Project acronym A-LIFE
Project Absorbing aerosol layers in a changing climate: aging, lifetime and dynamics
Researcher (PI) Bernadett Barbara Weinzierl
Host Institution (HI) UNIVERSITAT WIEN
Call Details Starting Grant (StG), PE10, ERC-2014-STG
Summary Aerosols (i.e. tiny particles suspended in the air) are regularly transported in huge amounts over long distances impacting air quality, health, weather and climate thousands of kilometers downwind of the source. Aerosols affect the atmospheric radiation budget through scattering and absorption of solar radiation and through their role as cloud/ice nuclei.
In particular, light absorption by aerosol particles such as mineral dust and black carbon (BC; thought to be the second strongest contribution to current global warming after CO2) is of fundamental importance from a climate perspective because the presence of absorbing particles (1) contributes to solar radiative forcing, (2) heats absorbing aerosol layers, (3) can evaporate clouds and (4) change atmospheric dynamics.
Considering this prominent role of aerosols, vertically-resolved in-situ data on absorbing aerosols are surprisingly scarce and aerosol-dynamic interactions are poorly understood in general. This is, as recognized in the last IPCC report, a serious barrier for taking the accuracy of climate models and predictions to the next level. To overcome this barrier, I propose to investigate aging, lifetime and dynamics of absorbing aerosol layers with a holistic end-to-end approach including laboratory studies, airborne field experiments and numerical model simulations.
Building on the internationally recognized results of my aerosol research group and my long-term experience with airborne aerosol measurements, the time seems ripe to systematically bridge the gap between in-situ measurements of aerosol microphysical and optical properties and the assessment of dynamical interactions of absorbing particles with aerosol layer lifetime through model simulations.
The outcomes of this project will provide fundamental new understanding of absorbing aerosol layers in the climate system and important information for addressing the benefits of BC emission controls for mitigating climate change.
Summary
Aerosols (i.e. tiny particles suspended in the air) are regularly transported in huge amounts over long distances impacting air quality, health, weather and climate thousands of kilometers downwind of the source. Aerosols affect the atmospheric radiation budget through scattering and absorption of solar radiation and through their role as cloud/ice nuclei.
In particular, light absorption by aerosol particles such as mineral dust and black carbon (BC; thought to be the second strongest contribution to current global warming after CO2) is of fundamental importance from a climate perspective because the presence of absorbing particles (1) contributes to solar radiative forcing, (2) heats absorbing aerosol layers, (3) can evaporate clouds and (4) change atmospheric dynamics.
Considering this prominent role of aerosols, vertically-resolved in-situ data on absorbing aerosols are surprisingly scarce and aerosol-dynamic interactions are poorly understood in general. This is, as recognized in the last IPCC report, a serious barrier for taking the accuracy of climate models and predictions to the next level. To overcome this barrier, I propose to investigate aging, lifetime and dynamics of absorbing aerosol layers with a holistic end-to-end approach including laboratory studies, airborne field experiments and numerical model simulations.
Building on the internationally recognized results of my aerosol research group and my long-term experience with airborne aerosol measurements, the time seems ripe to systematically bridge the gap between in-situ measurements of aerosol microphysical and optical properties and the assessment of dynamical interactions of absorbing particles with aerosol layer lifetime through model simulations.
The outcomes of this project will provide fundamental new understanding of absorbing aerosol layers in the climate system and important information for addressing the benefits of BC emission controls for mitigating climate change.
Max ERC Funding
1 987 980 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
Project acronym ANGULON
Project Angulon: physics and applications of a new quasiparticle
Researcher (PI) Mikhail Lemeshko
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Starting Grant (StG), PE3, ERC-2018-STG
Summary This project aims to develop a universal approach to angular momentum in quantum many-body systems based on the angulon quasiparticle recently discovered by the PI. We will establish a general theory of angulons in and out of equilibrium, and apply it to a variety of experimentally studied problems, ranging from chemical dynamics in solvents to solid-state systems (e.g. angular momentum transfer in the Einstein-de Haas effect and ultrafast magnetism).
