Advanced Mass Spectrometry Imaging of Metals and Biomolecules in Brain and Liver

脑和肝脏中金属和生物分子的先进质谱成像

• 批准号: 219007381
• 负责人: Dr. Johanna Sabine Becker
• 金额: --
• 依托单位: Zentralabteilung für Chemische Analysen (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Major Instrumentation Initiatives
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/219007381?language=en
• 关键词: Advanced; Mass; Spectrometry; Imaging; Metals

Metals and metalloproteins play a key-role in metabolism and formation of metal-containing deposits in brain and liver. In various diseases, analysis of metals and metalloproteins is essential for understanding the underlying cellular and systemic mechanisms. Mass spectrometry imaging (MSI) combined with other imaging modalities is a novel option to study the regional and cellular distribution of metals and related biomolecules. Thereby, imaging is a necessary step, particularly in the brain because of its inhomogeneous regional organization. Based on our experience in elemental imaging using LA-ICP-MSI with a spatial resolution between 200 to ∼10 μm, we propose: 1) to further develop LMD-ICP-MSI to imaging of metals at higher spatial resolution (10 to 0.3 μm; cellular level); 2) to develop a method combining elemental imaging by LA/LMD-ICP-MSI with molecular imaging by MALDI-MSI; 3) to apply these techniques to the normal and diseased brain and liver; 4) to study metals and metalloproteins distributions in normal and pathological human tissue as well as in knockout animal models of neurodegenerative and hepatic disorders and those lacking defined (metallo)proteins; 5) to transfer these methods to analyses of other brain disorders, e.g. epilepsy, and to other organs. In summary, we will develop the existing BrainMet platform to high mass resolution and high spatial resolution MSI techniques enabling the analysis of metals and metalloproteins from the single cell to the systemic level.

金属和金属蛋白在脑和肝中的代谢和含金属沉积物的形成中起关键作用。在各种疾病中，金属和金属蛋白的分析对于理解潜在的细胞和系统机制至关重要。质谱成像（MSI）结合其他成像方式是一种新的选择，研究区域和细胞分布的金属和相关的生物分子。因此，成像是一个必要的步骤，特别是在大脑中，因为它的不均匀的区域组织。根据我们使用空间分辨率为200至100 μm的LA-ICP-MSI进行元素成像的经验，我们建议：1）进一步开发LMD-ICP-MSI，以更高的空间分辨率进行金属成像（2）建立LA/LMD-ICP-MSI元素显像与MALDI-MSI分子显像相结合的方法; 3）将这些技术应用于正常和患病的脑和肝; 4）研究金属和金属蛋白在正常和病理人类组织中以及在神经变性和肝脏疾病的基因敲除动物模型和那些缺乏确定的（金属）蛋白的动物模型中的分布; 5）将这些方法转移到其他脑部疾病（如癫痫）和其他器官的分析。总之，我们将开发现有的BrainMet平台，以实现高质量分辨率和高空间分辨率MSI技术，从而能够从单细胞到系统水平分析金属和金属蛋白。