The overall theme of our group is how neurons communicate with each other to achieve the desired neural function. Our work splits into two major areas: Neurophysiology and Technology development.
Neurophysiological studies
Our interests presently concentrate around the investigation of chemical signalling in the brain. One common theme is purinergic signalling by ATP and adenosine and its roles in several different functional contexts such as: centrally mediated chemosensitive reflexes involved in the control of breathing and arousal; signalling by hypothalamic tanycytes in the context of the control of body weight and food intake; homeostatic control of sleep; endogenous neuroprotective mechanisms in the brain; and during early development. We use a combination of electrophysiological, imaging and biosensing methods to study these problems.
Technology development
We have an active program to provide novel analytical tools for neuroscience research. In particular we are developing microelectrode biosensors specific for a number of transmitters to enable better exploration of chemical signalling in the nervous system. We have concentrated on microelectrode biosensors for the purines and have formed the Warwick Biosensors Group to further this aim. We are also developing biosensors for other analytes (such as glutamate, lactate, D-serine, acetylcholine) and have developed a range of highly selective biosensors for clinical diagnostic purposes. This latter work is linked to a spin out company Sarissa Biomedical Ltd specifically devoted to the commercialization of our biosensors and the development of diagnostic tools.
BA, Zoology, 1981 Cambridge University
PhD, Neuroscience, 1984, Bristol University
CTO & Director Sarissa Biomedical Ltd
Scientific Advisory Board of the British Neuroscience Association
Associate Editor, Purinergic Signalling
Member of the Society for Neuroscience
Member of the British Neuroscience Association
- Nijjar, Sarbjit, Maddison, Daniel, Meigh, Louise, Wolf, Elizabeth, Rodgers, Thomas, Cann, Martin J., Dale, Nicholas, 2021. Opposing modulation of Cx26 gap junctions and hemichannels by CO 2. The Journal of Physiology, 599 (1), pp. 103-118
- Dale, Nicholas, 2021. CO2 sensing by Connexin26 and its role in the control of breathing. Interface Focus
- Bolborea, Matei, Pollatzek, Eric, Benford, Heather, Sotelo-Hitschfeld, Tamara, Dale, Nicholas, 2020. Hypothalamic tanycytes generate acute hyperphagia through activation of the arcuate neuronal network. Proceedings of the National Academy of Sciences of the United States of America, 117 (25), pp. 14473-14481
- Hill, Emily, Dale, Nicholas, Wall, Mark J., 2020. Moderate changes in CO2 modulate the firing of neurons in the VTA and substantia nigra. iScience, 23 (7)
- van de Wiel, Joseph, Meigh, Louise, Bhandare, Amol M., Cook, Jonathan P., Nijjar, Sarbjit, Huckstepp, Robert T. R., Dale, Nicholas, 2020. Connexin26 mediates CO2-dependent regulation of breathing via glial cells of the medulla oblongata. Communications Biology, 3 (1)
- Hill, Emily, Dale, Nicholas, Wall, Mark J., 2020. Detecting CO2-sensitive hemichannels in neurons in acute brain slices. STAR Protocols
- Dale, Nicholas, 2020. Real-time measurement of adenosine and ATP release in the central nervous system. Purinergic Signalling
