UCL Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, Faculty of Life Sciences
1) NPP academic/Fellowship/support staff or researcher/technician vacancies are posted when available on the UCL HR website:-
2) Current PhD vacancy in the lab of Prof Annette Dolphin, deadline 17 Mar 2014
Trafficking of voltage-gated calcium channel CaV2.2 subunits in neurons of the pain pathway
Voltage-gated calcium channels are essential for the function of all excitable cells and are implicated in many cellular processes including neurotransmitter release. Within the somatosensory nervous system, the N-type calcium channel CaV2.2 is the main type of calcium channel involved in transmission of nociceptive signals from dorsal root ganglion (DRG) neurons. The importance of this channel in nociception is highlighted by the therapeutic effectiveness of N-type calcium channel blockers in neuropathic pain. The therapeutically important calcium channel complex in DRG neurons is CaV2.2 complexed with the auxiliary subunits α2δ-1 and β. α2δ-1 is the therapeutic target of gabapentin, a drug which is used in various forms of neuropathic pain in humans.
One of the main hindrances to studying the trafficking of the therapeutically important CaV2.2 (N-type) channels has been the lack of tools (antibodies to extracellular loops or tags in these loops). We have now developed CaV2.2 with an extracellular tag which is fully functional, in order to study its trafficking in neurons. The main aim of this project is to utilise this tool both in vitro and in vivo. This will allow plasma membrane localisation and trafficking of the channel to be examined in neurons, including co-cultures of DRG neurons and dorsal horn neurons, to mimic the pain pathway.
Plan of investigation
Use of the exofacially tagged CaV2.2 for calcium channel trafficking studies
We will initially examine the trafficking of tagged CaV2.2 to presynaptic terminals in DRG-dorsal horn co-cultures, and the influence of trafficking proteins and calcium channel auxiliary subunits. We will use confocal microscopy and image analysis to quantify cell-surface expression in neurons and specifically at synapses, identified by fluorescent synaptic markers. We will then develop these studies using a variety of knockout and knockin mouse models.
Informal enquiries to: Prof Annette C Dolphin: email@example.com
Application procedure: Please send C.V. and personal statement to firstname.lastname@example.org
Shortlisted candidates only will be notified by e-mail - interviews will be conducted 4th week of March.
This award funds home/EU UCL fee level and London minimum stipend (living costs) for 3 years. International students may only apply if they can provide proof of self-support/ other sponsorship of 18K/annum for 3 years.
Hoppa MB, Lana B, Margas, W. Dolphin AC & Ryan TA (2012) α2δ couples calcium channels to neurotransmitter release sites to control release probability. Nature 486: 122-125.
Patel R, Bauer CS, Nieto-Rostro M, Margas W, Ferron L, Chaggar K, Crews K, Ramirez-Rozo J, Bennett DLH, Schwartz A, Dickenson AH and Dolphin AC. (2013) α2δ-1 gene deletion affects somatosensory neuron function and delays mechanical hypersensitivity in response to peripheral nerve damage. Journal of Neuroscience 33: 16412-26.
Cassidy, J. and Dolphin, AC (2014) Using exofacially tagged functional Cav2.2 to investigate the modulation of pore subunit trafficking by auxiliary calcium channel. subunits. 58th U.S. Biophysical Society meeting, San Francisco, CA, U.S.A., 15–19 February 2014, Abstract 1672-Pos