B.Sc. (Hons), Biochemistry with a Year in Industry, Imperial College London
Ph.D. Pharmacology, University College London
Postdoctoral Fellow, University of Miami Miller School of Medicine
Postdoctoral Fellow, University College London
Postdoctoral Fellow, University of Maryland School of Medicine
I am broadly interested in ion channel neurobiology, and how ion channel activation, for example by the binding of a ligand, leads to opening of the ion channel and subsequent current flow.
Current projects are focused on determining the mechanism of activation of the AMPA-type glutamate receptor channels in association with accessory subunits known as TARPs. These receptors are found throughout the vertebrate nervous systems and underlie the majority of fast excitatory neurotransmission within the brain. Being so integral to brain function they underlie many of the molecular events involved in learning, memory, cognition, and motor control, and their dysfunction has been associated with many different neurological disorders.
The principle techniques utilized within the laboratory are electrophysiology, in particular single channel patch clamp, as well as molecular biology for the cloning and maintenance of DNA stocks. The single channel patch clamp technique allows the monitoring of currents from single ion channels in real time, and from this data kinetic information can be obtained that can be used to construct microscopic kinetic models. Robust kinetic models enable the quantitative determination of rate constant that define binding, gating, and other facets of ion channel receptor function, and can direct hypotheses regarding the effects of receptor channel modulation on neuronal function.
Shelley C, Whitt JP, Montgomery JR, Meredith AL. (2013). Phosphorylation of a constitutive serine inhibits BK channel variants containing the alternate exon ‘SRKR’. Journal of General Physiology, 142, 585-598.
Shelley C, Farrant M, Cull-Candy SG. (2012). TARP-associated AMPA receptors display an increased maximum channel conductance and multiple kinetically distinct open states. Journal of Physiology, 590, 5723-5738.
Coombs ID, Soto D, Zonouzi M, Renzi M, Shelley C, Farrant M, Cull-Candy SG. (2012). Cornichons modify channel properties of recombinant and glial AMPA receptors. Journal of Neuroscience, 32, 9796-804.
Shelley C, Cull-Candy SG (2010). Desensitization and models of receptor-channel activation. Journal of Physiology, 588, 1395-7. Classical Perspective.
Shelley C, Niu X, Geng YY, Magleby KL (2010). Coupling and cooperativity in voltage activation of a limited state BK channel gating in saturating Ca2+. Journal of General Physiology, 135, 461-80.
Shelley C, Magleby KL (2008). Linking exponential components to kinetic states in Markov models for single-channel gating. Journal of General Physiology, 132, 295-312.
Shelley C, Colquhoun D (2005). A human congenital myasthenia-causing mutation (εL78P) of the muscle nicotinic acetylcholine receptor with unusual single channel properties. Journal of Physiology, 564, 377-96.
Beeson D, Webster R, Ealing J, Croxen R, Brownlow S, Brydson M, Newsom-Davis J, Slater C, Hatton C, Shelley C, Colquhoun D, Vincent A (2003). Structural abnormalities of the AChR caused by mutations underlying congenital myasthenic syndromes. Annals of the New York Academy of Science, 998, 114-24.
Hatton C, Shelley C, Brydson M, Beeson D, Colquhoun D (2003). Properties of the human muscle nicotinic receptor, and of the slow channel myasthenic mutant εL221F, inferred from maximum likelihood fits. Journal of Physiology, 547, 729-60.
Croxen R, Hatton C, Shelley C, Brydson M, Chauplannaz G, Oosterhuis H, Vincent A, Newsom-Davis J, Colquhoun D, Beeson D (2002). Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. Neurology, 59, 162-8.
Amour A, Slocombe PM, Webster A, Butler M, Knight CG, Smith BJ, Stephens PE, Shelley C, Hutton M, Knauper V, Docherty AJ, Murphy G (1998). TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3. FEBS Letters, 435, 39-44.