- Frenguelli, Bruno G., Dale, Nicholas, 2020. Purines : from diagnostic biomarkers to therapeutic agents in brain injury. Neuroscience bulletin, 36, pp. 1315-1326
- Dale, Nicholas, Tian, Faming, Sagoo, Ravjit, Phillips, Norman, Imray, C. (Chris), Roffe, Christine, 2019. Point-of-care measurements reveal release of purines into venous blood of stroke patients. Purinergic Signalling
- Martin, Alexander J., Dale, Nicholas, Imray, Christopher H. E., Roffe, Christine, Smith, Craig J., Tian, Faming, Price, Christopher I., 2019. The association between early neurological deterioration and whole blood purine concentration during acute stroke. Biomarker Research, 7 (1)
- Cook, Jonathan P., de Wolf, Elizabeth, Dale, Nicholas, 2019. Cx26 keratitis ichthyosis deafness syndrome mutations trigger alternative splicing of Cx26 to prevent expression and cause toxicity in vitro. Royal Society Open Science, 6 (8)
- Dospinescu, Valentin-Mihai, Nijjar, Sarbjit, Spanos, Fokion, Cook, Jonathan P., de Wolf, Elizabeth, Biscotti, Maria Assunta, Gerdol, Marco, Dale, Nicholas, 2019. Structural determinants of CO2-sensitivity in the ß connexin family suggested by evolutionary analysis. Communications Biology, 2 (1)
- Tian, Faming, Bibi, Fakhra, Dale, Nicholas, Imray, C. (Chris), 2017. Blood purine measurements as a rapid real-time indicator of reversible brain ischaemia. Purinergic Signalling, 13 (4), pp. 521-528
- de Wolf, Elizabeth, Cook, Jonathan, Dale, Nicholas, 2017. Evolutionary adaptation of the sensitivity of connexin26 hemichannels to CO2. Proceedings of the Royal Society B: Biological Sciences, 284
- Benford, Heather Elizabeth, Bolborea, Matei, Pollatzek, Eric, Lossow, Kristina, Hermans-Borgmeyer, Irm, Liu, Beihui, Meyerhof, Wolfgang, Kasparov, Sergey, Dale, Nicholas, 2017. A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes. Glia, 65 (5), pp. 773-789
- Lazutkaite, Greta, Soldà, Alice, Lossow, Kristina, Meyerhof, Wolfgang, Dale, Nicholas, 2017. Amino acid sensing in hypothalamic tanycytes via umami taste receptors. Molecular Metabolism, 6 (11), pp. 1480-1492
- Bjorness, T. E., Dale, Nicholas, Mettlach, G., Sonneborn, A., Sahin, B., Fienberg, A. A., Yanagisawa, M., Bibb, J. A., Greene, R. W., 2016. An adenosine-mediated Glial-Neuronal circuit for homeostatic sleep. Journal of Neuroscience, 36 (13), pp. 3709-3721
- de Wolf, Elizabeth, van de Wiel, Joseph, Cook, Jonathan, Dale, Nicholas, 2016. Altered CO2 sensitivity of connexin26 mutant hemichannels in vitro. Physiological Reports, 4 (22)
- Bjerring, Peter Nissen, Dale, Nicholas, Larsen, Fin Stolze, 2015. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats : a biosensor study. Neurochemical Research, 40 (2), pp. 258-264
- Lopatár, Ján, Dale, Nicholas, Frenguelli, Bruno G., 2015. Pannexin-1-mediated ATP release from area CA3 drives mGlu5-dependent neuronal oscillations. Neuropharmacology, 93, pp. 219-228
- Burnstock, Geoffrey, Dale, Nicholas, 2015. Purinergic signalling during development and ageing. Purinergic Signalling, 11 (3), pp. 277-305
- Meigh, Louise, Cook, Daniel Sean, Zhang, Jie, Dale, Nicholas, 2015. Rational design of new NO and redox sensitivity into connexin26 hemichannels. Open Biology, 5 (2), pp. 1-9
