@article{4158, abstract = {Together with cell growth, division and death, changes in cell shape are of central importance for tissue morphogenesis during development. Cell shape is the product of a cell's material and active properties balanced by external forces. Control of cell shape, therefore, relies on both tight regulation of intracellular mechanics and the cell's physical interaction with its environment. In this review, we first discuss the biological and physical mechanisms of cell shape control. We next examine a number of develop mental processes in which cell shape change - either individually or in a coordinated manner - drives embryonic morphogenesis and discuss how cell shape is controlled in these processes. Finally, we emphasize that cell shape control during tissue morphogenesis can only be fully understood by using a combination of cellular, molecular, developmental and biophysical approaches.}, author = {Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {Current Biology}, number = {17}, pages = {R790 -- R799}, publisher = {Cell Press}, title = {{Biology and physics of cell shape changes in development}}, doi = {10.1016/j.cub.2009.07.029}, volume = {19}, year = {2009}, } @article{4159, abstract = {Apical cell contraction triggers tissue folding and invagination in epithelia. During Drosophila gastrulation, ventral furrow formation was thought to be driven by smooth, purse-string-like constriction of an actomyosin belt underlying adherens junctions. Now Martin et al. report in Nature that ventral furrow formation is triggered by asynchronous pulsed contractions of the apical acto-myosin cortex in individual cells.}, author = {Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {Developmental Cell}, number = {1}, pages = {4 -- 6}, publisher = {Cell Press}, title = {{Chaos begets order: Asynchronous cell contractions drive epithelial morphogenesis}}, doi = {10.1016/j.devcel.2008.12.011}, volume = {16}, year = {2009}, } @article{4160, abstract = {While the function of patterning in organogenesis is being extensively studied, considerably less is known of reverse effects that organ formation imposes on patterning. In zebrafish, the Kupffer’s vesicle (KV) and parapineal (PP) are embryonic struc- tures that share mechanisms of organogenesis and whose func- tion is essential for normal patterning along the left–right axis. Early morphogenesis of KV and PP organs involve the compaction of progenitor cells into a tight cluster within which three-dimen- sional cellular rosettes are formed. Organisation into rosettes pre- cedes the detachment of progenitor cells from neighbouring tissue and thus represents a key step towards organ formation. Such morphogenetic event is essential for organ function and its disruption has profound effects on left–right patterning.}, author = {Oteíza, Pablo and Lemus, Carmen and Köppen, Mathias and Palma, Karina and Krieg, Michael and Melo, Cristina and Farias, Cecilia and Pulgar, Eduardo and Preibisch, Steffen and Hartel, Steffen and Heisenberg, Carl-Philipp J and Concha, Miguel}, journal = {Mechanisms of Development}, number = {Supplement 1}, pages = {S11 -- S11}, publisher = {Elsevier}, title = {{Linking organ formation to left-right patterning in the embryonic zebrafish}}, doi = {10.1016/j.mod.2009.06.970}, volume = {126}, year = {2009}, } @article{4162, abstract = {Organ formation requires the precise assembly of progenitor cells into a functional unit. Mechanical forces are likely to play a critical role in this process, but it is unclear how these are molecularly controlled during development. Here, we show that Wnt11/ Pk1a-mediated planar cell polarity (PCP) signalling coordinates formation of the zebrafish laterality organ (Kupffer’s vesicle, KV) by regulating adhesion forces between organ progenitor cells (the dorsal forerunner cells, DFCs).