Project acronym 3-TOP
Project Exploring the physics of 3-dimensional topological insulators
Researcher (PI) Laurens Wigbolt Molenkamp
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Call Details Advanced Grant (AdG), PE3, ERC-2010-AdG_20100224
Summary Topological insulators constitute a novel class of materials where the topological details of the bulk band structure induce a robust surface state on the edges of the material. While transport data for 2-dimensional topological insulators have recently become available, experiments on their 3-dimensional counterparts are mainly limited to photoelectron spectroscopy. At the same time, a plethora of interesting novel physical phenomena have been predicted to occur in such systems.
In this proposal, we sketch an approach to tackle the transport and magnetic properties of the surface states in these materials. This starts with high quality layer growth, using molecular beam epitaxy, of bulk layers of HgTe, Bi2Se3 and Bi2Te3, which are the prime candidates to show the novel physics expected in this field. The existence of the relevant surface states will be assessed spectroscopically, but from there on research will focus on fabricating and characterizing nanostructures designed to elucidate the transport and magnetic properties of the topological surfaces using electrical, optical and scanning probe techniques. Apart from a general characterization of the Dirac band structure of the surface states, research will focus on the predicted magnetic monopole-like response of the system to an electrical test charge. In addition, much effort will be devoted to contacting the surface state with superconducting and magnetic top layers, with the final aim of demonstrating Majorana fermion behavior. As a final benefit, growth of thin high quality thin Bi2Se3 or Bi2Te3 layers could allow for a demonstration of the (2-dimensional) quantum spin Hall effect at room temperature - offering a road map to dissipation-less transport for the semiconductor industry.
Summary
Topological insulators constitute a novel class of materials where the topological details of the bulk band structure induce a robust surface state on the edges of the material. While transport data for 2-dimensional topological insulators have recently become available, experiments on their 3-dimensional counterparts are mainly limited to photoelectron spectroscopy. At the same time, a plethora of interesting novel physical phenomena have been predicted to occur in such systems.
In this proposal, we sketch an approach to tackle the transport and magnetic properties of the surface states in these materials. This starts with high quality layer growth, using molecular beam epitaxy, of bulk layers of HgTe, Bi2Se3 and Bi2Te3, which are the prime candidates to show the novel physics expected in this field. The existence of the relevant surface states will be assessed spectroscopically, but from there on research will focus on fabricating and characterizing nanostructures designed to elucidate the transport and magnetic properties of the topological surfaces using electrical, optical and scanning probe techniques. Apart from a general characterization of the Dirac band structure of the surface states, research will focus on the predicted magnetic monopole-like response of the system to an electrical test charge. In addition, much effort will be devoted to contacting the surface state with superconducting and magnetic top layers, with the final aim of demonstrating Majorana fermion behavior. As a final benefit, growth of thin high quality thin Bi2Se3 or Bi2Te3 layers could allow for a demonstration of the (2-dimensional) quantum spin Hall effect at room temperature - offering a road map to dissipation-less transport for the semiconductor industry.
Max ERC Funding
2 419 590 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym 4-TOPS
Project Four experiments in Topological Superconductivity.
Researcher (PI) Laurens Molenkamp
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Call Details Advanced Grant (AdG), PE3, ERC-2016-ADG
Summary Topological materials have developed rapidly in recent years, with my previous ERC-AG project 3-TOP playing a major role in this development. While so far no bulk topological superconductor has been unambiguously demonstrated, their properties can be studied in a very flexible manner by inducing superconductivity through the proximity effect into the surface or edge states of a topological insulator. In 4-TOPS we will explore the possibilities of this approach in full, and conduct a thorough study of induced superconductivity in both two and three dimensional HgTe based topological insulators. The 4 avenues we will follow are:
-SQUID based devices to investigate full phase dependent spectroscopy of the gapless Andreev bound state by studying their Josephson radiation and current-phase relationships.
-Experiments aimed at providing unambiguous proof of localized Majorana states in TI junctions by studying tunnelling transport into such states.
-Attempts to induce superconductivity in Quantum Hall states with the aim of creating a chiral topological superconductor. These chiral superconductors host Majorana fermions at their edges, which, at least in the case of a single QH edge mode, follow non-Abelian statistics and are therefore promising for explorations in topological quantum computing.
-Studies of induced superconductivity in Weyl semimetals, a completely unexplored state of matter.
Taken together, these four sets of experiments will greatly enhance our understanding of topological superconductivity, which is not only a subject of great academic interest as it constitutes the study of new phases of matter, but also has potential application in the field of quantum information processing.
Summary
Topological materials have developed rapidly in recent years, with my previous ERC-AG project 3-TOP playing a major role in this development. While so far no bulk topological superconductor has been unambiguously demonstrated, their properties can be studied in a very flexible manner by inducing superconductivity through the proximity effect into the surface or edge states of a topological insulator. In 4-TOPS we will explore the possibilities of this approach in full, and conduct a thorough study of induced superconductivity in both two and three dimensional HgTe based topological insulators. The 4 avenues we will follow are:
-SQUID based devices to investigate full phase dependent spectroscopy of the gapless Andreev bound state by studying their Josephson radiation and current-phase relationships.
-Experiments aimed at providing unambiguous proof of localized Majorana states in TI junctions by studying tunnelling transport into such states.
-Attempts to induce superconductivity in Quantum Hall states with the aim of creating a chiral topological superconductor. These chiral superconductors host Majorana fermions at their edges, which, at least in the case of a single QH edge mode, follow non-Abelian statistics and are therefore promising for explorations in topological quantum computing.
-Studies of induced superconductivity in Weyl semimetals, a completely unexplored state of matter.
Taken together, these four sets of experiments will greatly enhance our understanding of topological superconductivity, which is not only a subject of great academic interest as it constitutes the study of new phases of matter, but also has potential application in the field of quantum information processing.
Max ERC Funding
2 497 567 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym ADMIRE
Project Atomic-scale Design of Majorana states and their Innovative Real-space Exploration
Researcher (PI) Roland WIESENDANGER
Host Institution (HI) UNIVERSITAET HAMBURG
Call Details Advanced Grant (AdG), PE3, ERC-2017-ADG
Summary Fault-tolerant topological quantum computation has become one of the most exciting research directions in modern condensed matter physics. As a key operation the braiding of non-Abelian anyons has been proposed theoretically. Such exotic quasiparticles can be realized as zero-energy Majorana bound states at the ends of one-dimensional magnetic nanowires in proximity to s-wave superconductors in the presence of high spin-orbit coupling. In contrast to previous attempts to realize such systems experimentally, based on the growth of semiconducting nanowires or the self-assembly of ferromagnetic nanowires on s-wave superconductors, we propose to design Majorana bound states in artificially constructed single-atom chains with non-collinear spin-textures on elemental superconducting substrates using scanning tunnelling microscope (STM)-based atom manipulation techniques. We would like to study at the atomic level the formation of Shiba bands as a result of hybridization of individual Shiba impurity states as well as the emergence of zero-energy Majorana bound states as a function of chain structure, length, and composition. Moreover, we will construct model-type platforms, such as T-junctions, rings, and more complex network structures with atomic-scale precision as a basis for demonstrating the manipulation and braiding of Majorana bound states. We will make use of sophisticated experimental techniques, such as spin-resolved scanning tunnelling spectroscopy (STS) at micro-eV energy resolution, scanning Josephson tunnelling spectroscopy, and multi-probe STS under well-defined ultra-high vacuum conditions, in order to directly probe the nature of the magnetic state of the atomic wires, the spin-polarization of the emergent Majorana states, as well as the spatial nature of the superconducting order parameter in real space. Finally, we will try to directly probe the quantum exchange statistics of non-Abelian anyons in these atomically precise fabricated model-type systems.
