Neuroblastoma Toponome Maps and Lead Protein Characterization

Coordinator:    Prof Dr. W. Schubert, Dr. A. Oberthür, Prof. Dr. F. Berthold
Institution: Molecular Pattern Recognition Research Group, Universität. Magdeburg
The Subproject 9 relies on a new Technology, termed MELC/TIS. This technology enables investigators for the first time to localize in a single cell or tissue section coherent protein networks that are responsible for the myriads of normal cellular functions and dysfunctions in disease (Figures, Literature, international honours, see attached). The technology is based on cyclical fluorescence imaging procedures on the same biological sample, thereby breaking the limitations of traditional fluorescence microscopy. This procedure leads to an exponential increase of biological information: higher order assemblies of proteins (protein clusters) interlocked as networks are readily recognized as a mosaic and can be quantified by exact mathematical methods uncovering the hierarchical rules governing as what we term the toponome (the complete protein network code of cells and tissues). As we have already shown earlier, toponome data contain and unravel relevant information on so called lead proteins that control abnormal molecular networks in disease (proof of concept). The aim (long term) of the present work is to decipher the disease specific protein network code of neuroblastoma cells. In cooperation of two clinical groups in Cologne/Essen and one technology based group in Magdeburg, we expect that we will be able to find both new predictive protein networks for the different disease courses and lead proteins as highly relevant targets for drug developments.


Links: Mehr als 7.000 verschiedene Protein Cluster innerhalb einer einzelnen Zelle.
Schubert W, Bonnekoh B, Pommer AJ, Philipsen L, Boeckelmann R, Malykh Y, Gollnick H, Friedenberger M, Bode M., Dress AW. Analyzing proteome topology and function by automated multidimensional fluorescence microscopy.
Nature Biotechnology 2006; 24(10): 1270 – 1278 (mit Titelbild, siehe oben).

Mitte: Abbott A. Mapping Togetherness. Nature 443, 609, 2006 (Proteomics Research Highlight zu Ref 1)

Rechts: Ein umfassendes Proteinnetzwerk der Zelloberfläche einer einzelnen Zelle.
Friedenberger M, Bode M, Krusche A, Schubert W. Fluorescence detection of protein clusters in individual cells and tissue sections by using toponome imaging system (TIS): sample preparation and measuring procedures.
Nature Protocols 2007;2(9):2285-94 (mit Titelbild, siehe oben).

Abbildung 2
Oben: Supermolekül in der Zelloberflächenmembran (aggressives Neuoblastom, Gewebeschnitt).

Unten: Supermolekül in der Zelloberflächenmembran (regressives Neuoblastom, Gewebeschnitt). Diese Supermoleküle kommen in quasi allen Neuroblastomzellen als Leitmotif vor. Sie sind charakteristisch für Neuoblastomzellen im Gewebeverband, also direkt im kranken Gewebe der Patienten. Die einzelnen Farben bezeichnen verschiedene Eiweißmoleküle, die gemeinsam, einem „Plan“ folgend, den räumlichen Bau der jeweils krankheitsspezifischen Funktion festlegen.

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