Funktionelle Genomik mit mRNA-Protein-Konjugaten und DNA Mikrochips

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In recent years, technology for very fast automated genome sequencing has been developed at an amazing speed due to strong efforts in several genome projects. In contrast, development of methods for highly parallel investigation of the actual function of the genome`s translated message - the proteins - is in lagging far behind.This project will investigate a new strategy of functional interaction studies on proteins in a bio-combinatorial approach. Therefore, a method for the generation of mRNA-protein fusions, developed in Prof. Dr. Szostaks laboatory, will be combined with DNA microarray technology. Starting from a cDNA library, a corresponding mRNA-protein fusion library will be generated where every protein is covalently linked to its encoding mRNA. These fusions are subjected to an actvity selection procedure, specifically affinity to a certain protein target. As a result of the attached mRNA, the genetic information of the selectively enriched protein can be amplified by PCR an read out by hybridizing the fluorescently labeled PCR product with an appropriate DNA microarray. This strategy will allow screening for protein-protein and protein-small molecule interactions at genomic scale for virtually any organism. The method has great potential in the search for new drug targets an investigating metabolic pathways in general.