Summary
Fault-tolerant topological quantum computation has become one of the most exciting research directions in modern condensed matter physics. As a key operation the braiding of non-Abelian anyons has been proposed theoretically. Such exotic quasiparticles can be realized as zero-energy Majorana bound states at the ends of one-dimensional magnetic nanowires in proximity to s-wave superconductors in the presence of high spin-orbit coupling. In contrast to previous attempts to realize such systems experimentally, based on the growth of semiconducting nanowires or the self-assembly of ferromagnetic nanowires on s-wave superconductors, we propose to design Majorana bound states in artificially constructed single-atom chains with non-collinear spin-textures on elemental superconducting substrates using scanning tunnelling microscope (STM)-based atom manipulation techniques. We would like to study at the atomic level the formation of Shiba bands as a result of hybridization of individual Shiba impurity states as well as the emergence of zero-energy Majorana bound states as a function of chain structure, length, and composition. Moreover, we will construct model-type platforms, such as T-junctions, rings, and more complex network structures with atomic-scale precision as a basis for demonstrating the manipulation and braiding of Majorana bound states. We will make use of sophisticated experimental techniques, such as spin-resolved scanning tunnelling spectroscopy (STS) at micro-eV energy resolution, scanning Josephson tunnelling spectroscopy, and multi-probe STS under well-defined ultra-high vacuum conditions, in order to directly probe the nature of the magnetic state of the atomic wires, the spin-polarization of the emergent Majorana states, as well as the spatial nature of the superconducting order parameter in real space. Finally, we will try to directly probe the quantum exchange statistics of non-Abelian anyons in these atomically precise fabricated model-type systems.
Max ERC Funding
2 499 750 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym AngioBone
Project Angiogenic growth, specialization, ageing and regeneration
of bone vessels
Researcher (PI) Ralf Heinrich Adams
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Call Details Advanced Grant (AdG), LS3, ERC-2013-ADG
Summary The skeleton and the sinusoidal vasculature form a functional unit with great relevance in health, regeneration, and disease. Currently, fundamental aspects of sinusoidal vessel growth, specialization, arteriovenous organization and the consequences for tissue perfusion, or the changes occurring during ageing remain unknown. Our preliminary data indicate that key principles of bone vascularization and the role of molecular regulators are highly distinct from other organs. I therefore propose to use powerful combination of mouse genetics, fate mapping, transcriptional profiling, computational biology, confocal and two-photon microscopy, micro-CT and PET imaging, biochemistry and cell biology to characterize the growth, differentiation, dynamics, and ageing of the bone vasculature. In addition to established angiogenic pathways, the role of highly promising novel candidate regulators will be investigated in endothelial cells and perivascular osteoprogenitors with sophisticated inducible and cell type-specific genetic methods in the mouse. Complementing these powerful in vivo approaches, 3D co-cultures generated by cell printing technologies will provide insight into the communication between different cell types. The dynamics of sinusoidal vessel growth and regeneration will be monitored by two-photon imaging in the skull. Finally, I will explore the architectural, cellular and molecular changes and the role of capillary endothelial subpopulations in the sinusoidal vasculature of ageing and osteoporotic mice.
Technological advancements, such as new transgenic strains, mutant models or cell printing approaches, are important aspects of this proposal. AngioBone will provide a first conceptual framework for normal and deregulated function of the bone sinusoidal vasculature. It will also break new ground by analyzing the role of blood vessels in ageing and identifying novel strategies for tissue engineering and, potentially, the prevention/treatment of osteoporosis.
Summary
The skeleton and the sinusoidal vasculature form a functional unit with great relevance in health, regeneration, and disease. Currently, fundamental aspects of sinusoidal vessel growth, specialization, arteriovenous organization and the consequences for tissue perfusion, or the changes occurring during ageing remain unknown. Our preliminary data indicate that key principles of bone vascularization and the role of molecular regulators are highly distinct from other organs. I therefore propose to use powerful combination of mouse genetics, fate mapping, transcriptional profiling, computational biology, confocal and two-photon microscopy, micro-CT and PET imaging, biochemistry and cell biology to characterize the growth, differentiation, dynamics, and ageing of the bone vasculature. In addition to established angiogenic pathways, the role of highly promising novel candidate regulators will be investigated in endothelial cells and perivascular osteoprogenitors with sophisticated inducible and cell type-specific genetic methods in the mouse. Complementing these powerful in vivo approaches, 3D co-cultures generated by cell printing technologies will provide insight into the communication between different cell types. The dynamics of sinusoidal vessel growth and regeneration will be monitored by two-photon imaging in the skull. Finally, I will explore the architectural, cellular and molecular changes and the role of capillary endothelial subpopulations in the sinusoidal vasculature of ageing and osteoporotic mice.
Technological advancements, such as new transgenic strains, mutant models or cell printing approaches, are important aspects of this proposal. AngioBone will provide a first conceptual framework for normal and deregulated function of the bone sinusoidal vasculature. It will also break new ground by analyzing the role of blood vessels in ageing and identifying novel strategies for tissue engineering and, potentially, the prevention/treatment of osteoporosis.
Max ERC Funding
2 478 750 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym ASCIR
Project Active Suspensions with Controlled Interaction Rules
Researcher (PI) Clemens Bechinger
Host Institution (HI) UNIVERSITAT KONSTANZ
Call Details Advanced Grant (AdG), PE3, ERC-2015-AdG
Summary Self-propelling, i.e., active colloidal particles constitute a novel class of non-equilibrium systems which exhibit structural and dynamical features similar to those in assemblies of bacteria or other motile organisms. Due to their reduced complexity, they provide an intriguing chance to understand the formation of dynamical structures in non-equilibrium systems in unprecedented detail. A central question in this rapidly growing field is, how interaction-rules determine the creation of e.g. swarms or complex networks. In addition to ordinary inter particle and hydrodynamic forces, interaction-rules can be much more complex. For example, they can regulate the particle motility depending on their relative orientation, their local density or otherwise distinct particle configurations.
Here, we propose an experimental approach which aims towards controlling the amplitude and direction of the particle’s motility in dense active suspensions on a single particle level. Particle-propulsion is achieved by a light-activated diffusiophoretic mechanism, where the particle motility is controlled by an incident light field. By means of an acoustic-optical modulator and a feed-back loop, we create dynamical and spatially-resolved light fields which depend on the current configuration of active particles and user-defined interaction rules. Because these rules are imposed externally and not by internal forces, this permits the experimental realization of a wide range of rules (linear, non-linear, and even non-reciprocal) in dense, two-dimensional active systems. We expect, that the experimental realization of user-defined interaction-rules largely extends our understanding how active matter can organize in dynamical structures. In addition, the perspective of enhanced control of active particles, as suggested within this proposal, will be of considerable importance for their use as autonomous micro robots which will deliver payloads in liquid environments.
Summary
Self-propelling, i.e., active colloidal particles constitute a novel class of non-equilibrium systems which exhibit structural and dynamical features similar to those in assemblies of bacteria or other motile organisms. Due to their reduced complexity, they provide an intriguing chance to understand the formation of dynamical structures in non-equilibrium systems in unprecedented detail. A central question in this rapidly growing field is, how interaction-rules determine the creation of e.g. swarms or complex networks. In addition to ordinary inter particle and hydrodynamic forces, interaction-rules can be much more complex. For example, they can regulate the particle motility depending on their relative orientation, their local density or otherwise distinct particle configurations.
Here, we propose an experimental approach which aims towards controlling the amplitude and direction of the particle’s motility in dense active suspensions on a single particle level. Particle-propulsion is achieved by a light-activated diffusiophoretic mechanism, where the particle motility is controlled by an incident light field. By means of an acoustic-optical modulator and a feed-back loop, we create dynamical and spatially-resolved light fields which depend on the current configuration of active particles and user-defined interaction rules. Because these rules are imposed externally and not by internal forces, this permits the experimental realization of a wide range of rules (linear, non-linear, and even non-reciprocal) in dense, two-dimensional active systems. We expect, that the experimental realization of user-defined interaction-rules largely extends our understanding how active matter can organize in dynamical structures. In addition, the perspective of enhanced control of active particles, as suggested within this proposal, will be of considerable importance for their use as autonomous micro robots which will deliver payloads in liquid environments.
