Project acronym 4D IMAGING
Project Towards 4D Imaging of Fundamental Processes on the Atomic and Sub-Atomic Scale
Researcher (PI) Ferenc Krausz
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), PE2, ERC-2009-AdG
Summary State-of-the-art microscopy and diffraction imaging provides insight into the atomic and sub-atomic structure of matter. They permit determination of the positions of atoms in a crystal lattice or in a molecule as well as the distribution of electrons inside atoms. State-of-the-art time-resolved spectroscopy with femtosecond and attosecond resolution provides access to dynamic changes in the atomic and electronic structure of matter. Our proposal aims at combining these two frontier techniques of XXI century science to make a long-standing dream of scientist come true: the direct observation of atoms and electrons in their natural state: in motion. Shifts in the atoms positions by tens to hundreds of picometers can make chemical bonds break apart or newly form, changing the structure and/or chemical composition of matter. Electronic motion on similar scales may result in the emission of light, or the initiation of processes that lead to a change in physical or chemical properties, or biological function. These motions happen within femtoseconds and attoseconds, respectively. To make them observable, we need a 4-dimensional (4D) imaging technique capable of recording freeze-frame snapshots of microscopic systems with picometer spatial resolution and femtosecond to attosecond exposure time. The motion can then be visualized by slow-motion replay of the freeze-frame shots. The goal of this project is to develop a 4D imaging technique that will ultimately offer picometer resolution is space and attosecond resolution in time.
Summary
State-of-the-art microscopy and diffraction imaging provides insight into the atomic and sub-atomic structure of matter. They permit determination of the positions of atoms in a crystal lattice or in a molecule as well as the distribution of electrons inside atoms. State-of-the-art time-resolved spectroscopy with femtosecond and attosecond resolution provides access to dynamic changes in the atomic and electronic structure of matter. Our proposal aims at combining these two frontier techniques of XXI century science to make a long-standing dream of scientist come true: the direct observation of atoms and electrons in their natural state: in motion. Shifts in the atoms positions by tens to hundreds of picometers can make chemical bonds break apart or newly form, changing the structure and/or chemical composition of matter. Electronic motion on similar scales may result in the emission of light, or the initiation of processes that lead to a change in physical or chemical properties, or biological function. These motions happen within femtoseconds and attoseconds, respectively. To make them observable, we need a 4-dimensional (4D) imaging technique capable of recording freeze-frame snapshots of microscopic systems with picometer spatial resolution and femtosecond to attosecond exposure time. The motion can then be visualized by slow-motion replay of the freeze-frame shots. The goal of this project is to develop a 4D imaging technique that will ultimately offer picometer resolution is space and attosecond resolution in time.
Max ERC Funding
2 500 000 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym AIM2 INFLAMMASOME
Project Cytosolic recognition of foreign nucleic acids: Molecular and functional characterization of AIM2, a central player in DNA-triggered inflammasome activation
Researcher (PI) Veit Hornung
Host Institution (HI) UNIVERSITAETSKLINIKUM BONN
Call Details Starting Grant (StG), LS6, ERC-2009-StG
Summary Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.
Summary
Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.
Max ERC Funding
1 727 920 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym ASC3
Project Asymmetric Cluster Catalysis & Chemistry
Researcher (PI) Ulrich Kaspar Heiz
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), PE4, ERC-2009-AdG
Summary The objective of the present scientific proposal is the implementation of a novel approach in selective and asymmetric heterogeneous catalysis. We aim to exploit the structure and chirality of small, supported metal and bimetal clusters for triggering selective and enantioselective reactions. Our Ansatz is beyond doubt of fundamental nature. Although chemistry and in particular catalysis evolved on a largely empirical basis in the past, we strongly believe the complexity of the challenges at hand to make this a less ideal approach. In consequence, developing selective and asymmetric cluster catalysis will be based on a detailed molecular understanding and will not only require intense methodological developments for the synthesis and characterization of asymmetric catalysts and the detection of chiral and isomeric product molecules but also make use of innovative basic science in the fields of surface chemistry, cluster science, spectroscopy and kinetics. As complex as the involved challenges are, we aim at mastering the following ground-breaking steps: (a) development of cutting-edge spectroscopic methodologies for the isomer and enantiomer sensitive in situ detection of product molecules. (b) preparation and characterization of isomer- and enantioselective heterogeneous catalysts based on chiral metal clusters or molecule-cluster-complexes. (c) investigations of the selectivity and enantioselectivity of cluster based heterogeneous catalysts and formulation of concepts for understanding the observed selective and asymmetric chemistry.
