Professor Nanna MacAulay
Department of Neuroscience
The Panum Institute, room 24-6-34
Phone: +45 3532 7566
The research group focuses on elucidation of the molecular mechanisms underlying water and ion homeostasis in the mammalian brain under both physiological and pathophysiological conditions.
Professor Nanna MacAulay
Department of Neuroscience
The Panum Institute, room 24-6-34
Nanna MacAulay researches the large quantity of water in the mammalian brain which is continuously shifted between the circulating blood and the brain parenchyma as well as between different compartments and cellular structures within the brain tissue. One presumes that the transport of water between these different compartments is under tight control since a disturbance in the cerebral water homeostasis (with associated changes in ion concentrations) may lead to neuronal dysfunction, hydrocephalus, and/or brain edema. However, the incomplete knowledge of the molecular mechanisms responsible for the maintenance of cerebral water transport and their regulation currently prevents the research field from gaining a full understanding of this intricate and crucial (patho)physiological issue. With this lack of identification of the implicated transport mechanisms and their dysregulation in pathology, pharmacological therapy is essentially unavailable for potentially life-threatening conditions involving brain water accumulation, i.e. hydrocephalus, brain edema, acute liver failure, idiopathic intracranial hypertension, etc.
The research group focuses on elucidation of the molecular mechanisms underlying water and ion homeostasis in the mammalian brain under both physiological and pathophysiological conditions. More specifically, the laboratory investigates the transport mechanisms underlying cerebrospinal fluid secretion, brain extracellular fluid generation, activity-dependent glial cell swelling during stimulus-evoked K+ management, and dendritic beading observed during spreading depolarization. The technical approach spans from molecular and biophysical properties of water transport proteins (including aquaporins and cotransporters) to their regulation at the cellular level and their integral function in acutely prepared brain slices and rodent in vivo models.
Born 15th December 1972
2002 PhD from Department of Medical Physiology, UCPH (biophysical measurements of water transport and protein structure/function with Professors Thomas Zeuthen and Ulrik Gether)
1998 MSc in biochemistry at McGill University, Canada (protein kinetics with Professor Rhoda Blostein)
1995-1996 Student exchange to Department of Physiology, McGill University, Canada (molecular biology and transport physiology with Professor John Hanrahan)
1995 BSc in biology at UCPH (membrane transport with Professors Dan Klærke, Ian Lambert, and Peter Leth Jørgensen)
2019- Professor at Department of Neuroscience UCPH
2015-2018 Associate professor at Department of Neuroscience UCPH
2006-2015 Associate professor at Department of Cellular and Molecular Medicine, UCPH
2004-2006 Associate professor at Department of Medical Physiology, UCPH
2002-2003 Postdoc at Department of Neuroscience and Pharmacology, UCPH (neurophysiology with Prof Jørn Hounsgaard)
Professional affiliations and activities
2017- Member of departmental management team at Department of Neuroscience
2016- Head of Graduate Programme in Neuroscience, Faculty of Health and Medical Sciences, UCPH
2016- Organizer of the Neuroseminars
2013-2016 Co-chair of the Society of Physiology’s special interest group “Molecular physiology of channels and transporters’
2011-2016 Member of the strategic research committee at the Faculty of Health and Medical Sciences, UCPH
2008-2015 Member of the research committee at Dept of Cellular and Molecular Medicine, UCPH
2012 Recipient of the Danish Research Council’s career programme ‘Sapere Aude’
2008 Recipient of L’Oreal, Unesco and the Royal Danish Academy of Sciences’ scholarship to ‘Young Women in Natural Sciences’
2006 Recipient of the Danish Independent Research Council’s ’Young Elite Researcher’s Award’
In vivo animal experimentation on anesthetized rodents (including artificial ventilation and measurements of blood gases in addition to determination of brain water and electrolyte content)
In vivo determination of cerebrospinal fluid production (ventriculo-cisternal perfusion and whole animal live imaging; Li-cor Biosciences’ Pearl small animal imaging)
Ion-sensitive microelectrode measurements of (K+, pH, extracellular space) in rodent brain slices
Micro-fluidic chip-based volume measurements of mammalian cells
Two-electrode voltage clamp of Xenopus oocytes (heterologously expressing transport proteins)
Volume measurements of Xenopus oocytes (heterologously expressing transport proteins)
Radio-isotope flux measurements (in ex vivo tissue, cell culture, Xenopus oocytes)
Molecular biology (plasmid preparation, mutagenesis, subcloning, sequencing, in vitro RNA transcription, etc.)