}, author = {Oteíza, Pablo and Köppen, Mathias and Krieg, Michael and Preibisch, Steffen and Haertel, Steffen and Müller, Daniel and Heisenberg, Carl-Philipp J and Concha, Miguel}, journal = {Mechanisms of Development}, number = {Supplement 1}, pages = {S80 -- S80}, publisher = {Elsevier}, title = {{Wnt11/Pk1a-mediated planar cell polarity signalling orchestrates epithelial organ morphogenesis by regulating N-cadherin dependent cell adhesion forces}}, doi = {10.1016/j.mod.2009.06.098}, volume = {126}, year = {2009}, } @article{4165, abstract = {The tissues of a developing embryo are simultaneously patterned, moved and differentiated according to an exchange of information between their constituent cells. We argue that these complex self-organizing phenomena can only be fully understood with quantitative mathematical frameworks that allow specific hypotheses to be formulated and tested. The quantitative and dynamic imaging of growing embryos at the molecular, cellular and tissue level is the key experimental advance required to achieve this interaction between theory and experiment. Here we describe how mathematical modelling has become an invaluable method to integrate quantitative biological information across temporal and spatial scales, serving to connect the activity of regulatory molecules with the morphological development of organisms.}, author = {Oates, Andrew and Gorfinkiel, Nicole and Gonzalez Gaitan, Marcos and Heisenberg, Carl-Philipp J}, journal = {Nature Reviews Genetics}, number = {8}, pages = {517 -- 530}, publisher = {Nature Publishing Group}, title = {{Quantitative approaches in developmental biology}}, doi = {10.1038/nrg2548}, volume = {10}, year = {2009}, } @article{4192, abstract = {During vertebrate gastrulation, the body axis is established by a variety of co-ordinated and directed movements of cells. One of these movements is convergence and extension (CE), which is regulated by a non-canonical Wnt/planar cell polarity (PCP) pathway. From our forward genetic screen, we have identified 3-hydroxy-3-methyglutaryl-coenzyme A reductase 1b (hmgcr1b) gene as a dominant enhancer of the silberblick (slb)/wnt11 CE phenotype. hmgcr1b mutant embryos exhibit only very mild CE phenotype during gastrulation while showing a thicker yolk extension at pharyngula stages. Notably, abrogation of hmgcr1b also enhances the CE defects of other core PCP mutants/morphants. The prenylation pathway is one of branches downstream of HMGCR, and has been implicated for lipid modification at the C-terminus of proteins. To test the possibility that the prenylation pathway regulates activities of the PCP pathway, we abrogated farnesyl transferase (FT) or geranylgeranyl transferase (GGT) function using morpholinos on PCP mutant/morphant backgrounds. Consistent with the notion that FT preferentially performs lipid modification on to proteins with the CAAX motif including the core PCP protein Prickle (Pk), abrogation of FT, but not GGT, enhances the pk1a or pk1b morphant CE phenotype, suggesting the specif icity for targets of the prenylation enzymes. }, author = {Kai, Masatake and Buchan, Nina and Heisenberg, Carl-Philipp J and Tada, Masazumi}, journal = {Mechanisms of Development}, number = {Supplement 1}, pages = {S132 -- S132}, publisher = {Elsevier}, title = {{Regulation of planar cell polarity signalling by the prenylation pathway}}, doi = {10.1016/j.mod.2009.06.269}, volume = {126}, year = {2009}, } @article{4206, abstract = {Dorsal closure (DC), the closure of a hole in the dorsal epidermis of Drosophila embryos by the joining of opposing epithelial cell sheets, has been used as a model process to study the molecular and cellular mechanisms underlying epithelial spreading and wound healing. Recent studies have provided novel insights into how different tissues function cooperatively in this process. Specifically, they demonstrate a critical function of the epidermis surrounding the hole in modulating the behavior of the amnioserosa cells inside. These findings shed light not only on the mechanisms by which the behavior of different tissues is coordinated during DC, but also on the general mechanisms by which tissues interact to trigger global morphogenesis, an essential but yet poorly explored aspect of embryogenesis.