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

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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.