The concept of angular momentum is ubiquitous across physics, whether one deals with nuclear collisions, chemical reactions, or formation of galaxies. In the microscopic world, quantum rotations are described by non-commuting operators. This makes the angular momentum theory extremely involved, even for systems consisting of only a few interacting particles, such as gas-phase atoms or molecules.
Furthermore, in most experiments the behavior of quantum particles is inevitably altered by a many-body environment of some kind. For example, molecular rotation – and therefore reactivity – depends on the presence of a solvent, electronic angular momentum in solids is coupled to lattice phonons, highly excited atomic levels can be perturbed by a surrounding ultracold gas. If approached in a brute-force fashion, understanding angular momentum in such systems is an impossible task, since a macroscopic number of particles is involved.
Recently, the PI and his team have shown that this challenge can be met by introducing a new quasiparticle – the angulon. In 2017, the PI has demonstrated the existence of angulons by comparing his theory with 20 years of measurements on molecules rotating in superfluids. Most importantly, the angulon concept allows one to gain analytical insights inaccessible to the state-of-the-art techniques of condensed matter and chemical physics. The angulon approach holds the promise of opening up a new interdisciplinary research area with applications reaching far beyond what is proposed here.
Summary
This project aims to develop a universal approach to angular momentum in quantum many-body systems based on the angulon quasiparticle recently discovered by the PI. We will establish a general theory of angulons in and out of equilibrium, and apply it to a variety of experimentally studied problems, ranging from chemical dynamics in solvents to solid-state systems (e.g. angular momentum transfer in the Einstein-de Haas effect and ultrafast magnetism).
The concept of angular momentum is ubiquitous across physics, whether one deals with nuclear collisions, chemical reactions, or formation of galaxies. In the microscopic world, quantum rotations are described by non-commuting operators. This makes the angular momentum theory extremely involved, even for systems consisting of only a few interacting particles, such as gas-phase atoms or molecules.
Furthermore, in most experiments the behavior of quantum particles is inevitably altered by a many-body environment of some kind. For example, molecular rotation – and therefore reactivity – depends on the presence of a solvent, electronic angular momentum in solids is coupled to lattice phonons, highly excited atomic levels can be perturbed by a surrounding ultracold gas. If approached in a brute-force fashion, understanding angular momentum in such systems is an impossible task, since a macroscopic number of particles is involved.
Recently, the PI and his team have shown that this challenge can be met by introducing a new quasiparticle – the angulon. In 2017, the PI has demonstrated the existence of angulons by comparing his theory with 20 years of measurements on molecules rotating in superfluids. Most importantly, the angulon concept allows one to gain analytical insights inaccessible to the state-of-the-art techniques of condensed matter and chemical physics. The angulon approach holds the promise of opening up a new interdisciplinary research area with applications reaching far beyond what is proposed here.
Max ERC Funding
1 499 588 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym AQSuS
Project Analog Quantum Simulation using Superconducting Qubits
Researcher (PI) Gerhard KIRCHMAIR
Host Institution (HI) UNIVERSITAET INNSBRUCK
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary AQSuS aims at experimentally implementing analogue quantum simulation of interacting spin models in two-dimensional geometries. The proposed experimental approach paves the way to investigate a broad range of currently inaccessible quantum phenomena, for which existing analytical and numerical methods reach their limitations. Developing precisely controlled interacting quantum systems in 2D is an important current goal well beyond the field of quantum simulation and has applications in e.g. solid state physics, computing and metrology.
To access these models, I propose to develop a novel circuit quantum-electrodynamics (cQED) platform based on the 3D transmon qubit architecture. This platform utilizes the highly engineerable properties and long coherence times of these qubits. A central novel idea behind AQSuS is to exploit the spatial dependence of the naturally occurring dipolar interactions between the qubits to engineer the desired spin-spin interactions. This approach avoids the complicated wiring, typical for other cQED experiments and reduces the complexity of the experimental setup. The scheme is therefore directly scalable to larger systems. The experimental goals are:
1) Demonstrate analogue quantum simulation of an interacting spin system in 1D & 2D.
