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Dr Hugh Robinson

Dr Hugh Robinson

University Senior Lecturer


Office Phone: +44 (0) 1223 333828 Lab: 333835, Fax: 333840

Research Interests

Ion channels and signalling in cancer cells and neurons

My lab studies the ways in which ion channels control membrane potential and intracellular calcium signalling, particularly in neuroendocrine-differentiated cancer cells. Cancers such as pancreatic neuroendocrine tumours, small-cell lung cancer and some breast and prostate cancers show neural characteristics, including excitability and vesicular release of peptides and neurotransmitters. We are interested in how such signalling participates in the invasiveness and progression of these cancers. We are also interested in membrane potential and calcium signalling in mammalian central neurons. We use a combination of patch-clamp and optical recording techniques, cell culture and computational modelling.

Collaborators

Ole Paulsen (PDN)
Rick Livesey (Gurdon Institute)
Bill Colledge (PDN)

 

Teaching

Lectures in: 1B Neurobiology; Part 2 PDN, Modules P7 (Pathophysiology of Cancer), N2 (Molecular and Cellular Neuroscience), N7 (Local Circuits and Neural Networks)

Key Publications

Li, L., Zeng, Q., Bhutkar, A., Galván, J.A., Karamitopoulou, E., Noordermeer, D., Peng, M.-W., Piersigilli, A., Perren, A., Zlobec, I., Robinson, H., Iruela-Arispe M.L. and Hanahan, D. (2018). GKAP acts as a genetic modulator of NMDAR signaling to govern invasive tumor growth. Cancer Cell 33, 1–16.

Mendonça, P.R.F., Kyle, V., Yeo, S.-H., Colledge, W.H., and Robinson, H.P.C. (2018). Kv4.2 channel activity controls intrinsic firing dynamics of arcuate kisspeptin neurons: Kv4.2 potassium channels and firing irregularity in kisspeptin neurons. J. Physiol. 596, 885–899.

Robinson, H.P.C., and Li, L. (2017). Autocrine, paracrine and necrotic NMDA receptor signalling in mouse pancreatic neuroendocrine tumour cells. Open Biol. 7, 170221.

Scheppach, C., and Robinson, H.P.C. (2017). Fluctuation analysis in nonstationary conditions: single Ca2+ channel current in pyramidal neurons. Biophys. J. 113, 2383–2395.

Butler, J.L., Mendonca, P.R.F., Robinson, H.P.C., and Paulsen, O. (2016). Intrinsic Cornu Ammonis Area 1 theta-nested gamma oscillations induced by optogenetic theta frequency stimulation. J. Neurosci. 36, 4155–4169.

Mendonça, P.R., Vargas-Caballero, M., Erdélyi, F., Szabó, G., Paulsen, O., and Robinson, H.P. (2016). Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons. Elife 5, e16475.

Spike generation in the neocortex

Zeberg H, Robinson HPC, Århem P, (2015), Density of voltage-gated potassium channels is a bifurcation parameter in pyramidal neurons, J. Neurophysiol, 113:537-49

Robinson HPC, (2013), Dynamic clamp - synthetic conductances and their influence on membrane potential, Encyclopedia of Biophysics, Springer, pp 527-533

Catterall WA, Raman IM, Robinson HPC, Sejnowski TJ, Paulsen O, (2012), The Hodgkin-Huxley heritage: from channels to circuits, J. Neurosci, 32:14064–14073

Gouwens NW, Zeberg H, Tsumoto K, Tateno T, Aihara K, Robinson HPC, (2010), Synchronization of firing in cortical fast-spiking interneurons at gamma frequencies: a phase-resetting analysis, PLoS Comp Biol, 6: e1000951

Tateno T, Robinson HPC (2009), Integration of broadband conductance input in rat somatosensory cortical inhibitory interneurons: an inhibition-controlled switch between intrinsic and input-driven spiking in fast-spiking cells, J Neurophysiol, 101: 1056-72

Morita K, Kalra R, Aihara K, Robinson HPC, (2008), Recurrent synaptic input and the timing of gamma-frequency-modulated firing of pyramidal cells during neocortical "UP" states, J Neurosci, 28: 1871-81

Electrophysiology of human pluripotent stem-cell (hPSC) derived cortical neurons

Kirwan P, Turner-Bridger B, Peter M, Momoh A, Arambepola D, Robinson HPC, Livesey FJ, (2015), Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro, Development, 142:3178-3187

Shi Y, Kirwan P, Smith J, Robinson HPC, Livesey FJ, (2012), Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses, Nat Neurosci, 15: 477-86, S1

NMDA receptor gating

Kim N-K, Robinson HPC, (2011), Effects of divalent cations on slow unblock of native NMDA receptors in mouse neocortical pyramidal neurons, Eur J Neurosci, 34: 199-212

Vargas-Caballero M, Robinson HPC, (2004), Fast and slow voltage-dependent dynamics of magnesium block in the NMDA receptor: the asymmetric trapping block model, J Neurosci, 24: 6171-80

Computational modelling

Vella M, Cannon RC, Crook S, Davison AP, Ganapathy G, Robinson HPC, Silver RA, Gleeson P, (2014), libNeuroML and PyLEMS: using Python to combine procedural and declarative modeling approaches in computational neuroscience, Front Neuroinform, 8:38

Li X, Morita K, Robinson HPC, Small M, (2013), Control of layer 5 pyramidal cell spiking by oscillatory inhibition in the distal apical dendrites: a computational modeling study, J Neurophysiol, 109:2739-56

Plain English

Ion channels are proteins on the surface of cells that allow ions (molecules with an electrical charge) to pass through the membrane. Our lab studies ion channels in cancer cells, and how they influence the electrical activity, growth and invasiveness of cancer cells. We measure electrical currents using a variety of microscopy and computational techniques.

Above: Technique used to induce mechanical-rupture-induced necrosis of a mouse PanNET cell, while recording from another with a patch-clamp electrode (right). The fire-polished glass microprobe is advanced rapidly at time 0 through the cell at the left, using a piezoelectric manipulator, and withdrawn after 1 second, causing immediate membrane rupture and consequent cell death.

Above: Cell membrane rupture activates NMDARs. Rupture of one cell (during gray bar) evokes a large activation of NMDARs, over tens of seconds (black trace), in another cell situated at a distance of 80 μm. Low-noise whole-cell recording allows resolution of single NMDAR channel openings (right). The approximate time course of glutamate concentration at the surface of the recorded cell is shown in red. This is obtained by solving the diffusion equation for an instantaneous point release of 2×10-14 moles of glutamate at the site of necrosis (release of the cytoplasm of a 2 pL cell containing 10 mM glutamate). See Robinson & Li, 2017.