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Molecular mechanism of innate immunity mediated by the Toll/IL1 receptor signalling pathways.


Department of Biochemistry

Prof N J Gay Applications accepted all year round Awaiting Funding Decision/Possible External Funding

About the Project

This group participates in the Wellcome Trust 4 year PhD programme in Developmental biology., MRC and BBSRC Doctoral Training Programmes.

Common inflammatory diseases such as rheumatoid arthritis and sepsis are caused by the abnormal activation of pattern recognition receptors, proteins that recognise pathogen associated molecules such as bacterial lipopolysaccharide. NG’s lab studies the molecular mechanism of of signalling by PRRs focussing on the Toll - like receptors (see Gay et Nature Rev Immunol, 14, 546 and other recent papers in the reference list)

Methods. Protein expression in bacteria and culture cells. Purificaion using FPLC, affinity chromatography and allied techniques. Crystallographic screening. X-ray crystallography. CryoEM, Super resolution microscopy,


Funding Notes

Funding is available from several sources including AstraZeneca funded studentships, MRC and BBSRC Doctoral Training programmes.

References

References (recent)
106. Gay, N. J.*, Symmons, M. F., Gangloff, M., and Bryant, C. E. (2014) Assembly and localization of Toll-like receptor signalling complexes. Nature Rev. Immunol. 14, 546-558.



111. Dossang, A. C., Motshwene, P. G., Yang, Y., Symmons, M. F., Bryant, C. E., Borman, S., George, J., Weber, A. N., and Gay, N. J. (2016) The N-terminal loop of IRAK-4 death domain regulates ordered assembly of the Myddosome signalling scaffold. Sci Rep 6, 37267

112. Halabi, S., Sekine, E., Verstak, B., Gay, N. J., and Moncrieffe, M. C. (2017) Structure of the Toll/Interleukin-1 Receptor (TIR) Domain of the B-cell Adaptor That Links Phosphoinositide Metabolism with the Negative Regulation of the Toll-like Receptor (TLR) Signalosome. J. Biol. Chem. 292, 652-660.

113. Pizzuto, M., Gangloff, M., Scherman, D., Gay, N. J., Escriou, V., Ruysschaert, J. M., and Lonez, C. (2017) Toll-like receptor 2 promiscuity is responsible for the immunostimulatory activity of nucleic acid nanocarriers. J Control Release 247, 182-193.



114. Foldi, I., Anthoney, N., Harrison, N., Gangloff, M., Verstak, B., Nallasivan, M. P., AlAhmed, S., Zhu, B., Phizacklea, M., Losada-Perez, M., Moreira, M., Gay, N. J., and Hidalgo, A. (2017) Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila. J. Cell Biol. 216, 1421-1438

115. Fels Elliott, D. R., Perner, J., Li, X., Symmons, M. F., Verstak, B., Eldridge, M., Bower, L., O'Donovan, M., Gay, N. J., Consortium, O., and Fitzgerald, R. C. (2017) Impact of mutations in Toll-like receptor pathway genes on esophageal carcinogenesis. PLoS Genet 13, e1006808.

116. Ulian-Benitez, S., Bishop, S., Foldi, I., Wentzell, J., Okenwa, C., Forero, M. G., Zhu, B., Moreira, M., Phizacklea, M., McIlroy, G., Li, G., Gay, N. J., and Hidalgo, A. (2017) Kek-6: A truncated-Trk-like receptor for Drosophila neurotrophin 2 regulates structural synaptic plasticity. PLoS Genet 13, e1006968.

117. Latty, S, Sakai, J, Hopkins, L., Verstak, B., Paramo, T., Berglund, R.A. Gay, N.J., Bond, P.J., Klenerman, D., Bryant, C.E. Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub. (2017) eLIFE, under revision




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