Neuroscience in Denmark


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General information

Name (center, department, group or other)
Cell Signalling Pharmacology Lab, University of Copenhagen
Contact name
Lasse K. Bak
Contact email
laba#at#sund#dot#ku#dot#dk
Contact title
Assoc. prof.
Date
17. August 2018


Brief description of research activities

Signals may arise inside cells in the absence of direct activation of a receptor. Also, signals elicited by activation of receptors may be either reinforced or curbed by interaction with other signalling pathways operating inside the cell. Thus, drugs acting solely on receptors are not able to modify such signals.

However, activation of receptors on the surface of cells remain the largest single group of targets for currently marketed drugs.

In the Cell Signalling Pharmacology (CSP) Lab, we aim to better understand receptor- and non receptor-mediated intracellular signals, how parallel signalling trains interact laterally, and which cellular functions are under the control of these signals.

A major interest in CSP is 3’,5’-cyclic adenosine monophosphate (cAMP) signals, how these interact with concurrent Ca2+ signals, and how such intersecting signals control cellular metabolism - we call that signalling-metabolism coupling, and this is a major focus in CSP across projects.

We believe that knowledge about these intersecting signals is necessary for developing novel strategies to treat a range of neurological diseases.

Our current questions are:
- How do intracellular signals regulate the cellular functions involved in memory formation?
- Why are between 10 and 30% of epilepsy patients resistant to the current drug-based treatments?
- Are there any novel drug targets for dementias or epilepsy to be found within the compartmentalised signalling or signalling-metabolism coupling in brain cells?

Keywords

Signalling, cAMP, calcium, metabolism, astrocyte, dementia, epilepsy

Research tools and techniques

- Cell-based model systems and isolated mitochondria
- Biosensor-based live cell assays of intracellular signalling (cAMP, calcium)
- Biochemical assays
- Molecular biology
- Metabolic assays (e.g. Seahorse XF)

Scientific Personnel

No of Associate Professors/Postdocs: 1
No of PhD students: 3
Other: 8

Key references from within the last 5 years

Jakobsen E., Lange S. C., Andersen J. V., Desler C, Kihl H. F., Hohnholt M. C., Stridh M. H., Rasmussen L. J., Waagepetersen H. S., and Bak L. K. (2018) The inhibitors of soluble adenylate cyclase 2-OHE, KH7, and bithionol compromise mitochondrial ATP production by distinct mechanisms. Biochem Pharmacol. 155:92-101.

Bak L. K., Walls A. B., Schousboe A., Waagepetersen H. S. (2018) Astrocytic glycogen metabolism in the healthy and diseased brain. J. Biol. Chem. 293(19):7108-7116.

Bak L. K. and Walls A. B. (2018) Rebuttal from Lasse K. Bak and Anne B. Walls. J Physiol. 596(3): 357.

Bak L. K. and Walls A. B. (2018) Lack of evidence supporting an astrocyte-to-neuron lactate shuttle coupling neuronal activity to glucose utilisation in the brain. J. Physiol. 596(3): 351-353.

Bak L. K. (2017) Astrocytes take the stage in a tale of signaling-metabolism coupling. J. Biol. Chem. 292(22):9439-9440.

Bak L. K. and Schousboe A. (2016) Misconceptions regarding basic thermodynamics and enzyme kinetics have led to erroneous conclusions regarding the metabolic importance of lactate dehydrogenase isoenzyme expression. J. Neurosci. Res. 95(11):2098-2102.

Satrústegui J. and Bak L. K. (2015) Fluctuations in cytosolic calcium regulate the neuronal malate-aspartate NADH shuttle: implications for neuronal energy metabolism. Neurochem. Res. 40(12):2425-30.

Lange S. C., Winkler U., Andresen L., Byhrø M., Waagepetersen H. S., Hirrlinger J., Bak L. K. (2015) Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate. Neurochem. Res. 40(12):2517-2526.

Müller M. S., Pedersen S. E., Walls A. B., Waagepetersen H. S., Bak L. K. (2015) Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes. GLIA 63(1):154-162.

Müller M. S., Fox R., Shousboe A., Waagepetersen H. S., Bak L. K. (2014) Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis. GLIA 62(4):526-534.

Scherfigsvej 7
2100 Copenhagen Ø
Denmark
Tel. +45 39 12 80 00
CVR-nr. 11 81 49 13
thebrainprize@lundbeckfonden.com
www.thebrainprize.org
Nils Axelsen Ralf Hemmingsen Lauritz Holm-Nielsen Ralf Hemmingsen Jens Oddershede Jens Frederik Rehfeld Anders Bjørklund