2) Establish methods to precisely initialize the state of the system, control the interactions and readout single qubit states and multi-qubit correlations.
3) Investigate unobserved quantum phenomena on 2D geometries e.g. kagome and triangular lattices.
4) Study open system dynamics with interacting spin systems.
AQSuS builds on my backgrounds in both superconducting qubits and quantum simulation with trapped-ions. With theory collaborators my young research group and I have recently published an article in PRB [9] describing and analysing the proposed platform. The ERC starting grant would allow me to open a big new research direction and capitalize on the foundations established over the last two years.
Summary
AQSuS aims at experimentally implementing analogue quantum simulation of interacting spin models in two-dimensional geometries. The proposed experimental approach paves the way to investigate a broad range of currently inaccessible quantum phenomena, for which existing analytical and numerical methods reach their limitations. Developing precisely controlled interacting quantum systems in 2D is an important current goal well beyond the field of quantum simulation and has applications in e.g. solid state physics, computing and metrology.
To access these models, I propose to develop a novel circuit quantum-electrodynamics (cQED) platform based on the 3D transmon qubit architecture. This platform utilizes the highly engineerable properties and long coherence times of these qubits. A central novel idea behind AQSuS is to exploit the spatial dependence of the naturally occurring dipolar interactions between the qubits to engineer the desired spin-spin interactions. This approach avoids the complicated wiring, typical for other cQED experiments and reduces the complexity of the experimental setup. The scheme is therefore directly scalable to larger systems. The experimental goals are:
1) Demonstrate analogue quantum simulation of an interacting spin system in 1D & 2D.
2) Establish methods to precisely initialize the state of the system, control the interactions and readout single qubit states and multi-qubit correlations.
3) Investigate unobserved quantum phenomena on 2D geometries e.g. kagome and triangular lattices.
4) Study open system dynamics with interacting spin systems.
AQSuS builds on my backgrounds in both superconducting qubits and quantum simulation with trapped-ions. With theory collaborators my young research group and I have recently published an article in PRB [9] describing and analysing the proposed platform. The ERC starting grant would allow me to open a big new research direction and capitalize on the foundations established over the last two years.
Max ERC Funding
1 498 515 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym Big Splash
Project Big Splash: Efficient Simulation of Natural Phenomena at Extremely Large Scales
Researcher (PI) Christopher John Wojtan
Host Institution (HI) Institute of Science and Technology Austria
Call Details Starting Grant (StG), PE6, ERC-2014-STG
Summary Computational simulations of natural phenomena are essential in science, engineering, product design, architecture, and computer graphics applications. However, despite progress in numerical algorithms and computational power, it is still unfeasible to compute detailed simulations at large scales. To make matters worse, important phenomena like turbulent splashing liquids and fracturing solids rely on delicate coupling between small-scale details and large-scale behavior. Brute-force computation of such phenomena is intractable, and current adaptive techniques are too fragile, too costly, or too crude to capture subtle instabilities at small scales. Increases in computational power and parallel algorithms will improve the situation, but progress will only be incremental until we address the problem at its source.
I propose two main approaches to this problem of efficiently simulating large-scale liquid and solid dynamics. My first avenue of research combines numerics and shape: I will investigate a careful de-coupling of dynamics from geometry, allowing essential shape details to be preserved and retrieved without wasting computation. I will also develop methods for merging small-scale analytical solutions with large-scale numerical algorithms. (These ideas show particular promise for phenomena like splashing liquids and fracturing solids, whose small-scale behaviors are poorly captured by standard finite element methods.) My second main research direction is the manipulation of large-scale simulation data: Given the redundant and parallel nature of physics computation, we will drastically speed up computation with novel dimension reduction and data compression approaches. We can also minimize unnecessary computation by re-using existing simulation data. The novel approaches resulting from this work will undoubtedly synergize to enable the simulation and understanding of complicated natural and biological processes that are presently unfeasible to compute.