Western blot, surface biotinylation, immunostaining, etc.
74. Trine Lisberg Toft-Bertelsen, Brian Roland Larsen, Sofie Kjellerup Christensen, Himanshu Khandelia, Helle S. Waagepetersen & Nanna MacAulay (2020) Clearance of activity-evoked K+ transients and associated glia cell swelling occur independently of AQP4; A study with an isoform-selective AQP4 inhibitor. GLIA, accepted for publication
73. Nanna MacAulay (2020) Molecular mechanisms of K+ clearance and extracellular space shrinkage-Glia cells as the stars. GLIA, epub ahead of print (invited review)
72. Brian Skriver Nielsen, Trine Lisberg Toft-Bertelsen, Sara D. Lolansen, Connor L. Anderson, Morten Schak Nielsen, Roger J. Thompson & Nanna MacAulay (2020) Pannexin 1 activation and inhibition is permeant-selective. Journal of Physiology 598:361-379
71. Trine Lisberg Toft-Bertelsen, Oleg Yarishkin, Sara Redmon,Tam TT Phuong, David Krizaj & Nanna MacAulay (2019) Volume sensing in the transient receptor potential vanilloid 4 ion channel is cell type-specific and mediated by an N-terminus volume-sensing domain. Journal of Biological Chemistry 294:18421-18434
70. Brian Skriver Nielsen, Francesco Zonta, Thomas Farkas, Thomas Litman, Morten Schak Nielsen & Nanna MacAulay (2019) Structural determinants underlying permeant discrimination of the Cx43 hemichannel. Journal of Biological Chemistry 294:16789-16803
69. Kasper Lykke, Mette Assentoft, Sofie Hørlyck, Hans Christian C. Helms, Anca Stoica, Trine L. Toft-Bertelsen, Katerina Tritsaris, Frederik Vilhardt, Birger Brodin & Nanna MacAulay (2019) Evaluating the involvement of cerebralmicrovascular endothelial Na+/K+-ATPase and Na+-K+-2Cl- co-transporter (NKCC1) in electrolyte fluxes in an in vitro BBB model of dehydration. Journal of Cerebral Blood Flow and Metabolism 39: 497-512.
68. Brian Roland Larsen, Anca Stoica, Nanna MacAulay (2019) Developmental maturation of activity-induced K+and pH transients and the associated extracellular space dynamics in the rat hippocampus. Journal of Physiology, 597: 583-597
67. Claudia Brandt, P Seja, Katrin Töllner, Kerstin Römermann, Philip Hampel, M Kalesse, A Kipper, Peter W Feit, Kasper Lykke, Trine L Toft-Bertelsen, P Paavilainen, I Spoljaric, Martin Puskarjov , Nanna MacAulay, Kai Kaila, Wolfgang Löscher (2018) Bumepamine, a brain-permeant benzylamine derivative of bumetanide, does not inhibit NKCC1 but is more potent to enhance phenobarbital's anti-seizure efficacy. Neuropharmacology 143:186-204
66. Eva Kjer Oernbo, Kasper Lykke, Annette B. Steffensen, Kathrin Töllner, Christina Kruuse, Martin Fredensborg Rath, Wolfgang Löscher & Nanna MacAulay (2018) Cerebral influx of Na+ and Cl- as the osmotherapy-mediated rebound response in rats. Fluids and Barriers in the CNS 15:27
65. Philip Hampel, Kerstin Römermann, Nanna MacAulay, Wolfgang Löscher (2018) Azosemide is more potent than bumetanide and various other loop diuretics to inhibit the sodium-potassium-chloride-cotransporter human variants hNKCC1A and hNKCC1B. Scientific Reports 8:9877
64. Annette B. Steffensen, Eva K. Oernbo, Anca Stoica, Niklas J. Gerkau, Dagne Barbuskaite, Katerina Tritsaris, Christine R. Rose & Nanna MacAulay (2018) Cotransporter-mediated water transport underlying cerebrospinal fluid formation. Nature Communications 9:2167
