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Professor of Molecular Biophysics

Sandro Keller

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Curriculum vitae:

  • 2003–2006 Dissertation, Department of Chemical Biology, Leibniz Institute of Molecular Pharmacology (FMP), Berlin
  • 2006 Dr. rer. nat., Faculty of Natural Sciences - Chemistry and Physics, Martin Luther University Halle–Wittenberg, Halle
  • 2006 Friedrich Weygand Prize by the Max Bergmann Circle, Potsdam
  • 2006–2010 Junior Research Group Leader, Department of Chemical Biology, Leibniz Institute of Molecular Pharmacology (FMP), Berlin
  • 2007 Luther Certificate by the Martin Luther University Halle–Wittenberg, Halle
  • 2009–present Assistant Professor of Molecular Biophysics (with tenure track), Department of Biology, University of Kaiserslautern, Kaiserslautern
  • 2010 Stig Sunner Memorial Award by the North American Calorimetry Conference (CALCON), Colorado Springs
  • 2010 Advancement Award by the Cantonal Government of Graubünden, Chur

Major Research Interest

The research focus of our group is on the complex interplay among proteins, peptides, lipids and detergents. Our principal methods include isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), pressure perturbation calorimetry (PPC), absorption spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, as well as a range of chromatographic techniques. Currently, we are working on the following projects:

• Membrane binding and translocation: A molecule’s ability to bind to and translocate across lipid membranes is of uttermost importance for the extracellular application of intracellularly active compounds in cell biology, medicinal chemistry, and drug development. We have developed and validated calorimetric and spectroscopic approaches to quantify membrane binding and translocation of peptides and proteins as well as a wide range of small molecules.

• Reconstitution of membrane proteins: Membrane proteins often need to be reconstituted from a purified, detergent-solubilised state into lipid bilayers in order to regain their native structures and activities. This is usually achieved in a lengthy trial-and-error approach. To put reconstitution on a more rational basis, we have established ITC as a powerful method for monitoring the reconstitution of membrane proteins into lipid vesicles. Thus, complex changes in the physical state of a protein/lipid/detergent mixture during reconstitution can be followed in a non-invasive and fully automated manner.

• Membrane-protein folding: Membrane proteins play key roles in many physiological and pathological processes. However, the molecular forces that govern their structures and dynamics remain poorly understood. We are employing a combination of protein engineering and various biophysical techniques to study the folding and unfolding thermodynamics and kinetics of membrane proteins as a function of their environment (lipid bilayers, mixed bicelles, and detergent micelles).

• High- and low-affinity interactions: Many protein–ligand interactions are so strong or so weak that their dissociation constants exceed the range directly accessible to titration methods. Such interactions can be assessed indirectly, provided that a suitable competitive ligand is available whose affinity falls within the directly accessible window. We have developed a new calorimetric competition assay that overcomes the limitations of established protocols, thus allowing for a precise thermodynamic description of high- and low-affinity protein–ligand interactions involving poorly water-soluble compounds.

 

Selected Recent Publication

     

  • Kemmer, G.; Keller, S. Nonlinear least-squares data fitting in Excel spreadsheets. Nat. Protoc. 2010, 5, 267–281.

  • Fiedler, S.; Broecker, J.; Keller, S. Protein folding in membranes. Cell. Mol. Life Sci. 2010, 67, 1779–1798.

  • Heerklotz, H.; Tsamaloukas, A. D.; Keller, S. Monitoring detergent-mediated solubilization and reconstitution of lipid membranes by isothermal titration calorimetry. Nat. Protoc. 2009, 4, 686–697.

  • Keller, S.; Tsamaloukas, A.; Heerklotz, H. A quantitative model describing the selective solubilization of membrane domains. J. Am. Chem. Soc. 2005, 127, 11469–11476.

  • Keller, S.; Sauer, I.; Strauss, H.; Gast, K.; Dathe, M.; Bienert, M. Membrane-mimetic nanocarriers formed by a dipalmitoylated cell-penetrating peptide. Angew. Chem. Int. Ed. 2005, 44, 5252–5255.

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