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Nissen Group

Structural Neurobiology - Structural and Functional Studies of Membrane Proteins in Brain


The Nissen group investigates the structure and molecular mechanisms of membrane transport processes, receptors, and biomembrane ultrastructure. Activities are mainly focused on using cryo-electron microscopy (Cryo-EM), protein crystallography, biochemistry, electrophysiology, and include also small-angle X-ray scattering and cryo-electron tomography.

A major topic of research interest is membrane transporters and receptors involved with neurological and psychiatric disorders, e.g. P-type ATPase that include ion pumps and lipid flippases, but also sodium-dependent amino acid, neurotransmitter transporters, and insulin receptor signaling are studied, as well as supramolecular structures of neuronal membranes addressing cooperative networks governing e.g. action potentials and synaptic functions. Studies also include structure-based drug discovery and protein engineering.

Our investigations link also to translational studies of neurological and psychiatric disorders associated with perturbed ion transport or metabolic control. 

Methods development, integrative structural biology, and bioimaging are also of great interest to the group.

Research Areas: Membrane proteins, Membrane transport and signaling, single-particle Cryo-EM, Cryo-Electron Tomography, Crystallography, Biochemistry, Drug discover

Available projects

The Nissen group currently has projects available for Master and PhD students.

See current research projects in the laboratory here (link opens pdf)

See overview of current study opportunities in the laboratory (link opens new page)

Please contact Group Leader Poul Nissen directly, if interested.


Previous news from the research group


New publication from Poul Nissen's group - Engineering a Prototypic P-type ATPase Listeria monocytogenes Ca2+-ATPase 1 for Single-Molecule FRET Studies

- Research news

Approximately 30% of the ATP generated in the living cell is utilized by P-type ATPase primary active transporters to generate and maintain electrochemical gradients across biological membranes. P-type ATPases undergo large conformational changes during their functional cycle to couple ATP hydrolysis in the cytoplasmic domains to ion transport across the membrane. The Ca2+-ATPase from Listeria monocytogenes, LMCA1, was found to be a suitable model of P-type ATPases and was engineered to facilitate single-molecule FRET studies of transport-related structural changes. Mutational analyses of the endogenous cysteine residues in LMCA1 were performed to reduce background labeling without compromising activity. Pairs of cysteines were introduced into the optimized low-reactivity background, and labeled with maleimide derivatives of Cy3 and Cy5 resulting in site-specifically double-labeled protein with moderate activity. Ensemble and confocal single-molecule FRET studies revealed changes in FRET distribution related to structural changes during the transport cycle, consistent with those observed by X-ray crystallography for the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). Notably, the cytosolic headpiece of LMCA1 was found to be distinctly more compact in the E1 state than in the E2 state. Thus, the established experimental system should allow future real-time FRET studies of the structural dynamics of LMCA1 as a representative P-type ATPase.