student profile: Mr Taylor Syme


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Thesis work

Thesis title: Regulation and function of strawberry notch homolog 2 � A novel inflammatory response factor in astroglia and other CNS cells

Supervisors: Iain CAMPBELL , Hannah NICHOLAS

Thesis abstract:

We have identified a novel putative transcriptional regulator called strawberry notch homolog 2 (Sbno2) as a prominent IL-6-stimulated gene in astrocytes. The aim of this study was to: (i) examine the regulation of Sbno2 in astrocytes in vitro and in vivo, and (ii) establish lentiviral transduction of cells with a Sbno2 transgene for the functional characterization of Sbno2. In murine cultured astrocytes Sbno2 gene expression was significantly up-regulated in a dose- and time-dependent fashion following treatment with hyper-IL-6 (IL-6 + soluble IL-6 receptor). These changes were reflected by corresponding alterations in the level of the SBNO2 protein. The level of Sbno2 mRNA was up-regulated significantly in murine astrocytes by other glycoprotein130 cytokine-family members and the pro-inflammatory cytokines IL-1β and TNF-α. Cycloheximide treatment resulted in markedly higher Sbno2 mRNA and did not abolish the up-regulation of Sbno2 mRNA mediated by hyper-IL-6. Following intra-peritoneal LPS injection in mice, Sbno2 mRNA levels in the brain increased significantly and was localized predominantly to astrocytes and the choroid plexus, and to a lesser extent to microglia, endothelial cells, and neurons. Characterisation of transduced NIH-3T3 fibroblasts revealed transgenic SBNO2 localised exclusively to the nucleus but not the nucleoli. Our findings indicate that the Sbno2 gene is broadly regulated in astrocytes and likely encodes a nuclear factor involved in the innate host response. A mouse model for the conditional deletion of the Sbno2 gene in astrocytes developed by us will provide an invaluable tool for evaluating function of Sbno2 in mammalian cells.

Selected publications

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Journals

  • Grill, M., Syme, T., Nocon, A., Lu, A., Hancock, D., Rose-John, S., Campbell, I. (2015). Strawberry notch homolog 2 is a novel inflammatory response factor predominantly but not exclusively expressed by astrocytes in the central nervous system. GLIA, 63(10), 1738-1752. [More Information]

2015

  • Grill, M., Syme, T., Nocon, A., Lu, A., Hancock, D., Rose-John, S., Campbell, I. (2015). Strawberry notch homolog 2 is a novel inflammatory response factor predominantly but not exclusively expressed by astrocytes in the central nervous system. GLIA, 63(10), 1738-1752. [More Information]

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