Toponomics and neurotoponomics: a new way to medical systems biology

Abstract

The fluorescence robot imaging technology multi-epitope-ligand-cartography/toponome imaging system has revolutionized the field of proteomics/functional genomics, because it enables the investigator to locate and decipher functional protein networks, the toponome, consisting of hundreds of different proteins in a single cell or tissue section. The technology has been proven to solve key problems in biology and therapy research. It has uncovered a new cellular transdifferentiation mechanism of vascular cells giving rise to myogenic cells in situ and in vivo; a finding that has led to efficient cell therapy models of muscle disorders, and discovered a new target protein in sporadic amyotrophic lateral sclerosis by hierarchical protein network analysis, a finding that has been confirmed by a mouse knockout model. A lead target protein in tumor cells that controls cell polarization as a mechanism that is fundamental for migration and metastasis formation has also been uncovered, and new functional territories in the CNS defined by high-dimensional synaptic protein clusters have been unveiled. The technology can be effectively interlocked with genomics and proteomics to optimize time-to-market and the overall attrition rate of new drugs. This review outlines major proofs of principle with an emphasis on neurotoponomics.

Keywords::

• CNS
• hippocampus
• medical systems biology
• MELC
• spinal cord
• synapses
• synaptic toponome
• TIS
• toponome

Financial & competing interests disclosure

Toponome research was supported by DFGSchu 627/10-1, DFG Innovationskolleg INK15, the Land Saxony-Anhalt and the BMBF through projects ‘Biochance’ and ‘CELLECT’, NGFN2 and NBL3. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.