The innovative research project hopes to pave the way for better prevention and treatment of cancer.
Commenting on receipt of the grant Monika said: “Kaspar and I are thrilled about this great news. This fellowship helps us to continue in our ground breaking research.”
Created in 1987, Rosetrees, a family Trust, uses venture philanthropy to fund cutting edge medical research.
Further information on the research project:
Human Dicer is a largely cytoplasmic enzyme that processes double-stranded RNA (dsRNA) precursors into various small non-coding RNA, such as micro RNA (miRNA) to regulate gene expression in both cytoplasmic and nuclear RNA interference. Recent findings suggest an additional, non-canonical function for Dicer in the DNA damage response (DDR). Efficient DNA repair is crucial for genome stability and tumour suppression. We have previously identified that catalytically active, phosphorylated Dicer (p-Dicer) localizes in the nucleus to prevent dsRNA accumulation. p-Dicer is recruited to DNA double strand breaks (DSBs) to generate DNA damage-induced RNA (DDRNA) from dsRNA precursors that originate at DSBs. While complete loss of Dicer triggers deleterious accumulation of DNA damage, cell death and decreased tumour burden in mouse models, heterozygous mutations in the DICER1 gene cause sub-lethal DNA damage and are associated with a rare clinical phenotype termed ‘DICER1 syndrome’, including pleuropulmonary blastoma and ovarian cancers. These findings establish DICER1 as a haploinsufficient tumour suppressor gene with relevance for genomic stability, cellular growth and proliferation in a both miRNA- and DDRNA-dependent manner.
However, the underlying molecular mechanisms that control the DDRNA metabolism are poorly understood. Collectively, we aim to establish a molecular link between RNAPII transcription, nuclear Dicer function and DNA repair. Our research may pave the way for pharmacological inhibition of Dicer or Dicer-regulating factors as a novel, non-genotoxic therapeutic option to prevent cancer development or sensitize tumours to chemotherapy.