High throughput LC-MS/MS mass spectrometry system

LMU基因中心功能基因组分析实验室（LAFUGA）的蛋白质组学部门参与了大量第三方资助的转化医学研究项目。其中一个重点是人类疾病（包括糖尿病和杜氏肌营养不良症）的转基因大型动物模型（猪）器官的蛋白质组学表征。在以前的研究中，我们清楚地证明了这些动物模型对人类系统的相关性，以及蛋白质组谱对疾病模式的分子表征和新的诊断和治疗概念的发展的重要性。近年来出现了更多的重要问题。例如，已经建立了用于人类疾病（例如糖尿病、克隆造血、杜氏/贝克肌营养不良、囊性纤维化和Laron综合征）的进一步创新的大型动物模型。此外，已生成用于异种移植的转基因猪器官的蛋白质组谱。在这里，我们也能够证明蛋白质组谱对于研究专门引入的遗传修饰（旨在防止排斥反应）影响这些器官的蛋白质组的程度是重要的。这对于异种移植的临床转化也将是重要的。由于能力原因，目前必须在质谱仪上进行分析，该质谱仪使用时间约为10年，是2014年购买的二手质谱仪，在灵敏度和扫描速率方面不再符合当前要求。为了保持国际竞争力，迫切需要获得最先进的质谱仪。所要求的质谱仪的主要用途仍然是对来自人类疾病的大型动物模型（猪）的各种组织进行系统的蛋白质组表型分析，其中已经建立了广泛的组织库。重点在于糖尿病，肌肉疾病，如杜氏和贝克尔营养不良，和心血管疾病。这些调查在ICON-LMU研究大楼的背景下也具有重要意义，该大楼现已基本完成。

The proteomics department of the Laboratory for Functional Genome Analysis (LAFUGA) at the Gene Center of the LMU is involved in a large number of third-party funded research projects in translational medicine. One focus is the proteomic characterization of organs from transgenic large animal models (pigs) for human diseases (including diabetes mellitus and Duchenne muscular dystrophy). In previous studies, we clearly demonstrated the relevance of these animal models for the human system and the importance of proteome profiles for the molecular characterization of disease patterns and the development of new diagnostic and therapeutic concepts. Further important questions have arisen in recent years. For example, further innovative large animal models for human diseases (e.g. for diabetes, clonal haematopoiesis, Duchenne/Becker muscular dystrophy, cystic fibrosis and Laron syndrome) have been established. In addition, proteome profiles of transgenic pig organs for xenotransplantation have been generated. Here, too, we were able to show that proteome profiles are important to investigate the extent to which the specifically introduced genetic modifications, which are intended to prevent rejection reactions, affect the proteomes of these organs. This will also be important for the clinical translation of xenotransplantation. Due to capacity reasons, analyses must currently be carried out on a mass spectrometer that is approximately 10 years old and was purchased second-hand in 2014 and does no longer meet current requirements in terms of sensitivity and scan rates. To maintain international competitiveness, the aquisition of a state-of-the-art mass spectrometer is urgently required. The primary use of the requested mass spectrometer remains the systematic proteomic phenotyping of various tissues from large animal models (pigs) for human diseases, of which extensive tissue banks have already been established. The focus lies on diabetes, muscle diseases such as Duchenne and Becker dystrophy, and cardiovascular diseases. These investigations are also of great relevance in the context of the ICON-LMU research building, which has now been largely completed.