Project acronym ACTMECH
Project Emergent Active Mechanical Behaviour of the Actomyosin Cell Cortex
Researcher (PI) Stephan Wolfgang Grill
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Country Germany
Call Details Starting Grant (StG), LS3, ERC-2011-StG_20101109
Summary The cell cortex is a highly dynamic layer of crosslinked actin filaments and myosin molecular motors beneath the cell membrane. It plays a central role in large scale rearrangements that occur inside cells. Many molecular mechanisms contribute to cortex structure and dynamics. However, cell scale physical properties of the cortex are difficult to grasp. This is problematic because for large scale rearrangements inside a cell, such as coherent flow of the cell cortex, it is the cell scale emergent properties that are important for the realization of such events. I will investigate how the actomyosin cytoskeleton behaves at a coarse grained and cellular scale, and will study how this emergent active behaviour is influenced by molecular mechanisms. We will study the cell cortex in the one cell stage C. elegans embryo, which undergoes large scale cortical flow during polarization and cytokinesis. We will combine theory and experiment. We will characterize cortex structure and dynamics with biophysical techniques such as cortical laser ablation and quantitative photobleaching experiments. We will develop and employ novel theoretical approaches to describe the cell scale mechanical behaviour in terms of an active complex fluid. We will utilize genetic approaches to understand how these emergent mechanical properties are influenced by molecular activities. A central goal is to arrive at a coarse grained description of the cortex that can predict future dynamic behaviour from the past structure, which is conceptually similar to how weather forecasting is accomplished. To date, systematic approaches to link molecular scale physical mechanisms to those on cellular scales are missing. This work will open new opportunities for cell biological and cell biophysical research, by providing a methodological approach for bridging scales, for studying emergent and large-scale active mechanical behaviours and linking them to molecular mechanisms.
Summary
The cell cortex is a highly dynamic layer of crosslinked actin filaments and myosin molecular motors beneath the cell membrane. It plays a central role in large scale rearrangements that occur inside cells. Many molecular mechanisms contribute to cortex structure and dynamics. However, cell scale physical properties of the cortex are difficult to grasp. This is problematic because for large scale rearrangements inside a cell, such as coherent flow of the cell cortex, it is the cell scale emergent properties that are important for the realization of such events. I will investigate how the actomyosin cytoskeleton behaves at a coarse grained and cellular scale, and will study how this emergent active behaviour is influenced by molecular mechanisms. We will study the cell cortex in the one cell stage C. elegans embryo, which undergoes large scale cortical flow during polarization and cytokinesis. We will combine theory and experiment. We will characterize cortex structure and dynamics with biophysical techniques such as cortical laser ablation and quantitative photobleaching experiments. We will develop and employ novel theoretical approaches to describe the cell scale mechanical behaviour in terms of an active complex fluid. We will utilize genetic approaches to understand how these emergent mechanical properties are influenced by molecular activities. A central goal is to arrive at a coarse grained description of the cortex that can predict future dynamic behaviour from the past structure, which is conceptually similar to how weather forecasting is accomplished. To date, systematic approaches to link molecular scale physical mechanisms to those on cellular scales are missing. This work will open new opportunities for cell biological and cell biophysical research, by providing a methodological approach for bridging scales, for studying emergent and large-scale active mechanical behaviours and linking them to molecular mechanisms.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-12-01, End date: 2017-08-31
Project acronym ASMIDIAS
Project Asymmetric microenvironments by directed assembly: Control of geometry, topography, surface biochemistry and mechanical properties via a microscale modular design principle
Researcher (PI) Holger Dr. Schoenherr
Host Institution (HI) UNIVERSITAET SIEGEN
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2011-StG_20101014