Max ERC Funding
2 036 750 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym ASTONISH
Project Atomic-scale STudies Of the Nature of and conditions for Inducing Superconductivity at High-temperatures
Researcher (PI) Roland Martin Wiesendanger
Host Institution (HI) UNIVERSITAET HAMBURG
Call Details Advanced Grant (AdG), PE3, ERC-2013-ADG
Summary "One of the greatest challenges these days in condensed matter physics is the fundamental understanding of the mechanisms leading to high-Tc superconductivity and ultimately, as a result of that, the discovery of a material system exhibiting a superconducting state with a transition temperature Tc above room temperature. While several different classes of high-Tc materials have been discovered in the past decades, including the well-known CuO-based superconductors (cuprates) or the more recently discovered class of Fe-based superconductors (pnictides), the mechanisms behind high-Tc superconductivity remain controversial. Up to date, no theory exists which would allow for a rational design of a superconducting material with a transition temperature above room temperature. On the other hand, experiments on rather complex material systems often suffer from material imperfections or from a lack of tunability of materials’ properties within a wide range. Our experimental studies within this project therefore will focus on model-type systems which can be prepared and thoroughly characterized with atomic level precision. The growth of the model-type samples will be controlled vertically one atomic layer at a time and laterally by making use of single-atom manipulation techniques. Atomic-scale characterization at low energy-scales will be performed by low-temperature spin-resolved elastic and inelastic scanning tunnelling microscopy (STM) and spectroscopy (STS) as well as by non-contact atomic force microscopy and spectroscopy based techniques. Transport experiments will be conducted by a four-probe STM setup under well-defined ultra-high vacuum conditions. By having access to the electronic and spin, as well as to the vibrational degrees of freedom down to the atomic level, we hope to be able to identify the nature of and the conditions for inducing superconductivity at high temperatures, which could ultimately lead a knowledge-based design of high-Tc superconductors."
Summary
"One of the greatest challenges these days in condensed matter physics is the fundamental understanding of the mechanisms leading to high-Tc superconductivity and ultimately, as a result of that, the discovery of a material system exhibiting a superconducting state with a transition temperature Tc above room temperature. While several different classes of high-Tc materials have been discovered in the past decades, including the well-known CuO-based superconductors (cuprates) or the more recently discovered class of Fe-based superconductors (pnictides), the mechanisms behind high-Tc superconductivity remain controversial. Up to date, no theory exists which would allow for a rational design of a superconducting material with a transition temperature above room temperature. On the other hand, experiments on rather complex material systems often suffer from material imperfections or from a lack of tunability of materials’ properties within a wide range. Our experimental studies within this project therefore will focus on model-type systems which can be prepared and thoroughly characterized with atomic level precision. The growth of the model-type samples will be controlled vertically one atomic layer at a time and laterally by making use of single-atom manipulation techniques. Atomic-scale characterization at low energy-scales will be performed by low-temperature spin-resolved elastic and inelastic scanning tunnelling microscopy (STM) and spectroscopy (STS) as well as by non-contact atomic force microscopy and spectroscopy based techniques. Transport experiments will be conducted by a four-probe STM setup under well-defined ultra-high vacuum conditions. By having access to the electronic and spin, as well as to the vibrational degrees of freedom down to the atomic level, we hope to be able to identify the nature of and the conditions for inducing superconductivity at high temperatures, which could ultimately lead a knowledge-based design of high-Tc superconductors."
Max ERC Funding
2 170 696 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym BRAINEVODEVO
Project A Neuron Type Atlas of the Annelid Brain: Development and Evolution of Chemosensory-Motor Circuits
Researcher (PI) Detlev Arendt
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Call Details Advanced Grant (AdG), LS3, ERC-2011-ADG_20110310
Summary Neural circuits, composed of interconnected neurons, represent the basic unit of the nervous system. One way to understand the highly complex arrangement of cross-talking, serial and parallel circuits is to resolve its developmental and evolutionary emergence. The rationale of the research proposal presented here is to elucidate the complex circuitry of the vertebrate and insect forebrain by comparison to the much simpler and evolutionary ancient “connectome” of the marine annelid Platynereis dumerilii. We will build a unique resource, the Platynereis Neuron Type Atlas, combining, for the first time, neuronal morphologies, axonal projections, cellular expression profiling and developmental lineage for an entire bilaterian brain. We will focus on five days old larvae when most adult neuron types are already present in small number and large part of the axonal scaffold in place.
Building on the Neuron Type Atlas, the second part of the proposal envisages the functional dissection of the Platynereis chemosensory-motor forebrain circuits. A newly developed microfluidics behavioural assay system, together with a cell-based GPCR screening will identify partaking neurons. Zinc finger nuclease-mediated knockout of circuit-specific transcription factors as identified from the Atlas will reveal circuit-specific gene regulatory networks, downstream effector genes and functional characteristics. Laser ablation of GFP-labeled single neurons and axonal connections will yield further insight into the function of circuit components and subcircuits. Given the ancient nature of the Platynereis brain, this research is expected to reveal a simple, developmental and evolutionary “blueprint” for the olfactory circuits in mice and flies and to shed new light on the evolution of information processing in glomeruli and higher-level integration in sensory-associative brain centres.
Summary
Neural circuits, composed of interconnected neurons, represent the basic unit of the nervous system. One way to understand the highly complex arrangement of cross-talking, serial and parallel circuits is to resolve its developmental and evolutionary emergence. The rationale of the research proposal presented here is to elucidate the complex circuitry of the vertebrate and insect forebrain by comparison to the much simpler and evolutionary ancient “connectome” of the marine annelid Platynereis dumerilii. We will build a unique resource, the Platynereis Neuron Type Atlas, combining, for the first time, neuronal morphologies, axonal projections, cellular expression profiling and developmental lineage for an entire bilaterian brain. We will focus on five days old larvae when most adult neuron types are already present in small number and large part of the axonal scaffold in place.
Building on the Neuron Type Atlas, the second part of the proposal envisages the functional dissection of the Platynereis chemosensory-motor forebrain circuits. A newly developed microfluidics behavioural assay system, together with a cell-based GPCR screening will identify partaking neurons. Zinc finger nuclease-mediated knockout of circuit-specific transcription factors as identified from the Atlas will reveal circuit-specific gene regulatory networks, downstream effector genes and functional characteristics. Laser ablation of GFP-labeled single neurons and axonal connections will yield further insight into the function of circuit components and subcircuits. Given the ancient nature of the Platynereis brain, this research is expected to reveal a simple, developmental and evolutionary “blueprint” for the olfactory circuits in mice and flies and to shed new light on the evolution of information processing in glomeruli and higher-level integration in sensory-associative brain centres.
Max ERC Funding
2 489 048 €
Duration
Start date: 2012-03-01, End date: 2017-02-28
Project acronym CellMechanoControl
Project The physical basis of cellular mechanochemical
control circuits
Researcher (PI) Christoph Friedrich Schmidt
Host Institution (HI) GEORG-AUGUST-UNIVERSITAT GOTTINGENSTIFTUNG OFFENTLICHEN RECHTS
Call Details Advanced Grant (AdG), PE3, ERC-2013-ADG
Summary Biological cells possess a chemical “sense of smell” and a physical “sense of touch”. Structure, dynamics, development, differentiation and even apoptosis of cells are guided by physical stimuli feeding into a regulatory network integrating biochemical and mechanical signals. Cells are equipped with both, force-generating structures, and stress sensors including force-sensitive structural proteins or mechanosensitive ion channels. Pathways from force sensing to structural and transcriptional controls are not yet understood.
The goal of the proposed interdisciplinary project is to quantitatively establish such pathways, connecting the statistical physics and the mechanics to the biochemistry. We will measure and model the complex non-equilibrium mechanical structures in cells, and we will study how external and cell-generated forces activate sensory processes that (i) act (back) on the morphology of the cell structures, and (ii) lead to cell-fate decisions, such as differentiation. The most prominent stress-bearing and -generating structures in cells are actin/myosin based, and the most prominent mechanoactive and -sensitive cell types are fibroblasts in connective tissue and myocytes in muscle. We will first focus on actin/myosin bundles in fibroblasts and in sarcomeres in developing heart muscle cells. We will observe cells under the influence of exactly controlled external stresses. Forces on suspended single cells or cell clusters will be exerted by laser trapping and sensitively detected by laser interferometry. We furthermore will monitor mechanically triggered transcriptional regulation by detecting mRNA in the nucleus of mouse stem cells differentiating to cardiomyocytes. We will develop fluorescent mRNA sensors that can be imaged in cells, based on near-IR fluorescent single-walled carbon nanotubes.
Understanding mechanical cell regulation has far-ranging relevance for fundamental cell biophysics, developmental biology and for human health.