- Sims, Robert E., Dale, Nicholas, 2014. Activity-dependent adenosine release may be linked to activation of Na+-K+ ATPase : an in vitro rat study. PLoS One, 9 (1)
- Tian, Faming, Greplová, Marta, Frébort, Ivo, Dale, Nicholas, Napier, R. (Richard), 2014. A highly selective biosensor with nanomolar sensitivity based on cytokinin dehydrogenase. PLoS One, 9 (3)
- Meigh, Louise, Hussain, Naveed, Mulkey, Daniel K., Dale, Nicholas, 2014. Connexin26 hemichannels with a mutation that causes KID syndrome in humans lack sensitivity to CO2. eLife, 3
- Meigh, Louise, Greenhalgh, Sophie A., Rodgers, Thomas L., Cann, Martin J., Roper, David I., Dale, Nicholas, 2013. CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits. eLife, 2
- Bolborea, Matei, Dale, Nicholas, 2013. Hypothalamic tanycytes : potential roles in the control of feeding and energy balance. Trends in Neurosciences, Vol.36 (No.2), pp. 91-100
- Wall, Mark J., Dale, Nicholas, 2013. Neuronal transporter and astrocytic ATP exocytosis underlie activity-dependent adenosine release in the hippocampus. The Journal of Physiology, 591 (16), pp. 3853-3871
- Sims, Robert E., Wu, Houdini Ho Tin, Dale, Nicholas, 2013. Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study. PLoS One, Vol.8 (No.1)
- Dale, Nicholas, 2012. A classic review on extracellular ATP and its signalling functions that helped to define the field's agenda for many years. Biochemical Journal, 2012 (1), pp. c3-c6
- Klyuch, Boris P., Dale, Nicholas, Wall, Mark J., 2012. Deletion of ecto-5'-nucleotidase (CD73) reveals direct action potential-dependent adenosine release. Journal of Neuroscience, Vol.32 (No.11), pp. 3842-3847
- Yang, G. K., Squires, Paul E., Tian, Faming, Kieffer, T. J., Kwok, Y. N., Dale, Nicholas, 2012. Glucose decreases extracellular adenosine levels in isolated mouse and rat pancreatic islets. Islets, Vol.4 (No.1)
- Dale, Nicholas, Frenguelli, Bruno G., 2012. Measurement of purine release with microelectrode biosensors. Purinergic Signalling, Vol.8 (No.S1), pp. 27-40
- Masse, Karine, Dale, Nicholas, 2012. Purines as potential morphogens during embryonic development. Purinergic Signalling, Vol.8 (No.3), pp. 503-521
- Klyuch, Boris P., Dale, Nicholas, Wall, Mark J., 2012. Receptor-mediated modulation of activity-dependent adenosine release in rat cerebellum. Neuropharmacology, Vol.62 (No.2), pp. 815-824
- Schmitt, L. Ian, Sims, Robert E., Dale, Nicholas, Haydon, Philip G, 2012. Wakefulness affects synaptic and network activity by increasing extracellular astrocyte-derived adenosine. The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol.32 (No.13), pp. 4417-4425
- Frayling, Cameron, Britton, Ruth, Dale, Nicholas, 2011. ATP-mediated glucosensing by hypothalamic tanycytes. Journal of Physiology, 589 (9), pp. 2275-2286
- Huckstepp, Robert T. R., Dale, Nicholas, 2011. CO2-dependent opening of an inwardly rectifying K+ channel. Pfluegers Archiv, Vol.461 (No.3), pp. 337-344
- Lopatár, Ján, Dale, Nicholas, Frenguelli, Bruno G., 2011. Minor contribution of ATP P2 receptors to electrically-evoked electrographic seizure activity in hippocampal slices : evidence from purine biosensors and P2 receptor agonists and antagonists. Neuropharmacology, Vol.61 (No.1-2), pp. 25-34