Besides the importance of the science carried out within this proposal, the proposed experimental methodology will also open up opportunities in other fields of chemistry like catalysis, analytical chemistry, spectroscopy, surface science, and nanomaterials.
Summary
The objective of the present scientific proposal is the implementation of a novel approach in selective and asymmetric heterogeneous catalysis. We aim to exploit the structure and chirality of small, supported metal and bimetal clusters for triggering selective and enantioselective reactions. Our Ansatz is beyond doubt of fundamental nature. Although chemistry and in particular catalysis evolved on a largely empirical basis in the past, we strongly believe the complexity of the challenges at hand to make this a less ideal approach. In consequence, developing selective and asymmetric cluster catalysis will be based on a detailed molecular understanding and will not only require intense methodological developments for the synthesis and characterization of asymmetric catalysts and the detection of chiral and isomeric product molecules but also make use of innovative basic science in the fields of surface chemistry, cluster science, spectroscopy and kinetics. As complex as the involved challenges are, we aim at mastering the following ground-breaking steps: (a) development of cutting-edge spectroscopic methodologies for the isomer and enantiomer sensitive in situ detection of product molecules. (b) preparation and characterization of isomer- and enantioselective heterogeneous catalysts based on chiral metal clusters or molecule-cluster-complexes. (c) investigations of the selectivity and enantioselectivity of cluster based heterogeneous catalysts and formulation of concepts for understanding the observed selective and asymmetric chemistry.
Besides the importance of the science carried out within this proposal, the proposed experimental methodology will also open up opportunities in other fields of chemistry like catalysis, analytical chemistry, spectroscopy, surface science, and nanomaterials.
Max ERC Funding
2 301 600 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
Project acronym ATHEROPROTECT
Project Structure-Function Analysis of the Chemokine Interactome for Therapeutic Targeting and Imaging in Atherosclerosis
Researcher (PI) Christian Weber
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS4, ERC-2009-AdG
Summary Atherosclerosis is characterized by chronic inflammation of the arterial wall. Mononuclear cell recruitment is driven by chemokines that can be deposited e.g. by activated platelets on inflamed endothelium. Chemokines require oligomerization and immobilization for efficient function, and recent evidence supports the notion that heterodimer formation between chemokines constitutes a new regulatory principle amplifying specific chemokine activities while suppressing others. Although crucial to inflammatory disease, this has been difficult to prove in vivo, primarily as chemokine heterodimers exist in equilibrium with their homodimer counterparts. We introduce the paradigm that heteromerization of chemokines provides the combinatorial diversity for functional plasticity and fine-tuning, coining this interactome. Given the relevance of chemokine heteromers in vivo, we aim to exploit this in an anti-inflammatory approach to selectively target vascular disease. In a multidisciplinary project, we plan to generate covalently-linked heterodimers to establish their biological significance. Obligate heterodimers of CC and CXC chemokines will be designed using computer-assisted modeling, chemically synthesized and cross-linked, structurally assessed using NMR spectroscopy and crystallography, and subjected to functional characterization in vitro and reconstitution in vivo. Conversely, we will develop cyclic beta-sheet-based peptides binding chemokines to specifically disrupt heteromers and we will generate mice with conditional deletion or knock-in of chemokine mutants with defects in heteromerization or proteoglycan binding to be analyzed in models of atherosclerosis. Peptides will be used for molecular imaging and chemokine heteromers will be quantified in cardiovascular patients.