Summary
Biological cells possess a chemical “sense of smell” and a physical “sense of touch”. Structure, dynamics, development, differentiation and even apoptosis of cells are guided by physical stimuli feeding into a regulatory network integrating biochemical and mechanical signals. Cells are equipped with both, force-generating structures, and stress sensors including force-sensitive structural proteins or mechanosensitive ion channels. Pathways from force sensing to structural and transcriptional controls are not yet understood.
The goal of the proposed interdisciplinary project is to quantitatively establish such pathways, connecting the statistical physics and the mechanics to the biochemistry. We will measure and model the complex non-equilibrium mechanical structures in cells, and we will study how external and cell-generated forces activate sensory processes that (i) act (back) on the morphology of the cell structures, and (ii) lead to cell-fate decisions, such as differentiation. The most prominent stress-bearing and -generating structures in cells are actin/myosin based, and the most prominent mechanoactive and -sensitive cell types are fibroblasts in connective tissue and myocytes in muscle. We will first focus on actin/myosin bundles in fibroblasts and in sarcomeres in developing heart muscle cells. We will observe cells under the influence of exactly controlled external stresses. Forces on suspended single cells or cell clusters will be exerted by laser trapping and sensitively detected by laser interferometry. We furthermore will monitor mechanically triggered transcriptional regulation by detecting mRNA in the nucleus of mouse stem cells differentiating to cardiomyocytes. We will develop fluorescent mRNA sensors that can be imaged in cells, based on near-IR fluorescent single-walled carbon nanotubes.
Understanding mechanical cell regulation has far-ranging relevance for fundamental cell biophysics, developmental biology and for human health.
Max ERC Funding
2 425 200 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym CELLMIG
Project Molecular and Cellular Mechanisms Promoting Single-Cell Migration in vivo
Researcher (PI) Erez Raz
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Call Details Advanced Grant (AdG), LS3, ERC-2010-AdG_20100317
Summary The regulation of cell migration is central in pattern formation, homeostasis and disease. The proposed research is aimed at investigating the molecular basis for cell motility and the associated polarization of the cell. In view of the dynamic nature of these processes, we have chosen to utilize the migration of Primoridal Germ Cells (PGCs) in zebrafish - a model that offers unique experimental advantages for imaging and experimental manipulations. The fact that molecules facilitating the motility of zebrafish PGCs are evolutionary conserved and the finding that the cells are directed by chemokines, molecules that control a wide range of cell trafficking events in vertebrates, make this in vivo study of particular importance.
The proposed work involves both the functional analysis of previously identified candidates and the identification of molecules, which have a presently unknown effect on the migration process. For both objectives, we will employ novel experimental schemes. We will examine the role of proteins in achieving functional cell polarity compatible with efficient motility and response to directional cues, using unique techniques and analysis tools in the context of the living organism. The precise function of the identified proteins will be determined by combining mathematical tools aimed at quantitatively gauging the role of the molecules in conferring proper cell shape, biophysical methods aimed at measuring forces, rigidity and cytoplasm flow and determination of the effect on the organization of relevant structures using cryo electron tomography.
Together, this approach would provide a non-conventional understanding of cell migration by correlating structural, morphological and dynamic cellular properties with the ability of cells to effectively migrate towards their target.
Summary
The regulation of cell migration is central in pattern formation, homeostasis and disease. The proposed research is aimed at investigating the molecular basis for cell motility and the associated polarization of the cell. In view of the dynamic nature of these processes, we have chosen to utilize the migration of Primoridal Germ Cells (PGCs) in zebrafish - a model that offers unique experimental advantages for imaging and experimental manipulations. The fact that molecules facilitating the motility of zebrafish PGCs are evolutionary conserved and the finding that the cells are directed by chemokines, molecules that control a wide range of cell trafficking events in vertebrates, make this in vivo study of particular importance.
The proposed work involves both the functional analysis of previously identified candidates and the identification of molecules, which have a presently unknown effect on the migration process. For both objectives, we will employ novel experimental schemes. We will examine the role of proteins in achieving functional cell polarity compatible with efficient motility and response to directional cues, using unique techniques and analysis tools in the context of the living organism. The precise function of the identified proteins will be determined by combining mathematical tools aimed at quantitatively gauging the role of the molecules in conferring proper cell shape, biophysical methods aimed at measuring forces, rigidity and cytoplasm flow and determination of the effect on the organization of relevant structures using cryo electron tomography.
Together, this approach would provide a non-conventional understanding of cell migration by correlating structural, morphological and dynamic cellular properties with the ability of cells to effectively migrate towards their target.
Max ERC Funding
1 960 600 €
Duration
Start date: 2011-06-01, End date: 2017-05-31
Project acronym CHIMO
Project Chiral Morphogenesis - Physical Mechanisms of Actomyosin-Based Left/Right Symmetry Breaking in Biological Systems
Researcher (PI) Stephan Grill
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Call Details Advanced Grant (AdG), PE3, ERC-2016-ADG
Summary The aim of this grant is to understand how cellular, tissue-scale and organismal left-right asymmetry arises
from the chirality of molecular constituents. In many instances the actomyosin cortex, a thin and
mechanically active layer of dynamically cross-linked filaments and molecular motors at the surface of cells,
drives the emergence of chiral morphogenetic events. In the nematode Caenorhabditis elegans, mesoscale
chiral active torques generated by this active layer establish the embryo’s left-right body axis. Here we want
to understand how mesoscale actomyosin active torques are generated at the molecular level, and how active
torque generation in the actomyosin surface drives chiral morphogenesis of cells, tissues and organisms.
Cells and tissues represent a new class of active chiral materials where both the force and the torque balance
need to be considered, and we will perform a systematic and cross-scale characterization of active chiral
biological matter. We will pursue an interdisciplinary approach at the interface of physics and biology. At the
molecular-scale, we will use optical tweezers to measure active torques generated by single molecules of the
molecular myosin and the actin polymerizing protein formin. At the cell-scale, we will reconstitute chiral
actomyosin flows in vitro and characterize chiral dynamics of single molecules in vivo. At the tissue-scale,
we will investigate chiral cell movements in a multicellular environment and unravel the physical basis of
chiral tissue flow in vertebrates. Theory is essential at all stages, and we will build a molecular-scale model
of actomyosin torque generation that will be coarse-grained to a generalized hydrodynamic description of
active chiral matter. This interdisciplinary and cross-scale approach will provide fundamentally new insights
into active chiral materials and the mechanisms by which left-right asymmetries arise in development.
Summary
The aim of this grant is to understand how cellular, tissue-scale and organismal left-right asymmetry arises
from the chirality of molecular constituents. In many instances the actomyosin cortex, a thin and
mechanically active layer of dynamically cross-linked filaments and molecular motors at the surface of cells,
drives the emergence of chiral morphogenetic events. In the nematode Caenorhabditis elegans, mesoscale
chiral active torques generated by this active layer establish the embryo’s left-right body axis. Here we want
to understand how mesoscale actomyosin active torques are generated at the molecular level, and how active
torque generation in the actomyosin surface drives chiral morphogenesis of cells, tissues and organisms.
Cells and tissues represent a new class of active chiral materials where both the force and the torque balance
need to be considered, and we will perform a systematic and cross-scale characterization of active chiral
biological matter. We will pursue an interdisciplinary approach at the interface of physics and biology. At the
molecular-scale, we will use optical tweezers to measure active torques generated by single molecules of the
molecular myosin and the actin polymerizing protein formin. At the cell-scale, we will reconstitute chiral
actomyosin flows in vitro and characterize chiral dynamics of single molecules in vivo. At the tissue-scale,
we will investigate chiral cell movements in a multicellular environment and unravel the physical basis of
chiral tissue flow in vertebrates. Theory is essential at all stages, and we will build a molecular-scale model
of actomyosin torque generation that will be coarse-grained to a generalized hydrodynamic description of
active chiral matter. This interdisciplinary and cross-scale approach will provide fundamentally new insights
into active chiral materials and the mechanisms by which left-right asymmetries arise in development.