- Kowalska, Marta, Tian, Faming, ?mehilová, Mária, Galuszka, Petr, Frébort, Ivo, Napier, R. (Richard), Dale, Nicholas, 2011. Prussian Blue acts as a mediator in a reagentless cytokinin biosensor. Analytica Chimica Acta, Vol.701 (No.2), pp. 218-223
- Dale, Nicholas, 2011. Purinergic signaling in hypothalamic tanycytes : potential roles in chemosensing. Seminars in Cell and Developmental Biology, Vol.22 (No.2), pp. 237-244
- Huckstepp, Robert T. R., Dale, Nicholas, 2011. Redefining the components of central CO2chemosensitivity - towards a better understanding of mechanism. The Journal of Physiology, 589 (23), pp. 5561-5579
- Klyuch, Boris P., Richardson, Magnus J. E., Dale, Nicholas, Wall, Mark J., 2011. The dynamics of single spike-evoked adenosine releasein the cerebellum. Journal of Physiology, The, Vol.589 (No.2), pp. 283-295
- Wall, Mark J., Eason, Robert, Dale, Nicholas, 2010. Biosensor measurement of purine release from cerebellar cultures and slices. Purinergic Signalling, Vol.6 (No.3), pp. 339-348
- Huckstepp, Robert T. R., Eason, Robert, Sachdev, Anshu, Dale, Nicholas, 2010. CO2-dependent opening of connexin 26 and related beta connexins. Journal of Physiology, Vol.588 (No.20), pp. 3921-3931
- Huckstepp, Robert T. R., Bihi, Rachid Id, Eason, Robert, Spyer, K. Michael, Dicke, Nikolai, Willecke, Klaus, Marina, Nephtali, Gourine, Alexander V., Dale, Nicholas, 2010. Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. Journal of Physiology, Vol.588 (No.20), pp. 3901-3920
- Masse, Karine, Bhamra, Surinder, Allsop, Gavin, Dale, Nicholas, Jones, Elizabeth A., 2010. Ectophosphodiesterase/nucleotide phosphohydrolase (Enpp) nucleotidases: cloning, conservation and developmental restriction. International Journal of Developmental Biology, Vol.54 (No.1), pp. 181-193
- Tian, Faming, Wu, Wenjue, Broderick, Michael, Vamvakaki, Vicky, Chaniotakis, Nikos, Dale, Nicholas, 2010. Novel microbiosensors prepared utilizing biomimetic silicification method. Biosensors and Bioelectronics, Vol.25 (No.11), pp. 2408-2413
- Tian, Faming, Gourine, Alexander V., Huckstepp, Robert T. R., Dale, Nicholas, 2009. A microelectrode biosensor for real time monitoring of L-glutamate release. Analytica Chimica Acta, Vol.645 (No.1-2), pp. 86-91
- Etherington, Lori-An V., Patterson, Graham E., Meechan, Louise, Boison, Detlev, Irving, Andrew J., Dale, Nicholas, Frenguelli, Bruno G., 2009. Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus. Neuropharmacology, Vol.56 (No.2), pp. 429-437
- Wall, Mark J., Dale, Nicholas, 2008. Activity-dependent release of Adenosine: a critical re-evaluation of mechanism. Current Neuropharmacology, Vol.6 (No.4), pp. 329-337
- Gourine, Alexander V., Dale, Nicholas, Korsak, Alla, Llaudet, Enrique, Tian, Faming, Huckstepp, Robert T. R., Spyer, K. Michael, 2008. Release of ATP and glutamate in the nucleus tractus solitarii mediate pulmonary stretch receptor (Breuer-Hering) reflex pathway. The Journal of Physiology, 586 (16), pp. 3963-3978
- Wall, Mark J., Wigmore, Geoffery, Lopatár, Ján, Frenguelli, Bruno G., Dale, Nicholas, 2008. The novel NTPDase inhibitor sodium polyoxotungstate (POM-1) inhibits ATP breakdown but also blocks central synaptic transmission, an action independent of NTPDase inhibition. Neuropharmacology, Vol.55 (No.7), pp. 1251-1258