Summary
Atherosclerosis is characterized by chronic inflammation of the arterial wall. Mononuclear cell recruitment is driven by chemokines that can be deposited e.g. by activated platelets on inflamed endothelium. Chemokines require oligomerization and immobilization for efficient function, and recent evidence supports the notion that heterodimer formation between chemokines constitutes a new regulatory principle amplifying specific chemokine activities while suppressing others. Although crucial to inflammatory disease, this has been difficult to prove in vivo, primarily as chemokine heterodimers exist in equilibrium with their homodimer counterparts. We introduce the paradigm that heteromerization of chemokines provides the combinatorial diversity for functional plasticity and fine-tuning, coining this interactome. Given the relevance of chemokine heteromers in vivo, we aim to exploit this in an anti-inflammatory approach to selectively target vascular disease. In a multidisciplinary project, we plan to generate covalently-linked heterodimers to establish their biological significance. Obligate heterodimers of CC and CXC chemokines will be designed using computer-assisted modeling, chemically synthesized and cross-linked, structurally assessed using NMR spectroscopy and crystallography, and subjected to functional characterization in vitro and reconstitution in vivo. Conversely, we will develop cyclic beta-sheet-based peptides binding chemokines to specifically disrupt heteromers and we will generate mice with conditional deletion or knock-in of chemokine mutants with defects in heteromerization or proteoglycan binding to be analyzed in models of atherosclerosis. Peptides will be used for molecular imaging and chemokine heteromers will be quantified in cardiovascular patients.
Max ERC Funding
2 500 000 €
Duration
Start date: 2010-04-01, End date: 2016-03-31
Project acronym ATOMION
Project Exploring hybrid quantum systems of ultracold atoms and ions
Researcher (PI) Michael Karl Koehl
Host Institution (HI) RHEINISCHE FRIEDRICH-WILHELMS-UNIVERSITAT BONN
Call Details Starting Grant (StG), PE2, ERC-2009-StG
Summary We propose to investigate hybrid quantum systems composed of ultracold atoms and ions. The mutual interaction of the cold neutral atoms and the trapped ion offers a wealth of interesting new physical problems. They span from ultracold quantum chemistry over new concepts for quantum information processing to genuine quantum many-body physics. We plan to explore aspects of quantum chemistry with ultracold atoms and ions to obtain a full understanding of the interactions in this hybrid system. We will investigate the regime of low energy collisions and search for Feshbach resonances to tune the interaction strength between atoms and ions. Moreover, we will study collective effects in chemical reactions between a Bose-Einstein condensate and a single ion. Taking advantage of the extraordinary properties of the atom-ion mixture quantum information processing with hybrid systems will be performed. In particular, we plan to realize sympathetic ground state cooling of the ion with a Bose-Einstein condensate. When the ion is immersed into the ultracold neutral atom environment the nature of the decoherence will be tailored by tuning properties of the environment: A dissipative quantum phase transition is predicted when the ion is coupled to a one-dimensional Bose gas. Moreover, we plan to realize a scalable hybrid quantum processor composed of a single ion and an array of neutral atoms in an optical lattice. The third direction we will pursue is related to impurity effects in quantum many-body physics. We plan to study transport through a single impurity or atomic quantum dot with the goal of realizing a single atom transistor. A single atom transistor transfers the quantum state of the impurity coherently to a macroscopic neutral atom current. Finally, we plan to observe Anderson s orthogonality catastrophe in which the presence of a single impurity in a quantum gas orthogonalizes the quantum many-body function of a quantum state with respect to the unperturbed one.
