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Molecular Biomedical Research
Aston Research Centre for Healthy Ageing (ARCHA)
I graduated in Natural Sciences from Cambridge University in 1981 and then stayed to do a Ph.D in the pharmacology department under the supervision of Prof. Sir Arnold Burgen. I subsequently did post-doctoral work at the National Institute for Medical Research, working with Drs Ed Hulme and Nigel Birdsall and then at the MRC Molecular Neurobiology Unit in Cambridge with Dr Mike Hanley. It was here that I first started to work on the pharmacology of calcitonin gene related peptide (CGRP). I was appointed to a lectureship at Aston University in 1991 where I have continued my work on this and allied peptides.
PH2509 (module coordinator): The Pharmacological basis of clinical care
NE1001 (module coordinator); Biochemistry for Neuroscience
4th year tutor; MPharm programme
1982 - 1985 PhD University of Cambridge
1978 - 1982 BA, Pharmacology (Class I), University of Cambridge
I specialise in the teaching of molecular pharmacology, especially cell receptors and signal transduction, reflecting my research interests. I also teach general pharamacology and physiology, cell biology and biochemistry. I teach at all levels of the programme and I am head of the pharmacology teaching group.Main modules taught:
Both CGRP and adrenomedullin produce their effects at G-protein coupled receptors (GPCRs). Something like 70% of all drugs act at GPCRs; thus this family is of particular interest in drug discovery. However, the receptors for CGRP and adrenomedullin are of especial interest as they are made up of two subunits; a most unusual arrangement for GPCRs. They share a common subunit called calcitonin receptor-like receptor (CRLR or CL). This has the structure of a typical GPCR with seven transmembrane helices. However, to respond to CGRP a second protein is required, called receptor activity modifying protein 1 (RAMP1). When CL complexes with the related proteins RAMP2 or RAMP3, adrenomedullin receptors are formed.
In my laboratory we are interested in the molecular and pharmacological characterisation of CGRP and adrenomedullin receptors. Thus we wish to discover how CGRP and adrenomedullin bind to their receptors, how the receptors then activate the cells, how drugs discriminate between these receptors and what other receptors CGRP and adrenomedullin can activate besides CL/RAMP complexes. We also have a more general interest in GPCRs and we are working on the adenosine 2a receptor (found in the brain and implicated in Parkinsons disease), using novel polymers called SMALPs that allow us to purify it in its native form.
Molecular Pharmacology of Family B GPCRs
Use of SMA to solubilise receptors
2018 BBSRC Pathfinder £9,346.42, A new method of in-silico drug discovery using essential dynamics, BB/S000100/1
2018-20, BBSRC, £ 27,542.54, Investigating GPCR:RAMP interactions using nanobodies, BB/R016755/1 (CI with Profs Mark Wheatley and Tim Dafforn, Birmingham and Prof RM Bill, Aston; IPA with UCB).
Membership of Professional Bodies
Aston Research Explorer
Interactions between RAMP2 and CRF receptors: The effect of receptor subtypes, splice variants and cell context. Bailey, S., Harris, M., Barkan, K., Winfield, I., Harper, M.T., Simms, J., Ladds, G., Wheatley, M. and Poyner, D (2019) BBA-Biomembranes (in press).
hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with lymphatic dysplasia. Mackie DI, Al Mutairi F, Davis RB, Kechele DO, Nielsen NR, Snyder JC, Caron MG, Kliman HJ, Berg JS, Simms J, Poyner DR, Caron KM. J Exp Med. 2018 Sep 3;215(9):2339-2353.
Photoaffinity Cross-Linking and Unnatural Amino Acid Mutagenesis Reveal Insights into Calcitonin Gene-Related Peptide Binding to the Calcitonin Receptor-like Receptor/Receptor Activity-Modifying Protein 1 (CLR/RAMP1) Complex. Simms J, Uddin R, Sakmar TP, Gingell JJ, Garelja ML, Hay DL, Brimble MA, Harris PW, Reynolds CA, Poyner DR. Biochemistry. 2018 Aug 14;57(32):4915-4922
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