Summary The interaction of cells with the extracellular matrix or neighboring cells plays a crucial role in many cellular functions, such as motility, differentiation and controlled cell death. Expanding on pioneering studies on defined 2-D model systems, the role of the currently known determinants (geometry, topography, biochemical functionality and mechanical properties) is currently addressed in more relevant 3-D matrices. However, there is a clear lack in currently available approaches to fabricate well defined microenvironments, which are asymmetric or in which these factors can be varied independently. The central objective of ASMIDIAS is the development of a novel route to asymmetric microenvironments for cell-matrix interaction studies. Inspired by molecular self-assembly on the one hand and guided macroscale assembly on the other hand, directed assembly of highly defined microfabricated building blocks will be exploited to this end. In this modular design approach different building blocks position themselves during assembly on pre-structured surfaces to afford enclosed volumes that are restricted by the walls of the blocks. The project relies on two central elements. For the guided assembly, the balance of attractive and repulsive interactions between the building blocks (and its dependence on the object dimensions) and the structured surface shall be controlled by appropriate surface chemistry and suitable guiding structures. To afford the required functionality, new approaches to (i) topographically structure, (ii) biochemically functionalize and pattern selected sides of the microscale building blocks and (iii) to control their surface elastic properties via surface-attached polymers and hydrogels, will be developed.The resulting unique asymmetric environments will facilitate novel insight into cell-matrix interactions, which possess considerable relevance in the areas of tissue engineering, cell (de)differentiation, bacteria-surface interactions and beyond.
Summary
The interaction of cells with the extracellular matrix or neighboring cells plays a crucial role in many cellular functions, such as motility, differentiation and controlled cell death. Expanding on pioneering studies on defined 2-D model systems, the role of the currently known determinants (geometry, topography, biochemical functionality and mechanical properties) is currently addressed in more relevant 3-D matrices. However, there is a clear lack in currently available approaches to fabricate well defined microenvironments, which are asymmetric or in which these factors can be varied independently. The central objective of ASMIDIAS is the development of a novel route to asymmetric microenvironments for cell-matrix interaction studies. Inspired by molecular self-assembly on the one hand and guided macroscale assembly on the other hand, directed assembly of highly defined microfabricated building blocks will be exploited to this end. In this modular design approach different building blocks position themselves during assembly on pre-structured surfaces to afford enclosed volumes that are restricted by the walls of the blocks. The project relies on two central elements. For the guided assembly, the balance of attractive and repulsive interactions between the building blocks (and its dependence on the object dimensions) and the structured surface shall be controlled by appropriate surface chemistry and suitable guiding structures. To afford the required functionality, new approaches to (i) topographically structure, (ii) biochemically functionalize and pattern selected sides of the microscale building blocks and (iii) to control their surface elastic properties via surface-attached polymers and hydrogels, will be developed.The resulting unique asymmetric environments will facilitate novel insight into cell-matrix interactions, which possess considerable relevance in the areas of tissue engineering, cell (de)differentiation, bacteria-surface interactions and beyond.
Max ERC Funding
1 484 100 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
Project acronym CARDIOSPLICE
Project A systems and targeted approach to alternative splicing in the developing and diseased heart: Translating basic cell biology to improved cardiac function
Researcher (PI) Michael Gotthardt
Host Institution (HI) MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC)
Country Germany
Call Details Starting Grant (StG), LS4, ERC-2011-StG_20101109
Summary Cardiovascular disease keeps the top spot in mortality statistics in Europe with 2 million deaths annually and although prevention and therapy have continuously been improved, the prevalence of heart failure continues to rise. While contractile (systolic) dysfunction is readily accessible to pharmacological treatment, there is a lack of therapeutic options for reduced ventricular filling (diastolic dysfunction). The diastolic properties of the heart are largely determined by the giant sarcomeric protein titin, which is alternatively spliced to adjust the elastic properties of the cardiomyocyte. We have recently identified a titin splice factor that plays a parallel role in cardiac disease and postnatal development. It targets a subset of genes that concertedly affect biomechanics, electrical activity, and signal transduction and suggests alternative splicing as a novel therapeutic target in heart disease. Here we will build on the titin splice factor to identify regulatory principles and cofactors that adjust cardiac isoform expression. In a complementary approach we will investigate titin mRNA binding proteins to provide a comprehensive analysis of factors governing titin’s differential splicing in cardiac development, health, and disease. Based on its distinctive role in ventricular filling we will evaluate titin splicing as a therapeutic target in diastolic heart failure and use a titin based reporter assay to identify small molecules to interfere with titin isoform expression. Finally, we will evaluate the effects of altered alternative splicing on diastolic dysfunction in vivo utilizing the splice deficient mutant and our available animal models for diastolic dysfunction.
