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News Article | February 16, 2017
Site: phys.org

Bright-field images of a zebrafish embryo at sequential stages from the beginning to the end of doming 90 minutes later. Credit: IST The little striped zebrafish starts out as single big cell sitting on top of the yolk. During the next 3 days, cells divide and tissues move to give the fish its final shape. But how do tissues coordinate their often-complicated movements? The physical basis of tissue coordination in early zebrafish development is subject of a study by Carl-Philipp Heisenberg, Professor at the Institute of Science and Technology Austria (IST Austria) and his group, including first author and postdoc Hitoshi Morita, and colleagues at The Francis Crick Institute in London and the Max-Planck-Institute for the Physics of Complex Systems in Dresden. Until now, little has been known about how tissues coordinate their movement both temporally and spatially during development. In the study, published today in Developmental Cell, Heisenberg and co-authors investigated how tissues coordinate their movements and how the forces required for tissue movements are generated. In the paper, they show that cells at the surface are crucial for coordination. Carl-Philipp Heisenberg explains: "A reduction of surface tension by cells on the surface of the embryo is the key process that coordinates tissue movements at this timepoint." Tissue spreading is a key process both in development and disease, for example in wound healing. For a tissue, especially a complex tissue with several layers, to spread, it needs to simultaneously thin and expand. One example of such spreading is the so-called doming in the zebrafish embryo. During doming, the blastoderm, a tissue composed of surface epithelial cells and inner mesenchymal cells, thins and spreads over the yolk cell. Doming involves two tissue movements: the epithelial cell layer at the surface expands, and inner cells undergo intercalations thereby thinning and spreading the inner cell mass. In the present study, Heisenberg and his colleague asked how the two tissue movements - surface cell expansion and inner cell intercalation - coordinate their movements during blastoderm spreading. Combining theory and experiments, they show that surface cells, by undergoing active expansion, reduce the surface tension of the blastoderm. Strikingly, this loosening at the blastoderm surface not only triggers surface cell layer expansion, but also induces inner cell intercalation leading to inner cell layer thinning and spreading. Thus, the reduction in blastoderm surface tension represents the key process coordinating surface cell layer expansion with inner cell layer thinning and spreading during doming. First author Hitoshi Morita explains the significance of this study for understanding tissue spreading: "We have unravelled the force-generating processes that drive doming. Our study shows that by reducing its surface tension, the layer of epithelial cells simultaneously drives expansion and thinning of the blastoderm, and so coordinates these two processes. Coordinated tissue spreading is a universal mechanism by which embryos take shape. Understanding the force-generating mechanism is central for understanding the physical basis of embryo development. We have uncovered the key role surface cells play in this process." Explore further: Healing powers: Team detects mechanism in cell division relevant for closing wounds


News Article | February 16, 2017
Site: www.eurekalert.org

The little striped zebrafish starts out as single big cell sitting on top of the yolk. During the next 3 days, cells divide and tissues move to give the fish its final shape. But how do tissues coordinate their often-complicated movements? The physical basis of tissue coordination in early zebrafish development is subject of a study by Carl-Philipp Heisenberg, Professor at the Institute of Science and Technology Austria (IST Austria) and his group, including first author and postdoc Hitoshi Morita, and colleagues at The Francis Crick Institute in London and the Max-Planck-Institute for the Physics of Complex Systems in Dresden. Until now, little has been known about how tissues coordinate their movement both temporally and spatially during development. In the study, published today in Developmental Cell, Heisenberg and co-authors investigated how tissues coordinate their movements and how the forces required for tissue movements are generated. In the paper, they show that cells at the surface are crucial for coordination. Carl-Philipp Heisenberg explains: "A reduction of surface tension by cells on the surface of the embryo is the key process that coordinates tissue movements at this timepoint." Tissue spreading is a key process both in development and disease, for example in wound healing. For a tissue, especially a complex tissue with several layers, to spread, it needs to simultaneously thin and expand. One example of such spreading is the so-called doming in the zebrafish embryo. During doming, the blastoderm, a tissue composed of surface epithelial cells and inner mesenchymal cells, thins and spreads over the yolk cell. Doming involves two tissue movements: the epithelial cell layer at the surface expands, and inner cells undergo intercalations thereby thinning and spreading the inner cell mass. In the present study, Heisenberg and his colleague asked how the two tissue movements - surface cell expansion and inner cell intercalation - coordinate their movements during blastoderm spreading. Combining theory and experiments, they show that surface cells, by undergoing active expansion, reduce the surface tension of the blastoderm. Strikingly, this loosening at the blastoderm surface not only triggers surface cell layer expansion, but also induces inner cell intercalation leading to inner cell layer thinning and spreading. Thus, the reduction in blastoderm surface tension represents the key process coordinating surface cell layer expansion with inner cell layer thinning and spreading during doming. First author Hitoshi Morita explains the significance of this study for understanding tissue spreading: "We have unravelled the force-generating processes that drive doming. Our study shows that by reducing its surface tension, the layer of epithelial cells simultaneously drives expansion and thinning of the blastoderm, and so coordinates these two processes. Coordinated tissue spreading is a universal mechanism by which embryos take shape. Understanding the force-generating mechanism is central for understanding the physical basis of embryo development. We have uncovered the key role surface cells play in this process."


