Heads of Laboratories
RNA is not only a carrier of genetic information; it is also a catalyst and can function as a guide in protein complexes processing or regulating other RNA molecules. Dr. Tuschl is investigating different gene regulatory mechanisms that are triggered by doublestranded RNA and RNA-binding proteins in mostly human cells, with the goal of developing a new generation of therapeutic treatments for genetic diseases.
Dr. Tuschl molecularly characterized small interfering RNAs (siRNAs), a class of double-stranded molecules 21 nucleotides long that guide sequence-specific gene silencing, and was the first to demonstrate their utility in knocking down human gene expression. These siRNAs are processed from longer double-stranded RNA precursors and assemble into effector complexes that destabilize messenger RNAs partially or fully complementary to one of the siRNA strands. Eukaryotic cells express a variety of classes of small RNAs to control gene expression. The Tuschl lab identified these classes and their many members using specialized cloning techniques. The most important classes represent microRNAs and piwi-interacting RNAs (piRNAs).
microRNAs are made from larger RNA precursors containing about 30 base pair stem-loops. These microRNAs are involved in many biological processes and are even expressed in viruses — in particular, members of the herpesvirus family — by controlling messenger RNA stability and translation of hundreds of messenger RNA targets. piRNAs are specifically expressed in male and female germ line cells and are required for normal germ cell development. Although researchers know that knocking out the piwi genes in mice causes male infertility, the targets and molecular function of piRNAs remain unknown. Efforts to characterize their biogenesis and targets are ongoing but are hampered by the lack of cell lines expressing piRNAs.
In a global effort to clarify the role of RNAs in development and in various diseases, the Tuschl lab continues to catalogue and annotate all cellular RNAs, including conventional noncoding RNAs and messenger RNA isoforms. RNAs have been difficult to detect and measure in archival tissue sections using traditional histological techniques. The Tuschl lab continues to develop new fluorescence-based methods to visualize RNA molecules in distinct subcellular compartments and granules to assess their displacement observed in neurodegenerative and inflammatory diseases. The work will help researchers better understand the roles of regulatory RNAs and possibly defective RNA biogenesis processes in the onset of disease.
In a broader perspective, messenger RNAs interact during their life cycle in a sequence-specific manner with a large number of small RNA-containing ribonucleoprotein complexes (RNPs) as well as directly RNA-binding proteins (RBPs). In order to understand these regulatory networks, the Tuschl lab has developed experimental approaches to precisely define the binding sites of RBPs and RNPs on messenger RNAs and their precursors. Current studies focus on characterizing RBPs where mutations are known causes of genetic diseases, such as fragile X mental retardation and amyotrophic lateral sclerosis. The identification of their messenger RNA targets shed light on their function and may lead to the design of new therapeutic agents.
Dr. Tuschl received his Ph.D. in chemistry from the University of Regensburg, in Germany, in 1995. He went to the Max Planck Institute for Experimental Medicine in GoÅNttingen, Germany, pursuing research with Fritz Eckstein. He next joined the biology department at the Massachusetts Institute of Technology and the Whitehead Institute for Biomedical Research, where he worked with Phillip A. Sharp and David P. Bartel. Dr. Tuschl was a junior investigator at the Max Planck Institute for Biophysical Chemistry before coming to Rockefeller in 2003 as associate professor. He was named professor in 2009. Since 2005, he is also a Howard Hughes Medical Institute investigator.
Dr. Tuschl is a member of the German National Academy of Sciences Leopoldina, and his most recent honors include a 2012 NIH Director’s Transformative Research Project Award, the Ernst Jung Prize for Medicine in 2008 and the Max Delbrück Medal and the Karl Heinz Beckurtz Award in 2007. In 2006 he received the Molecular Bioanalytics Prize from Roche Diagnostics. In 2005 he was named a fellow of the New York Academy of Sciences and received the Meyenburg Prize, the Irma T. Hirschl Trust Career Scientist Award and the Ernst Schering Award. In 2003 he received the Wiley Prize in Biomedical Sciences, the New York City Mayor’s Award for Excellence in Science and Technology and the Newcomb Cleveland Prize from the American Association for the Advancement of Science. Dr. Tuschl was the recipient of the European Molecular Biology Organization Young Investigator Award in 2001.
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