Summary
We propose to investigate hybrid quantum systems composed of ultracold atoms and ions. The mutual interaction of the cold neutral atoms and the trapped ion offers a wealth of interesting new physical problems. They span from ultracold quantum chemistry over new concepts for quantum information processing to genuine quantum many-body physics. We plan to explore aspects of quantum chemistry with ultracold atoms and ions to obtain a full understanding of the interactions in this hybrid system. We will investigate the regime of low energy collisions and search for Feshbach resonances to tune the interaction strength between atoms and ions. Moreover, we will study collective effects in chemical reactions between a Bose-Einstein condensate and a single ion. Taking advantage of the extraordinary properties of the atom-ion mixture quantum information processing with hybrid systems will be performed. In particular, we plan to realize sympathetic ground state cooling of the ion with a Bose-Einstein condensate. When the ion is immersed into the ultracold neutral atom environment the nature of the decoherence will be tailored by tuning properties of the environment: A dissipative quantum phase transition is predicted when the ion is coupled to a one-dimensional Bose gas. Moreover, we plan to realize a scalable hybrid quantum processor composed of a single ion and an array of neutral atoms in an optical lattice. The third direction we will pursue is related to impurity effects in quantum many-body physics. We plan to study transport through a single impurity or atomic quantum dot with the goal of realizing a single atom transistor. A single atom transistor transfers the quantum state of the impurity coherently to a macroscopic neutral atom current. Finally, we plan to observe Anderson s orthogonality catastrophe in which the presence of a single impurity in a quantum gas orthogonalizes the quantum many-body function of a quantum state with respect to the unperturbed one.
Max ERC Funding
1 405 000 €
Duration
Start date: 2009-10-01, End date: 2014-09-30
Project acronym BIOSENSORIMAGING
Project Hyperpolarized Biosensors in Molecular Imaging
Researcher (PI) Leif Schröder
Host Institution (HI) FORSCHUNGSVERBUND BERLIN EV
Call Details Starting Grant (StG), LS7, ERC-2009-StG
Summary Xenon biosensors have an outstanding potential to increase the significance of magnetic resonance imaging (MRI) in molecular imaging and to combine the advantages of MRI with the high sensitivity of hyperpolarized Xe-129 and the specificity of a functionalized contrast agent. Based on new detection schemes (Hyper-CEST method) in Xe MRI, this novel concept in molecular diagnostics will be made available for biomedical applications. The advancement focuses on high-sensitivity in vitro diagnostics for localization of tumour cells in cell cultures and first demonstrations on animal models based on a transferrin-functionalized biosensor. Such a sensor will enable detection of subcutaneous tumours at high sensitivity without any background signal. More detailed work on the different available Hyper-CEST contrast parameters focuses on an absolute quantification of new molecular markers that will improve non-invasive tumour diagnostics significantly. NMR detection of functionalized Xe biosensors have the potential to close the sensitivity gap between modalities of nuclear medicine like PET/SPECT and MRI without using ionizing radiation or making compromises in penetration depth like in optical methods.
Summary
Xenon biosensors have an outstanding potential to increase the significance of magnetic resonance imaging (MRI) in molecular imaging and to combine the advantages of MRI with the high sensitivity of hyperpolarized Xe-129 and the specificity of a functionalized contrast agent. Based on new detection schemes (Hyper-CEST method) in Xe MRI, this novel concept in molecular diagnostics will be made available for biomedical applications. The advancement focuses on high-sensitivity in vitro diagnostics for localization of tumour cells in cell cultures and first demonstrations on animal models based on a transferrin-functionalized biosensor. Such a sensor will enable detection of subcutaneous tumours at high sensitivity without any background signal. More detailed work on the different available Hyper-CEST contrast parameters focuses on an absolute quantification of new molecular markers that will improve non-invasive tumour diagnostics significantly. NMR detection of functionalized Xe biosensors have the potential to close the sensitivity gap between modalities of nuclear medicine like PET/SPECT and MRI without using ionizing radiation or making compromises in penetration depth like in optical methods.