News Article | February 28, 2017
Site: phys.org

Artist's impression of the angulon quasiparticle formed from a methane molecule in superfluid helium. Credit: IST Austria How do molecules rotate in a solvent? Answering this question is complicated, since molecular rotation is perturbed by a very large number of surrounding atoms. For a long time, large-scale computer simulations have been the main approach to model molecule-solvent interactions. However, they are extremely time consuming and sometimes infeasible. Now, Mikhail Lemeshko from the Institute of Science and Technology Austria (IST Austria) has proven that angulons—a certain type of quasiparticle he proposed two years ago—do, in fact, form when a molecule is immersed in superfluid helium. This offers a quick and simple description for rotation of molecules in solvents. In physics, the concept of quasiparticles is used as a technique to simplify the description of many-particle systems. Namely, instead of modeling strong interactions between trillions of individual particles, one identifies building blocks of the system that are only weakly interacting with one another. These building blocks are called quasiparticles and might consist of groups of particles. For example, to describe air bubbles rising up in water from first principles, one would need to solve an enormous set of equations describing the position and momentum of each water molecule. On the other hand, the bubbles themselves can be treated as individual particles—or quasiparticles—which drastically simplifies the description of the system. As another example, consider a running horse engulfed in a cloud of dust. One can think of it as a quasiparticle consisting of the horse itself and the dust cloud moving along with it. Understanding what is going on in terms of such a 'quasi-horse' is substantially easier compared to treating every dust grain, as well as the horse, separately in a complicated simulation. The latter example is similar to what Mikhail Lemeshko did in his study. Instead of treating the rotating molecule and all the atoms of the surrounding material separately, he used angulons to look at the problem from a different perspective. Angulon quasiparticles, which form when a rotating object interacts with a surrounding environment, were predicted theoretically two years ago by Lemeshko and Schmidt. Until now, however, they were considered only theoretical. Lemeshko's study, which was published today in Physical Review Letters, is based on experimental data collected by several laboratories over the last two decades. All the experiments had one thing in common: Molecules of different types were observed to rotate inside tiny droplets of superfluid helium. As Lemeshko has shown, independent of which molecule was studied, whether heavy or light species, methane, water, carbon dioxide or ammonia, the outcome of the angulon theory was always in good agreement with the measurements. This indicates that the angulon quasiparticles do, indeed, form inside helium droplets. "In our first study, we proposed angulons as a possibility for describing the rotation of molecules in solvents. Now, we have provided strong evidence that angulons actually exist," says Lemeshko. This substantially simplifies existing many-particle theories and could lead to applications in molecular physics, theoretical chemistry, and even biology. A first application of the angulon theory was found by Enderalp Yakaboylu, a postdoc in Lemeshko's group. The authors predicted that even a medium that is non-polarizable can shield an immersed impurity from an external electromagnetic field. This effect, which seems to contradict intuition, is called "anomalous screening" and is caused by an exchange of angular momentum on quantum level. The discovery, which the authors published in Physical Review Letters, was made possible by describing the charged particle and the interacting surroundings as an angulon quasiparticle. Future measurements will show if the prediction can be proven experimentally. Explore further: A novel canonical transformation provides insights into many-particle physics More information: Mikhail Lemeshko, Quasiparticle Approach to Molecules Interacting with Quantum Solvents, Physical Review Letters (2017). DOI: 10.1103/PhysRevLett.118.095301


