Graduate Research Prize Winners 2011
I grew up in Huddersfield, West Yorkshire and completed my undergraduate degree in chemistry here in Oxford, at University College, in 2006. I spent the fourth year of my course carrying out a research project on the role of asparginyl hydroxylation in cell signalling in the laboratory of Prof. Chris Schofield. This experience motivated me to continue in research and to apply for the Wellcome Trust DPhil Programme in Structural Biology. I used this opportunity to pursue the theme of cell-cell signalling further. Alongside a series of taught courses in biophysical techniques, I spent my first six month rotation in the laboratory of Prof. Iain Campbell in the biochemistry department, using NMR spectroscopy to investigate interactions of the cytoplasmic scaffolding protein filamin with cell surface integrin receptors. During the second rotation project and the remainder of my DPhil studies, my main focus was on the interactions of the trans-membrane type IIa receptor protein tyrosine phosphatases (RPTPs) with their extracellular ligands, supervised by Dr Radu Aricescu and Prof. Yvonne Jones in the Division of Structural Biology at the Wellcome Trust Centre for Human Genetics.
In collaboration with the group of Prof. John Flanagan at Harvard Medical School, the main finding from my DPhil was that two different but related types of ligand, HSPGs and CSPGs, have opposite consequences on the growth of nerve cells, although they signal via the same receptor on the surface of the nerve cells, RPTPσ. We demonstrated that only HSPGs, and not CSPGs, were able to promote clustering of RPTPσ molecules. This implies that molecules able to cluster RPTPσ and simulate the action of HSPGs, rather than those that simply block RPTPσ-CSPG interactions, may prove the most beneficial in strategies to aid nerve regeneration following nervous system injury. In following this research question, I had the chance to learn a variety of experimental techniques including protein expression in both mammalian and bacterial cell lines, protein purification, fluorescence microscopy, X-ray crystallography and many biophysical techniques, such as surface plasmon resonance.
During my DPhil. studies, I have also had the opportunity to be involved in undergraduate teaching. After two years teaching maths classes in the chemistry department, I held a position as graduate teaching assistant in biochemistry at Oriel College for the remaining two years, which I found a challenging but also very rewarding experience.
Outside science, I have enjoyed playing lots of sport in Oxford, including Blues football for the University, running with Headington Road Runners and more recently taking up triathlon with OxfordTri.
- Proteoglycan-specific RPTPσ clustering as a molecular switch for neuronal outgrowth. C.H. Coles, Y. Shen, A.P. Tenney, C. Siebold, G.C. Sutton, W. Lu, J.T. Gallagher, E.Y. Jones, J.G. Flanagan, A.R. Aricescu. Science. 2011, 332 (6028): pages 484-488. PMID: 21454754
- Structural basis for cell surface patterning through NetrinG-NGL interactions. E. Seiradake, C.H. Coles, P.V. Perestenko, K. Harlos, R.A.J. McIlhinney, A.R. Aricescu, E.Y. Jones. EMBO J. 2011 Sep 23. Epub ahead of print. PMID: 21946559
- Carbohydrate and Domain Architecture of an Immature Antibody Glycoform Exhibiting Enhanced Effector Functions. M. Crispin, T.A. Bowden, C.H. Coles, Karl Harlos, A.R. Aricescu, D.J. Harvey, D.I. Stuart, E.Y. Jones. Journal of Molecular Biology. 2009, 387 (5): pages 1061-1066. PMID: 19236877
- Structure of three tandem filamin domains reveals auto-inhibition of ligand binding. Y. Lad, T. Kiema, P. Jiang, O.T. Pentikäinen, C.H. Coles, I.D. Campbell, D.A. Calderwood and J. Ylänne. EMBO J. 2007, 26(17): pages 3993-4004. PMID: 17690686
- Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. M.L. Coleman, M.A. McDonough, K.S. Hewitson, C.H. Coles, J. Mecinovic, M. Batycka, K.M. Cook, M.E. Cockman, D.E. Lancaster, B.M. Kessler, N.J. Oldham, P.J. Ratcliffe and C.J. Schofield. J. Biol. Chem. 2007, 282 (33): pages 24027-24038. PMID: 17573339
- Post-translational hydroxylation of ankyrin repeats in IKB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF. M.E. Cockman, D.E. Lancaster, I.P. Stolze, K.S. Hewitson, M.A. McDonough, M.L. Coleman, C.H. Coles, X. Yu, R.T. Hay, S.C Ley, C.W. Pugh, N.J Oldham, N. Masson, C.J. Schofield and P.J. Ratcliffe. PNAS 2006, 103: pages 14767-14772. PMID: 17003112