Petra Schwille - Biophysics
The Biophysics group develops single molecule methods for ultrasensitive analysis of biomolecular dynamics in membranes, cells, and organisms. Besides the /in vivo/ work, we are concerned with reconstituting biological functions in physically controllable systems, such as model membranes or artificial cell modules. Our desire is to identify minimal functional units in a synthetic biology approach, to be able to understand self-organization of biological systems in quantitative terms.
Scientific Profile
Our group is primarily concerned with the development and application of novel spectroscopic and microscopic techniques for the quantitative investigation of sparse and single molecules in solution and living cells. Additionally, we aim for the design of appropriate fluorescence-based protein and enzyme assays for rapid but ultrasensitive characterization. In addition to basic research, the integration of such ultrasensitive detection modules in so-called lab-on-a-chip microfluidic structures is pursued, to facilitate manipulation of minute analyte quantities, subsequent to multiparameter fluorescence analysis. The ultimate goal here is to rapidly and efficiently select cells and molecules with desired characteristics from large heterogeneous libraries.
Motivation and Techniques
Scientific discoveries are often stimulated by the invention of new scientific tools. The enormous progress in the life sciences in recent years is a direct result of the emergence of new powerful bioanalytical technologies. At the dawn of the modern proteomics age, methods are required which greatly simplify the quantitative analysis of protein dynamics and interactions. Ideally, different kinds of proteins should be directly and simultaneously observed in their native environment, i.e., the living cell or even organism, at physiological, i.e. mostly submicromolar, concentrations. Single molecule fluorescence microscopy and spectroscopy, relatively young disciplines at the interface of physics, chemistry and biology, provide excellent conditions for such investigations. During the past years, confocal fluorescence correlation spectroscopy (FCS) and related techniques have enabled us to study a masnifold of different parameters such as diffusion and transport rates, molecular association and dissociation, enzyme dynamics and intramolecular dynamics in vitro, but also in the living cell. Employing cross-correlation schemes and nonlinear fluorescence excitation modes, many different fluorescent species can be observed simulateously. Fluorescence lifetime and anistotropy measurements can further be integrated as they add even more information. In the context of basic cell biological research, these novel techniques open up fascinating perspectives to unravel complex intracellular processes involving multiple species of biomolecules, such as signal transduction and protein trafficking with high spatial and temporal precision. Besides the scientific relevance for single molecule analysis in physics, chemistry and biology, these techniques are of increasing importance also in pharmacologic drug screening. One challenge here is the miniaturized manipulation and selection of biomolecules with respect to their individual properties. The requirement of only minute amounts of analytes without having to synchronize their dynamics, and the possibility to distinguish subpopulations of molecular species which would in bulk analysis be hidden in a statistic mean, open up great perspectives for high-throughput screening applications. To this end, we combine our detection modules with home-designed microfluidic structures of various transparent materials, fabricated by means of standard litographic processes.
Selected Publications
García-Sáez, A. J., Ries, J., Orzáez, M., Pérez-Payà, E. & Schwille, P. Membrane promotes tBID interaction with BCL(XL). /Nat Struct Mol Biol/ 16 (2009) 1178 - 1185
Yu, S. R., Burkhardt, M., Nowak, M., Ries, J., Petrásek, Z., Scholpp, S., Schwille, P. & Brand, M. Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules. /Nature/ 461 (2009) 533-536
Ries, J., Yu, S. R., Burkhardt, M., Brand, M. & Schwille, P. Modular scanning FCS quantifies receptor-ligand interactions in living multicellular organisms. /Nat Methods/ 6 (2009) 643-645
Loose, M., Fischer-Friedrich, E., Ries, J., Kruse, K. and Schwille, P. (2008) Spatial regulators for bacterial cell division self-organize into surface waves in vitro, Science, 320, 789-792
Kim, S.A., Heinze, K. G. and Schwille, P. (2007) Fluorescence correlation spectroscopy in living cells, Nat Methods, 4, 963-973