Max ERC Funding
1 848 600 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym CARNIVOROM
Project Molecular basis of carnivory Excitability, movement, and endocrinology of plant traps
Researcher (PI) Rainer Franz Hedrich
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Call Details Advanced Grant (AdG), LS9, ERC-2009-AdG
Summary Predation plays a major role in energy and nutrient flow in the biological food chain. Carnivory is best known from the animal kingdom, but the plant kingdom has flesh eaters as well. This field has attracted much interest since Darwin s time, but many fundamental properties of the carnivorous life style remain largely unexplored. This project will close this gap by a multidisciplinary approach based on state-of-art bioinformatics, molecular biology, chemistry and biophysics. It will focus on 1. Genome/Transcriptome Profiling to study the genetic make-up of carnivorous plants (CPs) and the evolution of carnivory 2. Origin of Excitability to investigate whether CPs gained the inventory to fire action potentials from captured animals or rather evolved excitability independently 3. Prey Recognition on the basis of mechanical- and chemical senses 4. Endocrinology Structure and function of exocrine glands - CPs offer a unique system to study the biology of digestive glands (exo-/endocytosis) in plants. Over 600 plant species use special structures to capture animals such as insects. The genome/transcriptome of major trap types such as snap traps, tentacles traps, suction traps, corkscrew traps, and pitfall traps will be compared and trap-specific genes identified. Among them those giving rise to membrane excitation, excitation-contraction coupling and exocrine systems (glands) will be functionally characterized in detail. Using loss-of-function mutants and transformed plants with respect to CP-specific the role of CP-specific in electrical signalling, excitation contraction coupling, and excretion will be unravelled. The evolution of electrical activity and carnivory of plants is worth being examined not only for its importance in general, but also as a model for understanding the evolution of the human nervous and endocrine system.
Summary
Predation plays a major role in energy and nutrient flow in the biological food chain. Carnivory is best known from the animal kingdom, but the plant kingdom has flesh eaters as well. This field has attracted much interest since Darwin s time, but many fundamental properties of the carnivorous life style remain largely unexplored. This project will close this gap by a multidisciplinary approach based on state-of-art bioinformatics, molecular biology, chemistry and biophysics. It will focus on 1. Genome/Transcriptome Profiling to study the genetic make-up of carnivorous plants (CPs) and the evolution of carnivory 2. Origin of Excitability to investigate whether CPs gained the inventory to fire action potentials from captured animals or rather evolved excitability independently 3. Prey Recognition on the basis of mechanical- and chemical senses 4. Endocrinology Structure and function of exocrine glands - CPs offer a unique system to study the biology of digestive glands (exo-/endocytosis) in plants. Over 600 plant species use special structures to capture animals such as insects. The genome/transcriptome of major trap types such as snap traps, tentacles traps, suction traps, corkscrew traps, and pitfall traps will be compared and trap-specific genes identified. Among them those giving rise to membrane excitation, excitation-contraction coupling and exocrine systems (glands) will be functionally characterized in detail. Using loss-of-function mutants and transformed plants with respect to CP-specific the role of CP-specific in electrical signalling, excitation contraction coupling, and excretion will be unravelled. The evolution of electrical activity and carnivory of plants is worth being examined not only for its importance in general, but also as a model for understanding the evolution of the human nervous and endocrine system.
Max ERC Funding
2 481 057 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym CCMP
Project Physics Of Magma Propagation and Emplacement: a multi-methodological Investigation
Researcher (PI) Eleonora Rivalta
Host Institution (HI) HELMHOLTZ ZENTRUM POTSDAM DEUTSCHESGEOFORSCHUNGSZENTRUM GFZ
Call Details Starting Grant (StG), PE10, ERC-2009-StG
Summary Dikes and sills are large sheet-like intrusions transporting and storing magma in the Earth’s crust.
When propagating, they generate seismicity and deformation and may lead to volcanic eruption. The physics of magma-filled structures is similar to that of any fluid-filled reservoir, such as oil fields and CO2 reservoirs created by sequestration. This project aims to address old and new unresolved challenging questions related to dike propagation, sill emplacement and in general to the dynamics of fluid and gas-filled reservoirs. I propose to focus on crustal deformation, induced seismicity and external stress fields to study the signals dikes
and sills produce, how they grow and why they reactivate after years of non-detected activity. I will combine experimental, numerical and analytical techniques, in close cooperation with volcano observatories providing us with the data necessary to validate our models. In the lab, I will simulate magma propagation injecting fluid into solidified gelatin. I will also contribute to a project, currently under evaluation, on the monitoring of a CO2
sequestration site. At the same time, I will address theoretical aspects, extending static models to dynamic cases and eventually developing a comprehensive picture of the multi faceted interaction between external stress field,
magma and rock properties, crustal deformation and seismicity. I also plan, besides presenting my team’s work in the major national and international geophysical conferences, to produce, with technical support from the media services of DKRZ (Deutsches Klimarechenzentrum), an audiovisual teaching DVD illustrating scientific advances and unresolved issues in magma dynamics, in the prediction of eruptive activity and in the physics of reservoirs.
