Project acronym ALEM
Project ADDITIONAL LOSSES IN ELECTRICAL MACHINES
Researcher (PI) Matti Antero Arkkio
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Advanced Grant (AdG), PE8, ERC-2013-ADG
Summary "Electrical motors consume about 40 % of the electrical energy produced in the European Union. About 90 % of this energy is converted to mechanical work. However, 0.5-2.5 % of it goes to so called additional load losses whose exact origins are unknown. Our ambitious aim is to reveal the origins of these losses, build up numerical tools for modeling them and optimize electrical motors to minimize the losses.
As the hypothesis of the research, we assume that the additional losses mainly result from the deterioration of the core materials during the manufacturing process of the machine. By calorimetric measurements, we have found that the core losses of electrical machines may be twice as large as comprehensive loss models predict. The electrical steel sheets are punched, welded together and shrink fit to the frame. This causes residual strains in the core sheets deteriorating their magnetic characteristics. The cutting burrs make galvanic contacts between the sheets and form paths for inter-lamination currents. Another potential source of additional losses are the circulating currents between the parallel strands of random-wound armature windings. The stochastic nature of these potential sources of additional losses puts more challenge on the research.
We shall develop a physical loss model that couples the mechanical strains and electromagnetic losses in electrical steel sheets and apply the new model for comprehensive loss analysis of electrical machines. The stochastic variables related to the core losses and circulating-current losses will be discretized together with the temporal and spatial discretization of the electromechanical field variables. The numerical stochastic loss model will be used to search for such machine constructions that are insensitive to the manufacturing defects. We shall validate the new numerical loss models by electromechanical and calorimetric measurements."
Summary
"Electrical motors consume about 40 % of the electrical energy produced in the European Union. About 90 % of this energy is converted to mechanical work. However, 0.5-2.5 % of it goes to so called additional load losses whose exact origins are unknown. Our ambitious aim is to reveal the origins of these losses, build up numerical tools for modeling them and optimize electrical motors to minimize the losses.
As the hypothesis of the research, we assume that the additional losses mainly result from the deterioration of the core materials during the manufacturing process of the machine. By calorimetric measurements, we have found that the core losses of electrical machines may be twice as large as comprehensive loss models predict. The electrical steel sheets are punched, welded together and shrink fit to the frame. This causes residual strains in the core sheets deteriorating their magnetic characteristics. The cutting burrs make galvanic contacts between the sheets and form paths for inter-lamination currents. Another potential source of additional losses are the circulating currents between the parallel strands of random-wound armature windings. The stochastic nature of these potential sources of additional losses puts more challenge on the research.
We shall develop a physical loss model that couples the mechanical strains and electromagnetic losses in electrical steel sheets and apply the new model for comprehensive loss analysis of electrical machines. The stochastic variables related to the core losses and circulating-current losses will be discretized together with the temporal and spatial discretization of the electromechanical field variables. The numerical stochastic loss model will be used to search for such machine constructions that are insensitive to the manufacturing defects. We shall validate the new numerical loss models by electromechanical and calorimetric measurements."
Max ERC Funding
2 489 949 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym CODE
Project Condensation in designed systems
Researcher (PI) Paeivi Elina Toermae
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Advanced Grant (AdG), PE2, ERC-2013-ADG
Summary "Quantum coherent phenomena, especially marcoscopic quantum coherence, are among the most striking predictions of quantum mechanics. They have lead to remarkable applications such as lasers and modern optical technologies, and in the future, breakthroughs such as quantum information processing are envisioned. Macroscopic quantum coherence is manifested in Bose-Einstein condensation (BEC), superfluidity, and superconductivity, which have been observed in a variety of systems and continue to be at the front line of scientific research. Here my objective is to extend the realm of Bose-Einstein condensation into new conceptual and practical directions. I focus on the role of a hybrid character of the object that condenses and on the role of non-equilibrium in the BEC phenomenon. The work is mostly theoretical but has also an experimental part. I study two new types of hybrids, fundamentally different from each other. First, I consider pairing and superfluidity in a mixed geometry. Experimental realization of mixed geometries is becoming feasible in ultracold gases. Second, I explore the possibility of finding novel hybrids of light and matter excitations that may display condensation. By combining insight from these two cases, my goal is to understand how the hybrid and non-equilibrium nature can be exploited to design desirable properties, such as high critical temperatures. In particular, in case of the new light-matter hybrids, the goal is to provide realistic scenarios for, and also experimentally demonstrate, a room temperature BEC."
