Mass spectrometer LC-ESI-MS UHR QTOF

质谱仪 LC-ESI-MS UHR QTOF

• 批准号: 438807818
• 金额: --
• 依托单位: Universität Hamburg
• 依托单位国家: 德国
• 项目类别: Major Research Instrumentation
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/438807818?language=en
• 关键词: Mass; spectrometer; LC; ESI; MS

Understanding the cellular processes of living systems requires a deep molecular understanding of the underlying biomolecules. Proteins play a key role in this because they are involved in all processes of the cell. The malfunction of proteins plays a significant role in many diseases.The approximately 20,000 genes of humans form the basis for the cellular production of approximately 500,000-1,000,000 different proteins and proteoforms. Proteoforms are modifications of an individual protein, which is converted into its physiologically active form by mostly biochemical changes. This alteration due to the chemical (covalent) linkage with small or large modifications.Both the production and the analysis of physiologically important proteoforms represent a considerable scientific hurdle. For the identification of a proteoform, the high-precision determination of the molecular mass is the most accurate and reliable method. This applies in particular the unambiguous assignment to different modification states. Modern ultra-high-resolution mass spectrometers guarantee this accuracy and have therefore revolutionized the molecular and systemic life sciences in recent decades.In the proposed project, we want to use an ultrahigh-resolution mass spectrometer to accurately map and determine proteoforms. We are interested in proteins that are isolated and characterized from their cellular context, as well manufactured purified protein and their complexes. We are particularly interested in proteins that are relevant in different diseases (such as bacterial infections). It is crucial that different modification states can be analyzed by mass spectrometry using intact proteins of various sizes. Since the mass changes due to protein modification are usually small, but the proteins themselves are relatively large, this analysis requires the latest generation of high-resolution mass spectrometers.We expect the requested device to enable us to identify and characterize proteoforms. It thus forms the basis for the understanding of the functional coupling of different modification sites in the cell, allows the validation of isolated or produced proteoforms in vitro and enables the quantitative investigation of enzymatic or chemical modification reactions. This will pave the way for us to understand the molecular importance of different proteoforms in health and disease.

理解生命系统的细胞过程需要对潜在的生物分子有深刻的分子理解。蛋白质在其中起着关键作用，因为它们参与细胞的所有过程。蛋白质的功能障碍在许多疾病中起着重要作用。人类大约20,000个基因构成了大约500,000-1,000,000种不同蛋白质和蛋白质形式的细胞生产的基础。蛋白质形态是单个蛋白质的修饰，主要通过生化变化将其转化为其生理活性形式。这种变化是由化学（共价）连接或大或小的修饰引起的。生理上重要的蛋白质形态的生产和分析都是一个相当大的科学障碍。对于一种变形生物的鉴定，高精度的分子质量测定是最准确、最可靠的方法。这尤其适用于对不同修改状态的明确赋值。现代超高分辨率质谱仪保证了这种准确性，因此在近几十年来彻底改变了分子和系统生命科学。在这个项目中，我们希望使用超高分辨率质谱仪来精确地绘制和确定变形形式。我们感兴趣的是从细胞环境中分离和表征的蛋白质，以及制造的纯化蛋白质及其复合物。我们对与不同疾病（如细菌感染）相关的蛋白质特别感兴趣。至关重要的是，不同的修饰状态可以通过质谱分析使用不同大小的完整蛋白质。由于蛋白质修饰引起的质量变化通常很小，但蛋白质本身相对较大，因此这种分析需要最新一代的高分辨率质谱仪。我们期望所要求的设备使我们能够识别和表征变形形态。因此，它为理解细胞中不同修饰位点的功能偶联奠定了基础，允许在体外验证分离或产生的蛋白质形式，并使酶或化学修饰反应的定量研究成为可能。这将为我们理解不同蛋白质形态在健康和疾病中的分子重要性铺平道路。