Royal Society University Research Fellow
PhD on pre-mRNA splicing with Prof. Reinhard Lührmann (Philipps-University Marburg, Germany)
2004-2011 Postdoctoral research on RNA surveillance in budding yeast with Prof. David Tollervey (Wellcome Trust Centre for Cell Biology, University of Edinburgh). During this time I held independent Fellowships from the Human Frontier Science Program Organisation and the European Molecular Biology Organisation.
2011-2016 Royal Society University Research Fellowship (URF)
2005-2008 Human Frontier Science Program (HFSP) Long-Term Fellowship
2005 European Molecular Biology Organisation (EMBO) Long-Term Fellowship
2004 Prize for the best PhD at the Faculty of Medicine, Philipps-University Marburg
Quality control of coding and non-coding RNAs plays a vital role in assuring the fidelity of gene expression and overall fitness of all organisms. Specialised RNA surveillance systems, each employing a distinct network of ribonucleases and co-factors, detect and remove faulty RNA molecules. An important paradigm for mRNA quality control is the nonsense mediated decay (NMD) pathway, which prevents translation of potentially harmful truncated proteins from aberrant mRNAs. NMD has been linked to several genetic diseases and cancer.
In many cases it is unclear how target RNAs are recognised and degraded, and exonucleases were long believed to be the main players. However, this model was recently challenged by the identification of endonucleases containing PIN (PilT N-terminus) domains, which appear to play key roles in RNA surveillance in yeast and metazoans.
My laboratory is interested in the functions of novel PIN domain endonucleases in NMD and other surveillance pathways. During my postdoctoral work, I detected endonuclease activity in three PIN domain proteins in Saccharomyces cerevisiae; the exosome component Rrp44 (Schneider et al., 2009), the ribosome biogenesis factor Nob1 (Pertschy et al., 2009) and the mRNP quality control factor Swt1 (Skruzny et al., 2009). Five further PIN domain proteins are encoded in the genome of budding yeast: three largely uncharacterised proteins and two ribosome biogenesis factors.
Key to understand the roles of RNA surveillance factors is the identification of their substrates. We therefore apply in vivo crosslinking and high-throughput sequencing approaches (CRAC) to identify RNA binding sites of PIN domain proteins on a genome-wide scale. This will provide the starting points for biochemical, genetic and structural analyses.