לוח שנה משולב

While phenotypic plasticity -the capability to respond to the environment- is vital to organisms, tests of its adaptation have remained indecisive because constraints and selection in variable environments are unknown and entangled. We show that one can determine the phenotype-fitness landscape that specifies selection on plasticity, by uncoupling the environmental cue and stress in a genetically
engineered microbial system. Evolutionary trajectories revealed genetic constraints in a regulatory protein, which imposed cross-environment trade-offs that favored specialization. However, depending on the synchronicity and amplitude of the applied cue and stress variations, adaptation could break constraints, resolve trade-offs, and evolve optimal phenotypes that exhibit qualitatively altered (inverse) responses to the cue. Our results provide a first step to explain the adaptive origins of complex behavior in heterogeneous environments.

"NMR spectroscopy: from structure and dynamics to function"
N.-A. Lakomek1, O. F. Lange2, K.F.A. Walter1, M. Funk1, D. Ban1, D. Lee1, H. Schmidt1, K. Seidel1, C. Farès 3, D. Egger4, P. Lunkenheimer4, R. Kree5, J. Meiler6, Ö. Poyraz7, M. Kolbe7, A. Zychlinsky7, H. Grubmuller2, X. Salvatella8, R.B. Fenwick8, S. Becker1, B. de Groot2, P. Karpinar1,10, S. Ryazanov1,10, M. Babu1,9,10, H. Heise1,10, J. Wagner13, C.O. Fernandez11, A. Fischer10,12, N. Wender10,12, N. Resaei, Ghaleh1,10, S. Eimer10,12, H. Jäckle9, A. Leonov1,10, A. Giese13, J. Schulz10,14, A. Lange1, M. Baldus1,10, M. Zweckstetter1,10, and C. Griesinger1,10

1Dept. for NMR-based Struct. Biology, Max-Planck Institute for Biophysical Chemistry; 2Dept. for Theoretical Biophysics, Max-Planck Institute for Biophysical Chemistry; 3 Max-Planck Institute fürKohleforschung; 4University of Augsburg, Experimental Physics V; 5University of Göttingen, Institute for Theoretical Physics; 6Vanderbilt University, Department of Chemistry, Center of Structural Biology; 7Max-Planck-Institute for Infection Biology, Cellular Microbiology; 8Institute for Research in Biomedicine Barcelona; 9Molecular Evolution Biology, Max Planck Institute for Biophysical Chemistry; 10 DFG-Center for the Molecular Physiology of the Brain; 11Instituto de Biología Molecular y Celular de Rosario - Facultad de Ciencias Bioquímicas y Farmacéuticas - Universidad Nacional de Rosario Suipacha; 12European Neuroscience Institute Göttingen; 13Center for Neuropathology and prion research, LMU; 14Dept. of Neurodegeneration and Restaurative Research, Center of Neurological Medicine

The impact of structural dynamics on the function of proteins will be demonstrated on PrgI, the needle protein of Salmonella (1) as well as VDAC, the most abundant membrane protein in the outer mitochondrial membrane responsible for energy homeostasis and implicated in apoptosis (2).
A more biophysics oriented study will be presented that addresses protein/protein recognition on the example of ubiquitin. This protein adopts many different structures in the complex with other proteins that have been clarified by X-ray crystallography. By measuring a large number of residual dipolar couplings and constructing ensembles from those, we found in the “free” ensemble that all these different conformations are there in solution, suggesting conformational selection as the mechanism (3). I will present our efforts in measuring the time scale of the “recognition” dynamics with NMR and dielectric relaxation spectroscopy. The found in the “free” ensemble a large number of correlated motions. I will describe our efforts to determine them experimentally by cross correlated relaxation. Substantial amounts of correlated motion are found in the ensembles.
Further research on neurodegeneration will be reported. This includes the elucidation of the structures from monomer via oligomer to fibril, interfering with the aggregation by small molecules, characterization of the formed toxic and non-toxic oligomers in-vitro and in-vivo (4), animal experiments and metabonomics of the small molecules in vivo with mass spectrometry (5).

(1) Ö. Poyraz, H. Schmidt, K. Seidel, F Delissen, C Ader, H Tenenboim, C Goosmann, B. Laube, A.F. Thünemann, A. Zychlinsky, M. Baldus, A. Lange, C. Griesinger, and M. Kolbe, Nat. Struct. Mol. Biol. in press 2010
(2) M. Bayrhuber, T. Meins, M. Habeck, S. Becker, K. Giller, S. Villinger, C. Vonrhein, C. Griesinger, M. Zweckstetter, Kornelius Zeth, Proc. Natl. Acad. Sci USA 105, 15370-5 (2008); R. Schneider, M. Etzkorn, K. Giller, V. Daebel, J. Eisfeld, M. Zweckstetter, C. Griesinger, S. Becker, A. Lange, Angew. Chem. Int. Ed. 49, 1882-5 (2010)
(3) Lange, O., Lakomek, N. A., Farès, C., Schröder, G.,Becker, S., Meiler, J., Grubmüller, H., Griesinger, C., de Groot, B. Science, 2008, 320, 1471-1475; Lakomek, N.. A., Walter, K., Fares, C., Lange, O.F., de Groot, B., Grubmüller, H., Brüschweiler, R., Munk, A., Becker, S., Meiler, J., Griesinger, C. J. Biomol. NMR , 2008, 41, 139-155
(4) P. Karpinar, M. Babu Gajula Balija, S. Eimer, S. Kügler, B. H. Falkenburger, G. Taschenberger, F. Opazo, H. Heise, D. Riedel, L. Fichtner, A. Voigt, G. H. Braus, M. Baldus, A. Herzig, H. Jäckle, J. B. Schulz, C. Griesinger, M. Zweckstetter, EMBO J 28, 3256 (2009)
(5) WO 2010/000372 A2: International Publication date: 7 January 2010; Giese, Bertsch, Habeck, Wagner, Weber, Kretzschmar, Hirschberger, Tavan, Geissen, Groschup, Griesinger, Leonov, Ryazanov

1,2,9 Am Fassberg 11, 37077 Goettingen, Germany; 3Mühlheim,Germany; 4 Augsburg, Germany; 5Friedrich Hund Platz, 37077 Göttingen, Germany; 6 Nashville, TN, USA; 7Charitéplatz 1, Berlin, Germany; 8Barcelona, Spain; 10 Göttingen, Germany; 11 Rosario, Argentina; 12 Göttingen, Germany; 13Feodor Lynenstr. 23, München, Germany; 14Waldweg 33, 37073 Göttingen, Germany

This series of three lectures will be an introduction to the physics of low
dimensional interacting quantum systems. Such systems are now, thanks to the progress of physical chemistry and nanofabrication ubiquitous in condensed matter. Recently cold atomic systems have also proved to be remarkable realizations of such low dimensional systems. The lectures will discuss the basic concepts and methods, both analytical and numerical that are relevant for one dimensional physics, as well as present the recent progress that have been made in this field, and the challenges that still awaits us.