Motor Systems

Our group is interested in the physical mechanisms underlying the generation, coordination and regulation of force and movement in biological systems. We pursue a combined theoretical and experimental approach and focus on two systems that reach from the single molecule to the single cell level.

Transcriptional Systems

We study the mechanisms underlying the movement of RNA Polymerase II along its DNA template at the single molecule level. RNA Polymerase II is responsible for the generation of all mRNA, and a central control point for cellular function and behavior.

We intend to focus on the force dependence of rate-limiting off-pathway events, looking at the dynamics of backtracking, the detailed role of the newly polymerized RNA chain, and the cooperative interaction with other RNAP molecules to ultimately reveal the regulatory details that are at the heart of transcription in eukaryotic cells.

Cytoskeletal Systems

We study the mechanisms underlying cytoskeletal dynamics during early Caenorhabditis elegans embryogenesis. The cytoskeleton is the mechanical scaffold of the cell providing all intracellular mobility. C. elegans offers the possibility of pursuing a “systems” approach at the biophysical level: For a particular cytoskeletal activity, we devise an initial theoretical description. To refine, we then perturb in a controlled manner, both mechanically and genetically, and study the subsequent response, both in theory and experiment. We have successfully applied this strategy to improve our understanding of spindle positioning during mitosis, and intend to expand to other microtubule- and actin-based cytoskeletal processes such as pronuclear migration and cleavage furrow ingression. We hope to ultimately reveal the precise biophysical in situ properties and functions of all key cytoskeletal components involved in these processes.

Theory and Experiment

Our group is jointly appointed to the MPI-PKS and the MPI-CBG. We apply methods from non-equilibrium statistical mechanics and non-linear dynamics to devise theoretical descriptions we test using a high-resolution dual-trap optical tweezer (for single molecule experiments performed in reconstituted minimal systems), a UV-lasercutter (for mechanical perturbations of the living cell) and dosage-response RNA-mediated interference (for genetic perturbations of the living cell).

External Collaborators

Work on eukaryotic RNA Polymerase II is performed in collaboration with Prof. Dr. Carlos Bustamante at the University of California, Berkeley.

Selected Publications

E. A. Galburt*, S. W. Grill*, A. Wiedmann, L. Lubkowska, J. Choy, E. Nogales, M. Kashlev, C. Bustamante
Backtracking determines the force sensitivity of RNAP II in a factor-dependent manner.
Nature 446, 820-823 (2007)
* equal first author

S. W. Grill, K. Kruse, F. Jülicher
Theory of Mitotic Spindle Oscillations.
Phys. Rev. Lett. 94 (10), 108104 (2005)

S. W. Grill, J. Howard, E. Schäffer, E. H. K. Stelzer, A. A. Hyman
The Distribution of Active Force Generators Controls Mitotic Spindle Position.
Science 301, 518-521 (2003)

S. W. Grill, P. Gönczy, E. H. K. Stelzer, A. A. Hyman
Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo.
Nature 409 (6820), 630-633 (2001)