The overall scientific goal of the proposed work is to investigate the regulation of cardiac alternative splicing in development and disease and to evaluate if splice directed therapy can be used to improve diastolic function and specifically the elastic properties of the heart.
Summary
Cardiovascular disease keeps the top spot in mortality statistics in Europe with 2 million deaths annually and although prevention and therapy have continuously been improved, the prevalence of heart failure continues to rise. While contractile (systolic) dysfunction is readily accessible to pharmacological treatment, there is a lack of therapeutic options for reduced ventricular filling (diastolic dysfunction). The diastolic properties of the heart are largely determined by the giant sarcomeric protein titin, which is alternatively spliced to adjust the elastic properties of the cardiomyocyte. We have recently identified a titin splice factor that plays a parallel role in cardiac disease and postnatal development. It targets a subset of genes that concertedly affect biomechanics, electrical activity, and signal transduction and suggests alternative splicing as a novel therapeutic target in heart disease. Here we will build on the titin splice factor to identify regulatory principles and cofactors that adjust cardiac isoform expression. In a complementary approach we will investigate titin mRNA binding proteins to provide a comprehensive analysis of factors governing titin’s differential splicing in cardiac development, health, and disease. Based on its distinctive role in ventricular filling we will evaluate titin splicing as a therapeutic target in diastolic heart failure and use a titin based reporter assay to identify small molecules to interfere with titin isoform expression. Finally, we will evaluate the effects of altered alternative splicing on diastolic dysfunction in vivo utilizing the splice deficient mutant and our available animal models for diastolic dysfunction.
The overall scientific goal of the proposed work is to investigate the regulation of cardiac alternative splicing in development and disease and to evaluate if splice directed therapy can be used to improve diastolic function and specifically the elastic properties of the heart.
Max ERC Funding
1 499 191 €
Duration
Start date: 2012-01-01, End date: 2017-06-30
Project acronym COMPLEXNMD
Project NMD Complexes: Eukaryotic mRNA Quality Control
Researcher (PI) Christiane Helene Berger-Schaffitzel
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Country Germany
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary Nonsense-mediated mRNA decay (NMD) is an essential mechanism controlling translation in the eukaryotic cell. NMD ascertains accurate expression of the genetic information by quality controlling messenger RNA (mRNA). During translation, NMD factors recognize and target to degradation aberrant mRNAs that have a premature stop codon (PTC) and that would otherwise lead to the production of truncated proteins which could be harmful for the cell. A wide range of genetic diseases have their origin in the mechanisms of NMD. Discrimination of a PTC from a correct termination codon depends on splicing and translation, and it is the first and foremost step in human NMD. The molecular mechanism of this process remains elusive to date.
In the research proposed, I will undertake to elucidate the molecular basis of translation termination and induction of NMD. I will study complexes involved in human translation termination at a normal stop codon and involved in NMD. I will employ an array of innovative techniques including recombinant production of human protein complexes by the MultiBac system, mammalian in vitro translation, mass spectrometry for detecting relevant protein modifications, biophysical techniques, mutational analyses and RNA-interference experiments. Stable ribosomal complexes with termination factors and complexes of NMD factors will be used for structure determination by cryo-electron microscopy. State-of-the-art image processing will be applied to address the inherent heterogeneity of the complexes. Hybrid approaches will allow the combination of cryo-EM structures with existing high-resolution structures of factors involved for generation of quasi-atomic models thereby visualizing molecular mechanisms of NMD action. This interdisciplinary work will foster our understanding at a molecular level of a paramount step in mRNA quality control, which is a vital prerequisite for the development of new treatment strategies in NMD-related diseases.