Summary
Dikes and sills are large sheet-like intrusions transporting and storing magma in the Earth’s crust.
When propagating, they generate seismicity and deformation and may lead to volcanic eruption. The physics of magma-filled structures is similar to that of any fluid-filled reservoir, such as oil fields and CO2 reservoirs created by sequestration. This project aims to address old and new unresolved challenging questions related to dike propagation, sill emplacement and in general to the dynamics of fluid and gas-filled reservoirs. I propose to focus on crustal deformation, induced seismicity and external stress fields to study the signals dikes
and sills produce, how they grow and why they reactivate after years of non-detected activity. I will combine experimental, numerical and analytical techniques, in close cooperation with volcano observatories providing us with the data necessary to validate our models. In the lab, I will simulate magma propagation injecting fluid into solidified gelatin. I will also contribute to a project, currently under evaluation, on the monitoring of a CO2
sequestration site. At the same time, I will address theoretical aspects, extending static models to dynamic cases and eventually developing a comprehensive picture of the multi faceted interaction between external stress field,
magma and rock properties, crustal deformation and seismicity. I also plan, besides presenting my team’s work in the major national and international geophysical conferences, to produce, with technical support from the media services of DKRZ (Deutsches Klimarechenzentrum), an audiovisual teaching DVD illustrating scientific advances and unresolved issues in magma dynamics, in the prediction of eruptive activity and in the physics of reservoirs.
Max ERC Funding
1 507 679 €
Duration
Start date: 2010-07-01, End date: 2015-06-30
Project acronym CILIARYDISEASE
Project Deciphering mechanisms of ciliary disease
Researcher (PI) Heiko Lickert
Host Institution (HI) HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Call Details Starting Grant (StG), LS3, ERC-2009-StG
Summary Ciliopathies are pleiotropic diseases with a wide spectrum of human phenotypes. These include cyst formation in the liver and pancreas, respiratory disorders and a predisposition to diabetes and cancer. The pleiotropic nature of these disorders may reflect the many roles cilia play in physiology and signalling, highlighting the clinical importance of understanding their function in organ development and homeostasis. Despite the biological importance of cilia and decades of research, many aspects of cilia assembly and disassembly remain elusive. The earliest steps of cilia assembly involve conversion of the centrosome into a basal body, which anchors the cilia to the plasma membrane. Odf2 is one of the only proteins known to be important for this process, thus Ofd2 mutant cells lack cilia. During cell cycle re-entry primary cilia disassemble, the basal body dislodges from the plasma membrane and duplicates to serve as the mitotic centrosome. We recently identified Pitchfork, which functions in basal body-to-centrosome conversion and regulates embryonic patterning. The overall aim of this proposal is to better understand the cellular and bio-molecular mechanisms underlying ciliary disease. We will conditionally delete Odf2 and Pitchfork during embryogenesis and organogenesis. This will reveal the different requirements for the process of cilia assembly and disassembly in embryonic development, organ formation and homeostasis. The phenotypes will be analyzed at all levels of complexity. Subcellular imaging and identification of protein interaction partners will uncover the molecular basis of cilia assembly and disassembly. In summary, this project will decipher mechanisms underlying a wide spectrum of human ciliary disease and will open new avenues of clinical research.
