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Poul Nissen


Keywords

  • Membrane Proteins
  • Transporters
  • Crystallography
  • Structural Biology
  • Drug Discovery

Director of DANDRITE
Head of Nissen group (Structural and Functional Studies of Membrane Transporters in Brain)

Professor Poul Nissen
PhD in Molecular Biology

Membrane proteins in neurobiology and drug discovery

We study the atomic structure, mechanism and cellular function of membrane transport proteins with main focus on neuroscience, how membrane transport proteins orchestrate neuronal signaling networks in the brain, and how these are affected in neurological and psychiatric disorders. We use electron microscopy and X-ray diffraction as our key methodologies.

40-80% of energy consumed in the brain is used by P-type ATPase ion pumps that maintain electrochemical gradients for, e.g. Na+, K+ and Ca2+. These gradients energize numerous other processes in cell membranes such as neurotransmitter transporters, ion channel receptors, and Ca2+ signaling. Similarly, P4-ATPase lipid flippases maintain the asymmetric distributions of lipids in the biological membranes as required for, e.g. vesicle-mediated signal transmission, cellular trafficking, and lipid-based signaling.

We study the structure and function of these membrane transporters and how they relate to brain function and diseases with the long-term goal of understanding higher-order molecular networks in brain cell membranes. We use primarily membrane protein crystallography, biochemical assays, electrophysiology, and fluorescence spectroscopy, and are implementing cryo-EM and EM tomography and establishing XFEL and neutron scattering studies on biomembrane samples.

Our research provides a “first view” of new opportunities in drug discovery and biotechnology, so we are also pursuing spin-out and start-up activities, as well as industry collaborations.

Recent publications

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Lazarov, E., Hillebrand, M., Schröder, S., Ternka, K., Hofhuis, J., Ohlenbusch, A., Barrantes-Freer, A., Pardo, L. A., Fruergaard, M. U., Nissen, P., Brockmann, K., Gärtner, J. & Rosewich, H. (2020). Comparative analysis of alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism ATP1A3 mutations reveals functional deficits, which do not correlate with disease severity. Neurobiology of Disease, 143, Article 105012. https://doi.org/10.1016/j.nbd.2020.105012
Hjorth-Jensen, S. J., Oksanen, E., Nissen, P. & Sørensen, T. L. M. (2020). Prospects for membrane protein crystals in NMX. In P. C. E. Moody (Ed.), Neutron Crystallography in Structural Biology (pp. 47-68). Elsevier. https://doi.org/10.1016/bs.mie.2019.11.019
Nissen, P. (2020). The a-minor motif. In Structural Insights into Gene Expression and Protein Synthesis (pp. 461-463). World Scientific. https://doi.org/10.1142/9789811215865_0055