63. Katja Stahl, S. Rahmani, A. Prydz, N. Skauli, Nanna MacAulay, M.N. Mylonakou, R. Torp, Ø. Skare, T. Berg, T.B. Leergaard, R.E. Paulsen, O.P. Ottersen, Mahmood Amiry-Moghaddam (2018) Targeted deletion of the aquaglyceroporin AQP9 is protective in a mouse model of Parkinson's disease. PLoS One 13:e0194896
62. Trine L. Toft-Bertelsen, Brian Roland Larsen & Nanna MacAulay (2018) Sensing and regulation of cell volume - we know so much and yet understand so little: TRPV4 as a sensor of volume changes but possibly without a volume-regulatory role? Channels 12;100-108
61. Siren Berland, Trine L. Toft-Bertelsen, Ingvild Aukrust, Jan Byska, Marc Vaudel, Laurence A. Bindoff, Nanna MacAulay (shared senior authorship) & Gunnar Houge (2018) A de novo Ser111Thr variant in aquaporin-4 in a patient with intellectual disability, transient signs of brain ischemia, transient cardiac hypertrophy, and progressive gait disturbance. Molecular Case Studies 4(1), pii: a002303
60. Brian Skriver Nielsen, Jette Skov Alstrom,Bruce J. Nicholson, Morten Schak Nielsen & Nanna MacAulay (2017) Permeant-specific gating of connexin 30 hemichannels. Journal of Biological Chemistry 292:19999-20009
59. Lena Rosenbaek, Federica Rizzo, Qi Wu, Lorena Rojas-Vega, Gerardo Gamba Ayala, Nanna MacAulay, Oliver Staub & Robert A. Fenton (2017) The thiazide sensitive sodium chloride co-transporter NCC is modulated by site-specific ubiquitylation. Scientific
58. Anca Stoica, Brian Roland Larsen, Mette Assentoft, Rikke Holm, Leanne M. Holt, Frederik Vilhardt, Bente Vilsen, Karin Lykke-Hartmann, Michelle L. Olsen & Nanna MacAulay (2017) The α2β2 isoform combination dominates the astrocytic Na+ /K+-ATPase activity and is rendered nonfunctional by the α2.G301R familial hemiplegic migraine type 2-associated mutation. GLIA 65:1777-1793
57. Brian Roland Larsen & Nanna MacAulay (2017) Activity-dependent astrocyte swelling is mediated by pH-regulating mechanisms. GLIA 65:1668-1681
56. Lena L. Rosenbaek. F. Rizzo, Nanna MacAulay, Olivier Staub & Robert A. Fenton (2017) Functional Assessment of Sodium Chloride Co-transporter NCC Mutants in Polarized Mammalian Epithelial Cells. American Journal of Physiology - Renal Physiology 313:F495-F504
55. Brian s. Nielsen, Daniel B. Hansen, Bruce R. Ransom, Morten S. Nielsen & Nanna MacAulay (2017) Connexin hemichannels in astrocytes: An assessment of controversies regarding their functional characteristics. Neurochemical
54. Trine L. Toft-Bertelsen, David Krízaj & Nanna MacAulay (2017) When size matters: transient receptor potential vanilloid 4 channel as a volume-sensor rather than an osmo-sensor. Journal of Physiology 595:3287-3302
53. Emma Olesen, Hanne Moeller, Mette Assentoft, Nanna MacAulay & Robert Fenton (2016) The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway. American Journal of Physiology – Renal Physiology 311:935-944
52. Mette Assentoft, Shreyas Kaptan, Hans-Peter Schneider, Joachim W. Deitmer, Bert L. de Groot & Nanna MacAulay (2016) Aquaporin 4 as a NH3 channel. Journal of Biological Chemistry 291:19184-19195
51. P. Wanitchakool, J. Ousingsawat, L. Sirianant, Nanna MacAulay, Rainer Schreiber & Karl Kunzelmann (2016) Cl- channels in apoptosis. European Biophysical Journal 45: 599-610
