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Stephan W. Grill
Motor systems
Previous and current research
Our group is interested in the biological and physical mechanisms underlying movement at the cellular level. 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 focus on the force dependence of rate-limiting off-pathway events, looking at the dynamics of backtracking and the detailed role of the newly polymerized RNA chain 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 great 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 are expanding 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).
Future prospects and goals
Our group studies molecular motor function, both at level of
mechanochemistry of individual enzymes and at the level of cooperative
behavior and function inside a living cell.
At the single
molecule level we focus on RNA Polymerase II, where we intend to study
the relationship between backtracking and transcriptional fidelity, the
cooperative interaction between a number of transcribing molecules, and
internal protein dynamics.
At the cytoskeletal level we focus on early events in C. elegans
embryogenesis, where we intend to study the positioning the mitotic
spindle by pulling from the cortex, critical oscillations in the
presence of shot noise resulting from low motor number, and the
mechanics of cleavage furrow ingression during cell division.
About
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Selected publications
S. W. Grill, P. Gönczy, E. H. K. Stelzer, A. A. Hyman (2001): Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans
embryo, Nature 409 (6820), 630-633.
K. Colombo, S. W. Grill, R. J. Kimple, F. S. Willard, D. P. Siderovski, P. Gönczy (2003): Translation of Polarity Cues into Asymmetric Spindle Positioning in Caenorhabditis
elegans embryos, Science 300, 1957-1961.
S. W. Grill, J. Howard, E. Schäffer, E. H. K. Stelzer, A. A. Hyman (2003): The Distribution of Active Force Generators Controls Mitotic Spindle Position,
Science 301, 518-521.
S. W. Grill, K. Kruse, F. Jülicher (2005): Theory of Mitotic Spindle Oscillations, Phys. Rev. Lett. 94 (10), 108104.