Dr John Taylor
Research | Current
- Cell biology
The main interest of our lab is the pathogenesis of viral infections. Our research uses rotavirus, a major cause of gastroenteritis in infants, as an experimental tool to reveal ways in which infection can influence cellular, immunological and physiological function in the host. Our goal is to understand the mechanisms that underpin viral disease at a molecular level and thereby identify new opportunities for therapeutic control of disease.
A second area of research is the engineering of viruses as gene vectors for antigen delivery to immune cells as a strategy for the development of novel vaccines and immunotherapeutics.
Specific Research Areas
Pathogenesis of rotavirus infection
Rotavirus causes acute gastroenteritis in young children and animals and is associated with fever, diarrhea and vomiting. We are interested in the role played in the disease process by NSP4, a virus-encoded protein secreted from infected cells intestinal epithelial cells. NSP4 is a unique virus protein because it function as a toxin. Our studies have revealed that NSP4 is secreted as a hydrophobic lipoprotein that can bind to a wide range of cell types and elicits intracellular signalling through Toll-like receptor 2 (TLR). Binding of NSP4 to macrophages triggers secretion of inflammatory cytokines and we are interested to explore further the role played by NSP4 and TLRs in the development of disease symptoms.
Viruses as vectors in cellular engineering and vaccine development
Viruses have an intrinsic ability to deliver genetic material across the plasma membrane of mammalian cells and this ability can be exploited to produce gene vectors capable of the selective genetic engineering of specific cells and tissues in vivo. We are exploring the development of novel viral vectors that target human dendritic cells, essential for the initiation of potent immunity to antigens and vaccines. We have identified certain serotypes of adeno-associated virus that transduce both DCs and adipose-derived mesenchymal stem cells optimally and further increased the transduction potential by selective mutation of capsid residues. Another virus whose potential as a cancer vaccine vector is under study in the lab is a sheep adenovirus. Ovine atadenovirus 27 (OvAd27) has proved a potent vaccine vector in mice priming an immune response capable of killing tumour cells in both a prophylactic and therapeutic setting. In collaboration with Broadvector, an Australian biotech company, we are currently evaluating its ability to transduce DCs and activate antigen specific T cells in the laboratory.potential in human cells in the laboratory.
We have developed collaborative relationships with pharmaceutical and agricultural/food industry partners to undertake laboratory testing of their products for antiviral activity and welcome further enquiries from all such organisations who wish to acquire scientific data.
Tracking the uptake of recombinant hepatitis B virus core antigen (HBcAg, shown in green) into human monocyte derived dendritic cells. The particles are coupled to SMEZ-M1, a bacterial superantigen, enabling receptor-mediated uptake via Class II MHC. After 10 minutes most of the viral antigen is co-localised with the early endosomal marker EEA1 (red).
Rotavirus infection blocks autophagic flux in MDCK cells expressing LC3-GFP (green). Immunofluorescent microscopy reveals virus-infected cells using antibody against VP2, a marker of viroplasms (red). Note the aggregation of GFP-labelled autophagosomes in infected cells due to inhihibtion of fusion with lysosomes.
Areas of expertise
Proteomics & Biomedicine
Selected publications and creative works (Research Outputs)
- Young Jeong, J., Sperry, J., Taylor, J. A., & Brimble, M. A. (2014). Synthesis and evaluation of 9-deoxy analogues of (-)-thysanone, an inhibitor of HRV 3C protease. European journal of medicinal chemistry, 87, 220-227. 10.1016/j.ejmech.2014.09.063
Other University of Auckland co-authors: Jonathan Sperry, Margaret Brimble
- McIntosh, J. D., Manning, K., Chokshi, S., Naoumov, N. V., Fraser, J. D., Dunbar, P. R., & Taylor, J. A. (2014). An engineered non-toxic superantigen increases cross presentation of hepatitis B virus nucleocapsids by human dendritic cells. PLoS One, 9 (4)10.1371/journal.pone.0093598
Other University of Auckland co-authors: Julie McIntosh, Rod Dunbar, John Fraser
- Ge, Y., Mansell, A., Ussher, J. E., Brooks, A. E., Manning, K., Wang, C., & Taylor, J. A. (2013). Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2. Journal of Virology, 87 (20), 11160-11167. 10.1128/JVI.03099-12
Other University of Auckland co-authors: Anna Brooks, Yi Ge, Jing Wang
- Sheppard, H. M., Ussher, J. E., Verdon, D., Chen, J., Taylor, J. A., & Dunbar, P. R. (2013). Recombinant adeno-associated virus serotype 6 efficiently transduces primary human melanocytes. PLoS One, 8 (4)10.1371/journal.pone.0062753
Other University of Auckland co-authors: Rod Dunbar, Hilary Sheppard
- Locke, M., Ussher, J. E., Mistry, R., Taylor, J. A., & Dunbar, P. R. (2011). Transduction of Human Adipose-Derived Mesenchymal Stem Cells by Recombinant Adeno-Associated Virus Vectors. TISSUE ENGINEERING PART C-METHODS, 17 (9), 949-959. 10.1089/ten.tec.2011.0153
Other University of Auckland co-authors: Rod Dunbar, Michelle Locke
- Verdon, J. V., Ussher, J. E., Sheppard, H. M., Taylor, J. A., & Dunbar, P. R. (30/6/2011). Leukocyte transduction and CD8+ T cell activation by recombinant adeno-associated virus vectors. Poster presented at New Zealand Australasian Society Immunology Branch Meeting, Wellington, New Zealand.
Other University of Auckland co-authors: Hilary Sheppard
- Taylor, J. A., Mansell, A, Ussher, JE, Brooks, AES, Manning, K, Wealthall, R, ... Ge, Y (2011). Rotavirus NSP4 triggers secretion of pro-inflammatory cytokines from macrophages via Toll-Like Receptor-2.. Paper presented at Gordon Research Conference: Viruses and Cells, Lucca, Italy. 27 May - 4 June 2011.
Other University of Auckland co-authors: Anna Brooks, Jing Wang
- Didsbury, A., Wang, C., Verdon, D., Sewell, M., McIntosh, J. D., & Taylor, J. A. (2011). Rotavirus NSP4 is secreted from infected cells as an oligomeric lipoprotein and binds to glycosaminoglycans on the surface of non-infected cells. Virology Journal
Other University of Auckland co-authors: Mary Sewell