Summary
"Quantum coherent phenomena, especially marcoscopic quantum coherence, are among the most striking predictions of quantum mechanics. They have lead to remarkable applications such as lasers and modern optical technologies, and in the future, breakthroughs such as quantum information processing are envisioned. Macroscopic quantum coherence is manifested in Bose-Einstein condensation (BEC), superfluidity, and superconductivity, which have been observed in a variety of systems and continue to be at the front line of scientific research. Here my objective is to extend the realm of Bose-Einstein condensation into new conceptual and practical directions. I focus on the role of a hybrid character of the object that condenses and on the role of non-equilibrium in the BEC phenomenon. The work is mostly theoretical but has also an experimental part. I study two new types of hybrids, fundamentally different from each other. First, I consider pairing and superfluidity in a mixed geometry. Experimental realization of mixed geometries is becoming feasible in ultracold gases. Second, I explore the possibility of finding novel hybrids of light and matter excitations that may display condensation. By combining insight from these two cases, my goal is to understand how the hybrid and non-equilibrium nature can be exploited to design desirable properties, such as high critical temperatures. In particular, in case of the new light-matter hybrids, the goal is to provide realistic scenarios for, and also experimentally demonstrate, a room temperature BEC."
Max ERC Funding
1 559 608 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
Project acronym COMPASS
Project Colloids with complex interactions: from model atoms to colloidal recognition and bio-inspired self assembly
Researcher (PI) Peter Schurtenberger
Host Institution (HI) MAX IV Laboratory, Lund University
Country Sweden
Call Details Advanced Grant (AdG), PE3, ERC-2013-ADG
Summary Self-assembly is the key construction principle that nature uses so successfully to fabricate its molecular machinery and highly elaborate structures. In this project we will follow nature’s strategies and make a concerted experimental and theoretical effort to study, understand and control self-assembly for a new generation of colloidal building blocks. Starting point will be recent advances in colloid synthesis strategies that have led to a spectacular array of colloids of different shapes, compositions, patterns and functionalities. These allow us to investigate the influence of anisotropy in shape and interactions on aggregation and self-assembly in colloidal suspensions and mixtures. Using responsive particles we will implement colloidal lock-and-key mechanisms and then assemble a library of “colloidal molecules” with well-defined and externally tunable binding sites using microfluidics-based and externally controlled fabrication and sorting principles. We will use them to explore the equilibrium phase behavior of particle systems interacting through a finite number of binding sites. In parallel, we will exploit them and investigate colloid self-assembly into well-defined nanostructures. Here we aim at achieving much more refined control than currently possible by implementing a protein-inspired approach to controlled self-assembly. We combine molecule-like colloidal building blocks that possess directional interactions and externally triggerable specific recognition sites with directed self-assembly where external fields not only facilitate assembly, but also allow fabricating novel structures. We will use the tunable combination of different contributions to the interaction potential between the colloidal building blocks and the ability to create chirality in the assembly to establish the requirements for the controlled formation of tubular shells and thus create a colloid-based minimal model of synthetic virus capsid proteins.