Max ERC Funding
2 500 000 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym ChroNeuroRepair
Project Chromatin states in neurogenesis – from understanding chromatin loops to eliciting neurogenesis for repair
Researcher (PI) Magdalena Götz
Host Institution (HI) HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Call Details Advanced Grant (AdG), LS3, ERC-2013-ADG
Summary The mechanisms regulating neural stem cells and their progression to neurogenesis are important not only to understand brain development and evolution, but also to elicit neurogenesis after brain injury. Our recent findings imply novel chromatin-associated proteins in the regulation of neural stem cell fate and neurogenesis. Therefore this project aims to understand the molecular mechanisms of how these factors regulate neurogenesis in developing and adult mice (Aim1) and implement this knowledge for reprogramming glia into neurons after brain injury (Aim2). This will be pursued in mouse models in vivo (2.1) and with human glial cells derived from patient brain resections in vitro (2.2). It is well known that transcription factors need to alter the chromatin structure to achieve transcriptional regulation, but the factors involved in this regulation in neural stem and progenitor cells are still ill understood. Therefore the molecular function of the novel chromatin interacting protein Trnp1 with essential roles in neural stem cell (NSC) fate and the chromatin conformation mediated at neurogenic target genes by Pax6/Brg1-containing BAF complexes will be addressed in Aim1. Combined with genome-wide approaches to determine changes in chromatin conformation at neurogenic target gene sites this will greatly further our understanding of key roles of chromatin conformation in neural stem cells and neurogenesis. In Aim2 Trnp1 promoting neural stem cells fate and later acting neurogenic transcription factors will be used to improve neuronal reprogramming after stab wound injury in the murine brain in vivo and in patient-derived glial cells in vitro. Together with novel strategies to induce chromatin looping in a sequence-specific manner this project will not only advance our knowledge at the frontier of transcriptional regulation in neurogenesis, but also implement highly innovative approaches to utilize this knowledge for neuronal repair by direct reprogramming.
Summary
The mechanisms regulating neural stem cells and their progression to neurogenesis are important not only to understand brain development and evolution, but also to elicit neurogenesis after brain injury. Our recent findings imply novel chromatin-associated proteins in the regulation of neural stem cell fate and neurogenesis. Therefore this project aims to understand the molecular mechanisms of how these factors regulate neurogenesis in developing and adult mice (Aim1) and implement this knowledge for reprogramming glia into neurons after brain injury (Aim2). This will be pursued in mouse models in vivo (2.1) and with human glial cells derived from patient brain resections in vitro (2.2). It is well known that transcription factors need to alter the chromatin structure to achieve transcriptional regulation, but the factors involved in this regulation in neural stem and progenitor cells are still ill understood. Therefore the molecular function of the novel chromatin interacting protein Trnp1 with essential roles in neural stem cell (NSC) fate and the chromatin conformation mediated at neurogenic target genes by Pax6/Brg1-containing BAF complexes will be addressed in Aim1. Combined with genome-wide approaches to determine changes in chromatin conformation at neurogenic target gene sites this will greatly further our understanding of key roles of chromatin conformation in neural stem cells and neurogenesis. In Aim2 Trnp1 promoting neural stem cells fate and later acting neurogenic transcription factors will be used to improve neuronal reprogramming after stab wound injury in the murine brain in vivo and in patient-derived glial cells in vitro. Together with novel strategies to induce chromatin looping in a sequence-specific manner this project will not only advance our knowledge at the frontier of transcriptional regulation in neurogenesis, but also implement highly innovative approaches to utilize this knowledge for neuronal repair by direct reprogramming.
Max ERC Funding
2 376 560 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym COCO2CASA
Project Modeling Stellar Collapse and Explosion: Evolving Progenitor Stars to Supernova Remnants
Researcher (PI) Hans-Thomas Janka
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), PE9, ERC-2013-ADG
Summary "This project intends to make groundbreaking progress towards the solution of one of the most pestering and long-standing riddles of stellar astrophysics, namely the question how massive stars explode as supernovae (SNe).
State-of-the-art simulations in two dimensions (2D) now yield neutrino-powered (through underenergetic) explosions for a growing variety of progenitors and thus support the delayed neutrino-heating mechanism. However, sophisticated, fully self-consistent, 3D simulations are still lacking, the spherical symmetry of the progenitor star models is becoming a serious handicap, and better exploitation of observational constraints of the SN mechanism is urgently needed.
For these reasons we plan a novel, comprehensive modeling approach, in which 3D hydrodynamics including all relevant microphysics will not only be employed for the launch phase of the SN blast wave by neutrino-energy deposition. Different from previous initiatives, 3D hydrodynamics will also be applied to the final stages of convective shell burning in the progenitor core before collapse in order to derive --for the first time-- self-consistent, multidimensional progenitor data for adopting them as initial conditions in the SN modeling. Moreover, the 3D explosion simulations will be continued consistently through the long-time evolution of the SN outburst into the gaseous remnant phase. This challenging approach promises fundamentally new insights into the processes that trigger and shape SN explosions and will revise our understanding of how SNe depend on the properties of their progenitor stars. Moreover, heading for a direct comparison of the derived theoretical models with nearby young SN remnants like Crab, Cassiopeia A, and SN 1987A, whose 3D morphology and composition are currently unfolded in stunning detail by multiwavelength observations, the project will lay the foundations of a powerful, innovative, and so far not exploited way of probing the physics deep inside the SN core."
Summary
"This project intends to make groundbreaking progress towards the solution of one of the most pestering and long-standing riddles of stellar astrophysics, namely the question how massive stars explode as supernovae (SNe).
State-of-the-art simulations in two dimensions (2D) now yield neutrino-powered (through underenergetic) explosions for a growing variety of progenitors and thus support the delayed neutrino-heating mechanism. However, sophisticated, fully self-consistent, 3D simulations are still lacking, the spherical symmetry of the progenitor star models is becoming a serious handicap, and better exploitation of observational constraints of the SN mechanism is urgently needed.
For these reasons we plan a novel, comprehensive modeling approach, in which 3D hydrodynamics including all relevant microphysics will not only be employed for the launch phase of the SN blast wave by neutrino-energy deposition. Different from previous initiatives, 3D hydrodynamics will also be applied to the final stages of convective shell burning in the progenitor core before collapse in order to derive --for the first time-- self-consistent, multidimensional progenitor data for adopting them as initial conditions in the SN modeling. Moreover, the 3D explosion simulations will be continued consistently through the long-time evolution of the SN outburst into the gaseous remnant phase. This challenging approach promises fundamentally new insights into the processes that trigger and shape SN explosions and will revise our understanding of how SNe depend on the properties of their progenitor stars. Moreover, heading for a direct comparison of the derived theoretical models with nearby young SN remnants like Crab, Cassiopeia A, and SN 1987A, whose 3D morphology and composition are currently unfolded in stunning detail by multiwavelength observations, the project will lay the foundations of a powerful, innovative, and so far not exploited way of probing the physics deep inside the SN core."
Max ERC Funding
2 898 600 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym Com4Com
Project Collective modes in 4d-metal compounds and heterostructures
Researcher (PI) Bernhard Keimer
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), PE3, ERC-2014-ADG
Summary Compounds of transition metals with 4d valence electrons (“4d metals”) play eminent roles in many areas of condensed matter physics ranging from unconventional superconductivity to oxide electronics, but fundamental questions about the interplay between the spin-orbit coupling and electronic correlations at the atomic scale remain unanswered. Momentum-resolved spectroscopies of collective electronic excitations yield detailed insight into the magnitude and spatial range of the electronic correlations, and have thus decisively shaped the conceptual understanding of quantum many-body phenomena in 3d-electron systems. We will devise and build a novel resonant inelastic x-ray scattering (RIXS) instrument capable of determining the dispersion relations of electronic collective modes in 4d-metal compounds with full momentum-space coverage, high energy resolution, and monolayer sensitivity.
Data from this instrument will yield comprehensive information about the interaction parameters specifying the electronic Hamiltonians of 4d-electron materials, unique insight into the spin-orbital composition of their excited-state wavefunctions, and definitive tests of proposals to realize Kitaev models with spin-liquid states that are potentially relevant in topological quantum computation. The element-specificity of RIXS will also allow us to determine the microscopic exchange interactions in complex materials with both 3d and 4d valence electrons, and its high sensitivity will enable experiments on operational device structures comprising only a few monolayers. We will thus be able to tightly integrate momentum-resolved spectroscopy with state-of-the-art, monolayer-by-monolayer deposition methods of 4d metal-oxide films and heterostructures. The results will fuel a feedback loop comprising synthesis, characterization, and modeling, which will greatly advance our ability to design materials and devices whose functionality derives from the collective organization of electrons.
