Improving MALDI-MSI spatial resolution and protein identification für a better characterisation of tumour cells and their environment

MALDI-MSI可以通过单次无标记测量确定复杂组织中未知化合物的空间分布，同时保持组织内细胞的完整性。该提案的中心目标是提高该技术的性能，通过跨学科方法实现改进和新的应用可能性。这四位申请人在化学（有机化学，质谱）和医学（蛋白质组学，肿瘤学）方面贡献了互补的能力，并且在FSU Jena的跨学院耶拿软物质中心（JCSM）中紧密联系，并嵌入到耶拿其他相关研究项目的几个现有合作中。因此，临床和理论研究将以紧密结合的方式进行。新的基质和沉积程序将以组合方法开发并测试。这些新发现是MALDI-MSI实现更高空间分辨率的先决条件，可检测化合物的范围扩大。所获得的结果将直接转移到临床和应用项目，其中重点将是肿瘤组织的空间蛋白质组学表征和生物标志物鉴定，特别是治疗反应的个体预测模式，耐药肿瘤细胞及其肿瘤微环境。为此目的，还将探索新的方法，蛋白质鉴定的结合在线纳米HPLC和电子转移解离（ETD）的显微组织区域。这些方法的结果将定义癌细胞发生和发展过程中的分子事件，确定适当的生物标志物，并促进癌症的个性化治疗。

MALDI-MSI can determine the spatial distribution of unknown compounds in complex tissues with a single label-free measurement while maintaining the cellular integrity within the tissue. The central target of this proposal is to enhance the performance of this technique, allowing improved and new application possibilities by an interdisciplinary approach. The four applicants contribute complementary competences in chemistry (Organic Chemistry, Mass Spectrometry) and medicine (Proteomics, Oncology) on a profound level and are closely connected in the inter-facultative Jena Center for Soft Matter (JCSM) at the FSU Jena and embedded in several existing collaborations to other related research programs in Jena. Thereby clinical and theoretical research will be performed in a closely integrated manner. New matrices and deposition procedures will be developed in a combinatorial approach and tested. The new findings are a prerequisite for a higher spatial resolution achievable in MALDI-MSI with an expanded range of detectable compounds. The obtained results will be directly transferred to clinical and applied projects, where the focus will be on the spatial proteomic characterisation of tumour tissue and biomarker identification, in particular of individual predictive patterns of therapy response, therapy resistant tumour cells and their tumour microenvironment. For this purpose also new ways for protein identification will be explored by a combination of on-line nano-HPLC and electron transfer dissociation (ETD) of microdissected tissue areas. The results of these approaches will define molecular incidents during genesis and progression of cancer cells, identify appropriate biomarkers, and promote a more individualised therapy for cancer.