Summary
Self-assembly is the key construction principle that nature uses so successfully to fabricate its molecular machinery and highly elaborate structures. In this project we will follow nature’s strategies and make a concerted experimental and theoretical effort to study, understand and control self-assembly for a new generation of colloidal building blocks. Starting point will be recent advances in colloid synthesis strategies that have led to a spectacular array of colloids of different shapes, compositions, patterns and functionalities. These allow us to investigate the influence of anisotropy in shape and interactions on aggregation and self-assembly in colloidal suspensions and mixtures. Using responsive particles we will implement colloidal lock-and-key mechanisms and then assemble a library of “colloidal molecules” with well-defined and externally tunable binding sites using microfluidics-based and externally controlled fabrication and sorting principles. We will use them to explore the equilibrium phase behavior of particle systems interacting through a finite number of binding sites. In parallel, we will exploit them and investigate colloid self-assembly into well-defined nanostructures. Here we aim at achieving much more refined control than currently possible by implementing a protein-inspired approach to controlled self-assembly. We combine molecule-like colloidal building blocks that possess directional interactions and externally triggerable specific recognition sites with directed self-assembly where external fields not only facilitate assembly, but also allow fabricating novel structures. We will use the tunable combination of different contributions to the interaction potential between the colloidal building blocks and the ability to create chirality in the assembly to establish the requirements for the controlled formation of tubular shells and thus create a colloid-based minimal model of synthetic virus capsid proteins.
Max ERC Funding
2 498 040 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym GRAPHALGAPP
Project Challenges in Graph Algorithms with Applications
Researcher (PI) Monika Hildegard Henzinger
Host Institution (HI) UNIVERSITAT WIEN
Country Austria
Call Details Advanced Grant (AdG), PE6, ERC-2013-ADG
Summary This project has two thrusts of equal importance. Firstly, it aims to develop new graph algorithmic techniques, specifically in the areas of dynamic graph algorithms, online algorithms and approximation algorithms for graph-based optimization problems. Thus, it proposes to solve long-standing, fundamental problems that are central to the field of algorithms. Secondly, it plans to apply these techniques to graph algorithmic problems in different fields of application, specifically in computer-aided verification, computational biology, and web-based advertisement with the goal of significantly advancing the state-of-the-art in these fields. This includes theoretical work as well as experimental evaluation on real-life data sets.
Thus, the goal of this project is a comprehensive approach to algorithms research which involves both excellent fundamental algorithms research as well as solving concrete applications.
Summary
This project has two thrusts of equal importance. Firstly, it aims to develop new graph algorithmic techniques, specifically in the areas of dynamic graph algorithms, online algorithms and approximation algorithms for graph-based optimization problems. Thus, it proposes to solve long-standing, fundamental problems that are central to the field of algorithms. Secondly, it plans to apply these techniques to graph algorithmic problems in different fields of application, specifically in computer-aided verification, computational biology, and web-based advertisement with the goal of significantly advancing the state-of-the-art in these fields. This includes theoretical work as well as experimental evaluation on real-life data sets.
Thus, the goal of this project is a comprehensive approach to algorithms research which involves both excellent fundamental algorithms research as well as solving concrete applications.
Max ERC Funding
2 428 258 €
Duration
Start date: 2014-03-01, End date: 2019-08-31
Project acronym INTEGRAL
Project Integrable Systems in Gauge and String Theory
Researcher (PI) Konstantin Zarembo
Host Institution (HI) STOCKHOLMS UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), PE2, ERC-2013-ADG
Summary The project is aimed at uncovering new links between integrable systems, string theory and quantum field theory. The goal is to study non-perturbative phenomena in strongly-coupled field theories, and to understand relationship between gauge fields and strings at a deeper level.
Summary
The project is aimed at uncovering new links between integrable systems, string theory and quantum field theory. The goal is to study non-perturbative phenomena in strongly-coupled field theories, and to understand relationship between gauge fields and strings at a deeper level.
