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My research interests cover a broad range of topics in theoretical soft condensed matterbiological physics, and quantitative (systems) biology. On the one hand, I am studying the mechanical and dynamical properties of biological and soft condensed matter. Here, main themes of my research are morphological transitions, shape fluctuations and instabilities, and the emergence of order. On the other, I am using physical methods to investigate the physiological properties of microbiological subsystems. Here, the long-term goal is to establish quantitative links between molecular scales and cell physiology.

My lab is also part of the Center for Synthetic Microbiology (SYNMIKRO). In this center we closely collaborate with the experimental groups of A. Brune, H.-U. Mösch, L. Søgaard-Andersen and M. Thanbichler and the theoretical groups of S. Dahlke and B. Freisleben.

 

Current research topics


virus-Mechanical properties of biological matter

  • Stability of phages and viral elasticity
  • Cell motility
  • Membrane fusion


 
mipz1-Bacterial Cellbiology
  • Cell division in bacteria (Caulobacter & Myxo)
  • Protein oscillations
 

mapkinase
 


-Quantitative Biology                                     

  • Nitrogen assimilation in bacteria
  • Physical aspects of bacterial metabolism
  • Decision making in bacterial populations
 



folding-Physical Properties of Macromolecules

  • Protein folding
  • Protein-DNA interactions
 

cilia

-Dynamical Transitions in Soft Condensed Matter Systems

  • Synchronization of ciliar beating
  • Active membranes in confining geometries
 

cancer

-Physics Approaches to Cancer

  • Analysis of gene expression data
  • Development of predictors for cancer subtypes

 

 



Recent Publications (full list can be found here):

 
pattern_prl.png
Stripe Formation in Bacterial Systems with Density-Suppressed Motility
(with X. Fu et al. PRL 108, 198102 (2012))
 
Engineered bacteria in which motility is reduced by local cell density generate periodic stripes of high and low density when spotted on agar plates. We study theoretically the origin and mechanism of this process in a kinetic model that includes growth and density-suppressed motility of the cells. The spreading of a region of immotile cells into an initially cell-free region is analyzed. From the calculated front profile we provide an analytic ansatz to determine the phase boundary between the stripe and the no-stripe phases. The influence of various parameters on the phase boundary is discussed.
 
 



diversity.png
Influence of molecular noise on the growth of single cells and bacterial populations
(with M. Schmidt and M. Creutziger, PLoS One 7(1): e29932 (2012))
 
During the last decades experimental studies have revealed that single cells of a growing bacterial population are significantly exposed to molecular noise giving rise to significant cell-to-cell variations. In this study we theoretically explore if there are evolutionary benefits of noise for a growing population of bacteria. We analyze different situations where noise is either suppressed or where it affects single cell behavior. We consider two specific examples that have been experimentally observed in wild-type Escherichia coli cells: (i) the precision of division site placement (at which molecular noise is highly suppressed) and (ii) the occurrence of noise-induced phenotypic variations in fluctuating environments. Surprisingly, our analysis reveals that in these specific situations both regulatory schemes [i.e. suppression of noise in example (i) and allowance of noise in example (ii)] do not lead to an increased growth rate of the population. Assuming that the observed regulatory schemes are indeed caused by the presence of noise our findings indicate that the evolutionary benefits of noise are more subtle than a simple growth advantage for a bacterial population in nutrient rich conditions.
 
 
 
science11
Sequential Establishment of Stripe Patterns in an Expanding Cell Population
(with C. Liu et al. Science 334, 238 (2011), see also press release)
 
Periodic stripe patterns are ubiquitous in living organisms. We describe a synthetic genetic circuit
that couples cell density and motility. This system enabled programmed Escherichia coli cells
to form periodic stripes of high and low cell densities sequentially and autonomously.
Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent
aggregation process at the front of the continuously expanding cell population. The number
of stripes formed could be tuned by modulating the basal expression of a single gene. The
results establish motility control as a simple route to establishing recurrent structures without
requiring an extrinsic pacemaker.
 