}, author = {Heisenberg, Carl-Philipp J}, journal = {Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology}, number = {12}, pages = {1284 -- 1287}, publisher = {Wiley-Blackwell}, title = {{Dorsal closure in Drosophila: cells cannot get out of the tight spot}}, doi = {10.1002/bies.200900109}, volume = {31}, year = {2009}, } @article{4217, abstract = {Nuclear movements play an essential role in metazoan development. Although the intracellular transport mechanisms underlying nuclear movements have been studied in detail, relatively little is known about signals from surrounding cells and tissues controlling these movements. Here, we show that, in gastrulating zebrafish embryos, convergence movements of nuclei within the yolk syncytial layer (YSL) are guided by mesoderm and endoderm progenitors migrating along the surface of the yolk towards the dorsal side of the developing gastrula. Progenitor cells direct the convergence movements of internal yolk syncytial nuclei (iYSN) by modulating cortical flow within the YSL in which the iYSN are entrained. The effect of mesoderm and endoderm progenitors on the convergence movement of iYSN depends on the expression of E-cadherin, indicating that adhesive contact between the cells and the YSL is required for the mesendoderm-modulated YSL cortical flow mediating nuclear convergence. In summary, our data reveal a crucial function for cortical flow in the coordination of syncytial nuclear movements with surrounding cells and tissues during zebrafish gastrulation.}, author = {Carvalho, Lara and Stuehmer, Jan and Bois, Justin and Kalaidzidis, Yannis and Lecaudey, Virginie and Heisenberg, Carl-Philipp J}, journal = {Development}, number = {8}, pages = {1305 -- 1315}, publisher = {Company of Biologists}, title = {{Control of convergent yolk syncytial layer nuclear movement in zebrafish}}, doi = {10.1242/dev.026922}, volume = {136}, year = {2009}, } @article{4223, abstract = {Both Gram-positive and Gram-negative bacteria contain bactoprenol-dependent biosynthetic pathways expressing non-essential cell surface polysaccharides that function as virulence factors. Although these polymers are not required for bacterial viability in vitro, genes in many of the biosynthetic pathways are conditionally essential: they cannot be deleted except in strains incapable of initiating polymer synthesis. We report a cell-based, pathway-specific strategy to screen for small molecule inhibitors of conditionally essential enzymes. The screen identifies molecules that prevent the growth of a wildtype bacterial strain but do not affect the growth of a mutant strain incapable of initiating polymer synthesis. We have applied this approach to discover inhibitors of wall teichoic acid (WTA) biosynthesis in Staphylococcus aureus. WTAs are anionic cell surface polysaccharides required for host colonization that have been suggested as targets for new antimicrobials. We have identified a small molecule, 7-chloro-N,N-diethyl-3-(phenylsulfonyl)-[1,2,3]triazolo[1,5-a]quinolin-5-amine (1835F03), that inhibits the growth of a panel of S. aureus strains (MIC = 1−3 μg mL−1), including clinical methicillin-resistant S. aureus (MRSA) isolates. Using a combination of biochemistry and genetics, we have identified the molecular target as TarG, the transmembrane component of the ABC transporter that exports WTAs to the cell surface. We also show that preventing the completion of WTA biosynthesis once it has been initiated triggers growth arrest. The discovery of 1835F03 validates our chemical genetics strategy for identifying inhibitors of conditionally essential enzymes, and the strategy should be applicable to many other bactoprenol-dependent biosynthetic pathways in the pursuit of novel antibacterials and probes of bacterial stress responses.}, author = {Swoboda, Jonathan and Meredith, Timothy and Campbell, Jennifer and Brown, Stephanie and Suzuki, Takashi and Bollenbach, Mark Tobias and Malhowski, Amy and Kishony, Roy and Gilmore, Michael and Walker, Suzanne}, journal = {ACS Chemical Biology}, number = {10}, pages = {875 -- 883}, publisher = {American Chemical Society}, title = {{Discovery of a Small Molecule that Blocks Wall Teichoic Acid Biosynthesis in Staphylococcus aureus}}, doi = {10.1021/cb900151k}, volume = {4}, year = {2009}, } @article{4228, abstract = {Suppressive drug interactions, in which one antibiotic can actually help bacterial cells to grow faster in the presence of another, occur between protein and DNA synthesis inhibitors. Here, we show that this suppression results from nonoptimal regulation of ribosomal genes in the presence of DNA stress. Using GFP-tagged transcription reporters in Escherichia coli, we find that ribosomal genes are not directly regulated by DNA stress, leading to an imbalance between cellular DNA and protein content. To test whether ribosomal gene expression under DNA stress is nonoptimal for growth rate, we sequentially deleted up to six of the seven ribosomal RNA operons. These synthetic manipulations of ribosomal gene expression correct the protein-DNA imbalance, lead to improved survival and growth, and completely remove the suppressive drug interaction. A simple mathematical model explains the nonoptimal regulation in different nutrient environments. These results reveal the genetic mechanism underlying an important class of suppressive drug interactions.