Max ERC Funding
1 693 692 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym INTELHYB
Project Next generation of complex metallic materials with intelligent hybrid structures
Researcher (PI) Juergen Eckert
Host Institution (HI) OESTERREICHISCHE AKADEMIE DER WISSENSCHAFTEN
Country Austria
Call Details Advanced Grant (AdG), PE8, ERC-2013-ADG
Summary In a modern society, metallic materials are crucially important (e.g. energy, safety, infrastructure, transportation, health, medicine, life sciences, IT). Contemporary examples with inherent challenges to be overcome are the design of ultrahigh specific strength materials. There is a critical need for successful developments in this area in particular for reduced energy consumption, reduction of pollutant emissions and passenger safety. Alternative approaches include improved thermal stability and creep resistance of high-temperature alloys for energy conversion, which are generally used in power plants and turbine engines, high temperature process technology, and fossil-fuel driven engines. The ageing European society makes biomedical materials for implant and stent design also crucially important. A drawback of nearly all current high strength metallic materials is that they lack ductility (i.e. are brittle and hard to form)- or on the opposite side, they may be highly ductile but lack strength. The key concept behind INTELHYB is to define new routes for creation of tailored metallic materials based on scale-bridging intelligent hybrid structures enabling property as well as function optimization. The novelty of this proposal as compared to conventional ideas is that they apply to monolithic amorphous materials or bulk microcrystalline. The basis will be founded on innovative strategies for the design, synthesis and characterization of intrinsic length-scale modulation and phase transformation under highly non-equilibrium conditions. This will include the incorporation of dispersed phases which are close to or beyond their thermodynamic and mechanical stability limit thus forming a hierarchically structured hybrid and ductile/tough alloys. Alternatively, the material itself will be designed in a manner such that it is at the verge of its thermodynamic/mechanical stability.
Summary
In a modern society, metallic materials are crucially important (e.g. energy, safety, infrastructure, transportation, health, medicine, life sciences, IT). Contemporary examples with inherent challenges to be overcome are the design of ultrahigh specific strength materials. There is a critical need for successful developments in this area in particular for reduced energy consumption, reduction of pollutant emissions and passenger safety. Alternative approaches include improved thermal stability and creep resistance of high-temperature alloys for energy conversion, which are generally used in power plants and turbine engines, high temperature process technology, and fossil-fuel driven engines. The ageing European society makes biomedical materials for implant and stent design also crucially important. A drawback of nearly all current high strength metallic materials is that they lack ductility (i.e. are brittle and hard to form)- or on the opposite side, they may be highly ductile but lack strength. The key concept behind INTELHYB is to define new routes for creation of tailored metallic materials based on scale-bridging intelligent hybrid structures enabling property as well as function optimization. The novelty of this proposal as compared to conventional ideas is that they apply to monolithic amorphous materials or bulk microcrystalline. The basis will be founded on innovative strategies for the design, synthesis and characterization of intrinsic length-scale modulation and phase transformation under highly non-equilibrium conditions. This will include the incorporation of dispersed phases which are close to or beyond their thermodynamic and mechanical stability limit thus forming a hierarchically structured hybrid and ductile/tough alloys. Alternatively, the material itself will be designed in a manner such that it is at the verge of its thermodynamic/mechanical stability.
Max ERC Funding
2 499 920 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym LAYERENG-HYBMAT
Project Molecular-Layer-Engineered Inorganic-Organic Hybrid Materials
Researcher (PI) Maarit Johanna Karppinen
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Advanced Grant (AdG), PE5, ERC-2013-ADG
Summary "On-demand-designed and precision-synthesized multicomponent or hybrid materials with unorthodox combinations of properties are potential keys to fascinating next-generation devices. At the same time there is a strong scientific desire to create a comprehensive repertory of basic understanding, design strategies and experimental tools to construct such outstanding smart materials from different building blocks and to shape them into sophisticated hierarchical architectures.
In LAYERENG-HYBMAT I propose a fundamentally new category of nanocomposite materials, that is, layer-by-layer grown coherent inorganic-organic hybrid materials where the cohesion between the layers is based on covalent bonding. Such materials are – once carefully designed and fabricated – able to display in a single material a tailored combination of properties of conventional inorganics and organics, and even beyond. The core hypothesis is that such intimately fused outstanding hybrids are materialized in a simple but extremely elegant manner by mimicking the state-of-the-art thin-film technology, i.e. ALD (atomic layer deposition), originally developed for purely inorganic thin films. The proposed method combines ALD and MLD (molecular layer deposition) cycles and enables the layer-by-layer deposition of coherent inorganic-organic thin films and coatings through sequential self-limiting gas-surface reactions with high precision for the composition and polymer-chain dispersity. With additional nanostructuring capacity these materials have the potential to open up new horizons in electronics, photonics, thermoelectrics, diagnostics, packaging, etc.