Summary
Nonsense-mediated mRNA decay (NMD) is an essential mechanism controlling translation in the eukaryotic cell. NMD ascertains accurate expression of the genetic information by quality controlling messenger RNA (mRNA). During translation, NMD factors recognize and target to degradation aberrant mRNAs that have a premature stop codon (PTC) and that would otherwise lead to the production of truncated proteins which could be harmful for the cell. A wide range of genetic diseases have their origin in the mechanisms of NMD. Discrimination of a PTC from a correct termination codon depends on splicing and translation, and it is the first and foremost step in human NMD. The molecular mechanism of this process remains elusive to date.
In the research proposed, I will undertake to elucidate the molecular basis of translation termination and induction of NMD. I will study complexes involved in human translation termination at a normal stop codon and involved in NMD. I will employ an array of innovative techniques including recombinant production of human protein complexes by the MultiBac system, mammalian in vitro translation, mass spectrometry for detecting relevant protein modifications, biophysical techniques, mutational analyses and RNA-interference experiments. Stable ribosomal complexes with termination factors and complexes of NMD factors will be used for structure determination by cryo-electron microscopy. State-of-the-art image processing will be applied to address the inherent heterogeneity of the complexes. Hybrid approaches will allow the combination of cryo-EM structures with existing high-resolution structures of factors involved for generation of quasi-atomic models thereby visualizing molecular mechanisms of NMD action. This interdisciplinary work will foster our understanding at a molecular level of a paramount step in mRNA quality control, which is a vital prerequisite for the development of new treatment strategies in NMD-related diseases.
Max ERC Funding
1 176 825 €
Duration
Start date: 2012-02-01, End date: 2016-11-30
Project acronym COMPNET
Project Dynamics and Self-organisation in Complex Cytoskeletal Networks
Researcher (PI) Andreas Bausch
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Starting Grant (StG), PE3, ERC-2011-StG_20101014
Summary The requirements on the eukaryotic cytoskeleton are not only of high complexity, but include demands that are actually contradictory in the first place: While the dynamic character of cytoskeletal structures is essential for the motility of cells, their ability for morphological reorganisations and cell division, the structural integrity of cells relies on the stability of cytoskeletal structures. From a biophysical point of view, this dynamic structure formation and stabilization stems from a self-organisation process that is tightly controlled by the simultaneous and competing function of a plethora of actin binding proteins (ABPs). To understand the self-organisation phenomena observed in the cytoskeleton it is therefore indispensable to first shed light on the functional role of ABPs and their underlying molecular mechanisms. Hereby development of reliable reconstituted model systems as has been proven by the great progress achieved in our understanding of individual crosslinking proteins that turn the cytoskeleton into a viscoelastic physical gel. The advantage of such reconstituted systems is that the biological complexity is decreased to an accessible level that the physical principles can be explored and identified.
It is the aim of the present proposal to successively increase the complexity in a well defined manner to further progress in understanding the functional units of a cell. On the way to a sound physical understanding of cellular self organizing principles, the planned major step comprises the incorporation of active processes like the active (de-)polymerisation of filaments and motor mediated active reorganisation and contraction. We plan to develop new tools and approaches to address how the different kinds of ABPs are interacting with each other and how the structure, dynamics and function of the cytoskeleton is locally governed by the competition and interplay between them.