}, author = {Bollenbach, Tobias and Quan, Selwyn and Remy Chait and Kishony, Roy}, journal = {Cell}, number = {4}, pages = {707 -- 718}, publisher = {Cell Press}, title = {{Nonoptimal Microbial Response to Antibiotics Underlies Suppressive Drug Interactions}}, doi = {10.1016/j.cell.2009.10.025}, volume = {139}, year = {2009}, } @article{4231, abstract = {The evolution of quantitative characters depends on the frequencies of the alleles involved, yet these frequencies cannot usually be measured. Previous groups have proposed an approximation to the dynamics of quantitative traits, based on an analogy with statistical mechanics. We present a modified version of that approach, which makes the analogy more precise and applies quite generally to describe the evolution of allele frequencies. We calculate explicitly how the macroscopic quantities (i.e., quantities that depend on the quantitative trait) depend on evolutionary forces, in a way that is independent of the microscopic details. We first show that the stationary distribution of allele frequencies under drift, selection, and mutation maximizes a certain measure of entropy, subject to constraints on the expectation of observable quantities. We then approximate the dynamical changes in these expectations, assuming that the distribution of allele frequencies always maximizes entropy, conditional on the expected values. When applied to directional selection on an additive trait, this gives a very good approximation to the evolution of the trait mean and the genetic variance, when the number of mutations per generation is sufficiently high (4Nμ > 1). We show how the method can be modified for small mutation rates (4Nμ → 0). We outline how this method describes epistatic interactions as, for example, with stabilizing selection.}, author = {Barton, Nicholas H and De Vladar, Harold}, journal = {Genetics}, number = {3}, pages = {997 -- 1011}, publisher = {Genetics Society of America}, title = {{Statistical mechanics and the evolution of polygenic quantitative traits}}, doi = {10.1534/genetics.108.099309}, volume = {181}, year = {2009}, } @phdthesis{4232, author = {Vladar, Harold}, publisher = {Faculty of mathematical and natural sciences, University of Groningen}, title = {{Stochasticity and Variability in the dynamics and genetics of populations}}, year = {2009}, } @article{4242, abstract = {Felsenstein distinguished two ways by which selection can directly strengthen isolation. First, a modifier that strengthens prezygotic isolation can be favored everywhere. This fits with the traditional view of reinforcement as an adaptation to reduce deleterious hybridization by strengthening assortative mating. Second, selection can favor association between different incompatibilities, despite recombination. We generalize this “two allele” model to follow associations among any number of incompatibilities, which may include both assortment and hybrid inviability. Our key argument is that this process, of coupling between incompatibilities, may be quite different from the usual view of reinforcement: strong isolation can evolve through the coupling of any kind of incompatibility, whether prezygotic or postzygotic. Single locus incompatibilities become coupled because associations between them increase the variance in compatibility, which in turn increases mean fitness if there is positive epistasis. Multiple incompatibilities, each maintained by epistasis, can become coupled in the same way. In contrast, a single-locus incompatibility can become coupled with loci that reduce the viability of haploid hybrids because this reduces harmful recombination. We obtain simple approximations for the limits of tight linkage, and strong assortment, and show how assortment alleles can invade through associations with other components of reproductive isolation.