50. Brian Roland Larsen, Rikke Holm, Bente Vilsen & Nanna MacAulay (2016) Glutamate transporter activity promotes enhanced Na+/K+-ATPase-mediated extracellular K+ management during neuronal activity. Journal of Physiology 594:6627-6641
49. Brian Roland Larsen, Anca Stoica & Nanna MacAulay (2016) Managing brain extracellular K+ during neuronal activity: The physiological role of the Na+/K+-ATPase subunit isoforms. Frontiers of Physiology 7(141), fphys.2016.00141
48. Kasper Lykke, Kathrin Töllner, Peter W. Feit, Thomas Erker, Nanna MacAulay & Wolfgang Löscher (2016) The search for NKCC1-selective drugs: Structure-function relationship of bumetanide and various bumetanide derivatives in inhibiting the human cation-chloride cotransporter NKCC1A. Epilepsy & Behavior 59:42-49
47. Nils Landegren, M. Pourmousa Lindberg, J. Skov, Å. Hallgren, D. Eriksson, Trine Lisberg Toft-Bertelsen, Nanna MacAulay, E. Hagforsen, A. Räisänen-Sokolowski, H. Saha, T. Nilsson, G. Nordmark, S. Ohlsson, J. Gustafsson, E.S. Husebye, E. Larsson, M.S. Anderson, J. Perheentupa, F. Rorsman, Robert A. Fenton & O. Kämpe (2016) Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis. Journal of American Society of Nephrology 27:3220-3228
46. Hanne B. Moeller, J. Slengerik-Hansen, T. Aroankins, Mette Assentoft, Nanna MacAulay, Søren K. Moestrup, V. Bhalla & Fenton RA (2016) Regulation of the Water Channel Aquaporin-2 via 14-3-3θ and -ζ. Journal of Biological Chemistry 291:2469-84
45. Andrew Jo, Daniel A. Ryskamp, Tam T.T. Phuong, Alan S. Verkman, Oleg Yarishkin, Nanna MacAulay & David Križaj (2015). TRPV4 and AQP4 channels synergistically regulate cell volume and calcium homeostasis in retinal Müller glia. Journal of Neuroscience 35:13525-13537
44. Shreyas Kaptan, Mette Assentoft, Hans Peter Schneider, Robert A. Fenton, Joachim Deitmer, Nanna MacAulay & Bert de Groot (2015) Is H95 a pH-dependent gate in aquaporin 4? Structure 23:2309-2318
43. Jette S. Alstrom, Daniel B. Hansen, Morten S. Nielsen & Nanna MacAulay (2015) Isoform-specific phosphorylation-dependent regulation of connexin hemichannels. Journal of Neurophysiology 14:3014-22
42. Annette B. Steffensen, Jeremy Sword, Deborah Croom, Sergei A. Kirov & Nanna MacAulay (2015) Cotransporters as a molecular mechanism underlying spreading depolarization-induced dendritic beading. Journal of Neuroscience 35:12172-12187
41. Kasper Lykke, Mette Assentoft, Robert A. Fenton, Mette M. Rosenkilde & Nanna MacAulay (2015). Vasopressin receptors V1a and V2 are not osmo-sensors. Physiological Reports 3(8), phy2.12519
40. Kasper Lykke, Kathrin Töllner, Kerstin Römermann, Peter W. Feit, Thomas Erker, Nanna MacAulay & Wolfgang Löscher (2015) Structure-activity relationships of bumetanide derivatives: correlation between diuretic activity in dogs and inhibition of human NKCC2 variant A. British Journal of Pharmacology, bph.13231
39. Mette Assentoft, Brian Roland Larsen & Nanna MacAulay (2015) Regulation and Function of AQP4 in the Central Nervous System. Neurochemical Research 40:2615-2627
38. Martin N. Andersen, Lasse Skibsbye, C. Tang, F. Petersen, Nanna MacAulay, Hanne B. Rasmussen & Thomas Jespersen (2015) PKC and AMPK regulation of Kv1.5 potassium channels. Channels 9:121-8
37. Jette S. Alstrom, Line W. Stroemlund, Morten S. Nielsen & Nanna MacAulay (2015) Protein kinase C-dependent regulation of connexin43 gap junctions and hemichannels. Biochemical Society Transaction 43:519-23
