A genetic model for Neurofibromatosis Type II: Identification and characterization of protein partners of the Merlin tumour suppressor protein
We study the underlying molecular mechanisms that link polarity and proliferation in epithelial cells. When cells lose this linkage they often become metastatic. We study a protein family that has a role in both proliferation and polarity. Specifically, we use Drosophila melanogaster (the fruit fly) as a genetic model to study Neurofibromatosis Type 2 (NF2), an inherited cancer of the brain and spinal cord. Mutation or loss of the NF2 gene is also associated with metastasis of several non-neuronal tumours. Merlin, the protein product of the NF2 gene, is a tumour suppressor that interacts with the plasma membrane and the cytoskeleton. However, the molecular mechanism of how Merlin acts as a tumour suppressor is not known. To address this question, we are taking the approach of identifying and characterizing proteins that interact with Merlin. Drosophila provides a unique toolbox of powerful genetic techniques to determine the function of Merlin and its interacting proteins. We have already identified several proteins that interact with Merlin, and are currently studying how these control proliferation and adhesion within the cell in epithelial cells, neural stem cells and the developing nervous system. We hypothesize that Merlin is functioning as part of a multi-protein complex to control proliferation and polarity. Other proteins include kinases, scaffold proteins and proteins involved in post-transcriptional regulation. The approaches we use include genetic analysis, molecular and cell biology, biochemistry, and advanced microscopy.
Moesin is involved in polarity maintenance and cortical remodelling during asymmetric cell division.
Namal Abeysundara, Andrew J. Simmonds, and Sarah C. Hughes. 2017.
Mol. Biol. Cell mbc.E17-05-0294; First Published on December 27, 2017;doi:10.1091/mbc.E17-05-0294
Loss of the Drosophila melanogaster RNA binding protein Ddx1 leads to reduced size and aberrant gametogenesis.
Devon R Germain, Lei Li, Matthew R Hildebrandt, Andrew J. Simmonds, Sarah C. Hughes, and Roseline Godbout. (2015).
Developmental Biology 407(2): 232-45.
Interaction with the effector Dynamin-Related Protein 1 (Drp1) is an ancient function of Rab32 subfamily proteins.
Carolina Ortiz Sandoval, Sarah Hughes, Joel Dacks, Thomas Simmen. (2014).
Cellular Logistics. 4(4): e986399-7.
Regulation of cell proliferation and adhesion by means of a novel region of drosophila merlin interacting with Sip1.
Abeysundara N, Leung AC, Primrose DA, Hughes SC.
Dev Dyn. 2014 Dec;243(12):1554-70. Epub 2014 Oct 1.
The Smc5/Smc6/MAGE complex confers resistance to caffeine and genotoxic stress in Drosophila melanogaster.
Li X, Zhuo R, Tiong S, Di Cara F, King-Jones K, Hughes SC, Campbell SD, Wevrick R.
PLoS One. 2013;(8)3:e59866. Epub 2013 Mar 28.