- Wall, Mark J., Dale, Nicholas, 2007. Auto-inhibition of rat parallel fibre-Purkinje cell synapses by activity-dependent adenosine release. Journal of Physiology, Vol.581 (No.2), pp. 553-565
- Wall, Mark J., Atterbury, Alison, Dale, Nicholas, 2007. Control of basal extracellular adenosine concentration in rat cerebellum. Journal of Physiology, Vol.582 (No.1), pp. 137-151
- Gourine, Alexander V., Dale, Nicholas, Llaudet, Enrique, Poputnikov, Dmitry M., Spyer, K. Michael, Gourine, Valery N., 2007. Release of ATP in the central nervous system during systemic inflammation : real-time measurement in the hypothalamus of conscious rabbits. Journal of Physiology, Vol.585 (No.1), pp. 305-316
- Tian, Faming, Llaudet, Enrique, Dale, Nicholas, 2007. Ruthenium purple-mediated microelectrode biosensors based on sol-gel film. Analytical Chemistry, Vol.79 (No.17), pp. 6760-6766
- Frenguelli, Bruno G., Wigmore, Geoffrey, Llaudet, Enrique, Dale, Nicholas, 2007. Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus. Journal of Neurochemistry, Vol.101 (No.5), pp. 1400-1413
- Masse, Karine, Eason, Robert, Bhamra, Surinder, Dale, Nicholas, Jones, Elizabeth A., 2006. Comparative genomic and expression analysis of the conserved NTPDase gene family in Xenopus. Genomics, Vol.87 (No.3), pp. 366-381
- Gourine, Alexander V., Llaudet, Enrique, Dale, Nicholas, Spyer, K. Michael, 2005. Release of ATP in the ventral medulla during hypoxia in rats: role in hypoxic ventilatory response. Journal of Neuroscience, Vol.25 (No.5), pp. 1211-1218
- Dale, Nicholas, 2002. Resetting intrinsic purinergic modulation of neural activity: an associative mechanism?. Journal of Neuroscience, Vol.22 (No.23), pp. 10461-10469
- Pearson, Tim, Nuritova, Feruza, Caldwell, Darren, Dale, Nicholas, Frenguelli, Bruno G., 2001. A depletable pool of adenosine in area CA1 of the rat hippocampus. Journal of Neuroscience, Vol.21 (No.7), pp. 2298-2307
- Dale, Nicholas, 2009. Novel mechanisms of central chemosensitivity. The XXXVI International Congress of Physiological Sciences (IUPS2009), Kyoto, Japan, July 27-August 01, 2009, Published in Journal of Physiological Sciences, pp. 73-73
- Dale, Nicholas, 2008. From chemoreception to eye development - fundamental roles of ATP signalling. Purines 2008 Meeting, Copenhagen, Denmark, 29 June ? 2 July 2008, Published in Purinergic Signalling, pp. S1-S1
- Kung, David, Beylin, Alexander, Miekisiak, Grzegorz Jerzy, Sandler, Adam Lance, Yoo, JiSuk Kristen, Dale, Nicholas, Winn, H. Richard, 2007. Changes in brain extracellular adenosine (ADOe) during acute hypoxia. Experimental Biology 2007 Annual Meeting, Washington, DC, April 28-May 02, 2007, Published in FASEB Journal, pp. A1387-A1387
- Forsythe, Ian D., Grubb, Blair D., Dale, Nicholas, 2010. An introduction to Peter Stanfield's festschrift. Journal of Physiology, The, Wiley-Blackwell Publishing Ltd, pp. 3139-3140
- Dale, Nicholas, Frenguelli, Bruno G., 2009. Release of adenosine and ATP during ischemia and epilepsy. Current Neuropharmacology, Bentham Science Publishers Ltd, pp. 160-179
- Dale, Nicholas, 2008. Dynamic ATP signalling and neural development. The Journal of Physiology, Wiley-Blackwell Publishing Ltd, pp. 2429-2436
- Masse, Karine, Bhamra, Surinder, Eason, Robert, Dale, Nicholas, Jones, Elizabeth A., 2007. Purine-mediated signalling triggers eye development. Nature, Nature Publishing Group, pp. 1058-1062
