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Elucidation of chemokine-receptor structure and signalling pathways to develop novel therapeutics. (#202008)

About This PhD Project

Project Description

Chemokines are small proteins that play a vital role in cell migration via their interactions with G protein coupled receptors (GCPR) on the surface of the target cells. The underlying molecular mechanism by which the chemokines interact with the GPCR is not well understood. Furthermore, in some instances, the chemokines may form complexes with additional binding partners which interact with the same GPCR, yet induce completely different downstream signalling pathways.

Using state-of-the art techniques available in the labs of the Structural Genomics Consortium, this project will focus on elucidation of the 3D structures of these hetero and ternary complexes involving chemokine receptors and regulators, to understand the basis of the conformational changes that lead to different cellular responses. This will open new avenues for drug development to promote healing of tissues, including bone and muscle.

Training Opportunities

Cutting-edge structural biology techniques available in-house, including mass spectrometry, cryo-electron microscopy, X-ray crystallography

Emphasis on Translational work: findings from these structures can be used for therapeutic development

Well-established DPhil programme (NDORMS) with defined milestones, ample training opportunities within the University and Department, and access to university/department-wide seminars by world-leading scientists

Highly collaborative environment with expertise ranging from protein biochemistry to molecular biology and in vivo models, as well as several other collaboration opportunities within the University of Oxford and worldwide

Key Publications

Dong YY et al. (2018) Structures of DPAGT1 explain glycosylation disease mechanisms and advance TB antibiotic design. Cell. 175:(4):1045-1058.

Dong YY et al. (2015) K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science. 347(6227):1256-9.

Burgess-Brown NA et al. (2014) Medium-throughput production of recombinant human proteins: protein production in E. coli. Methods Mol Biol. 2014;1091:73-94.

Berridge G et al. (2011) HPLC separation and intact mass analysis of detergent-solubilised integral membrane proteins. Anal. Biochem. 410(2): 272-80.

Savitsky P et al. (2010) High-throughput production of human proteins for crystallization: the SGC experience. J. Struct. Biol.172(1):3-13.

Related Subjects

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