The project builds on my long experience in frontier new-material research on other types of multilayered materials and successful proof-of-the-concept ALD/MLD experiments, and addresses all the fundamental aspects of new-material design, modelling, precision synthesis, property tailoring and function characterization."
Summary
"On-demand-designed and precision-synthesized multicomponent or hybrid materials with unorthodox combinations of properties are potential keys to fascinating next-generation devices. At the same time there is a strong scientific desire to create a comprehensive repertory of basic understanding, design strategies and experimental tools to construct such outstanding smart materials from different building blocks and to shape them into sophisticated hierarchical architectures.
In LAYERENG-HYBMAT I propose a fundamentally new category of nanocomposite materials, that is, layer-by-layer grown coherent inorganic-organic hybrid materials where the cohesion between the layers is based on covalent bonding. Such materials are – once carefully designed and fabricated – able to display in a single material a tailored combination of properties of conventional inorganics and organics, and even beyond. The core hypothesis is that such intimately fused outstanding hybrids are materialized in a simple but extremely elegant manner by mimicking the state-of-the-art thin-film technology, i.e. ALD (atomic layer deposition), originally developed for purely inorganic thin films. The proposed method combines ALD and MLD (molecular layer deposition) cycles and enables the layer-by-layer deposition of coherent inorganic-organic thin films and coatings through sequential self-limiting gas-surface reactions with high precision for the composition and polymer-chain dispersity. With additional nanostructuring capacity these materials have the potential to open up new horizons in electronics, photonics, thermoelectrics, diagnostics, packaging, etc.
The project builds on my long experience in frontier new-material research on other types of multilayered materials and successful proof-of-the-concept ALD/MLD experiments, and addresses all the fundamental aspects of new-material design, modelling, precision synthesis, property tailoring and function characterization."
Max ERC Funding
2 358 102 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym MAMBA
Project Molecular mechanism of amyloid β aggregation
Researcher (PI) Sara Elisabet Snogerup Linse
Host Institution (HI) MAX IV Laboratory, Lund University
Country Sweden
Call Details Advanced Grant (AdG), PE4, ERC-2013-ADG
Summary Generation of toxic oligomers during aggregation of amyloid beta peptide (Abeta42) into amyloid fibrils is a central event in Alzheimer disease. Understanding the aggregation process is therefore one important step towards therapy and diagnosis of the disease. We propose a physical chemistry approach with the goal of finding the molecular mechanisms behind the process in terms of the underlying microscopic steps and the molecular driving forces governing each step. We will use methodology developed recently in our laboratory yielding unprecedented reproducibility in the kinetic data. The methodology relies on optimization of every step from production and purification to isolation of highly pure monomeric peptide, and inertness and minimized area of all surfaces. We will use cell viability studies to detect toxic oligomeric species, and selective radio-labeling experiments to pinpoint the origin of those species. In order to obtain insight into the molecular determinants and the relative role of different kinds of intermolecular interactions for each microscopic step, we will study the concentration dependent aggregation kinetics as a function of extrinsic and intrinsic parameters. Extrinsic parameters include temperature, salt, pH, biological membranes, other proteins, and low and high Mw inhibitors. Intrinsic parameters include point mutations and sequence extension/truncation. We will perform detailed kinetic studies for each inhibitor to learn which step in the process is inhibited coupled to cell toxicity assays to learn whether the generation of toxic oligomers is limited. We will use spectroscopic techniques, dynamic light scattering, cryogenic transmission electron microscopy and mass spectrometry coupled to HD exchange to learn about structural transitions as a function of process progression under different conditions to favor different microscopic steps. The results may lead to improved diagnostics and therapeutics of Alzheimer disease.