Summary
Computational simulations of natural phenomena are essential in science, engineering, product design, architecture, and computer graphics applications. However, despite progress in numerical algorithms and computational power, it is still unfeasible to compute detailed simulations at large scales. To make matters worse, important phenomena like turbulent splashing liquids and fracturing solids rely on delicate coupling between small-scale details and large-scale behavior. Brute-force computation of such phenomena is intractable, and current adaptive techniques are too fragile, too costly, or too crude to capture subtle instabilities at small scales. Increases in computational power and parallel algorithms will improve the situation, but progress will only be incremental until we address the problem at its source.
I propose two main approaches to this problem of efficiently simulating large-scale liquid and solid dynamics. My first avenue of research combines numerics and shape: I will investigate a careful de-coupling of dynamics from geometry, allowing essential shape details to be preserved and retrieved without wasting computation. I will also develop methods for merging small-scale analytical solutions with large-scale numerical algorithms. (These ideas show particular promise for phenomena like splashing liquids and fracturing solids, whose small-scale behaviors are poorly captured by standard finite element methods.) My second main research direction is the manipulation of large-scale simulation data: Given the redundant and parallel nature of physics computation, we will drastically speed up computation with novel dimension reduction and data compression approaches. We can also minimize unnecessary computation by re-using existing simulation data. The novel approaches resulting from this work will undoubtedly synergize to enable the simulation and understanding of complicated natural and biological processes that are presently unfeasible to compute.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-03-01, End date: 2020-02-29
Project acronym CC4SOL
Project Towards chemical accuracy in computational materials science
Researcher (PI) Andreas GRÜNEIS
Host Institution (HI) TECHNISCHE UNIVERSITAET WIEN
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary This project aims at the development of a novel toolbox of ab-initio methods that approximate the true many-electron wavefunction using systematically improvable perturbation and coupled-cluster theories. The demand and prospects for these methods are excellent given that the highly-accurate coupled-cluster theories can predict atomization- and reaction energies in a wide range of solids and molecules with chemical accuracy (≈43 meV). However, the computational cost involved inhibits their widespread use in the field of materials science so far. A multitude of suggested developments in the present proposal hold the promise to reduce the computational cost beyond what is currently considered possible by the community. These include explicit correlation methods that augment the conventional wavefunction expansion with terms that depend on the electron pair correlation factors. In contrast to the widely-used homogeneous correlation factors, this proposal aims at the investigation of inhomogeneous correlation factors that can also capture van der Waals interactions. Furthermore this proposal seeks to employ a recently developed combination of atom-centered basis functions and plane wave basis sets, maximizing the compactness in the wavefunction expansion. The combination of these ideas bears the potential to reduce the computational cost of coupled-cluster calculations in solids by three orders of magnitude, leading to a breakthrough in the field of highly-accurate ab-initio simulations. As such the study of challenging solid state physics and chemistry problems forms an important part of this proposal. We seek to investigate molecular adsorption and reactions in zeolites and on surfaces, pressure-driven solid-solid phase transitions of two dimensional layered materials and defects in solids. These problems are paradigmatic for van der Waals interactions and strong correlation, and methods that describe their electronic structure accurately are highly sought after.