36. Daniel Ryskamp, Andrew Jo, Amber Frye, Felix Vazquez-Chona, Nanna MacAulay, Wallace Thoreson, and David Krizaj (2015) Swelling and eicosanoid metabolites differentially gate TRPV4 channels in retinal neurons and glia. Journal of Neuroscience 34:15689-15700
35. Brian Roland Larsen & Nanna MacAulay (2014) Kir4.1-mediated spatial buffering of K+: Experimental challenges in determination of its temporal and quantitative contribution to K+ clearance in the brain. Channels 8:544-560
34. Mette Assentoft, Brian Roland Larsen, Emma T.B. Olesen, Robert A. Fenton & Nanna MacAulay (2014) AQP4 plasma membrane trafficking or channel gating is not significantly modulated by phosphorylation at C-terminal serine residues. American Journal of Physiology – Cell Physiology 307:957-965
33. Daniel Bloch Hansen, Ye Zu-Cheng, Kirstine Calloe, Thomas H. Braunstein, Johannes P. Hofgaard, Bruce R. Ransom, Morten S. Nielsen & Nanna MacAulay (2014) Activation, permeability, and inhibition of astrocytic and neuronal large pore (hemi)channels. Journal of Biological Chemistry 289:26058-26073
32. Daniel Bloch Hansen, Thomas H. Braunstein, Morten S. Nielsen & Nanna MacAulay (2014) Distinct permeation profiles of the connexin 30 and 43 hemichannels. FEBS Letters 588:1446-1457
31. Brian Roland Larsen, Mette Assentoft, Maria L. Cotrina, Susan Z. Hua, Maiken Nedergaard, Kai Kaila, Juha Voipio & Nanna MacAulay (2014) Contributions of the Na+/K+-ATPase, NKCC1, and Kir4.1 to hippocampal K+-clearance and volume responses. GLIA 62:608-622
30. Thomas Zeuthen, Magnus Alsterfjord, Eric Beitz & Nanna MacAulay (2013) Osmotic water transport in aquaporins. Evidence for a stochastic mechanism. Journal of Physiology 591:5017-5029
29. Rikke Sogaard, Lars Borre, Thomas H. Braunstein, Kenneth L. Madsen & Nanna MacAulay (2013) Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1. Journal of Biological Chemistry 288:20195-20207
28. Mette Assentoft, Shreyas Kaptan, Robert A. Fenton, Susan Z. Hua, Bert L. de Groot & Nanna MacAulay (2013) Phosphorylation of rat aquaporin-4 at Ser111 is not required for channel gating. GLIA 61: 1101-1112
27. Lene L. Rosenbaek, Mette Assentoft, Nis B. Pedersen, Nanna MacAulay & Robert A. Fenton (2012) Characterization of a novel phosphorylations site in the sodium chloride transporter, NCC. Journal of Physiology 590:6121-6139
26. Nanna MacAulay & Thomas Zeuthen (2012) Glial K+ clearance and cell swelling: key roles for cotransporters and pumps. Neurochemical Research 37: 2299-2309
25. Thomas Zeuthen & Nanna MacAulay (2012) Transport of water against its concentration gradient: fact or fiction? WIREs Membrane Transport Signaling 1: 373-381 (doi:10.1002/wmts:54)
24. Thomas Zeuthen & Nanna MacAulay (2012) Cotransport of water by the Na+-K+-2Cl- cotransporter expressed in Xenopus oocytes: NKCC1 versus NKCC2. Journal of Physiology 590: 1139-1154
23. Rikke Søgaard, Ivana Novak & Nanna MacAulay (2012) Differential effect of ammonia on three glutamate transporter isoforms expressed in Xenopus oocytes. American Journal of Physiology – Cell Physiology, 302:880-891
22. Robert A. Fenton, Hanne B. Moeller, Marina Zelenina, Marteinn T. Snaebjornsson, Torgeir Holen & Nanna MacAulay (2010) Differential water permeability and regulation of three AQP4 isoforms. Cellular and Molecular Life Sciences. 67:829-840
