2002 Award Winner

Dr. Thomas Tuschl
Göttingen, Germany

The work of Thomas Tuschl
Dr Tuschl and his collegues could show that RNA interference does work well in mammalian cells and that it works best in transfection experiments with base-paired 21 or 22nucleotides long RNA duplices. Longer RNAs are ineffective. In order to identify these short RNA pieces, Dr. Tuschl has developed a novel cloning procedure for these small RNA duplices. Applying these techniques to an analysis of total RNA from HeLa cells, for example, they could clone 16 small RNA molecules which they termed micro RNAs (miRNAs). Some of these RNAs are highly conserved, some are unique in sequence and presumably are the traces of a post-transcriptional regulatory mechanism which controls or modulated translation of target mRNAs. Micro RNAs have recently been identified by Tom Tuschl and collaborators in the adult mouse. In some organs, like the heart, the liver and the brain, a single, tissue specifically expressed micro RNA dominates the population of expressed micro RNAs suggesting a specific role for these RNAs in tissue or organ specification.In order to be sure that the targeted cells have a RNAi machinery in them, a reporter assay was developed by Dr. Tuschl and his collegues which is based on coinfection with a plasmid expressing the luciferase gene and a subsequent measurement of the relative luminiscence of target versus control luciferase activity. Until recently these knock-out studies were restricted to the delivery of chemically synthesized or enzymatically prepared RNA. In the meantime, methods for intracellular expression of small RNAs have been developed. This is useful when cells cannot be transfected efficiently, i.e. primary cells, or for the construction of combinatorail libraries to be used in microarray assays.Dr. Tuschl has been present at the forefront of these developments. He started out as a chemistry student in Regensburg from where he moved to Göttingen in 1982 to start his Ph.D. thesis in the laboratory of Fritz Eckstein. Following the completion of his thesis he spent about three years at MIT in the lab of Prof. Philip Sharp, the discoverer of RNA splicing, for which he has received a Nobel Prize. He once called Dr. Tuschl the most gifted postdoc he ever had. The last three years Dr. Tuschl spent in Göttingen again, now in the Department of Prof. Klaus Weber with whom he has published on the identification of essential and non-essential cytoskeletal proteins in tissue cultured cells. He is about to leave from there to Rockefeller University in New York.

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