Post Genomics or Proteomics An Analysis of Manifold Systems and Functional Monitoring of Drugs

Genomics, transcriptomics, proteomics, metabolomics, glyconomics and topo-nomics are keywords that describe strategies for the investigation of the complex interacting regulatory networks in biological cells, tissues, and organs. The next generation of screening devices should be able to detect and analyze the dynamic network of proteins and signal transduction pathways within cells and tissues. The biohybrid technology at the interface of molecular cell biology, tissue engineering, sensor system, microsystem technology, nanobiotechnology, and nanoelectronics is able to provide HCS devices for the detection and monitoring of proteins in, for example, single cells, tissue models or stem cells with the same genetic programme but a varying toponome (arrangement of proteins within cells) and proteome, which in turn can define the cellular differentiation and maturation state. Ultra-sensitive high-content analytical screening of the proteome pattern on the level of single cells or tissues can be realized by a new generation of large-scale protein profiling-based modules. The Whole Cell Protein Fingerprinting system (WCPF; MelTec GmbH, Magdeburg, Germany) enables scientists to analyze and to decode the composition of the proteome on a single cell level. Along the lines of molecular mass scanning, proteins could be detected in specific subcellular areas. Each cell area corresponds to a protein fingerprint, which is finally represented in a data warehouse. Single cell analysis or proteome fingerprinting describing parameters of pathological versus normal cells could be a benefit for identifying novel targets for drugs or physiological active compounds. An automated multifunctional biohybrid screening system allows the functional real-time monitoring of the proteome and toponome, resulting in a characteristic cellular reading frame. These systems should realize the measurement, selection and comparison of proteome patterns in multidimensional data areas, predicting molecular targets, and experimental assessment. Using such biohybrid modules (cell-based biosensors or so-called "living chips"), targets and drug leads which influence, for example, the invasive process of immune cells and/or tumor cells can be identified. A coupling ofthese modules with other HTS and HCS systems as cell and tissue workbenches for drug discovery and identification should be possible. On the other hand, these novel screening systems represent an efficient platform for the validation of targets of genomics and proteomics studies. The importance of this biohybrid cell-based technology depends on the ability to identify targets that are specific for diseases and drug leads, and to connect various modified modules with a target factory.

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