21. Nanna MacAulay & Thomas Zeuthen (2010) Water transport between CNS compartments: contribution of aquaporins versus co-transporters. Neuroscience 168:941-956
20. Hanne B. Moeller, Robert A. Fenton, Thomas Zeuthen & Nanna MacAulay (2009) Vasopressin-dependent short-term regulation of AQP4 expressed in Xenopus oocytes. Neuroscience 164:1674-1684
19. Nanna MacAulay, Steffen Hamann & Thomas Zeuthen (2009) Chloride transporters as water pumps: Elements in a new model of epithelial water transport. In: Physiology and pathology of chloride transporters and channels in the nervous system. Eds FJ Alvarez-Leefmans & E Delpire. Academic Press, Elsevier pp 547-568
18. Rikke Soe, Nanna MacAulay & Dan Klaerke (2009) Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by small changes in cell volume. Neurosci. Lett. 457, 80-84
17. Anne-Kristine Meinild, Don D. Loo, Søren Skovstrup, Ulrik Gether & Nanna MacAulay (2009) Elucidating conformational changes in the gamma-aminobutyric acid (GABA)-transporter-1. J. Biol. Chem. 284:16226-15235
16. Rikke Søgaard, Magnus Alsterfjord, Nanna MacAulay & Thomas Zeuthen (2009) Ammonium ion transport by the AMT/Rh homolog TaAMT1;1 is stimulated by acidic pH. Pflugers Arch., 458: 733-743
15. Hanne B Moeller, Nanna MacAulay (shared first author), Mark A Knepper & Robert A Fenton (2009) Role of multiple phosphorylation sites in the carboxyl-terminal tail of aquaporin-2 for water transport: Evidence against channel gating. Am. J. Physiol. Renal Physiol.296, F649-657
14. Thomas Zeuthen, Emil Zeuthen & Nanna MacAulay (2007) Water transport by GLUT2 expressed in Xenopus laevis oocytes. J. Physiol. 579, 345-361
13. Aidas Alaburda, Raul Russo, Nanna MacAulay & Jørn Hounsgaard (2005) Periodic High and Low Conductance States in Spinal Motoneurons and Interneurons during Scratch-like Network Activity in Adult Turtles. J. Neuroscience 25, 6316-21
12. Nanna MacAulay, Steffen Hamann & Thomas Zeuthen (2004) Water Transport in the Brain: Role of Cotransporters. Neuroscience 129, 1031-1044
11. Nanna MacAulay, Anne-Kristine Meinild, Thomas Zeuthen & Ulrik Gether (2003) Residues in the Extracellular Loop 4 are Critical for Maintaining the Conformational Equilibrium of the g-Aminobutyric Acid (GABA) Transporter-1. J. Biol. Chem 278, 28771-28777
10. Morten Grunnet, Thomas Jespersen, Nanna MacAulay, Nanna K. Jørgensen, Nicole Schmitt, Olaf Pongs, Søren-Peter Olesen & Dan Klærke (2003) KCNQ1 Channels Sense Small Changes in Cell Volume. J. Physiol. 549, 419-427
9. Nanna MacAulay, Thomas Zeuthen & Ulrik Gether (2002) Conformational Basis for the Li+-Induced Leak Current in the rat g-Aminobutyric Acid (GABA) Transporter-1. J. Physiol. 544, 447-458
8. Nanna MacAulay, Ulrik Gether, Dan Klærke & Thomas Zeuthen (2002) Passive Water and Urea Permeability of a Human Na+/Glutamate Cotransporter expressed in Xenopus oocytes. J. Physiol. 542, 817-828
7. Morten Grunnet, Nanna MacAulay, Nanna K. Jørgensen, Bo S. Jensen, Søren-Peter Olesen & Dan Klærke (2002) Regulation of Cloned Ca2+-activated K+ Channels by Cell Volume Changes. Pflugers Arch. 444, 167-177
6. Thomas Zeuthen & Nanna MacAulay (2002) Passive Water Transport in Biological Pores. In International Review of Cytology, vol 215, eds T. Zeuthen & W.D. Stein., pp 259-284. Academic Press, San Diego.