Summary
The requirements on the eukaryotic cytoskeleton are not only of high complexity, but include demands that are actually contradictory in the first place: While the dynamic character of cytoskeletal structures is essential for the motility of cells, their ability for morphological reorganisations and cell division, the structural integrity of cells relies on the stability of cytoskeletal structures. From a biophysical point of view, this dynamic structure formation and stabilization stems from a self-organisation process that is tightly controlled by the simultaneous and competing function of a plethora of actin binding proteins (ABPs). To understand the self-organisation phenomena observed in the cytoskeleton it is therefore indispensable to first shed light on the functional role of ABPs and their underlying molecular mechanisms. Hereby development of reliable reconstituted model systems as has been proven by the great progress achieved in our understanding of individual crosslinking proteins that turn the cytoskeleton into a viscoelastic physical gel. The advantage of such reconstituted systems is that the biological complexity is decreased to an accessible level that the physical principles can be explored and identified.
It is the aim of the present proposal to successively increase the complexity in a well defined manner to further progress in understanding the functional units of a cell. On the way to a sound physical understanding of cellular self organizing principles, the planned major step comprises the incorporation of active processes like the active (de-)polymerisation of filaments and motor mediated active reorganisation and contraction. We plan to develop new tools and approaches to address how the different kinds of ABPs are interacting with each other and how the structure, dynamics and function of the cytoskeleton is locally governed by the competition and interplay between them.
Max ERC Funding
1 495 196 €
Duration
Start date: 2011-10-01, End date: 2012-03-31
Project acronym DYNAMOM
Project New magnetic resonance techniques to determine the dynamic structure of mitochondrial outer membrane proteins and their complexes
Researcher (PI) Markus Heinz-Georg Sebastian Zweckstetter
Host Institution (HI) DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Country Germany
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary Membrane proteins are coded by about 30% of the genes in the human genome and are primary targets for the action of drugs. I propose an interdisciplinary approach that will provide insight into the dynamic structure of membrane proteins of the outer mitochondrial membrane at unprecedented detail with respect to spatial resolution and time scale separation. Analysis of the dynamics and structure of membrane proteins is one of the biggest challenges in structural biology. I propose several new techniques mainly for solution NMR spectroscopy but also for solid-state NMR and electron paramagnetic resonance that go far beyond the state of art and enrich the sparse information from each of the individual techniques. The integration of complementary experimental information together with molecular dynamics simulations will push the description of the dynamic structure of membrane proteins to a new level. This new level is characterized by the possibility to determine structural ensembles of higher structural complexity and by access to dynamic time scales ranging from picoseconds to milliseconds. The characterization of motion is expected to establish the essential link between structure and function. The chosen outer mitochondrial membrane proteins are linked to several human pathologies that cannot be treated because structural and dynamic information at atomic resolution is missing. I expect that the novel insight into the dynamic structure of mitochondrial proteins will be critical to lay the basis for the development of novel, selective and improved therapies for cancer and age-related neurodegeneration.
Summary
Membrane proteins are coded by about 30% of the genes in the human genome and are primary targets for the action of drugs. I propose an interdisciplinary approach that will provide insight into the dynamic structure of membrane proteins of the outer mitochondrial membrane at unprecedented detail with respect to spatial resolution and time scale separation. Analysis of the dynamics and structure of membrane proteins is one of the biggest challenges in structural biology. I propose several new techniques mainly for solution NMR spectroscopy but also for solid-state NMR and electron paramagnetic resonance that go far beyond the state of art and enrich the sparse information from each of the individual techniques. The integration of complementary experimental information together with molecular dynamics simulations will push the description of the dynamic structure of membrane proteins to a new level. This new level is characterized by the possibility to determine structural ensembles of higher structural complexity and by access to dynamic time scales ranging from picoseconds to milliseconds. The characterization of motion is expected to establish the essential link between structure and function. The chosen outer mitochondrial membrane proteins are linked to several human pathologies that cannot be treated because structural and dynamic information at atomic resolution is missing. I expect that the novel insight into the dynamic structure of mitochondrial proteins will be critical to lay the basis for the development of novel, selective and improved therapies for cancer and age-related neurodegeneration.