Summary
Compounds of transition metals with 4d valence electrons (“4d metals”) play eminent roles in many areas of condensed matter physics ranging from unconventional superconductivity to oxide electronics, but fundamental questions about the interplay between the spin-orbit coupling and electronic correlations at the atomic scale remain unanswered. Momentum-resolved spectroscopies of collective electronic excitations yield detailed insight into the magnitude and spatial range of the electronic correlations, and have thus decisively shaped the conceptual understanding of quantum many-body phenomena in 3d-electron systems. We will devise and build a novel resonant inelastic x-ray scattering (RIXS) instrument capable of determining the dispersion relations of electronic collective modes in 4d-metal compounds with full momentum-space coverage, high energy resolution, and monolayer sensitivity.
Data from this instrument will yield comprehensive information about the interaction parameters specifying the electronic Hamiltonians of 4d-electron materials, unique insight into the spin-orbital composition of their excited-state wavefunctions, and definitive tests of proposals to realize Kitaev models with spin-liquid states that are potentially relevant in topological quantum computation. The element-specificity of RIXS will also allow us to determine the microscopic exchange interactions in complex materials with both 3d and 4d valence electrons, and its high sensitivity will enable experiments on operational device structures comprising only a few monolayers. We will thus be able to tightly integrate momentum-resolved spectroscopy with state-of-the-art, monolayer-by-monolayer deposition methods of 4d metal-oxide films and heterostructures. The results will fuel a feedback loop comprising synthesis, characterization, and modeling, which will greatly advance our ability to design materials and devices whose functionality derives from the collective organization of electrons.
Max ERC Funding
3 176 850 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym COMPLEXPLAS
Project Complex Plasmonics at the Ultimate Limit: Single Particle and Single Molecule Level
Researcher (PI) Harald Giessen
Host Institution (HI) UNIVERSITAET STUTTGART
Call Details Advanced Grant (AdG), PE3, ERC-2012-ADG_20120216
Summary "Nano-optical investigations using plasmonic resonances have revolutionized optics in the last few years. The ability to concentrate light in subwavelength dimensions and to locally enhance the strength of the electromagnetic field in a tailored fashion opened several new fields in materials research, such as tailoring the linear and nonlinear properties of optical materials at will. So-called metamaterials allow now to design and realize unprecedented optical properties on the submicrometer level and hence tailor dispersion as well as real and imaginary parts of the linear and nonlinear refractive indices as a function of wavelength and wavevector.
Our ability to create two- and three-dimensional nanostructures with advanced fabrication technologies have led to the new era of complex plasmonics. We are able to tailor the spectral response of complex metallic nanostructures, including the creation of very sharp and narrow resonances. In combination with strong field localization and hence large dependence on the material properties of the nanostructure geometry and its surrounding, unique sensors with sensitivities close to fundamental limits should be within reach.
In my proposal, I would like to explore the ultimate limits of light-matter interaction using complex plasmonic nanostructures. I would like to apply them to different physical, chemical, and biological situations and undertake the first steps from fundamental insight into first applications. Namely, I would like to investigate complex plasmonics in four different contexts: single molecule reactions on complex surfaces, antenna-enhanced structural analysis of large single molecules, such as proteins, motion sensing of conformational changes of single molecules, as well as chiral sensing down to the single molecule level, hence ultimately being able to distinguish a single D-glucose molecule from its L-glucose enantiomer. This would bridge the gap between nanophysics, chemistry, and biology."
Summary
"Nano-optical investigations using plasmonic resonances have revolutionized optics in the last few years. The ability to concentrate light in subwavelength dimensions and to locally enhance the strength of the electromagnetic field in a tailored fashion opened several new fields in materials research, such as tailoring the linear and nonlinear properties of optical materials at will. So-called metamaterials allow now to design and realize unprecedented optical properties on the submicrometer level and hence tailor dispersion as well as real and imaginary parts of the linear and nonlinear refractive indices as a function of wavelength and wavevector.
Our ability to create two- and three-dimensional nanostructures with advanced fabrication technologies have led to the new era of complex plasmonics. We are able to tailor the spectral response of complex metallic nanostructures, including the creation of very sharp and narrow resonances. In combination with strong field localization and hence large dependence on the material properties of the nanostructure geometry and its surrounding, unique sensors with sensitivities close to fundamental limits should be within reach.
In my proposal, I would like to explore the ultimate limits of light-matter interaction using complex plasmonic nanostructures. I would like to apply them to different physical, chemical, and biological situations and undertake the first steps from fundamental insight into first applications. Namely, I would like to investigate complex plasmonics in four different contexts: single molecule reactions on complex surfaces, antenna-enhanced structural analysis of large single molecules, such as proteins, motion sensing of conformational changes of single molecules, as well as chiral sensing down to the single molecule level, hence ultimately being able to distinguish a single D-glucose molecule from its L-glucose enantiomer. This would bridge the gap between nanophysics, chemistry, and biology."
Max ERC Funding
2 000 000 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym COREMA
Project Cell division and the origin of embryonic aneuploidy in preimplantation mouse development
Researcher (PI) Jan ELLENBERG
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Call Details Advanced Grant (AdG), LS3, ERC-2015-AdG
Summary Cell division is fundamental for development. In the early mammalian embryo it drives the rapid proliferation of totipotent cells, the basis for forming the fetus. Given its crucial importance, it is surprising that cell division is particularly error-prone at the beginning of mammalian life, resulting in spontaneous abortion or severe developmental retardation, the incidence of which is increasing with age of the mother. Why aneuploidy is so prevalent and how early embryonic development nevertheless achieves robustness is largely unknown. The goal of this project is a comprehensive analysis of cell divisions in the mouse preimplantation embryo to determine the molecular mechanisms underlying aneuploidy and its effects on normal development. Recent technological breakthroughs, including light sheet microscopy and rapid loss-of-function approaches in the mouse embryo will allow us for the first time to tackle the molecular mechanisms of aneuploidy generation and establish the preimplantation mouse embryo as a standard cell biological model system. For that purpose we will develop next generation light sheet microscopy to enable automated chromosome tracking in the whole embryo. Mapping of cell division errors will reveal when, where, and how aneuploidy occurs, what the fate of aneuploid cells is in the embryo, and how this changes with maternal age. We will then perform high resolution functional imaging assays to identify the mitotic pathways responsible for aneuploidy and understand why they do not fully function in early development. Key proteins will be functionally characterised in detail integrating light sheet imaging with single molecule biophysics in embryos from young and aged females to achieve a mechanistic understanding of the unique aspects of cell division underlying embryonic aneuploidy. The achieved knowledge gain will have an important impact for our understanding of mammalian, including human infertility.
Summary
Cell division is fundamental for development. In the early mammalian embryo it drives the rapid proliferation of totipotent cells, the basis for forming the fetus. Given its crucial importance, it is surprising that cell division is particularly error-prone at the beginning of mammalian life, resulting in spontaneous abortion or severe developmental retardation, the incidence of which is increasing with age of the mother. Why aneuploidy is so prevalent and how early embryonic development nevertheless achieves robustness is largely unknown. The goal of this project is a comprehensive analysis of cell divisions in the mouse preimplantation embryo to determine the molecular mechanisms underlying aneuploidy and its effects on normal development. Recent technological breakthroughs, including light sheet microscopy and rapid loss-of-function approaches in the mouse embryo will allow us for the first time to tackle the molecular mechanisms of aneuploidy generation and establish the preimplantation mouse embryo as a standard cell biological model system. For that purpose we will develop next generation light sheet microscopy to enable automated chromosome tracking in the whole embryo. Mapping of cell division errors will reveal when, where, and how aneuploidy occurs, what the fate of aneuploid cells is in the embryo, and how this changes with maternal age. We will then perform high resolution functional imaging assays to identify the mitotic pathways responsible for aneuploidy and understand why they do not fully function in early development. Key proteins will be functionally characterised in detail integrating light sheet imaging with single molecule biophysics in embryos from young and aged females to achieve a mechanistic understanding of the unique aspects of cell division underlying embryonic aneuploidy. The achieved knowledge gain will have an important impact for our understanding of mammalian, including human infertility.