Summary
This project aims at the development of a novel toolbox of ab-initio methods that approximate the true many-electron wavefunction using systematically improvable perturbation and coupled-cluster theories. The demand and prospects for these methods are excellent given that the highly-accurate coupled-cluster theories can predict atomization- and reaction energies in a wide range of solids and molecules with chemical accuracy (≈43 meV). However, the computational cost involved inhibits their widespread use in the field of materials science so far. A multitude of suggested developments in the present proposal hold the promise to reduce the computational cost beyond what is currently considered possible by the community. These include explicit correlation methods that augment the conventional wavefunction expansion with terms that depend on the electron pair correlation factors. In contrast to the widely-used homogeneous correlation factors, this proposal aims at the investigation of inhomogeneous correlation factors that can also capture van der Waals interactions. Furthermore this proposal seeks to employ a recently developed combination of atom-centered basis functions and plane wave basis sets, maximizing the compactness in the wavefunction expansion. The combination of these ideas bears the potential to reduce the computational cost of coupled-cluster calculations in solids by three orders of magnitude, leading to a breakthrough in the field of highly-accurate ab-initio simulations. As such the study of challenging solid state physics and chemistry problems forms an important part of this proposal. We seek to investigate molecular adsorption and reactions in zeolites and on surfaces, pressure-driven solid-solid phase transitions of two dimensional layered materials and defects in solids. These problems are paradigmatic for van der Waals interactions and strong correlation, and methods that describe their electronic structure accurately are highly sought after.
Max ERC Funding
1 460 826 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym COYOTE
Project Coherent Optics Everywhere: a New Dawn for Photonic Networks
Researcher (PI) Bernhard SCHRENK
Host Institution (HI) AIT AUSTRIAN INSTITUTE OF TECHNOLOGY GMBH
Call Details Starting Grant (StG), PE7, ERC-2018-STG
Summary The widespread adoption of the Internet and its influence on our daily life is unquestioned. Global Zettabyte traffic has rendered photonics as indispensable for the communication infrastructure. While direct signal detection has been dismissed in radio communications decades ago, it prevails in short- and medium-reach optics in virtue of its simplicity. In such an environment photonics can only rely on incremental improvements, whereas it desperately seeks for disruptive concepts.
COYOTE envisions a novel coherent homodyne transceiver concept for analogue signals and access to higher-order formats with efficiencies of 10 bits/symbol. On top of this, high-fidelity transport of multi-band 5G radio signals in the millimetre-wave range up to 100 GHz will be enabled by analogue coherent photonics while mitigating energy-hungry digital signal processing. COYOTE takes one more leap and dares the contradictory full-duplex data transmission in virtue of its novel reception engine to ultimately guarantee a lean solution with greatly simplified yet flexible “hardware”.
The key asset of COYOTE’s coherent engine will be a locked laser with improved coherence characteristics together with a flexible modulator-detector element, which is capable to emulate direct-detection systems in a transparent way while giving birth to novel networking concepts. Exploration of the 3D Stokes and 2D quadrature spaces through a segmented receiver architecture will boost the spectral efficiency to >10 bits/s/Hz.
It is the lean and yet efficient coherent transceiver methodology of COYOTE that will remove the currently existing boundary between direct-detection and coherent systems in the midst of network reaches. By coherently “reviving” these telecom segments of integrated wireline-wireless access networks, optical interconnects for intra-datacentre connectivity and even quantum communication, an order-of-magnitude improvement in terms of spectral efficiency x reach product will be gained.
Summary
The widespread adoption of the Internet and its influence on our daily life is unquestioned. Global Zettabyte traffic has rendered photonics as indispensable for the communication infrastructure. While direct signal detection has been dismissed in radio communications decades ago, it prevails in short- and medium-reach optics in virtue of its simplicity. In such an environment photonics can only rely on incremental improvements, whereas it desperately seeks for disruptive concepts.
COYOTE envisions a novel coherent homodyne transceiver concept for analogue signals and access to higher-order formats with efficiencies of 10 bits/symbol. On top of this, high-fidelity transport of multi-band 5G radio signals in the millimetre-wave range up to 100 GHz will be enabled by analogue coherent photonics while mitigating energy-hungry digital signal processing. COYOTE takes one more leap and dares the contradictory full-duplex data transmission in virtue of its novel reception engine to ultimately guarantee a lean solution with greatly simplified yet flexible “hardware”.