Max ERC Funding
1 496 200 €
Duration
Start date: 2011-11-01, End date: 2017-10-31
Project acronym E3
Project E3 - Extreme Event Ecology
Researcher (PI) Annette Menzel
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Starting Grant (StG), LS9, ERC-2011-StG_20101109
Summary With anthropogenic warming, extreme events have already increased in magnitude and frequency and are likely to continue to do so in the near future. These extreme events play decisive roles in climate change impacts. Natural and managed systems, such as agriculture and forestry, are more strongly affected by extremes than by a change in average conditions. Classical parameters considered have included temperature, precipitation and wind speed, but here we will concentrate on multi-factorial complex situations, such as drought, and subsequent ecological events, such as pests. Novel methods from finance mathematics and statistics will be transferred for application to natural systems in order to assess risks of extremes in past, present and future conditions. Special emphasis will be given to deriving critical thresholds and prediction for when they will be crossed. Here, analyses of long-term ecoclimatological data from dendrology, phenology, seed quality, as well as both manipulated experiments and simulations are needed to provide information on the effects stemming from multiple stressors and extremes. In contrast, real data, no matter how long-term, cannot model the risk of new threatening combinations of climatological and ecological parameters. Adaptation should therefore focus not only on retrospective but also on new extremes, in other words, should look forward to the future. In particular, low probabilities and high risk scenarios have to be taken into account. Adaptation measures can range from breeding, and selection of suitable species and varieties to management options, such as sanitation and forest protection. Insurance also needs to adapt to changes in climate and ecology and accurate forecasting becomes more critical in the face of unforeseen extremes and calamities. Thus, future risk management must be based on both adaptation and insurance, with new products, such as index insurance, facilitating the handling of customer claims.
Summary
With anthropogenic warming, extreme events have already increased in magnitude and frequency and are likely to continue to do so in the near future. These extreme events play decisive roles in climate change impacts. Natural and managed systems, such as agriculture and forestry, are more strongly affected by extremes than by a change in average conditions. Classical parameters considered have included temperature, precipitation and wind speed, but here we will concentrate on multi-factorial complex situations, such as drought, and subsequent ecological events, such as pests. Novel methods from finance mathematics and statistics will be transferred for application to natural systems in order to assess risks of extremes in past, present and future conditions. Special emphasis will be given to deriving critical thresholds and prediction for when they will be crossed. Here, analyses of long-term ecoclimatological data from dendrology, phenology, seed quality, as well as both manipulated experiments and simulations are needed to provide information on the effects stemming from multiple stressors and extremes. In contrast, real data, no matter how long-term, cannot model the risk of new threatening combinations of climatological and ecological parameters. Adaptation should therefore focus not only on retrospective but also on new extremes, in other words, should look forward to the future. In particular, low probabilities and high risk scenarios have to be taken into account. Adaptation measures can range from breeding, and selection of suitable species and varieties to management options, such as sanitation and forest protection. Insurance also needs to adapt to changes in climate and ecology and accurate forecasting becomes more critical in the face of unforeseen extremes and calamities. Thus, future risk management must be based on both adaptation and insurance, with new products, such as index insurance, facilitating the handling of customer claims.
Max ERC Funding
1 487 000 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym ECOMAGICS
Project Electric Control of Magnetization Dynamics
Researcher (PI) Georg Woltersdorf
Host Institution (HI) MARTIN-LUTHER-UNIVERSITAET HALLE-WITTENBERG
Country Germany
Call Details Starting Grant (StG), PE3, ERC-2011-StG_20101014
Summary In this proposal a new electric field based approach for the control of magnetization dynamics is discussed. The advantage of using electric fields compared to magnetic fields is twofold: (i) electric fields are easy to confine in nano-structures (screening), and (ii) no current flow is required which may allow for the development of new spintronic devices with ultra low power consumption.