News Article | February 28, 2017
Site: www.eurekalert.org

How do molecules rotate in a solvent? Answering this question is a complicated task since the molecular rotation is perturbed by a very large number of surrounding atoms. For a long time, large-scale computer simulations have been the main approach to model molecule-solvent interactions. However, they are extremely time consuming and sometimes completely infeasible. Now, Mikhail Lemeshko from the Institute of Science and Technology Austria (IST Austria) has proven that angulons -- a certain type of quasiparticle he proposed two years ago - do in fact form when a molecule is immersed in superfluid helium. This offers a quick and simple description for rotation of molecules in solvents. In physics, the concept of quasiparticles is used as a technique to simplify the description of many-particle systems. Namely, instead of modeling strong interactions between trillions of individual particles, one identifies building blocks of the system that are interacting with one another only weakly. These building blocks are called quasiparticles and might consist of groups of particles. For example, to describe air bubbles rising up in water from first principles, one would need to solve an enormous set of equations describing the position and momentum of each water molecule. On the other hand, one could notice that the bubbles themselves can be treated as individual particles -- or quasiparticles -- which drastically simplifies the description of the system. As another example, consider a running horse engulfed in a cloud of dust. One can think of it as a quasiparticle consisting of the horse itself and the dust cloud moving along with it. Understanding what is going on in terms of such a 'quasi-horse' is substantially easier compared to treating every dust grain, as well as the horse, separately in a complicated simulation. The latter example is similar to what Mikhail Lemeshko did in his study. Instead of treating the rotating molecule and all the atoms of the surrounding material separately, he used angulons to look at the problem from a different perspective. Angulon quasiparticles, which form when a rotating object interacts with a surrounding environment, were predicted theoretically two years ago by Lemeshko and Schmidt. Until now, however, they were considered only theoretically and their actual existence was still to be demonstrated. Lemeshko's study, which was published today in Physical Review Letters, is based on experimental data collected by several laboratories over the last two decades. All the experiments had one thing in common: molecules of different types were observed to rotate inside tiny droplets of superfluid helium. As Lemeshko has shown, independent of which molecule was studied, be it heavy or light species, methane, water, carbon dioxide or ammonia, the outcome of the angulon theory was always in good agreement with the measurements. This indicates that the angulon quasiparticles indeed form inside helium droplets. "In our first study we proposed angulons as a possibility for describing rotation of molecules in solvents. Now we have provided strong evidence that angulons actually exist," says Lemeshko. This substantially simplifies existing many-particle theories and could lead to applications in molecular physics, theoretical chemistry, and even biology. A first application of the angulon theory was already found by Enderalp Yakaboylu, a postdoc in Lemeshko's group. The authors predicted that even a medium that is non-polarizable can shield an immersed impurity from an external electromagnetic field. This effect, which seems to contradict intuition, is called "anomalous screening" and is caused by an exchange of angular momentum on quantum level. The discovery, which the authors also publish in Physical Review Letters, was made possible by describing the charged particle and the interacting surroundings as angulon quasiparticle. Future measurements will show if the prediction can be proven experimentally. Mikhail Lemeshko joined IST Austria in 2014 after having spent three years as an independent postdoctoral fellow at Harvard University. His research group entitled "Theoretical Atomic, Molecular, and Optical Physics" currently includes three postdocs and one PhD student. The main focus of study is the physics of quantum impurities possessing orbital angular momentum. He was recently awarded a standalone grant by the Austrian Science Fund (FWF) to continue his work on angulons. Enderalp Yakaboylu is a postdoc in IST Austria's ISTFELLOW program which is partially funded by the European Union.


