Lise Arleth's main research topics include biophysics and physical chemistry with the main focus on structural investigations of macromolecules and their aggregates in solution.
Our research involves self-organizing systems such as microemulsions, surfactants and polymers in solution as well as more complex biological and/or pharmaceutically relevant systems of e.g. proteins, enzymes and their interactions with lipids and surfactants. My main experimental technique is small-angle scattering (X-rays and neutrons), in which I am an international expert.
Another focus area is the examination of membrane proteins “in action”. However, these are challenging to study since they have to be situated in a cell membrane like environment in order not to be destabilized. The central challenge is to record a “movie” of the membrane proteins during their catalytic cycle. In order to do this one has to be able to measure soft structures with a size of only ~5 nm and with a time-resolution of as little as a millisecond. This is a major challenge that we are presently trying to address through development of combined microfluidics and Synchrotron X-ray based techniques.
If we are able to produce these movies of membrane proteins during their catalytic cycle, it will bring forth a far more precise and mechanical understanding of how the membrane proteins work and will be directly applicable in connection with developing medicine with fewer side-effects.
Membrane proteins are the targets for more than half of the pharmaceuticals on the market, but we know surprisingly little about how and why a certain combination of membrane protein and a drug works better than another. As a physicist, I have the drive to examine how things, e.g. membrane proteins, actually work and to move the borderline for what can be measured.
Head of studies, Niels Bohr Institute, University of Copenhagen (~700 MSc and BSc students in physics)
Professor MSO in Scattering and Synthetic Biology, Niels Bohr Institute, Faculty of Science, University of Copenhagen
Associate Professor, Department of Basic Sciences and Environment, Faculty of Life Sciences, Copenhagen University
|2004-2006||Assistant professor in the Biophysics group, Dept. Natural Sciences, Royal Veterinary and Agricultural University (KVL).|
|2001-2004||Postdoc positions at the Risø National Laboratory, Denmark and the 'Manuel Lujan Jr. Neutron Scattering Center', Los Alamos National Laboratory, New Mexico, USA.|
|1996-2001||Ph.D. Studies in Biophysics and Neutron Scattering in the Dept. Condensed Matter Physics and Chemistry, Risø National Laboratory and at the Royal Agricultural and Veterinary University. Supervisors: Jan Skov Pedersen and Rogert Bauer.|
Collaborations within the Center for Synthetic Biology
|Seong Wook Yang
Poul Erik Jensen
Bo Wegge Laursen
Jan H. Jensen
Knud J. Jensen
Selected Scientific Publications
Karlsen, M.L., Thorsen, T.S., Johner, N., Ammendrup-Johnsen, I., Erlendsson, S., Tian, X., Simonsen, J.B., Høiberg-Nielsen, R., Christensen, N.M., Khelashvili, G., Streicher, W., Teilum, K., Vestergaard, B., Weinstein, H., Gether, U., Arleth, L. and Madsen, K.L. Structure of Dimeric and Tetrameric Complexes of the BAR Domain Protein PICK1 Determined by Small-Angle X-Ray Scattering. Structure. 23(7):1258-70. doi:10.1016/j.str.2015.04.020 (2015)
Maric, S., Skar-Gislinge, N., Midtgaard, S., Thygesen, M.B., Schiller, J., Frielinghaus, H., Moulin, M., Haertlein, M., Forsyth, V.T., Pomorski, T.G., Arleth, L. Stealth carriers for low-resolution structure determination of membrane proteins in solution. Acta Crystallographica Section D-Biological Crystallography 70, 317-328, doi:10.1107/s1399004713027466 (2014).
Kynde, S. A. R., Skar-Gislinge, N., Pedersen, M.C., Midtgaard, S.R., Simonsen, J.B., Schweins, R., Mortensen, K., Arleth, L. Small-angle scattering gives direct structural information about a membrane protein inside a lipid environment. Acta Crystallographica Section D-Biological Crystallography 70, 371-383, doi:10.1107/s1399004713028344 (2014).
Midtgaard, S. R., Pedersen, M.C., Kirkensgaard, J.J.K., Sorensen, K.K., Mortensen, K., Jensen, K.J., and Arleth, L. Self-assembling peptides form nanodiscs that stabilize membrane proteins. Soft Matter 10, 738-752, doi:10.1039/c3sm51727f (2014).
Pedersen, M. C., Arleth, L. & Mortensen, K. WillItFit: a framework for fitting of constrained models to small-angle scattering data. Journal of Applied Crystallography 46, 1894-1898, doi:10.1107/s0021889813026022 (2013).
Pedersen, J. S., Oliveira, C.L.P., Hubschmann, H.B., Arleth, L., Manniche, S., Kirkby, N., and Nielsen, H.M. Structure of Immune Stimulating Complex Matrices and Immune Stimulating Complexes in Suspension Determined by Small-Angle X-Ray Scattering. Biophys. J. 102, 2372-2380, doi:10.1016/j.bpj.2012.03.071 (2012).
Malik, L., Nygaard, J., Hoiberg-Nielsen, R., Arleth, L., Hoeg-Jensen, T., and Jensen, K.J. Perfluoroalkyl Chains Direct Novel Self-Assembly of Insulin. Langmuir 28, 593-603, doi:10.1021/la203042c (2012).
Lafleur, J. P., Snakenborg, D., Nielsen, S.S., Møller, M., Toft, K.N., Menzel, A., Jacobsen, J.K., Vestergaard, B., Arleth, L., and Kutter, J.P. Automated microfluidic sample-preparation platform for high-throughput structural investigation of proteins by small-angle X-ray scattering. Journal of Applied Crystallography 44, 1090-1099, doi:10.1107/s0021889811030068 (2011).
Andersen, H. D., Wang, C., Arleth, L., Peters, G. H. & Westh, P. Reconciliation of opposing views on membrane-sugar interactions. Proceedings of the National Academy of Sciences of the USA 108, 1874-1878, doi:10.1073/pnas.1012516108 (2011).
Skar-Gislinge, N., Simonsen, J.B., Mortensen, K., Feidenhans'l, R., Sligar, S.G., Møller, B.L., Bjornholm, T., and Arleth, L. Elliptical Structure of Phospholipid Bilayer Nanodiscs Encapsulated by Scaffold Proteins: Casting the Roles of the Lipids and the Protein. Journal of the American Chemical Society 132, 13713-13722, doi:10.1021/ja1030613 (2010).
Castorph, S., Riedel, D., Arleth, L., Sztucki, M., Jahn, R., Holt, M., Salditt, T. Structure Parameters of Synaptic Vesicles Quantified by Small-Angle X-Ray Scattering. Biophysical J. 98, 1200-1208, doi:10.1016/j.bpj.2009.12.4278 (2010).