Max ERC Funding
2 497 156 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym Cosmic_Gas
Project Mapping the Cosmic Gas Supply with ALMA
Researcher (PI) Fabian WALTER
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), PE9, ERC-2016-ADG
Summary The molecular gas phase is the material in galaxies out of which stars form. As such, it is the quantity that controls the star formation rate of a galaxy, thereby the overall stellar mass build-up, and ultimately galaxy evolution through cosmic times. In contrast to studies of the stellar mass and star formation, characterizing this fuel supply in galaxies as a function of cosmic epoch is still in its infancy. The ALMA facility now redefines our ability to map out the cosmic cold gas supply, essentially unknown at present. This ERC proposal is based on extensive approved observational ALMA programs, led by the PI: ASPECS is the first-ever approved ALMA large (150h) program, aimed at providing a comprehensive view of the baryon cycle from gas to stars over cosmic time. ASPECS will provide 3D molecular scans in two ALMA bands of the Hubble Ultra Deep Field -- the iconic cosmological deep field. A second focus is the detailed characterization of the molecular gas content at z>6 in host galaxies of the most distant quasars via ALMA. This will assess the role of cold gas in the build-up of the first (t_Universe < 1 Gyr) massive cosmic structures in the Universe, again through significant approved ALMA programs led by the PI’s group. The studies outlined here will fully capitalize on the unparalleled capabilities of ALMA to map out the cosmic gas supply through cosmic history, and will provide crucial insights to define observational strategies for JWST (the PI is member of the European JWST/MIRI science team). Through his track record, past achievements in the field of galaxy evolution studies, and through the available proprietary data, the PI is uniquely positioned to lead this ambitious program, which will define the global state-of-the-art in cosmological galaxy evolution through high-redshift ISM studies.
Summary
The molecular gas phase is the material in galaxies out of which stars form. As such, it is the quantity that controls the star formation rate of a galaxy, thereby the overall stellar mass build-up, and ultimately galaxy evolution through cosmic times. In contrast to studies of the stellar mass and star formation, characterizing this fuel supply in galaxies as a function of cosmic epoch is still in its infancy. The ALMA facility now redefines our ability to map out the cosmic cold gas supply, essentially unknown at present. This ERC proposal is based on extensive approved observational ALMA programs, led by the PI: ASPECS is the first-ever approved ALMA large (150h) program, aimed at providing a comprehensive view of the baryon cycle from gas to stars over cosmic time. ASPECS will provide 3D molecular scans in two ALMA bands of the Hubble Ultra Deep Field -- the iconic cosmological deep field. A second focus is the detailed characterization of the molecular gas content at z>6 in host galaxies of the most distant quasars via ALMA. This will assess the role of cold gas in the build-up of the first (t_Universe < 1 Gyr) massive cosmic structures in the Universe, again through significant approved ALMA programs led by the PI’s group. The studies outlined here will fully capitalize on the unparalleled capabilities of ALMA to map out the cosmic gas supply through cosmic history, and will provide crucial insights to define observational strategies for JWST (the PI is member of the European JWST/MIRI science team). Through his track record, past achievements in the field of galaxy evolution studies, and through the available proprietary data, the PI is uniquely positioned to lead this ambitious program, which will define the global state-of-the-art in cosmological galaxy evolution through high-redshift ISM studies.
Max ERC Funding
2 457 500 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym DanioPattern
Project Development and Evolution of Colour Patterns in Danio species
Researcher (PI) Christiane NÜSSLEIN-VOLHARD
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS3, ERC-2015-AdG
Summary Colour patterns are prominent features of many animals and have important functions in communication such as camouflage, kin recognition and mate selection. Colour patterns are highly variable and evolve rapidly leading to large diversities even within a single genus. As targets for natural as well as sexual selection, they are of high evolutionary significance. The zebrafish (Danio rerio), a vertebrate model organism for the study of development and disease, displays a conspicuous pattern of alternating blue and golden stripes on the body and on the anal- and tailfins. Mutants with spectacularly altered patterns have been analysed, and novel approaches in lineage tracing have provided first insights into the cellular and molecular basis of colour patterning. These studies revealed that the mechanisms at play are novel and of fundamental interest to the biology of pattern formation. Closely related Danio species have very divergent colour patterns in body and fins offering the unique opportunity to study development and evolution of colour patterns in vertebrates building on the thorough analysis of one model species. Our research in zebrafish will explore the basis of direct interactions between chromatophores mediated by channels and junctions. We will investigate the divergent mode of stripe formation in the fins and the molecular influence of the cellular environment on chromatophore interactions. In closely related Danio species, we will investigate the cellular interactions during pattern formation. We will analyse transcriptomes and genome sequences to identify candidate genes providing the molecular basis for pigment pattern diversity. These candidate genes will be tested by creating mutants and exchanging allelic variants using the CRISPR/Cas9 system. The work will lay the foundation to understand not only the genetic basis of variation in colour pattern formation between Danio species, but also the evolution of biodiversity in other vertebrates.
Summary
Colour patterns are prominent features of many animals and have important functions in communication such as camouflage, kin recognition and mate selection. Colour patterns are highly variable and evolve rapidly leading to large diversities even within a single genus. As targets for natural as well as sexual selection, they are of high evolutionary significance. The zebrafish (Danio rerio), a vertebrate model organism for the study of development and disease, displays a conspicuous pattern of alternating blue and golden stripes on the body and on the anal- and tailfins. Mutants with spectacularly altered patterns have been analysed, and novel approaches in lineage tracing have provided first insights into the cellular and molecular basis of colour patterning. These studies revealed that the mechanisms at play are novel and of fundamental interest to the biology of pattern formation. Closely related Danio species have very divergent colour patterns in body and fins offering the unique opportunity to study development and evolution of colour patterns in vertebrates building on the thorough analysis of one model species. Our research in zebrafish will explore the basis of direct interactions between chromatophores mediated by channels and junctions. We will investigate the divergent mode of stripe formation in the fins and the molecular influence of the cellular environment on chromatophore interactions. In closely related Danio species, we will investigate the cellular interactions during pattern formation. We will analyse transcriptomes and genome sequences to identify candidate genes providing the molecular basis for pigment pattern diversity. These candidate genes will be tested by creating mutants and exchanging allelic variants using the CRISPR/Cas9 system. The work will lay the foundation to understand not only the genetic basis of variation in colour pattern formation between Danio species, but also the evolution of biodiversity in other vertebrates.
Max ERC Funding
2 250 000 €
Duration
Start date: 2016-11-01, End date: 2021-04-30
Project acronym DNADEMETHYLASE
Project Functions and mechanism of active DNA demethylation
Researcher (PI) Heinz Christof Niehrs
Host Institution (HI) INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH
Call Details Advanced Grant (AdG), LS3, ERC-2009-AdG
Summary Epigenetic gene regulation is of central importance for development and disease. Despite dramatic progress in epigenetics during the past decade, DNA demethylation remains one of the last big frontiers and very little is known about it. DNA demethylation is a widespread phenomenon and occurs in plants as well as in animals, during development, in the adult, and during somatic cell reprogramming of pluripotency genes. The molecular identity of the DNA demethylase in animal cells remained unresolved and has hampered progress in the field for decades. In 2007 we published that Growth Arrest and DNA Damage 45 a (Gadd45a) is a key player in active DNA demethylation, which opened new avenues in the study of this elusive process. The goal of this project is to further analyze the mechanism of DNA demethylation as well as the role played by Gadd45 in development. Given the many unresolved questions in this burgeoning field, our work promises to be ground-breaking and therefore have a profound impact in unraveling one of the least understood processes of gene regulation. Specifically we will address the following points. I) The biological role of Gadd45 mediated DNA demethylation in mouse embryos and adults is unknown. We have obtained mouse mutants for Gadd45a,b, and g and we will analyze them for developmental defects and dissect the methylation regulation of relevant genes. II) The targeting mechanism by which Gadd45 is binding to and demethylating specific sites in the genome is a central unresolved issue. We have identified a candidate DNA binding protein interacting with Gadd45 and we will analyze its role in site specific targeting of DNA demethylation in vitro and in mouse. III) We found that Gadd45 is an RNA binding protein and we will therefore analyze how non-coding RNAs are involved in targeting and/or activating Gadd45 during DNA demethylation.
