Heads of Laboratories
Investigator, Howard Hughes Medical Institute
Laboratory of RNA Molecular Biology
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 double-stranded 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 catalog 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 with 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 sheds light on their function and may lead to the design of new therapeutic agents.
Maîtrise in chemistry, 1989
Université Joseph Fourier
Diploma in chemistry, 1992
University of Regensburg
Ph.D. in chemistry, 1995
Max Planck Institute for Experimental Medicine and
University of Regensburg
Massachusetts Institute of Technology and Whitehead Institute for Biomedical Research, 1995–1999
Group Leader, 1999–2002
Max Planck Institute for Biophysical Chemistry
Associate Professor, 2003–2009
The Rockefeller University
Howard Hughes Medical Institute
EMBO Young Investigator Award, 2001
AAAS Newcomb Cleveland Prize, 2003
New York City Mayor’s Award for Excellence in Science and Technology, 2003
Wiley Prize, 2003
Ernst Schering Award, 2005
Irma T. Hirschl/Monique Weill-Caulier Trust Research Award, 2005
Meyenburg Prize, 2005
Molecular Bioanalytics Prize, Roche Diagnostics, 2006
Karl Heinz Beckurtz Award, 2007
Max Delbrück Medal, 2007
Ernst Jung Prize, 2008
National Institutes of Health Director’s Transformative Research Project Award, 2012
European Inventor Award Finalist, European Patent Office, 2014
German National Academy of Sciences Leopoldina
Renwick, N. et al. Multicolor microRNA FISH effectively differentiates tumor types. J. Clin. Invest. 123, 2694–2702 (2013).
Ascano, M. Jr. et al. FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature 492, 382–386 (2012).
Hafner, M. et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129–141 (2010).
Landgraf, P. et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401–1414 (2007).
Aravin, A. et al. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442, 203–207 (2006).