Summary
Generation of toxic oligomers during aggregation of amyloid beta peptide (Abeta42) into amyloid fibrils is a central event in Alzheimer disease. Understanding the aggregation process is therefore one important step towards therapy and diagnosis of the disease. We propose a physical chemistry approach with the goal of finding the molecular mechanisms behind the process in terms of the underlying microscopic steps and the molecular driving forces governing each step. We will use methodology developed recently in our laboratory yielding unprecedented reproducibility in the kinetic data. The methodology relies on optimization of every step from production and purification to isolation of highly pure monomeric peptide, and inertness and minimized area of all surfaces. We will use cell viability studies to detect toxic oligomeric species, and selective radio-labeling experiments to pinpoint the origin of those species. In order to obtain insight into the molecular determinants and the relative role of different kinds of intermolecular interactions for each microscopic step, we will study the concentration dependent aggregation kinetics as a function of extrinsic and intrinsic parameters. Extrinsic parameters include temperature, salt, pH, biological membranes, other proteins, and low and high Mw inhibitors. Intrinsic parameters include point mutations and sequence extension/truncation. We will perform detailed kinetic studies for each inhibitor to learn which step in the process is inhibited coupled to cell toxicity assays to learn whether the generation of toxic oligomers is limited. We will use spectroscopic techniques, dynamic light scattering, cryogenic transmission electron microscopy and mass spectrometry coupled to HD exchange to learn about structural transitions as a function of process progression under different conditions to favor different microscopic steps. The results may lead to improved diagnostics and therapeutics of Alzheimer disease.
Max ERC Funding
2 499 920 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym MECCA
Project Meeting Challenges in Computer Architecture
Researcher (PI) Per Orvar Stenstroem
Host Institution (HI) CHALMERS TEKNISKA HOEGSKOLA AB
Country Sweden
Call Details Advanced Grant (AdG), PE6, ERC-2013-ADG
Summary "Computer technology has doubled computational performance every 24 months, over the past several decades. This performance growth rate has been an enabler for the dramatic innovation in information technology that now embraces our society. Before 2004, application developers could exploit this performance growth rate with no effort. However, since 2004 power consumption of computer chips exceeded the allowable limits and from that point and onwards, parallel computer architectures became the norm. Currently, parallelism is completely exposed to application developers and managing it is difficult and time-consuming. This has a serious impact on software productivity that may stall progress in information technology.
Technology forecasts predict that by 2020 there will be hundreds of processors on a computer chip. Apart from managing parallelism, keeping power consumption within allowable limits will remain a key roadblock for maintaining historical performance growth rates. Power efficiency must increase by an order of magnitude in the next ten years to not limit the growth rate. Finally, computer chips are also key components in embedded controllers, where stringent timing responses are mandatory. Delivering predictable and tight response times using parallel architectures is a challenging and unsolved problem.
MECCA takes a novel, interdisciplinary and unconventional approach to address three important challenges facing computer architecture – the three Ps: Parallelism, Power, and Predictability in a unified framework. Unlike earlier, predominantly disciplinary approaches, MECCA bridges layers in computing systems from the programming language/model, to the compiler, to the run-time/OS, down to the architecture layer. This opens up for exchanging information across layers to manage parallelism and architectural resources in a
transparent way to application developers to meet challenging performance, power, and predictability requirements for future computers."
Summary
"Computer technology has doubled computational performance every 24 months, over the past several decades. This performance growth rate has been an enabler for the dramatic innovation in information technology that now embraces our society. Before 2004, application developers could exploit this performance growth rate with no effort. However, since 2004 power consumption of computer chips exceeded the allowable limits and from that point and onwards, parallel computer architectures became the norm. Currently, parallelism is completely exposed to application developers and managing it is difficult and time-consuming. This has a serious impact on software productivity that may stall progress in information technology.
Technology forecasts predict that by 2020 there will be hundreds of processors on a computer chip. Apart from managing parallelism, keeping power consumption within allowable limits will remain a key roadblock for maintaining historical performance growth rates. Power efficiency must increase by an order of magnitude in the next ten years to not limit the growth rate. Finally, computer chips are also key components in embedded controllers, where stringent timing responses are mandatory. Delivering predictable and tight response times using parallel architectures is a challenging and unsolved problem.
MECCA takes a novel, interdisciplinary and unconventional approach to address three important challenges facing computer architecture – the three Ps: Parallelism, Power, and Predictability in a unified framework. Unlike earlier, predominantly disciplinary approaches, MECCA bridges layers in computing systems from the programming language/model, to the compiler, to the run-time/OS, down to the architecture layer. This opens up for exchanging information across layers to manage parallelism and architectural resources in a
transparent way to application developers to meet challenging performance, power, and predictability requirements for future computers."