Physically the application of an electric field to an ultrathin ferromagnetic material gives rise to modification of the wave-function overlap at the interface between a ferromagnetic metal and a dielectric. This electronic tuning causes a modified occupation of the d-orbitals at the interface and leads to electrically induced anisotropies. Hence external electric fields generate internal magnetic fields. Due to the modified orbital moment also a large voltage induced effect on the Gilbert damping is expected in magnetization dynamic experiments. In principle these fields can be applied even on ultrafast time scales. This will be explored when rf-electric fields are used to drive internal magnetic fields in the GHz frequency range to generate spin-waves. Furthermore this technique will be used to excite monochromatic spin-waves with wave-vectors well in the exchange dominated regime in order to study their propagation properties.
I propose to use the spin-wave Doppler effect in order to break the intrinsic mirror symmetry required in for four-magnon scattering processes. In this way the resonance saturation may be tuned electrically to much larger values. Moreover electrically driven surface acoustic waves will be used to generate spin-waves which will be manipulated by an electric current using the spin-wave Doppler effect.
The research described in the proposal is likely to have a large impact as a shift to electric field controlled spintronic devices is favorable on small length scales. In addition the power consumption of these devices may be reduced significantly.
Summary
In this proposal a new electric field based approach for the control of magnetization dynamics is discussed. The advantage of using electric fields compared to magnetic fields is twofold: (i) electric fields are easy to confine in nano-structures (screening), and (ii) no current flow is required which may allow for the development of new spintronic devices with ultra low power consumption.
Physically the application of an electric field to an ultrathin ferromagnetic material gives rise to modification of the wave-function overlap at the interface between a ferromagnetic metal and a dielectric. This electronic tuning causes a modified occupation of the d-orbitals at the interface and leads to electrically induced anisotropies. Hence external electric fields generate internal magnetic fields. Due to the modified orbital moment also a large voltage induced effect on the Gilbert damping is expected in magnetization dynamic experiments. In principle these fields can be applied even on ultrafast time scales. This will be explored when rf-electric fields are used to drive internal magnetic fields in the GHz frequency range to generate spin-waves. Furthermore this technique will be used to excite monochromatic spin-waves with wave-vectors well in the exchange dominated regime in order to study their propagation properties.
I propose to use the spin-wave Doppler effect in order to break the intrinsic mirror symmetry required in for four-magnon scattering processes. In this way the resonance saturation may be tuned electrically to much larger values. Moreover electrically driven surface acoustic waves will be used to generate spin-waves which will be manipulated by an electric current using the spin-wave Doppler effect.
The research described in the proposal is likely to have a large impact as a shift to electric field controlled spintronic devices is favorable on small length scales. In addition the power consumption of these devices may be reduced significantly.
Max ERC Funding
1 495 860 €
Duration
Start date: 2012-01-01, End date: 2017-10-31
Project acronym ENDHOMRET
Project Endothelial homeostasis and dysfunction in metabolic-vascular retina disease: The role of endothelial cell-intrinsic and endothelial cell extrinsic inflammatory pathways
Researcher (PI) Triantafyllos Chavakis
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Country Germany
Call Details Starting Grant (StG), LS4, ERC-2011-StG_20101109
Summary Diabetic retinopathy (DR) is a major cause of blindness in adults and the underlying pathophysiology includes endothelial dysfunction. Endothelial dysfunction is a perturbation of endothelial homeostasis including changes in endothelial barrier integrity, alterations of the endothelial cell surface, which becomes proinflammatory and mediates increased leukocyte adhesion and changes in endothelial survival functions. Endothelial dysfunction is regulated by an intimate crosstalk of the endothelium with leukocytes and inflammatory pathways of the innate immunity (endothelial-extrinsic pathways), which are activated in the diabetic vasculature affecting the endothelial barrier and leukocyte adhesiveness, and by endothelial cell-intrinsic pathways affecting endothelial survival that are regulated by specific components of the diabetic microenvironement, e.g. hypoxia. The aims of the present proposal are (i) to assess how leukocyte-endothelial interactions (here a particular emphasis will be laid on novel components of the leukocyte adhesion cascade, such as Developmental endothelial locus-1 or Junctional Adhesion Molecule-C, recently identified by the group of the applicant), as well as how macrophage activation/polarization in the local retinal microenvironment affect endothelial homeostasis and dysfunction in the course of DR, and (ii) to investigate pathways regulating survival functions of the endothelium particularly under hypoxic/ischemic conditions in the diabetic retina. The proposal is highly innovative, since the knowledge about these pathways in the context of endothelial dysfunction in DR is scarce. Understanding the molecular contribution of endothelial cell-extrinsic inflammatory pathways and endothelial-cell intrinsic, survival-regulating pathways in the context of DR will have a high impact as it will provide the platform for developing novel specific therapeutic approaches for this major diabetic complication.
