Activities in MacAulay Lab
Brain K+ must be controlled
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.
When cells swell, the ion channel TRPV4 opens. But we did not know why! The MacAulay laboratory publishes a study in JBC revealing that TRPV4 – in some cell types – is able to directly sense the cell expansion by means of its most distal N-terminus and. See the publication here.
Beware of Hemichannels
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!
‘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
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.
Translational research into the dysregulation of the brain water homeostasis, with idiopathic intracranial hypertension (IIH) as the 'model disease'
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!
BrainH20 in Newsweek
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)