Sarah Newbury, Professor in RNA Biology at BSMS, has been awarded £474,748 from the Biotechnology and Biological Sciences Research Council (BBSRC). This project is entitled ‘Unlocking the molecular and cellular mechanisms regulated by the ribonuclease Dis3L2 in Drosophila and human cell proliferation’ and will use state-of-the-art techniques to uncover novel ways that cell proliferation can be controlled.
This research is also relevant to the new COVID-19 RNA vaccine technology recently used by Pfizer and Moderna. Sarah is Principal Investigator on the grant together with Dr Ben Towler (Research Co-Investigator) and Prof Simon Morley (Life Sciences at the University of Sussex). As well as the Research Co-Investigator Ben Towler, the grant will also fund a part-time technician, Clare Rizzo-Singh, reagents and equipment. The proposed research follows on from Prof Newbury’s current BBSRC grant, which has been extended by funding of £42,038 from the University of Sussex COVID-19 Extension Fund. The new grant will therefore start on 1 July, 2021.
The proposed project aims to investigate the function of a protein named Dis3L2 in cell proliferation and tissue growth in both the fruit fly Drosophila and in human cells. Dis3L2 is an enzyme known to ‘chew up’ and destroy mRNA molecules which instruct the cell to make particular proteins. Depletion or removal of this protein results in excess proliferation. These results are relevant to human disease as DIS3L2 has been shown to be mutated in an overgrowth syndrome (Perlman syndrome) where affected children are larger than normal, have abnormal enlargement of organs (e.g. kidneys) and susceptibility to Wilms’ tumour (a kidney cancer). In addition, up to 30% of sporadic Wilms’ tumours have mutations in DIS3L2. Interestingly, Dis3L2 has also been implicated in body weight and height variation in indigenous Ethiopian sheep, suggesting selection in our domestic animals.
The team will use modern molecular and cell biological methods (such as CRISPR-Cas9 for gene editing) to dissect this proliferation pathway and identify key components. Understanding the molecular mechanisms whereby Dis3L2 exerts its effects on tissue growth is likely to be relevant in normal growth as well as human overgrowth diseases and cancer. This project will therefore provide valuable insights into a new way of regulating cell proliferation which can be used in the development of new therapeutics.
Commenting on the award, Prof Newbury said: “I am delighted to be awarded this grant from the BBSRC. The work builds on extensive research which has been carried out by the Research Co-Investigator, Dr Ben Towler, and will allow us to continue at the cutting edge in the field of RNA Biology. This Research Council grant will benefit research in BSMS as our expertise in transcriptomics and other modern methods will foster collaborations with other groups.”