Summary
Diabetic retinopathy (DR) is a major cause of blindness in adults and the underlying pathophysiology includes endothelial dysfunction. Endothelial dysfunction is a perturbation of endothelial homeostasis including changes in endothelial barrier integrity, alterations of the endothelial cell surface, which becomes proinflammatory and mediates increased leukocyte adhesion and changes in endothelial survival functions. Endothelial dysfunction is regulated by an intimate crosstalk of the endothelium with leukocytes and inflammatory pathways of the innate immunity (endothelial-extrinsic pathways), which are activated in the diabetic vasculature affecting the endothelial barrier and leukocyte adhesiveness, and by endothelial cell-intrinsic pathways affecting endothelial survival that are regulated by specific components of the diabetic microenvironement, e.g. hypoxia. The aims of the present proposal are (i) to assess how leukocyte-endothelial interactions (here a particular emphasis will be laid on novel components of the leukocyte adhesion cascade, such as Developmental endothelial locus-1 or Junctional Adhesion Molecule-C, recently identified by the group of the applicant), as well as how macrophage activation/polarization in the local retinal microenvironment affect endothelial homeostasis and dysfunction in the course of DR, and (ii) to investigate pathways regulating survival functions of the endothelium particularly under hypoxic/ischemic conditions in the diabetic retina. The proposal is highly innovative, since the knowledge about these pathways in the context of endothelial dysfunction in DR is scarce. Understanding the molecular contribution of endothelial cell-extrinsic inflammatory pathways and endothelial-cell intrinsic, survival-regulating pathways in the context of DR will have a high impact as it will provide the platform for developing novel specific therapeutic approaches for this major diabetic complication.
Max ERC Funding
1 488 480 €
Duration
Start date: 2011-11-01, End date: 2016-12-31
Project acronym EPSILON
Project Elliptic Pdes and Symmetry of Interfaces and Layers for Odd Nonlinearities
Researcher (PI) Enrico Valdinoci
Host Institution (HI) FORSCHUNGSVERBUND BERLIN EV
Country Germany
Call Details Starting Grant (StG), PE1, ERC-2011-StG_20101014
Summary The scope of this project is to perform an analytical study of the geometric properties of the interafaces arising in the scalar Ginzburg-Landau-Allen-Cahn equation, with particular attention to possible 1D symmetries.
Also, we would like to analyze the cases in which the operator is singular, degenrate, subelliptic or fractional and to obtain results for PDEs in manifold and in inverse overdetermined problems, since all these models share some important features with classical semilinear PDEs and possess a wide range of potential applications.
To achieve our goals, we would like to build a small, mobile and specialized team of young researchers with outstanding professional skills, specialized in the above subjects, which
has a long history together, new upcoming projects and a network to spread out to.
Summary
The scope of this project is to perform an analytical study of the geometric properties of the interafaces arising in the scalar Ginzburg-Landau-Allen-Cahn equation, with particular attention to possible 1D symmetries.
Also, we would like to analyze the cases in which the operator is singular, degenrate, subelliptic or fractional and to obtain results for PDEs in manifold and in inverse overdetermined problems, since all these models share some important features with classical semilinear PDEs and possess a wide range of potential applications.
To achieve our goals, we would like to build a small, mobile and specialized team of young researchers with outstanding professional skills, specialized in the above subjects, which
has a long history together, new upcoming projects and a network to spread out to.
Max ERC Funding
850 000 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
