Return to project list

BMP regulated miRNA expression in human mesenchymal stem cells

Prof. Knaus (first supervisor), Prof. Mundlos (second supervisor); Free University Berlin and Institute for Medical Genetics

MicroRNAs (miRNAs) are small (20-24 nucleotides in length), single stranded, noncoding RNAs that regulate gene expression by directly binding to 3’ untranslated regions (3’ UTRs) of specific mRNA molecules, leading to either transcript degradation or translational repression. Recent studies have shown that miRNAs control cell fate decisions in various normal and pathological processes. The TGF-ß and BMP pathways have been demonstrated to regulate miRNA expression during osteogenesis and chondrogenesis (Lin EA et al., J Biol Chem 2009; Li Z et al., Proc Natl Acad Sci USA, 2008). The superfamily of TGF-ß and BMP growth factors comprises 33 members of dimeric secreted proteins, which signal via transmembrane serine/threonine kinase receptors (Sieber C et al., CGFR 2009). BMPs differ in their receptor affinities and vary in their potency to induce a subset of BMP signalling pathways, such as the canonical Smad pathway, MAPK and PI3K pathways (Nohe A et al. J Biol Chem, 2002). BMP binding to the receptors causes activation of the type I receptor, which subsequently phosphorylates Smad1/5/8 causing this cytosolic signaling component to translocate to the nucleus to regulate transcription of specific target genes. Smads have been shown to play a key role in the processing of miRNAs by interacting with Drosha, the miRNA processing subunit and p68 to facilitate pre-miRNA accumulation (Davis BN et al., Nature 2008).
In the PhD project we aim to investigate the regulation of miRNAS in human mesenchymal stem cells under specified BMP treatment conditions. Newly identified miRNAs will be characterized in a number of established functional cell assays (Hartung A et al., MCB 2006; Schwappacher R et al., EMBO J 2009; Bengtsson L et al., J Cell Sci, 2009) in order to define the impact of the target regulation in BMP signal transduction and tissue regeneration.
For this we would require students with some expertise in molecular and cell biology.