Summary
Ciliopathies are pleiotropic diseases with a wide spectrum of human phenotypes. These include cyst formation in the liver and pancreas, respiratory disorders and a predisposition to diabetes and cancer. The pleiotropic nature of these disorders may reflect the many roles cilia play in physiology and signalling, highlighting the clinical importance of understanding their function in organ development and homeostasis. Despite the biological importance of cilia and decades of research, many aspects of cilia assembly and disassembly remain elusive. The earliest steps of cilia assembly involve conversion of the centrosome into a basal body, which anchors the cilia to the plasma membrane. Odf2 is one of the only proteins known to be important for this process, thus Ofd2 mutant cells lack cilia. During cell cycle re-entry primary cilia disassemble, the basal body dislodges from the plasma membrane and duplicates to serve as the mitotic centrosome. We recently identified Pitchfork, which functions in basal body-to-centrosome conversion and regulates embryonic patterning. The overall aim of this proposal is to better understand the cellular and bio-molecular mechanisms underlying ciliary disease. We will conditionally delete Odf2 and Pitchfork during embryogenesis and organogenesis. This will reveal the different requirements for the process of cilia assembly and disassembly in embryonic development, organ formation and homeostasis. The phenotypes will be analyzed at all levels of complexity. Subcellular imaging and identification of protein interaction partners will uncover the molecular basis of cilia assembly and disassembly. In summary, this project will decipher mechanisms underlying a wide spectrum of human ciliary disease and will open new avenues of clinical research.
Max ERC Funding
1 449 640 €
Duration
Start date: 2010-02-01, End date: 2015-01-31
Project acronym CONVEXVISION
Project Convex Optimization Methods for Computer Vision and Image Analysis
Researcher (PI) Daniel Cremers
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), PE6, ERC-2009-StG
Summary Optimization methods have become an established paradigm to address most Computer Vision challenges including the
reconstruction of three-dimensional objects from multiple images, or the tracking of a deformable shape over time. Yet, it has
been largely overlooked that optimization approaches are practically useless if they do not come with efficient algorithms to
compute minimizers of respective energies. Most existing formulations give rise to non-convex energies. As a consequence,
solutions highly depend on the choice of minimization scheme and implementational (initialization, time step sizes, etc.), with
little or no guarantees regarding the quality of computed solutions and their robustness to perturbations of the input data.
In the proposed research project, we plan to develop optimization methods for Computer Vision which allow to efficiently
compute globally optimal solutions. Preliminary results indicate that this will drastically leverage the power of optimization
methods and their applicability in a substantially broader context. Specifically we will focus on three lines of research: 1) We
will develop convex formulations for a variety of challenges. While convex formulations are currently being developed for
low-level problems such as image segmentation, our main effort will focus on carrying convex optimization to higher level
problems of image understanding and scene interpretation. 2) We will investigate alternative strategies of global optimization
by means of discrete graph theoretic methods. We will characterize advantages and drawbacks of continuous and discrete
methods and thereby develop novel algorithms combining the advantages of both approaches. 3) We will go beyond convex
formulations, developing relaxation schemes that compute near-optimal solutions for problems that cannot be expressed by
convex functionals.
Summary
Optimization methods have become an established paradigm to address most Computer Vision challenges including the
reconstruction of three-dimensional objects from multiple images, or the tracking of a deformable shape over time. Yet, it has
been largely overlooked that optimization approaches are practically useless if they do not come with efficient algorithms to
compute minimizers of respective energies. Most existing formulations give rise to non-convex energies. As a consequence,
solutions highly depend on the choice of minimization scheme and implementational (initialization, time step sizes, etc.), with
little or no guarantees regarding the quality of computed solutions and their robustness to perturbations of the input data.
In the proposed research project, we plan to develop optimization methods for Computer Vision which allow to efficiently
compute globally optimal solutions. Preliminary results indicate that this will drastically leverage the power of optimization
methods and their applicability in a substantially broader context. Specifically we will focus on three lines of research: 1) We
will develop convex formulations for a variety of challenges. While convex formulations are currently being developed for
low-level problems such as image segmentation, our main effort will focus on carrying convex optimization to higher level
problems of image understanding and scene interpretation. 2) We will investigate alternative strategies of global optimization
by means of discrete graph theoretic methods. We will characterize advantages and drawbacks of continuous and discrete
methods and thereby develop novel algorithms combining the advantages of both approaches. 3) We will go beyond convex
formulations, developing relaxation schemes that compute near-optimal solutions for problems that cannot be expressed by
convex functionals.
Max ERC Funding
1 985 400 €
Duration
Start date: 2010-09-01, End date: 2015-08-31
