Z3 (new in 2nd funding period): Qualitative and quantitative proteomics for a comprehensive picture of protein dynamics in leukemia
The Z3 project will provide means to various groups within CRC 1074 to identify and quantify proteins in samples with varying complexity. In the context of the CRC, understanding protein phosphorylation as the central modification, subject to changes during cellular signalling, plays a crucial role. Recently, sev-eral other posttranslational modifications (PTM), such as glycosylation, acetylation, ubiquitination, and SUMOylation, have been shown to exert important functions in leukemic cells. Z3 will provide and devel-op methods to comprehensively identify and quantify these modifications and thus allow to generate a complete picture of cellular events during leukemogenesis and leukemia persistence.
Most proteins undergo multiple PTMs during their lifetime, resulting in differentially modified entities, referred to as proteoforms. Gaining knowledge of the specific nature of these proteoforms and the quantitative patterns of their dynamic changes is essential in understanding cellular signalling events. Z3 will engage in the development of methods to allow proteoform characterizations within the various pro-jects of the CRC.
In a prototypic case of this type of analysis, tailored proteomic methods will be established to qualita-tively and quantitatively analyse the B-cell receptor (BCR) signalosome under malignant and normal con-ditions. Emphasis will be given, but not restricted to the analysis of the BCR-complex-associated pro-teins CD79a and CD79b. The combination of bottom-up and top-down proteomics will allow to create a complete picture of the PTM dynamics of CD79 itself and of other B-cell signalosome components in normal and leukemic B cells.
For a current list of project-related publications, please go to this page