 
Nature Reviews cover
Temporal and spatial oscillations in bacteria
(with  L. Søgaard-Andersen, Nature Reviews Microbiology 9, 565 (2011), see also press release)
 
 Oscillations pervade biological systems at all scales. In bacteria, oscillations control fundamental processes, including gene expression, cell cycle progression, cell division, DNA segregation and cell polarity. Oscillations are generated by biochemical oscillators that incorporate the periodic variation in a parameter over time to generate an oscillatory output. Temporal oscillators incorporate the periodic accumulation or activity of a protein to drive temporal cycles such as the cell and circadian cycles. Spatial oscillators incorporate the periodic variation in the localization of a protein to define subcellular positions such as the site of cell division and the localization of DNA. In this Review, we focus on the mechanisms of oscillators and discuss the design principles of temporal and spatial oscillatory systems.
 
 


 
 
Cancer Research Fig
 Protein Kinase C Inhibitor Sotrastaurin Selectively Inhibits the Growth of CD79 Mutant Diffuse Large B-Cell Lymphomas
(with T. Naylor, H. Tang, A. Enns, W. Schuler, B. Dörken, M. Warmuth, G. Lenz, and F. Stegmeier, Cancer Research 71, 2643 (2011))
 
 The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) correlates with poor prognosis. In this study, we offer evidence of therapeutic potential for the selective PKC (protein kinase C) inhibitor sotrastaurin (STN) in preclinical models of DLBCL. A significant fraction of ABC DLBCL cell lines exhibited strong sensitivity to STN, and we found that the molecular nature of NF-kB pathway lesions predicted responsiveness. our findings offer a strong rationale for the clinical evaluation of STN in ABC DLBCL patients who harbor CD79 mutations also illustrating the necessity to stratify DLBCL patients according to their genetic abnormalities.
 
 
motors_steinberg
Transient binding of dynein controls bidirectional long-range motility of early endosomes
(with M. Schuster, R. Lipowsky, M.-A. Assmann, G. Steinberg, PNAS 108, 3618 (2011))
 
 In many cell types, bidirectional long-range endosome transport is mediated by the opposing motor proteins dynein and kinesin-3. Here we use a fungal model system to investigate how both motors cooperate in early endosome (EE) motility. We fused the green fluorescent protein to the endogenous dynein heavy chain and the kin3 gene and visualized both motors and their cargo in the living cells. Whereas kinesin-3 was found on anterograde and retrograde EEs, dynein motors localize only to retrograde organelles. Live cell imaging shows that binding of retrograde moving dynein to anterograde moving endosomes changes the transport direction of the organelles. Theoretical modeling shows that the observed in vivo trajectories are indeed compatible with a "loading on the run" mechanism.

cancerpnas


plosonepaperMB
Critical role of PI3K signaling for NF-κB–dependent survival in a subset of activated B-cell–like diffuse
large B-cell lymphoma cells

(with B. Kloo, D. Nagel, M. Pfeifer, M. Grau, M. Düwel, M. Vincendeau, B. Dörken, G. Lenz, and D. Krappmann, PNAS 108, 272 (2011)).

The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Here we report that constitutive activity of PI3K and the downstream kinase PDK1 are essential for the viability of two ABC DLBCL cell lines that carry mutations in the BCR proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF-κB activity and decreases the expression of NF-κB target genes.









A Geometrical Model for DNA Organization in Bacteria 
(with M. Buenemann, PLoS ONE 5(11): e13806)
 
In this paper we develop a geometrical model that explains the observed linear correlation (of the bacterium Caulobacter) between the spatial position of genes in the cellular volume and the position on the chromosomal map.
 



nitrogen

Reversible Adenylylation of Glutamine Synthetase Is Dynamically Counterbalanced during Steady-State Growth of Escherichia coli 
(with H. Okano, T. Hwa and D. Yan, J. Mol. Biol. (2010) 404, 522–536)
 
Glutamine synthetase (GS) is the central enzyme for nitrogen assimilation in Escherichia coli and is subject to reversible adenylylation (inactivation) by a bifunctional GS adenylyltransferase/adenylyl-removing enzyme (ATase). Here, we show that the adenylyl-removing (AR) activity of ATase is required to counterbalance its AT activity during steady-state growth under both nitrogen-excess and nitrogen-limiting conditions. The results suggest that dynamic counterbalance by reversible covalent modification may be a general strategy for controlling the activity of enzymes such as GS, whose physiological output allows adaptation to environmental fluctuations.