Max ERC Funding
2 379 822 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym Near-infrared probes
Project Near-infrared fluorescent probes based on bacterial phytochromes for in vivo imaging
Researcher (PI) Vladislav Verkhusha
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Advanced Grant (AdG), LS9, ERC-2013-ADG
Summary Non-invasive monitoring of deep-tissue developmental, metabolic and pathogenic processes will advance modern biology. Imaging of live mammals using fluorescent probes is more feasible within the near-infrared (NIR) transparency window (NIRW: 650-900 nm) where hemoglobin and melanin absorbance significantly decreases, and water absorbance is still low. The most red-shifted fluorescent proteins (FPs) of the GFP-like family exhibit fluorescence outside of the NIRW and suffer from low brightness and modest photostability. Natural bacterial phytochrome photoreceptors (BphPs) utilize low molecular weight biliverdin as a chromophore and provide many advantages over other chromophore binding proteins. First, unlike the chromophores of non-bacterial phytochromes, biliverdin is ubiquitous in mammals. This makes BphP applications in mammalian cells, tissues and mammals as easy as conventional GFP-like FPs, without supplying chromophore through an external solution. Second, BphPs exhibit NIR absorbance and fluorescence, which are red-shifted relative to that of any other phytochromes, and lie within the NIRW. This makes BphPs spectrally complementary to GFP-like FPs and available optogenetic tools. Third, independent domain architecture and conformational changes upon biliverdin photoisomerization make BphPs attractive templates to design various photoactivatable probes. Based on the analysis of the photochemistry and structural changes of BphPs we plan to develop three new types of the BphP-based probes. These include bright and spectrally resolvable permanently fluorescent NIRFPs, NIRFPs photoswitchable either irreversibly or repeatedly with non-phototoxic NIR light, and NIR reporters and biosensors. The resulting NIR probes will extend fluorescence imaging methods to deep-tissue in vivo macroscopy including multicolor cell and tissue labeling, cell photoactivation and tracking, detection of enzymatic activities and protein interactions in mammalian tissues and whole animals.
Summary
Non-invasive monitoring of deep-tissue developmental, metabolic and pathogenic processes will advance modern biology. Imaging of live mammals using fluorescent probes is more feasible within the near-infrared (NIR) transparency window (NIRW: 650-900 nm) where hemoglobin and melanin absorbance significantly decreases, and water absorbance is still low. The most red-shifted fluorescent proteins (FPs) of the GFP-like family exhibit fluorescence outside of the NIRW and suffer from low brightness and modest photostability. Natural bacterial phytochrome photoreceptors (BphPs) utilize low molecular weight biliverdin as a chromophore and provide many advantages over other chromophore binding proteins. First, unlike the chromophores of non-bacterial phytochromes, biliverdin is ubiquitous in mammals. This makes BphP applications in mammalian cells, tissues and mammals as easy as conventional GFP-like FPs, without supplying chromophore through an external solution. Second, BphPs exhibit NIR absorbance and fluorescence, which are red-shifted relative to that of any other phytochromes, and lie within the NIRW. This makes BphPs spectrally complementary to GFP-like FPs and available optogenetic tools. Third, independent domain architecture and conformational changes upon biliverdin photoisomerization make BphPs attractive templates to design various photoactivatable probes. Based on the analysis of the photochemistry and structural changes of BphPs we plan to develop three new types of the BphP-based probes. These include bright and spectrally resolvable permanently fluorescent NIRFPs, NIRFPs photoswitchable either irreversibly or repeatedly with non-phototoxic NIR light, and NIR reporters and biosensors. The resulting NIR probes will extend fluorescence imaging methods to deep-tissue in vivo macroscopy including multicolor cell and tissue labeling, cell photoactivation and tracking, detection of enzymatic activities and protein interactions in mammalian tissues and whole animals.
Max ERC Funding
2 496 946 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