5. Thomas Zeuthen & Nanna MacAulay (2002) Cotransporters as Molecular Water Pumps. In International Review of Cytology, vol 215, eds T. Zeuthen & W.D. Stein., pp 203-230. Academic Press, San Diego.
4. Nanna MacAulay, Annie Bendahan, Claus Juul Loland, Thomas Zeuthen, Baruch I.Kanner & Ulrik Gether (2001) Engineered Zn2+ Switches in the GABA Transporter-1: Differential Effects on GABA Uptake and Currents. J. Biol. Chem. 276, 40476-40485
3. Nanna MacAulay, Ulrik Gether, Dan Klærke & Thomas Zeuthen (2001) Water Transport by the Na+-coupled Glutamate Cotransporter Expressed in Xenopus Oocytes. J.Physiol. 530, 367-378
2. Rhoda Blostein, Stewart E. Daly, Nanna Boxenbaum, Lois K. Lane, José M. Arguello, Jerry B. Lingrel, Steve J. D. Karlish & Michael J. Caplan (1998) Conformational Alterations Resulting from Mutations in Cytoplasmic Domains of the Alpha Subunit of the Na,K-ATPase. Acta Physiol. Scand. (Suppl.) 643, 275-281
1. Nanna Boxenbaum, Stewart E. Daly, Zahid Z. Javaid, Lois K. Lane & Rhoda Blostein (1998) Changes in Steady-state Conformational Equilibrium Resulting from Cytoplasmic Mutations of the Na,K-ATPase α-Subunit. J. Biol. Chem. 273, 23086-23092
|Annette Buur Steffensen||Assistant professor||MacAulay lab|
|Dagne Barbuskaite||Postdoc||MacAulay lab|
|Eva Kjer Ørnbo||PhD fellow||MacAulay Lab|
|Joachim Birch Milan||Guest researcher||MacAulay lab|
|Jonathan Henry Wardman||Assistant professor||MacAulay Lab|
|Nanna MacAulay||Professor||MacAulay Lab|
|Nina Rostgaard||Guest researcher||MacAulay lab|
|Sara Diana Lolansen||PhD student||MacAulay Lab|
|Søren Norge Andreassen||PhD student||MacAulay lab|
|Trine Lind Devantier||Laboratory coordinator||MacAulay Lab|
|Trine Lisberg Toft-Bertelsen||Assistant professor||MacAulay lab|
We have known about cerebrospinal fluid for centuries, and yet we know very little about how this brain fluid is generated. Not even the very basics of which direction the involved proteins run, can we agree on. Go Figure!
The water transporting Na+/K+/2Cl- cotransporter, NKCC1, secretes approximately half of the cerebrospinal fluid. In a @Journal of Physiology CrossTalk, we present evidence for NKCC1 transporting electrolytes and water from the cerebrospinal fluid-secreting tissue and into the brain.
Research teams across the world have struggled to find an efficient and specific inhibitor for the brain water channel, aquaporin 4 (AQP4). Now it is here! The MacAulay lab demonstrates TGN-020 as such an isoform-specific pharmacological tool, with which the research community can test the plethora of proposed roles for AQP4 in brain (patho)physiology. For a start, this publication in #GLIA, cements that AQP4 and passive osmotic water permeability is not required for activity-evoked glia cell swelling.
All neuroscientists are well aware that neuronal signaling associates with K+ release. While we have known for nearly a century that this K+ is swiftly removed from the extracellular space to ensure continuous neuronal activity, the mechanisms by which this crucial (patho)physiological event occurs have remained partly unresolved and highly controversial. This review article from the MacAulay laboratory, recently published in the journal GLIA, condenses the research from the past century and provides a comprehensive introduction to the topic.
Thanks to all those joining me for an afternoon of brain water transport as I defended my Doctor dissertation to obtain the academic title of ’Doctor of Medical Sciences’ at University of Copenhagen (an academic degree above that of the PhD degree).