}, author = {Barton, Nicholas H and De Cara, Maria}, journal = {Evolution; International Journal of Organic Evolution}, number = {5}, pages = {1171 -- 1190}, publisher = {Wiley}, title = {{The evolution of strong reproductive isolation}}, doi = {10.1111/j.1558-5646.2009.00622.x}, volume = {63}, year = {2009}, } @article{1766, abstract = {We demonstrate the time-resolved driving of two-photon blue sideband transitions between superconducting qubits and a transmission line resonator. As an example of using these sideband transitions for a two-qubit operation, we implement a pulse sequence that first entangles one qubit with the resonator and subsequently distributes the entanglement between two qubits. We show the generation of 75% fidelity Bell states by this method. The full density matrix of the two-qubit system is extracted using joint measurement and quantum state tomography and shows close agreement with numerical simulation.}, author = {Leek, Peter J and Filipp, Stefan and Maurer, Patrick and Baur, Matthias P and Bianchetti, R and Johannes Fink and Göppl, M and Steffen, L. Kraig and Wallraff, Andreas}, journal = {Physical Review B - Condensed Matter and Materials Physics}, number = {18}, publisher = {American Physical Society}, title = {{Using sideband transitions for two-qubit operations in superconducting circuits}}, doi = {10.1103/PhysRevB.79.180511}, volume = {79}, year = {2009}, } @article{1767, abstract = {We present spectroscopic measurements of the Autler-Townes doublet and the sidebands of the Mollow triplet in a driven superconducting qubit. The ground to first excited state transition of the qubit is strongly pumped while the resulting dressed qubit spectrum is probed with a weak tone. The corresponding transitions are detected using dispersive readout of the qubit coupled off resonantly to a microwave transmission line resonator. The observed frequencies of the Autler-Townes and Mollow spectral lines are in good agreement with a dispersive Jaynes-Cummings model taking into account higher excited qubit states and dispersive level shifts due to off-resonant drives.}, author = {Baur, Matthias P and Filipp, Stefan and Bianchetti, R and Johannes Fink and Göppl, M and Steffen, L. Kraig and Leek, Peter J and Blais, Alexandre and Wallraff, Andreas}, journal = {Physical Review Letters}, number = {24}, publisher = {American Physical Society}, title = {{Measurement of autler-townes and mollow transitions in a strongly driven superconducting qubit}}, doi = {10.1103/PhysRevLett.102.243602}, volume = {102}, year = {2009}, } @article{1768, abstract = {Quantum state tomography is an important tool in quantum information science for complete characterization of multiqubit states and their correlations. Here we report a method to perform a joint simultaneous readout of two superconducting qubits dispersively coupled to the same mode of a microwave transmission line resonator. The nonlinear dependence of the resonator transmission on the qubit state dependent cavity frequency allows us to extract the full two-qubit correlations without the need for single-shot readout of individual qubits. We employ standard tomographic techniques to reconstruct the density matrix of two-qubit quantum states.}, author = {Filipp, Stefan and Maurer, Patrick and Leek, Peter J and Baur, Matthias P and Bianchetti, R and Johannes Fink and Göppl, M and Steffen, L. Kraig and Gambetta, Jay M and Blais, Alexandre and Wallraff, Andreas}, journal = {Physical Review Letters}, number = {20}, publisher = {American Physical Society}, title = {{Two-qubit state tomography using a joint dispersive readout}}, doi = {10.1103/PhysRevLett.102.200402}, volume = {102}, year = {2009}, } @article{1769, abstract = {We present an ideal realization of the Tavis-Cummings model in the absence of atom number and coupling fluctuations by embedding a discrete number of fully controllable superconducting qubits at fixed positions into a transmission line resonator. Measuring the vacuum Rabi mode splitting with one, two, and three qubits strongly coupled to the cavity field, we explore both bright and dark dressed collective multiqubit states and observe the discrete N scaling of the collective dipole coupling strength. Our experiments demonstrate a novel approach to explore collective states, such as the W state, in a fully globally and locally controllable quantum system. Our scalable approach is interesting for solid-state quantum information processing and for fundamental multiatom quantum optics experiments with fixed atom numbers.