- Dale, Nicholas, 2006. The acid nature of CO2-evoked adenosine release in the CNS. JOURNAL OF PHYSIOLOGY-LONDON, BLACKWELL PUBLISHING, pp. 633-633
Title | Funder | Award start | Award end |
---|---|---|---|
New tools for investigating connexin26 hemichannel function in physiological systems | BBSRC | 01 Feb 2021 | 31 Jan 2025 |
Do microglia prevent seizure-induced cardiorespiratory dysfunction in freely behaving mice? Full application | Epilepsy Research UK | 01 Oct 2019 | 30 Sep 2021 |
Structural and biophysical basis of Connexin26 channel mediated disease | MRC | 09 Jan 2017 | 08 Jan 2021 |
Connexin 26-mediated breathing control by the healthy and obese brain | MRC | 28 Sep 2015 | 21 Apr 2020 |
Amino acid sensing by hypothalamic tanycytes | BBSRC | 01 Jun 2015 | 30 Nov 2018 |
Connexin 32 evolution to a CO2 sensor - Wellcome Biomedical Vacation Scholarship for Valentin Dospinescu | Wellcome Trust | 02 Jul 2018 | 01 Sep 2018 |
Structural basis of the CO2 sensitivity of Cx26 and role in human physiology | Leverhulme Trust | 01 Jul 2015 | 31 Mar 2018 |
Imaging neural activity in freely behaving rodents at the single cell level | MRC | 01 Mar 2016 | 31 Aug 2017 |
The contribution of tanycyte signalling to the function of hypothalamic networks | MRC | 01 Feb 2012 | 31 Jul 2015 |
Wellcome Trust Vacation Scholarship 2014 - Louise Boeckmans | Wellcome Trust | 14 Jul 2014 | 30 Nov 2014 |
How the brain senses CO2 | MRC | 01 Apr 2011 | 31 Mar 2014 |
Wellcome Trust Summer Student 2013 Daniel Cook | Wellcome Trust | 01 Jun 2013 | 30 Sep 2013 |
Quantitative sensors for phytohormone signalling systems | BBSRC | 01 Aug 2011 | 31 Jul 2012 |
Adenosine release in the preoptic forebrain areas | Wellcome Trust | 01 Jun 2009 | 31 May 2012 |
Regulation of Cortical excitability and seizure activity by purines | Epilepsy Research UK | 01 Jan 2008 | 31 Dec 2010 |
Helping the brain itself: D-ribose to promote recovery after stroke | Research into Ageing | 01 Oct 2007 | 30 Sep 2010 |
All dressed up and nowhere to go - findong the glucosensing party for hypothalmic tanycytes. | MRC | 01 Jan 2007 | 31 Dec 2009 |
Tanycyte-neuron communication in the hypothalamus | Wellcome Trust | 01 Jul 2009 | 26 Aug 2009 |
Synthesis and Nanotechnological Application of Tethered Silicates | EU | 01 Jan 2006 | 31 Dec 2008 |
ATP - A mediator of central chemoreception in brain stem | MRC | 01 Aug 2005 | 31 Jul 2008 |
Novel real-time amperometric detection of extracellular ATP: characterisation of spontaneous ATP release in cerebellum | Wellcome Trust | 01 Jan 2005 | 31 Dec 2007 |
Characterization of ectonucleotidases in the basal forebrain of rat. | Wellcome Trust | 01 Jul 2006 | 31 Aug 2006 |
Commercialisation of purine biosensors: essential tools for scientific and clinical communities | Wellcome Trust | 01 Nov 2005 | 06 Jun 2006 |
Ectonucleotidases and the regulation of motor pattern generation | Wellcome Trust | 01 Mar 2003 | 28 Feb 2006 |
Commercialisation of purine biosensors: essential tools for scientific and clinical communities | Wellcome Trust | 01 Nov 2003 | 31 Oct 2005 |
Real-time detection of ATP-release in spinal cord | Royal Society | 16 Feb 2005 | 01 Mar 2005 |