High resolution mass spectrometry across the metabolome and lipidome: from single cells to cohorts

代谢组和脂质组的高分辨率质谱分析：从单细胞到群体

• 批准号: MR/X012700/1
• 负责人: Julian Griffin
• 金额: $ 63.3万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX012700%2F1
• 关键词: resolution; mass; spectrometry; across; metabolome

Mass spectrometry has revolutionised our understanding of life. It allows scientists to 'weigh' molecules - strictly speaking we measure the mass to charge ratio of a molecule that has lost or captured an electron called an ion. We can do that so accurately that its possible to determine molecular formulas and thus identify molecules according to their mass to charge ratio. Further advances allow us to smash ions into fragments further helping us to determine their structure. One recent advance is mass spectrometry imaging which creates ions directly from tissue and cell samples, and allows scientists to map the distribution of molecules across a tissue. This technology has become so powerful we can now perform this mapping towards a single-cell level. This equipment grant application is for the purchase of a state-of-the-art mass spectrometry imaging system that can be applied to a wide range of biological and medical applications to understand how diseases arise at the cellular level and spread across tissues. We will be able to detect ions directly from the tissues, allowing us to map how local changes in concentration of molecules influence how a disease progresses. Our applications include studies of fatty liver disease and how this develops to more severe outcomes and how our fat cells try to protect the body when we eat too much. Both projects are important if we are to address the issue of rising obesity levels across the UK and provide treatments for some of the consequences of obesity. We also have projects looking at heart failure and the consequences of age-onset frailty, again major issues facing the National Health Service and society in general. The technology will also investigate how the microbes that live in our gut help to maintain health but may also contribute to disease under certain circumstances. Modifying the front of the system to allow a different way to introduce ions which in turn allows us to image across larger areas, the technology will also be used to understand how changes to the placenta contribute to pre-term and still birth. In addition, the same equipment can be used to perform high throughput mass spectrometry to study large populations. This will be used to examine ageing and its interactions with chronic disease. We will also examine a large cohort of long COVID-19 patients to understand how metabolism contributes to the disease. There is no such technology at the University of Aberdeen to allow these applications to take place. In addition, the equipment will support a variety of researchers across the UK and in particular across Scotland given the lack of similar systems in this region. The equipment will be housed within dedicated laboratory space at The Rowett Institute, University of Aberdeen and maintained by a highly skilled core technical staff. Researchers external to the University will be able to make use of the world class facilities within the Rowett as part of a research hotel arrangement to widen the access to the equipment. In this manner we hope to have a unique research resource for the medical and biological community of the North of the UK.

质谱分析彻底改变了我们对生命的理解。它使科学家能够“称量”分子-严格地说，我们测量的是失去或捕获了一个电子（称为离子）的分子的质荷比。我们可以如此精确地做到这一点，以至于有可能确定分子式，从而根据分子的质荷比来识别分子。进一步的进展使我们能够将离子粉碎成碎片，进一步帮助我们确定它们的结构。最近的一个进展是质谱成像，它直接从组织和细胞样本中产生离子，并允许科学家绘制分子在组织中的分布。这项技术已经变得如此强大，我们现在可以在单细胞水平上执行这种映射。该设备补助金申请用于购买最先进的质谱成像系统，该系统可应用于广泛的生物和医学应用，以了解疾病如何在细胞水平上产生并在组织中传播。我们将能够直接从组织中检测到离子，使我们能够绘制分子浓度的局部变化如何影响疾病的进展。我们的应用包括脂肪肝疾病的研究，以及这种疾病如何发展到更严重的结果，以及当我们吃得太多时，我们的脂肪细胞如何保护身体。如果我们要解决英国肥胖水平上升的问题，并为肥胖的一些后果提供治疗，这两个项目都很重要。我们也有研究心力衰竭和老年性虚弱后果的项目，这也是国家卫生服务和整个社会面临的主要问题。该技术还将研究生活在我们肠道中的微生物如何帮助维持健康，但在某些情况下也可能导致疾病。修改系统的前部，以允许不同的方式引入离子，从而使我们能够在更大的区域成像，该技术还将用于了解胎盘的变化如何导致早产和死产。此外，相同的设备可用于进行高通量质谱分析，以研究大量人群。这将用于研究衰老及其与慢性疾病的相互作用。我们还将研究一个大型COVID-19长期患者队列，以了解代谢如何导致疾病。阿伯丁大学没有这样的技术来允许这些应用发生。此外，该设备将支持英国各地的各种研究人员，特别是在苏格兰，因为该地区缺乏类似的系统。这些设备将被安置在阿伯丁大学Rowett研究所的专用实验室空间内，并由高度熟练的核心技术人员进行维护。大学外部的研究人员将能够利用Rowett内的世界级设施，作为研究酒店安排的一部分，以扩大对设备的访问。通过这种方式，我们希望为英国北部的医学和生物界提供独特的研究资源。

项目成果

Multi-omics and imaging mass cytometry characterization of human kidneys to identify pathways and phenotypes associated with impaired kidney function.

• DOI: 10.1016/j.kint.2024.01.041
• 发表时间: 2024-02
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: E. Asowata;Simone Romoli;Rebecca Sargeant;Jennifer Y. Tan;Scott Hoffmann;Margaret M. Huang;Krishnaa T. Mahbubani;Fynn N. Krause;Daniel Jachimowicz;Rasmus Ågren;Albert Koulman;Benjamin Jenkins;Barbara Musial;Julian L. Griffin;Magnus Soderberg;Stephanie Ling;Pernille B. L. Hansen;K. Saeb‐Parsy;Kevin J. Woollard

Conjugating uncoupler compounds with hydrophobic hydrocarbon chains to achieve adipose tissue selective drug accumulation.

将解偶联剂化合物与疏水性烃链缀合以实现脂肪组织选择性药物积累。

• DOI: 10.1038/s41598-024-54466-2
• 发表时间: 2024
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ng MY

Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects.

• DOI: 10.1016/j.xcrm.2023.101157
• 发表时间: 2023-09-19
• 期刊: CELL REPORTS MEDICINE
• 影响因子: 14.3
• 作者: Han, Kim;Singh, Komudi;Meadows, Allison M.;Sharma, Rahul;Hassanzadeh, Shahin;Wu, Jing;Goss-Holmes, Haley;Huffstutler, Rebecca D.;Teague, Heather L.;Mehta, Nehal N.;Griffin, Julian L.;Tian, Rong;Traba, Javier;Sack, Michael N.
• 通讯作者: Sack, Michael N.