}, author = {Johannes Fink and Bianchetti, R and Baur, Matthias P and Göppl, M and Steffen, L. Kraig and Filipp, Stefan and Leek, Peter J and Blais, Alexandre and Wallraff, Andreas}, journal = {Physical Review Letters}, number = {8}, publisher = {American Physical Society}, title = {{Dressed collective qubit states and the Tavis-Cummings model in circuit QED}}, doi = {10.1103/PhysRevLett.103.083601}, volume = {103}, year = {2009}, } @article{1770, abstract = {The quantum state of a superconducting qubit nonresonantly coupled to a transmission line resonator can be determined by measuring the quadrature amplitudes of an electromagnetic field transmitted through the resonator. We present experiments in which we analyze in detail the dynamics of the transmitted field as a function of the measurement frequency for both weak continuous and pulsed measurements. We find excellent agreement between our data and calculations based on a set of Bloch-type differential equations for the cavity field derived from the dispersive Jaynes-Cummings Hamiltonian including dissipation. We show that the measured system response can be used to construct a measurement operator from which the qubit population can be inferred accurately. Such a measurement operator can be used in tomographic methods to reconstruct single and multiqubit states in ensemble-averaged measurements.}, author = {Bianchetti, R and Filipp, Stefan and Baur, Matthias P and Johannes Fink and Göppl, M and Leek, Peter J and Steffen, L. Kraig and Blais, Alexandre and Wallraff, Andreas}, journal = {Physical Review A - Atomic, Molecular, and Optical Physics}, number = {4}, publisher = {American Physical Society}, title = {{Dynamics of dispersive single-qubit readout in circuit quantum electrodynamics}}, doi = {10.1103/PhysRevA.80.043840}, volume = {80}, year = {2009}, } @article{1771, abstract = {The exceptionally strong coupling realizable between superconducting qubits and photons stored in an on-chip microwave resonator allows for the detailed study of matter-light interactions in the realm of circuit quantum electrodynamics (QED). Here we investigate the resonant interaction between a single transmon-type multilevel artificial atom and weak thermal and coherent fields. We explore up to three photon dressed states of the coupled system in a linear response heterodyne transmission measurement. The results are in good quantitative agreement with a generalized Jaynes-Cummings model. Our data indicate that the role of thermal fields in resonant cavity QED can be studied in detail using superconducting circuits.}, author = {Johannes Fink and Baur, Matthias P and Bianchetti, R and Filipp, Stefan and Göppl, M and Leek, Peter J and Steffen, L. Kraig and Blais, Alexandre and Wallraff, Andreas}, journal = {Physica Scripta T}, publisher = {IOP Publishing Ltd.}, title = {{Thermal excitation of multi-photon dressed states in circuit quantum electrodynamics}}, doi = {10.1088/0031-8949/2009/T137/014013}, volume = {T137}, year = {2009}, } @article{17719, abstract = {We propose to use a simple observable, the fractional area of "hot spots" in weak gravitational lensing mass maps, which are detected with high significance, to determine background cosmological parameters. Because these high-convergence regions are directly related to the physical nonlinear structures of the universe, they derive cosmological information mainly from the nonlinear regime of density fluctuations. We show that in combination with future cosmic microwave background anisotropy measurements, this method can place constraints on cosmological parameters that are comparable to those from the redshift distribution of galaxy cluster abundances. The main advantage of the statistic proposed in this paper is that projection effects, normally the main source of uncertainty when determining the presence and the mass of a galaxy cluster, here serve as a source of information.}, author = {Wang, Sheng and Haiman, Zoltán and May, Morgan}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {1}, pages = {547--559}, publisher = {American Astronomical Society}, title = {{Constraining cosmology with high-convergence regions in weak lensing surveys}}, doi = {10.1088/0004-637x/691/1/547}, volume = {691}, year = {2009}, }