A special thanks to my two overseas opponents (Professor O’Donnell, UC Davis and Professor MacVicar, UBC) and to the Chairs of the evaluation committee (Professor Lauritzen) and of the defense ceremony (Professor Bräuner-Osborne) – and to all those of you who continued the festive celebration in the evening.
It was a wonderful experience and I highly appreciate participation of so many wonderful people.
Neuroscience graduate students at University of Copenhagen, the NeuroGrads, share their science in a string of amazing poster and oral presentations at the NeuroGrad Winter School 2020. Our excellent young scientists were joined by BrainPrize winner Professor Hugues Chabriat and Impostor Syndrome expert Dr. Valerie Young.
Thanks to the Lundbeck Foundation and the PhD school at Health and Medical Sciences, University of Copenhagen for sponsoring the event and to all participating NeuroGrads for the marvelous presentations.
It has remained elusive what opens the Pannexin 1 large pore channel – and what permeates the channel when open. In this study from the MacAulay laboratory, we – by rigorous and comparative experiments in different cell types – demonstrate that an open channel is not just a hole that allows all molecules of a given size to enter. Pannexin 1, like its cousins the connexions hemichannels, is indeed able to act as a gated and selective channel. See publication and read the commentary in Journal of Physiology.
It has been highly controversial in the connexin field what can permeate an open Cx43 hemichannel. The>MacAulay laboratory publishes a study in Journal of Biological Chemistry on the structural determinants dictating that an open Cx43 hemichannel does not allow atomic ions to permeate: No Cx43 hemichannel-mediated ion conductance. See the publication here.
‘No more brain surgery’ is the dream for children with hydrocephalus, who undergo brain surgery when their shunt repeatedly fails.
Thanks to the Hydrocephalus association for hosting us researchers at their excellent workshop in St. Louis, MO earlier this week: ‘Driving Common Pathways: Extending Insights from Posthemorrhagic Hydrocephalus’.
It was inspiring to meet the brave and optimistic parents of children with hydrocephalus at your fundraising event – as well as so many great scientists and neurosurgeons working tirelessly towards understanding the etiology of this condition and find a cure!
No more brain surgery! Let’s do this!
Professor Nanna MacAulay from Department of Neuroscience receives the Lundbeck Foundation’s Ascending Investigator Grant (5 mio. DKK) to determine the molecular mechanisms underlying sleep-induced regulation of the cerebrospinal fluid secretion.
The project has received10 mio. DKK from the Lundbeck Foundation’s thematic call: ‘What causes brain diseases’.
The MacAulay Laboratory is very excited to initiate this translational collaboration with clinicians Professor Rigmor H. Jensen, the headache center, Glostrup-Rigshospitalet, DK and Professor Alexandra Sinclair, Birmingham University, UK, who are both leading experts in the clinical aspects of this puzzling disease where young, obese females experience debilitating elevations in intracranial pressure. With an additional experimental ‘arm’ governed by transcriptomics expert Associate Professor Tune H. Pers and metobolomics expert Associate Professor Matthew Gillum, both from Novo Nordic Center for Basic Metabolic Research, University of Copenhagen, we will resolve the molecular mechanisms signifying the etiology of this disease - with the vision to create future pharmacological therapy to aid this growing patient group, for which no efficient treatment currently exists.
Thanks to the Lundbeck Foundation for their generous support of our research!
The MacAulay laboratory’s recent discovery of a role for cotransporters in brain fluid dynamics was covered in an issue of Newsweek, see article. The study revealed a novel form of fluid transport underlying the elusive formation of half a liter of brain water each day in the adult human. With this new finding, researchers have a first molecular handle to initiate rational pharmacological targeting of the brain fluid secretory machinery in diseases with disturbed brain water dynamics and disabling elevated intracranial pressure, such as hydrocephalus, stroke, traumatic brain injury, and brain tumors. The MacAulay laboratory is committed to resolving the intricate mechanisms and regulatory pathways governing our brain’s fluid management.
Thanks to the funding agencies that supported the research underlying these important findings (i.e. the Novo Nordic Foundation, the Independent Research Fund Denmark, Thorberg’s Foundation)