Graduate Research Prize Winners 2011
I was born and completed my education in Bahrain, and then travelled to the UK to study for an MBiochem in Molecular and Cellular Biochemistry at University College, Oxford University. During my final year, and with a Wellcome Trust-funded Summer Studentship, I worked in the laboratories of Prof Jane Endicott, and Dr Chris Norbury towards the structural characterisation of the human cytoplasmic poly(A)polymerase cid1. This project really sparked my interest in structural biology, and I stayed on in Oxford as a Graduate Scholar at St Hilda's College studying for an MRC funded DPhil under Dr. Chris O'Callaghan at the Henry Wellcome Building for Molecular and Cellular Physiology. Here, I investigated the structural nature of protein-protein interactions in immune surveillance, successfully solving structures of three distinct immunologically relevant molecules: the human platelet receptor CLEC-2, the snake venom toxin rhodocytin, and the dengue virus receptor MDL-1. Additionally, I was able to identify binding features and propose a functional mechanism for each of these molecules using biophysical, computational and molecular techniques. The conclusions drawn from these analyses will help to elucidate the mechanisms of cardiovascular disease, snake envenomation, HIV-1 transmission and dengue virus-induced lethal disease.
I really enjoyed my DPhil experience and the opportunities that it afforded me. I am particularly grateful for the skills and techniques that it allowed me to learn and develop, the freedom and level of input I was able to provide to the project, and the great people I've encountered along the way. I am now a Sir Henry Wellcome Postdoctoral Fellow and a College Research Associate at St. John's College at Cambridge University. My research is based at the Biochemistry Department in Prof E.D. Laue's laboratory, with long-term collaborations with Dr B.D. Hendrich (Cambridge), and at EMBL (Grenoble and Hamburg), the Structural Genomics Consortium (Oxford), and the University of Antwerp (Belgium).
- Watson, A.A., and O'Callaghan, C.A. (2011). Molecular Analysis of the Interaction of the Snake Venom Rhodocytin with the Platelet Receptor CLEC-2. Toxins, 3(8), 991-1003.
- Watson, A.A., Christou, C.M., O'Callaghan, C.A. Expression, purification and crystallization of the human UL16-binding protein ULBP1. Protein Expr Purif. 2011 Sep;79(1):44-8. Epub 2011 May 7.
- Watson, A.A., Lebedev, A.A., Hall, B.A., Fenton-May, A.E., Vagin, A.A., Dejnirattisai, W., Felce, J., Mongkolsapaya, J., Palma, A.S., Liu, Y., Feizi, T., Screaton, G.R., Murshudov, G.N., O'Callaghan, C.A. (2011). Structural Flexibility of the Macrophage Dengue Virus Receptor CLEC5A: IMPLICATIONS FOR LIGAND BINDING AND SIGNALING. J Biol Chem. 2011 Jul 8;286(27):24208-18. Epub 2011 May 12. F1000 Recommendation.
- Watson, A.A., and O'Callaghan, C.A. (2009). Crystallization and X-ray diffraction analysis of human CLEC5A (MDL-1) - a Dengue virus receptor. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Jan 1;66(Pt 1):29-31.
- Watson, A.A., Christou, C.M., James, J.R., Fenton-May, A.E., Moncayo, G.E., Mistry, A.R., Davis, S.J., Gilbert, R.J., Chakera, A., O'Callaghan, C.A. (2009).The Platelet Receptor CLEC-2 is Active as a Dimer. Biochemistry. Nov 24;48(46):10988-96.
- Watson, A.A., and O'Callaghan, C.A. (2009). CLEC5. UCSD-Nature Molecule Pages. Published online: 26 Aug 2009 doi:10.1038/mp.a004147.01
- Watson, A.A., Eble, J.A., and O'Callaghan, C.A. (2008). Crystal structure of rhodocytin, a ligand for the platelet-activating receptor CLEC-2. Protein Sci 17, 1611-1616.
- Christou, C.M., Pearce, A.C., Watson, A.A., Mistry, A.R., Pollitt, A.Y., Fenton-May, A.E., Johnson, L.A., Jackson, D.G., Watson, S.P., and O'Callaghan, C.A. (2008). Renal cells activate the platelet receptor CLEC-2 through podoplanin. Biochem J 411, 133-140.
- Watson, A.A., Brown, J., Harlos, K., Eble, J.A., Walter, T.S., and O'Callaghan, C.A. (2007). The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2. J Biol Chem 282, 3165-3172.
- Watson, A.A., and O'Callaghan, C.A. (2005). Crystallization and X-ray diffraction analysis of human CLEC-2. Acta Crystallograph Sect F Struct Biol Cryst Commun 61(Pt 12), 1094-1096.