Petrov, E. P., Ohrt, T., Winkler, R. G. and Schwille, P. (2006) Diffusion and segmental dynamics of double-stranded DNA, Phys Rev Lett, 97, 258101
Bacia, K., Kim, S. A. and Schwille, P. (2006) Fluorescence cross-correlation spectroscopy in living cells, Nat Methods, 3, 83-89
Bacia, K., Schwille, P. and Kurzchalia, T. (2005) Sterol structure determines the separation of phases and the curvature of the liquid-ordered phase in model membranes, Proc Natl Acad Sci USA, 102, 3272-3277
Kim, S. A., Heinze, K. G., Waxham, M. N. and Schwille, P. (2004) Intracellular calmodulin availability accessed with two-photon cross-correlation, Proc Natl Acad Sci USA, 101,105-110
Kahya, N., Scherfeld, D., Bacia, K., Poolman, B. and Schwille, P. (2003) Probing lipid mobility of raft-exhibiting model membranes by fluorescence correlation spectroscopy, J Biol Chem, 278, 28109-28115
Heinze, K. G., Koltermann, A. and Schwille, P. (2000) Simultaneous two-photon excitation of distinct labels for dual-color fluorescence crosscorrelation analysis, Proc Natl Acad Sci USA, 97, 10377-10382
Korlach, J., Schwille P., Webb, W. W. and Feigenson, G. W. (1999) Characterization of lipid bilayer phases by confocal microscopy and fluorescence correlation spectroscopy, Proc Natl Acad Sci USA, 96, 8461-8466
Schwille, P., Meyer-Almes, F.J. and Rigler, R. (1997) Dual-color fluorescence cross-correlation spectroscopy for multicomponent diffusional analysis in solution, Biophys J 72, 1878-1886
Curriculum Vitae
PhD 1996 Max-Planck-Institute for Biophysical Chemistry, Göttingen/ TU Braunschweig- 1997-1999 Postdoctoral work at Cornell University, Ithaca, NY
- 1999-2002 Junior group leader at the MPIbpc Göttingen
- 2002-present Professor of Biophysics at the TU Dresden
Projects
Projects funded by the DFG
SCHW 716/4-2: Investigating the relevance of lipid microdomains for HI virus particle assembly in an artificial cell environment, by means of single molecule fluorescence spectroscopy and microscopy, 01.01.2009 - 31.12.2011
SCHW 716/6-1: Sächsische Forschergruppe ?From Local Constraints to Macroscopic Transport?, project no. 5 ?Brownian Motion and Internal Dynamics in Polymer-Decorated Phospholipid Membranes?, 01.11.2007 - 31.10.2010
HO 2584/6-1: Reconstitution of clathrin/AP-1 coated membrane microdomains on proteoliposomes, 15.07.2008 - 15.07.2011
DFG SO818/1-1: Molecular and biophysical approaches to study insulin secretory granules and lipid microdomains in vitro and in living insulinoma cells, 12/2008 ? 11/2011
DFG: Teilprojekt im Rahmen des SFB Transregio TRR67: Entwicklung einer optischen Plattform zur Charakterisierung von (Oberflächen-) Bindungsreaktionen zwischen Glykosaminoglycanen und Mediatormolekülen, approved, not started yet
DFG Graduiertenkolleg Nano- und Biotechniken für das Packaging elektronischer Systeme: PhD Project ?Von Lipidvesikeln zu künstlichen Chloroplasten: Kooperation von Motorproteinen?, 01.01.2007 ? 31.12.2009
DIGS-BB Projects: Funding of 2 PhD projects, 2008-2011
Projects funded by the European Commission
EU grant agreement No: 216027, Participant no. 9, TheraEDGE: An Integrated Platform Enabling Theranostics Applications at the Point of Primary Care, 03/2008 - 02/20012
Projects funded by the European Union
EFRE iMAD- Imaging and Manipulation Across Dimensions, 01.03.2009 ? 28.02.2011
Project funded by the European Science Foundation
08-EuroMEMBRANE-FP-007: Lipid-protein interactions in membrane organization (LIPIDPROD), granted, not started yet
Project funded by the VolkswagenStiftung
VolkswagenStiftung I/84 089, Towards Molecular Engines: Cooperative Coupling of Molecular Motors in Engineered Environments, 18.05.2009 ? 17.05.2012
Project funded by the Max-Planck-Gesellschaft
Set-up of a small research group at the MPI-CBG in Dresden, 01/2007 - 12/2010
Project funded by the Alexander von Humboldt-Stiftung
Fellowship for Dr. Remigiusz Worch, Research Project: ?Biophysical analysis of the Interleukin-4 signaling complex in artificial membranes?, 01.10.2008 -30.09.2010
Links
Teaching
Practical Courses in the Laboratory
Practical Courses at the Laboratory of the Schwille Group
New:
? Practical course for students of the master course ?Molecular Bioengineering?: 15.02.-17.02.2010.
? Practical course for students of the master course ?Nanobiophysics?: 18.02.-19.02.2010.
? Practical course for physics students: 05.10.-09.10.2009.
Lectures and Seminars
The Schwille group also contributes to two master courses:
Molecular Bioengineering
Nanobiophysics
General information on the master courses can be found here.
Funding
Group Members
All current group members are listed on the Staff Page.