Summary
Epigenetic gene regulation is of central importance for development and disease. Despite dramatic progress in epigenetics during the past decade, DNA demethylation remains one of the last big frontiers and very little is known about it. DNA demethylation is a widespread phenomenon and occurs in plants as well as in animals, during development, in the adult, and during somatic cell reprogramming of pluripotency genes. The molecular identity of the DNA demethylase in animal cells remained unresolved and has hampered progress in the field for decades. In 2007 we published that Growth Arrest and DNA Damage 45 a (Gadd45a) is a key player in active DNA demethylation, which opened new avenues in the study of this elusive process. The goal of this project is to further analyze the mechanism of DNA demethylation as well as the role played by Gadd45 in development. Given the many unresolved questions in this burgeoning field, our work promises to be ground-breaking and therefore have a profound impact in unraveling one of the least understood processes of gene regulation. Specifically we will address the following points. I) The biological role of Gadd45 mediated DNA demethylation in mouse embryos and adults is unknown. We have obtained mouse mutants for Gadd45a,b, and g and we will analyze them for developmental defects and dissect the methylation regulation of relevant genes. II) The targeting mechanism by which Gadd45 is binding to and demethylating specific sites in the genome is a central unresolved issue. We have identified a candidate DNA binding protein interacting with Gadd45 and we will analyze its role in site specific targeting of DNA demethylation in vitro and in mouse. III) We found that Gadd45 is an RNA binding protein and we will therefore analyze how non-coding RNAs are involved in targeting and/or activating Gadd45 during DNA demethylation.
Max ERC Funding
2 376 000 €
Duration
Start date: 2010-06-01, End date: 2015-05-31
Project acronym DYNASTEM
Project Dynamic, stem cell-mediated self-renewal in the Drosophila intestine
Researcher (PI) Bruce Alexander Edgar
Host Institution (HI) RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Call Details Advanced Grant (AdG), LS3, ERC-2010-AdG_20100317
Summary Cells in intestinal epithelia turn over rapidly due to aging, damage, and toxins produced by the enteric microbiota. Gut homeostasis is maintained by intestinal stem cells (ISCs) that divide to renew the intestinal epithelium, but little is known about how ISC division and differentiation are coordinated with the loss of spent gut epithelial cells. This proposal addresses the mechanisms of dynamic self-renewal in the intestine of Drosophila. Our recent work has outlined a paradigm explaining intestinal homeostasis in Drosophila that could apply also to humans. A new lab is being established in Heidelberg where we wish to extend these studies. Our objectives are to understand: 1) How intestinal stem cell pool sizes are regulated; 2) How the cytokines and growth factors that mediate gut homeostasis are controlled; and 3) How these signals regulate the ISC cell cycle. Established genetic and cell biological methods will be applied, supported by molecular assays (microarrays, qPCR, ChIP/Seq) of gene control. New pathways of ISC control will be discovered via comprehensive genetic screens using transgenic RNAi and gene over-expression. In vitro culture of ISCs will be developed and used for live imaging and molecular analysis of the mechanisms controlling ISC proliferation and differentiation. These studies should elaborate a paradigm explaining intestinal homeostasis in flies that can guide studies in mammals, eventually contributing to the diagnosis and treatment for diseases in which gut homeostasis is disrupted, such as colorectal cancer and inflammatory bowel disease. Because stem cell biology is so highly relevant to wound healing, regeneration, cancer, aging and degenerative disease, this research could impact human health at many levels.
Summary
Cells in intestinal epithelia turn over rapidly due to aging, damage, and toxins produced by the enteric microbiota. Gut homeostasis is maintained by intestinal stem cells (ISCs) that divide to renew the intestinal epithelium, but little is known about how ISC division and differentiation are coordinated with the loss of spent gut epithelial cells. This proposal addresses the mechanisms of dynamic self-renewal in the intestine of Drosophila. Our recent work has outlined a paradigm explaining intestinal homeostasis in Drosophila that could apply also to humans. A new lab is being established in Heidelberg where we wish to extend these studies. Our objectives are to understand: 1) How intestinal stem cell pool sizes are regulated; 2) How the cytokines and growth factors that mediate gut homeostasis are controlled; and 3) How these signals regulate the ISC cell cycle. Established genetic and cell biological methods will be applied, supported by molecular assays (microarrays, qPCR, ChIP/Seq) of gene control. New pathways of ISC control will be discovered via comprehensive genetic screens using transgenic RNAi and gene over-expression. In vitro culture of ISCs will be developed and used for live imaging and molecular analysis of the mechanisms controlling ISC proliferation and differentiation. These studies should elaborate a paradigm explaining intestinal homeostasis in flies that can guide studies in mammals, eventually contributing to the diagnosis and treatment for diseases in which gut homeostasis is disrupted, such as colorectal cancer and inflammatory bowel disease. Because stem cell biology is so highly relevant to wound healing, regeneration, cancer, aging and degenerative disease, this research could impact human health at many levels.
Max ERC Funding
2 682 080 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym EASY
Project Ejection Accretion Structures in YSOs (EASY)
Researcher (PI) Thomas RAY
Host Institution (HI) DUBLIN INSTITUTE FOR ADVANCED STUDIES
Call Details Advanced Grant (AdG), PE9, ERC-2016-ADG
Summary For a number of reasons, in particular their proximity and the abundant range of diagnostics to determine their characteristics, outflows from young stellar objects (YSOs) offer us the best opportunity of discovering how astrophysical jets are generated and the nature of the link between outflows and their accretion disks. Models predict that the jet is initially launched from within 0.1 to a few au of the star and focused on scales at most ten times larger. Thus, even for the nearest star formation region, we need high spatial resolution to image the “central engine” and test current models.
With these ideas in mind, and the availability of a whole new set of observational and computational resources, it is proposed to investigate the origin of YSO jets, and the jet/accretion zone link, using a number of highly novel approaches to test magneto-hydrodynamic (MHD) models including:
(a) Near-infrared interferometry to determine the spatial distribution and kinematics of the outflow as it is launched as a way of discriminating between competing models.
(b) A multi-epoch study of the strength and configuration of the magnetic field of the parent star to see whether model values and geometries agree with observations and the nature of its variability.
(c) Examining, through high spatial resolution radio observations, how the ionized component of these jets are collimated very close to the source and how shocks in the flow can give rise to low energy cosmic rays.
(d) Use the James Webb Space Telescope (JWST) and, in particular, the Mid-Infrared Instrument (MIRI) and Near-Infrared Spectrograph (NIRSpec) to investigate with high spatial resolution atomic jets from protostars that are still acquiring most of their mass. In addition, we will study how accretion is affected by metallicity by studying young solar-like stars in the low metallicity Magellanic Clouds.
In all cases the required observational campaigns have been approved.
Summary
For a number of reasons, in particular their proximity and the abundant range of diagnostics to determine their characteristics, outflows from young stellar objects (YSOs) offer us the best opportunity of discovering how astrophysical jets are generated and the nature of the link between outflows and their accretion disks. Models predict that the jet is initially launched from within 0.1 to a few au of the star and focused on scales at most ten times larger. Thus, even for the nearest star formation region, we need high spatial resolution to image the “central engine” and test current models.
With these ideas in mind, and the availability of a whole new set of observational and computational resources, it is proposed to investigate the origin of YSO jets, and the jet/accretion zone link, using a number of highly novel approaches to test magneto-hydrodynamic (MHD) models including:
(a) Near-infrared interferometry to determine the spatial distribution and kinematics of the outflow as it is launched as a way of discriminating between competing models.
(b) A multi-epoch study of the strength and configuration of the magnetic field of the parent star to see whether model values and geometries agree with observations and the nature of its variability.
(c) Examining, through high spatial resolution radio observations, how the ionized component of these jets are collimated very close to the source and how shocks in the flow can give rise to low energy cosmic rays.
(d) Use the James Webb Space Telescope (JWST) and, in particular, the Mid-Infrared Instrument (MIRI) and Near-Infrared Spectrograph (NIRSpec) to investigate with high spatial resolution atomic jets from protostars that are still acquiring most of their mass. In addition, we will study how accretion is affected by metallicity by studying young solar-like stars in the low metallicity Magellanic Clouds.
In all cases the required observational campaigns have been approved.
Max ERC Funding
1 853 090 €
Duration
Start date: 2017-10-01, End date: 2022-09-30