Chevereau G.,IST Austria | Bollenbach T.,IST Austria
Molecular Systems Biology | Year: 2015

Abstract Drug combinations are increasingly important in disease treatments, for combating drug resistance, and for elucidating fundamental relationships in cell physiology. When drugs are combined, their individual effects on cells may be amplified or weakened. Such drug interactions are crucial for treatment efficacy, but their underlying mechanisms remain largely unknown. To uncover the causes of drug interactions, we developed a systematic approach based on precise quantification of the individual and joint effects of antibiotics on growth of genome-wide Escherichia coli gene deletion strains. We found that drug interactions between antibiotics representing the main modes of action are highly robust to genetic perturbation. This robustness is encapsulated in a general principle of bacterial growth, which enables the quantitative prediction of mutant growth rates under drug combinations. Rare violations of this principle exposed recurring cellular functions controlling drug interactions. In particular, we found that polysaccharide and ATP synthesis control multiple drug interactions with previously unexplained mechanisms, and small molecule adjuvants targeting these functions synthetically reshape drug interactions in predictable ways. These results provide a new conceptual framework for the design of multidrug combinations and suggest that there are universal mechanisms at the heart of most drug interactions. Synopsis A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions and can be targeted by small molecules to alter drug interactions in predictable ways. Drug interactions between antibiotics are highly robust to genetic perturbations. A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions. Diverse drug interactions are controlled by recurring cellular functions, including LPS synthesis and ATP synthesis. A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions and can be targeted by small molecules to alter drug interactions in predictable ways. © 2015 The Authors.


Bollenbach T.,IST Austria
Current Opinion in Microbiology | Year: 2015

Combining antibiotics is a promising strategy for increasing treatment efficacy and for controlling resistance evolution. When drugs are combined, their effects on cells may be amplified or weakened, that is the drugs may show synergistic or antagonistic interactions. Recent work revealed the underlying mechanisms of such drug interactions by elucidating the drugs' joint effects on cell physiology. Moreover, new treatment strategies that use drug combinations to exploit evolutionary tradeoffs were shown to affect the rate of resistance evolution in predictable ways. High throughput studies have further identified drug candidates based on their interactions with established antibiotics and general principles that enable the prediction of drug interactions were suggested. Overall, the conceptual and technical foundation for the rational design of potent drug combinations is rapidly developing. © 2015 The Authors.


Csicsvari J.,IST Austria
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2014

Sharp wave/ripple (SWR, 150-250 Hz) hippocampal events have long been postulated to be involved in memory consolidation. However, more recent work has investigated SWRs that occur during active waking behaviour: findings that suggest that SWRs may also play a role in cell assembly strengthening or spatial working memory. Do such theories of SWR function apply to animal learning? This review discusses how general theories linking SWRs to memory-related function may explain circuit mechanisms related to rodent spatial learning and to the associated stabilization of new cognitive maps.


Csicsvari J.,IST Austria | Dupret D.,University of Oxford
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

Sharp wave/ripple (SWR, 150-250 Hz) hippocampal events have long been postulated to be involved in memory consolidation. However, more recent work has investigated SWRs that occur during active waking behaviour: findings that suggest that SWRs may also play a role in cell assembly strengthening or spatial working memory. Do such theories of SWR function apply to animal learning? This review discusses how general theories linking SWRs to memory-related function may explain circuit mechanisms related to rodent spatial learning and to the associated stabilization of new cognitive maps. © 2013 The Author(s) Published by the Royal Society. All rights reserved.


Maitre J.-L.,EMBL | Heisenberg C.-P.,IST Austria
Current Biology | Year: 2013

Cadherins are transmembrane proteins that mediate cell-cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis. Here, we review the three major functions of cadherins in cell-cell contact formation and stability. Two of those functions lead to a decrease in interfacial tension at the forming cell-cell contact, thereby promoting contact expansion - first, by providing adhesion tension that lowers interfacial tension at the cell-cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell-cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact. © 2013 Elsevier Ltd.


De Vladar H.P.,I.S.T. Austria | Barton N.H.,I.S.T. Austria | Barton N.H.,University of Edinburgh
Trends in Ecology and Evolution | Year: 2011

Evolutionary biology shares many concepts with statistical physics: both deal with populations, whether of molecules or organisms, and both seek to simplify evolution in very many dimensions. Often, methodologies have undergone parallel and independent development, as with stochastic methods in population genetics. Here, we discuss aspects of population genetics that have embraced methods from physics: non-equilibrium statistical mechanics, travelling waves and Monte-Carlo methods, among others, have been used to study polygenic evolution, rates of adaptation and range expansions. These applications indicate that evolutionary biology can further benefit from interactions with other areas of statistical physics; for example, by following the distribution of paths taken by a population through time. © 2011 Elsevier Ltd.

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