Spatial Cholesterol Metabolism: A Mass Spectrometer for Better Diagnosis and Understanding of Disease

空间胆固醇代谢：用于更好地诊断和了解疾病的质谱仪

• 批准号: MR/X012387/1
• 负责人: William Griffiths
• 金额: $ 101.86万
• 依托单位: Swansea University
• 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%2FX012387%2F1
• 关键词: Spatial; Cholesterol; Metabolism; Mass; Spectrometer

Disturbed cholesterol metabolism (including its synthesis and transport) is linked to many disease states including neurodegenerative, neurodevelopmental and metal health disorders, metabolic disease and microbial infections. In addition, many rare diseases show features of disturbed cholesterol metabolism. Research in many groups in the UK embraces cholesterol metabolism, but there are few laboratories which specifically focus on the analysis of the myriad of intermediates involved in pathways transforming cholesterol to bile acids and steroids. The Biomedical Mass Spectrometry Laboratory in Swansea University Medical School is one such laboratory and with new mass spectrometry (MS) equipment from the MRC Mid-Range Equipment Fund will provide a resource for researcher in the UK to access specialist MS equipment, expert knowledge in sample preparation, data analysis and its interpretation. MS represents the primary technology in the study of cholesterol metabolism (cholesterolomics) and when combined with liquid chromatography (LC) is suitable for the unbiased identification and quantification of the greatest number of metabolites in a complex mixture. Security of metabolite identification is provided by orthogonal data including retention time, accurate mass measurement, and fragmentation patterns, preferably, in the case of cholesterol metabolites, multistage fragmentation (MSn). A recent addition to MS-tool box is MS-imaging (MSI) adding further to the available bioimaging technologies. The current proposal is for a high-resolution MS instrument with MSn and UVPD capabilities which can be combined with existing interfaces for LC-MS, high spatial-resolution AP-MALDI-MSI and high sensitivity LESAplus-LC-MSI already in Swansea. The AP-MALDI source offers <10 micrometer spatial resolution while LESAplus-LC-MSI provides isomer separation and with pg/mg sensitivity. The instrument will be a resource for MRC-remit research in the UK. The new instrument will underpin scientific research in several key strategic priority areas for MRC which involve cholesterol metabolism, including (1) neuroscience and mental health; (2) infection and immunity; (3) molecular medicine; (4) clinical and translational research; and (5) global health.

胆固醇代谢紊乱（包括其合成和转运）与许多疾病状态有关，包括神经退行性疾病、神经发育和金属健康障碍、代谢疾病和微生物感染。此外，许多罕见疾病显示出胆固醇代谢紊乱的特征。在英国的许多研究小组包括胆固醇代谢，但很少有实验室专门专注于分析胆固醇转化为胆汁酸和类固醇的途径中涉及的无数中间体。斯旺西大学医学院的生物医学质谱实验室就是这样一个实验室，MRC中档设备基金的新质谱（MS）设备将为英国的研究人员提供资源，以获得专业的MS设备，样品制备，数据分析及其解释的专业知识。MS代表了胆固醇代谢（胆固醇组学）研究中的主要技术，当与液相色谱（LC）结合时，适用于对复杂混合物中最大数量的代谢物进行无偏鉴定和定量。代谢物鉴别的安全性由正交数据提供，包括保留时间、准确质量测量和裂解模式，对于胆固醇代谢物，优选多级裂解（MSn）。MS工具箱最近增加的是MS成像（MSI），进一步增加了可用的生物成像技术。目前的建议是一个高分辨率的MS仪器与MSn和UVPD的能力，可以结合现有的接口LC-MS，高空间分辨率AP-MALDI-MSI和高灵敏度LESAplus-LC-MSI已经在斯旺西。AP-MALDI源提供<10微米的空间分辨率，而LESAplus-LC-MSI提供异构体分离和pg/mg灵敏度。该工具将成为联合王国MRC-remit研究的资源。新仪器将支持MRC几个关键战略优先领域的科学研究，这些领域涉及胆固醇代谢，包括（1）神经科学和心理健康;（2）感染和免疫;（3）分子医学;（4）临床和转化研究;以及（5）全球健康。

项目成果

Role of Bile Acid Pathway Intermediates in Pathology of CTX

胆汁酸途径中间体在 CTX 病理学中的作用

• DOI: 10.5281/zenodo.10050200
• 发表时间: 2023
• 作者: Griffiths W