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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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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
Geurts, M. M. G., Clausen, J. D., Arnou, B., Montigny, C., Lenoir, G., Corey, R. A., Jaxel, C., Møller, J. V., Nissen, P., Andersen, J. P., Le Maire, M. & Bublitz, M. (2020). The SERCA residue Glu340 mediates interdomain communication that guides Ca2+transport. Proceedings of the National Academy of Sciences (PNAS), 117(49), 31114-31122. https://doi.org/10.1073/pnas.2014896117
Ravishankar, H., Pedersen, M. N., Eklund, M., Sitsel, A., Li, C., Duelli, A., Levantino, M., Wulff, M., Barth, A., Olesen, C., Nissen, P. & Andersson, M. (2020). Tracking Ca2+ ATPase intermediates in real time by x-ray solution scattering. Science Advances, 6(12), Article eaaz0981. https://doi.org/10.1126/sciadv.aaz0981
Gotfryd, K., Boesen, T., Mortensen, J. S., Khelashvili, G., Quick, M., Terry, D. S., Missel, J. W., LeVine, M. V., Gourdon, P., Blanchard, S. C., Javitch, J. A., Weinstein, H., Loland, C. J., Nissen, P. & Gether, U. (2020). X-ray structure of LeuT in an inward-facing occluded conformation reveals mechanism of substrate release. Nature Communications, 11(1), Article 1005. https://doi.org/10.1038/s41467-020-14735-w
Saleh, N., Wang, Y., Nissen, P. & Lindorff-Larsen, K. (2019). Allosteric modulation of the sarcoplasmic reticulum Ca2+ ATPase by thapsigargin via decoupling of functional motions. Physical Chemistry Chemical Physics, 21(39), 21991-21995. https://doi.org/10.1039/c9cp04736k