机器还可以让我们做其他事情。例如，新机器还可以让我们看到这些代谢物在哪里使用完整的组织。这被称为空间组学，结合了地点和数量的信息。比如拍分子照片。这就很有趣了比如在皮肤感染的情况下。我们可以取一个组织样本（比如一块皮肤），看看代谢物在皮肤上或皮肤里的确切位置。这可以告诉我们在分子水平上发生了什么，我们也许能够弄清楚是什么控制着我们感兴趣的生物学的这些方面，比如病毒在传播时做了什么，我们能否利用这些信息找到阻止它的方法。这三件事对我们至关重要：2.能够进行非靶向和靶向代谢组学研究；保持DART并使其更灵敏；能够做代谢成像。新设备将使我们能够在自己的研究中做到这一点，并帮助其他有相同兴趣和问题的研究人员跨越BBSRC生物研究优先级的范围。我们可以捐款291,207英镑，并向BBSRC索取565,055.75英镑。

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.