folding


Analysis of single molecule folding studies with replica correlation functions
(with S. Cho and P. Wolynes, Chem. Phys. Lett. 471 (2009) 310–314)

Single molecule experiments that can track individual trajectories of biomolecular processes provide a challenge for understanding how these stochastic trajectories relate to the global energy landscape. Using trajectories from a native structure based simulation, we use order parameters that accurately distinguish between protein folding mechanisms that involve a simple, single set of pathways versus a complex one with multiple sets of competing pathways. We show how the folding dynamics can be analyzed with replica correlation functions in a way that is compatible with single molecule experiments.





cilia2

Synchronization, phase locking, and metachronal wave formation in ciliary chains
(with T. Niedermayer and B. Eckhardt, Chaos (2008), 037128)

We develop a simple model for ciliary motion that is complex enough to describe well the behavior of beating cilia but simple enough to study collective effects analytically. Beating cilia are described as phase oscillators moving on circular trajectories with a variable radius. This radial degree of freedom turns out to be essential for the occurrence of hydrodynamically induced synchronization of ciliary beating between neighboring cilia. The transitions to the synchronized and phase-locked state of two cilia and the formation of metachronal waves in ciliary chains with different boundary conditions are discussed.


virus2



Mechanical limits of viral capsids
(with M. Buenemann, PNAS 104 (2007), 9925–9930)

We study the elastic properties and mechanical stability of viral capsids under external force-loading with computer simulations. We demonstrate how, in a combined numerical and experimental approach, the elastic parameters of specific phages can be determined with high precision. The experimentally observed bimodality of spring constants is shown to be of geometrical origin. We define a criterion for capsid breakage that explains well the experimentally observed rupture. We also discuss the influence of chirality and DNA packaging on the mechanical properties. Finally, we show how our numerically calculated energy maps can be used to extract information about the strength of protein–protein interactions from rupture experiments. [ pdf,  suppl. mater,press release]



bilayer3

Kinetics of DNA-mediated docking reactions between vesicles tethered to supported lipid bilayers
(with Y.-H. Chan and S. Boxer, PNAS 104 (2007), 18913–18918)

We intropduce a novel approach to study the dynamics of membrane–membrane recognition that plays an important for processes such as membrane fusion. We use DNA-tethered vesicles as a general scaffold for displaying membrane components. This system was used to characterize the docking reaction between two populations of tethered vesicles that display complementary DNA. Deposition of vesicles onto a supported lipid bilayer was performed by using a microfluidic device to prevent mixing of the vesicles in bulk during sample preparation. Once tethered onto the surface, vesicles mixed via two-dimensional diffusion. DNA-mediated docking of two reacting vesicles results in their colocalization after collision and their subsequent tandem motion. Individual docking events and population kinetics were observed via epifluorescence microscopy. A lattice-diffusion simulation was implemented to extract from experimental data the probability that a collision leads to docking. For individual vesicles displaying small numbers of docking DNA this probability shows a first-order relationship with copy number as well as a strong dependence on the DNA sequence. Both trends are explained by a model that includes both tethered vesicle diffusion on the supported bilayer and docking DNA diffusion over each vesicle’s surface. These results provide the basis for the application of tethered vesicles to study other membrane reactions including protein-mediated docking and fusion.

 



Current and Past Collaborators:

  • Steve Boxer (Stanford)
  • Jiandong Huang (Hong Kong)
  • Terry Hwa (UCSD)
  • Jean-François Joanny (Institut Curie, Paris) and Jacques Prost (ESPCI, Paris)
  • Sydney Kustu (Berkeley)
  • Daniel Riveline (Grenoble)
  • Peter Swain (McGill)
  • Yiping Wang (Bejing)
  • Peter Wolynes (UCSD)
 
 

Zuletzt aktualisiert: 09.05.2012 · lenzpe

 
 
 
Fb. 13 - Physik

AG Komplexe Systeme, Renthof 6, D-35032 Marburg
Tel. +49 6421 28-24201, Fax +49 6421 28-24291, E-Mail: beatrix.payer@physik.uni-marburg.de

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