Department of Molecular Biology and Genetics
Membrane transporters in neuroscience and drug discovery –
Nissen laboratory
Section of Structural Biology Gustav Wieds Vej 10C Contact: Poul
Nissen, [email protected]
BACKGROUND/OVERVIEW The Nissen group investigates molecular
mechanisms of membrane transport processes and biomembrane
structure. Activities are mainly focused on cryo-electron
microscopy (Cryo-EM), protein crystallography, biochemistry,
electrophysiology, and include also small-angle X-ray scattering
and cryo-electron tomography. Main subjects of research concern
membrane transporters involved with neurological and psychiatric
disorders, i.e. P-type ATPase (Na,K-ATPase, Ca-ATPases, lipid
flippases) and Na+ dependent transporters, but include also
structure based drug discovery, protein engineering, and
biomembrane suprastructures of neurons. Research Areas: Membrane
proteins, Membrane transport, Electron microscopy, Crystallography,
Biochemistry, Drug discovery, Tomography
+
Cloning
Expression
Bacteria
Yeast
Mammalian cells
Purification
Workflow Current research projects – incl. student projects
Ca2+-ATPases
Crystallography
Sarco/Endoplasmic Reticulum Ca-ATPase (SERCA) Neutron
crystallography Regulation by histidine rich protein
Plasma membrane Ca-ATPase (PMCA) Structural and functional
characterization of isoforms Regulation by lipids, autoinhibition
& α-synuclein Calcium signalling
Electron microscopy
Neuronal ultrastructure • CryoEM studies of membrane protein
complexes from neurons (axon initial segment, dendritic spines,
synapses)
• Characterization of the axon initial segment by tomography
• FRMD7
J Neurosci 2018, 38:2135
Na,K-ATPase
AHC RDP CAPOS
• Structural and functional studies of mutations causing rare
neurological disorders (Alternating hemiplegia of childhood,
CAPOS)
• Structural characterization of isoforms
Functional characterization
Phospholipid flippases / P4- and P5-ATPases
• Lipid flippases • Lysosomal defects • Structural and
functional characterization
of yeast and mammalian pumps • Substrate identification •
Mechanism of auto-inhibition
Na-symporters • Structure determination of Na-K-Cl
cotransporters and • Na/neurotransmitter symporters
Na+ dependent transporters • NKCC1, GlyT1
Drug discovery
• Drug discovery in neurological / neurodegenerative
disorders
Data processing/modelling
3.1 Å resolution cryo-EM structure
Receptors, mechano-sensation
• Sodium-dependent phosphate transporters: functional and
structural characterisation of dimerisation
• Disease mutant forms of pumps such as Na,K-ATPase and
Ca2+-ATPases and interaction sites for toxic amyloids form
potential targets for drug discovery than can be revealed by
structural studies
• Compound screening for the potential treatment of Wilson’s
disease (Cu-ATPase)
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Structural neurobiology – Nissen group
Professor Poul Nissen
P4- and P5-ATPases Neuronal ultrastructure Lipid flippases,
lysosomal function Axon initial segment, synapses, K2P
Joseph Lyons Esben Quistgaard Ronja Driller Michael Clausen
Milena Timcenko Josephine D. Nissen Thibaud Dieudonné Simon
Rolighed Line Marie Christiansen
Amalie B. Poulsen Michelle J. Laursen Ca2+-ATPases Carl Helmer
PMCA/α-synuclein, SERCA, calcium signaling
Na,K-ATPase Antoni Kowalski Alternating Hemiplegia of Childhood
Sigrid T. Larsen
Michael Habeck Sara Basse Hansen Mads Christiansen Samuel
Hjort-Jensen Marlene Fruergaard Line C. Hansen Sabrina Krepel
Na+ dependent transporters Receptors, mechanosensation NKCC1,
DAT, GlyT1 InsR, sortilins, FRMD7/syndecan
Caroline Neumann Sofia Trampari Jeppe A. Nielsen Azadeh
Shahsavar Charlott Stock
Rasmus K. Flygaard (Sep. 2020)
Postdocs Senior researchers Graduate students Bsc students
2021-22: recruiting 4 PhD students
Deep learning image analysis (cryo-EM)
Jonathan Juul
Research assistants and technicians Anna Marie Nielsen Tanja
Klymchuk Søren Brag
Christine J. F. Nielsen Dorthe Strandbygaard Bente Andersen
Administration and accounting Karen Bech-Pedersen Personal
assistent
Lene Høgenhof Kristensen Accounting
Fellowships
Slide Number 1Structural neurobiology – Nissen group
