Dr Sarah Newbury

Dr Sarah Newbury is a reader in Cell Biology and her area of expertise is RNA stability in development. Her current research areas are Cancer and Cell and Developmental Biology

Research focus:

Development of an organism from egg to adult requires sets of genes to be switched on and off at particular times and in the correct order. If genes are not switched off when necessary, cells can continue to multiply in an uncontrolled way leading to cancer. One of the ways in which genes can be switched off is by destroying RNA, which is the molecule that transmits the information from the DNA in the nucleus to the cytoplasm, where the proteins are made. It is now known that degradation of messenger RNAs and microRNAs is controlled by ribonucleases and other factors that work together as a “molecular machine”. The research of my group aims to understand the ways in which this novel mechanism of gene regulation can control early development, stem cell differentiation and cell movement in the model organism Drosophila melanogaster.

Current research:

• Role of RNA stability in growth, differentiation and cell movement: Using the fruit fly Drosophila as a model organism, we have recently discovered that an enzyme named Pacman is involved in the growth and differentiation of imaginal discs, which form adult structures such as wings and legs. Imaginal discs are similar to stem cells in that they carry the information to build the adult tissue. We have shown that Pacman normally affects the production of a protein called Simjang which in turn controls a gene silencing complex (the NuRD complex) which shuts down parts of the chromosome, preventing genes from being turned on. This gene silencing complex is important because it is known to be involved in many critical cellular events including tissue regeneration, ageing and spread of cancer cells. The aim of this project is to understand the molecular mechanisms whereby Pacman affects growth, differentiation and cell movement.
• Role of RNA turnover in testis stem cells: Stem cells have a vast potential in regenerative medicine for the replacement of defective tissue. They therefore offer a potential cure for injuries and also for degenerative diseases such as Alzheimers and Duchenne muscular dystrophy. We have recently shown that the conserved exoribonuclease Pacman, which is known to be involved in the cytoplasmic degradation of mRNA, RNA interference and degradation of microRNAs, is necessary for stem cell function in the testis of the fruit fly Drosophila. In common with mammals, self-renewing germline stem cells are critical for supplying cells which differentiate into sperm. Since the role of mRNA stability in controlling gene expression in stem cells has not been well studied, these results have uncovered a novel mechanism of gene regulation which is likely to be important in stem cells in other organisms.
• MicroRNAs as biomarkers in plasma cell disorders: In collaboration with Dr Tim Chevassut, we have initiated a project to use microRNAs as biomarkers for plasma cell disorders. MicroRNAs (miRNAs) are non-coding RNAs known to be involved with the normal cellular physiology through regulation of gene expression and, moreover, are implicated in cancer where they can act as oncogenes or tumour suppressors. Using genome-wide profiling studies, miRNAs have already been shown to have distinct signatures in a number of human cancers, including various leukaemias (such as chronic lymphocytic leukaemia) and carcinomas (such as prostate and breast cancer. Our aim is to identify microRNA biomarkers indicative of the cancerous and pre-cancerous state and validate them using existing prognostic methods.