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Systematic Molecular and Cellular Functional Gene Analysis

Coordinator: PD Dr. Stefan Wiemann

Summary:

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The SMP-Cell will perform functional analysis of genes and proteins at the molecular and cellular levels. Based on the pioneering concepts and work of the German cDNA Consortium, the SMP-Cell will generate and systematically exploit ORF resources of disease-relevant human genes.

The building blocks of the SMP-Cell are technology development and application in the fields of

1.) the generation of cDNA resources.
2.) their exploitation in cell-assays.
3.) the bioinformatic analysis, integration and mining of the information.

We will continue to develop and establish automation technologies, resources and cell-based assays which are selected based on their clinical relevance. Experimental data and information is integrated with bioinformatics and we thus attach functional knowledge to anonymous ESTs, novel genes and the encoded proteins. In the past years we have established a leading position in this highly competitive field of international research, which we will work to keep and extend.

Employing standardised procedures and tight quality control, the SMP-Cell generates ORF resources from cloned material, and increasingly from modelled gene structures. The expression constructs are analysed in mammalian cells, to determine the subcellular localisation of the encoded proteins, and to unravel the effects of over- and under-expression in large-scale cell based assays. Currently assays are operational that address cell proliferation, apoptosis, MAPK signalling, protein-tyrosine phosphorylation, and protein secretion. Novel assays will be developed to meet the demand especially in KGs. For example, a Calcium sensor assay is under development in a collaboration between SMP-Cell and the cardiovascular network (KG-CV), a protein translocation assay has been developed in collaboration with the CancerNet (KG-CA).

The standardised resources generated are in addition exploited in other SMPs also in bacterial and other systems, adding further functional information (e.g. protein-protein interaction) on the respective proteins. Bioinformatic infrastructure and know-how has been established to cope with a variety of data structures and sources. Databases and applications will be enhanced within the National Genome Research Network (NGFN) to allow e.g. for remote up- and downloading of primary data and computed information.

SMP-Cell offers a straight functional genomics pipeline for the systematic molecular and cellular functional gene analysis, aiming at the identification and validation of disease targets.

SMP-Cell is one key component of the SMP-Consortium, which has been established to form a functional analysis pipeline that shall synergistically contribute to the goals of the NGFN – the identification and validation of disease targets for diagnostics and therapy.

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