Graduate Research Prize Winners Autumn 2014
I studied for my undergraduate degree in Cambridge where I read Natural Sciences, eventually specialising in Biochemistry. In the fourth year of my degree I completed a research project in Stefan Marciniak’s Lab at the Cambridge Institute for Medical Research. I was working towards solving the structure of the kinase PERK. This receptor kinase is involved in the unfolded protein response, a pathway initiated to correct an accumulation of misfolded proteins in the endoplasmic reticulum. I really enjoyed this brief experience of research and despite failing to grow a single protein crystal I was inspired to apply for the Wellcome Trust DPhil Programme in Structural Biology at Oxford. Here, after completing my rotation projects, I joined Christian Siebold’s group in STRUBI at the Wellcome Trust Centre for Human Genetics, for another go at x-ray crystallography.
My DPhil project has focussed on the Repulsive Guidance Molecules (RGMs), a family of membrane-anchored glycoproteins that are involved in a wide range of functions from axon guidance to blood iron regulation. Particularly, mutations in one family member are known to cause the severe blood iron overload disease Juvenile Hemochromatosis (JHH). In the first year of my DPhil, I continued work begun by a previous lab member, building on the structure of RGM bound to its receptor Neogenin. Our work elucidated the signalling mechanism for RGM-mediated axon guidance and this paper was published in Science. My DPhil since then has focussed on the other arm of RGM signalling through bone morphogenetic proteins (BMPs). My work has shed light on the disease-causing mechanism of the JHH-linked mutations in the RGM protein, and has also shown for the first time that the Neogenin and BMP signalling pathways are physically linked by RGMs.
The training I have received in STRUBI has allowed my DPhil to span many different techniques including mammalian cell culture, x-ray crystallography, biophysical techniques such as MALS and SAXS and fluorescence microscopy. I am very grateful to my supervisor and other collaborators and lab members who have helped me to gain this experience.
Outside of the lab I have had opportunities to teach, including Biological Chemistry classes for first year undergraduates and tutorials for the UNIQ summer school for sixth form students applying for Biochemistry at Oxford. I also enjoyed rowing for my college and being part of my college graduate social committee.
Repulsive Guidance Molecule (RGM) is a structural bridge between Neogenin and Bone Morphogenetic Protein signalling. E.G. Healey, B. Bishop, J. Elegheert, C.H. Bell, S. Padilla-Parra, C. Siebold. Submitted. 2014.
Structure of the repulsive guidance molecule (RGM)-neogenin signaling hub. C.H. Bell, E. Healey, S. van Erp, B. Bishop, C. Tang, R.J. Gilbert, A.R. Aricescu, R.J. Pasterkamp, C. Siebold. Science. 2013, 341 (6141): pages 77-80. PMID: 23744777.
Phosphoproteins in stress-induced disease. L.E. Dalton, E. Healey, J. Irving, S.J. Marciniak. Prog. Mol. Biol. Transl. Sci. 2012, 106: pages 189-221. PMID: 22340719