The key asset of COYOTE’s coherent engine will be a locked laser with improved coherence characteristics together with a flexible modulator-detector element, which is capable to emulate direct-detection systems in a transparent way while giving birth to novel networking concepts. Exploration of the 3D Stokes and 2D quadrature spaces through a segmented receiver architecture will boost the spectral efficiency to >10 bits/s/Hz.
It is the lean and yet efficient coherent transceiver methodology of COYOTE that will remove the currently existing boundary between direct-detection and coherent systems in the midst of network reaches. By coherently “reviving” these telecom segments of integrated wireline-wireless access networks, optical interconnects for intra-datacentre connectivity and even quantum communication, an order-of-magnitude improvement in terms of spectral efficiency x reach product will be gained.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym GUTPEPTIDES
Project Novel therapeutic approaches to improve gastrointestinal wound healing
Researcher (PI) Markus MUTTENTHALER
Host Institution (HI) UNIVERSITAT WIEN
Call Details Starting Grant (StG), PE5, ERC-2016-STG
Summary The gastrointestinal epithelium is a major physical barrier that protects us from diverse and potentially immunogenic or toxic content. A compromised epithelium results in increased permeability to such content, thus leading to inflammation, immune response, pain, and diseases, such as irritable bowel syndrome and inflammatory bowel disease. A therapeutic strategy that controls inflammation and restores the barrier represents an innovative approach for the prevention and treatment of such diseases. This proposal focuses on how gut peptides regulate epithelial protection and repair, and explores novel therapeutic opportunities by targeting gut receptors that become accessible once the epithelium is compromised. We propose to tackle the overall aim of improving gastrointestinal wound healing via three complementary objectives: (I) to investigate the therapeutic potential of the oxytocin receptor during gastrointestinal inflammation, (II) to elucidate the mechanism of trefoil factor peptide-induced gastrointestinal wound healing, and (III) to discover and characterise novel ligands suitable for epithelial repair. To achieve these objectives, we employ a multidisciplinary approach that includes state-of-the-art peptide synthesis, scaffold grafting, pharmacology, gut stability and wound healing assays, and inflammatory mouse models. We will develop probes to study the mechanisms of action at a molecular level that is not possible with current tools, and explore the biological diversity of venoms for novel therapeutic leads. This project will significantly advance our understanding of epithelial protection/repair and reveal drug targets that treat the source of the problems rather than the symptoms. This project has the potential to change the way we think about treating gut disorders and how to develop peptide therapeutics, and it will pave the way towards the intriguing and longer-term goal of modulating the central nervous system via the gut-brain axis.
Summary
The gastrointestinal epithelium is a major physical barrier that protects us from diverse and potentially immunogenic or toxic content. A compromised epithelium results in increased permeability to such content, thus leading to inflammation, immune response, pain, and diseases, such as irritable bowel syndrome and inflammatory bowel disease. A therapeutic strategy that controls inflammation and restores the barrier represents an innovative approach for the prevention and treatment of such diseases. This proposal focuses on how gut peptides regulate epithelial protection and repair, and explores novel therapeutic opportunities by targeting gut receptors that become accessible once the epithelium is compromised. We propose to tackle the overall aim of improving gastrointestinal wound healing via three complementary objectives: (I) to investigate the therapeutic potential of the oxytocin receptor during gastrointestinal inflammation, (II) to elucidate the mechanism of trefoil factor peptide-induced gastrointestinal wound healing, and (III) to discover and characterise novel ligands suitable for epithelial repair. To achieve these objectives, we employ a multidisciplinary approach that includes state-of-the-art peptide synthesis, scaffold grafting, pharmacology, gut stability and wound healing assays, and inflammatory mouse models. We will develop probes to study the mechanisms of action at a molecular level that is not possible with current tools, and explore the biological diversity of venoms for novel therapeutic leads. This project will significantly advance our understanding of epithelial protection/repair and reveal drug targets that treat the source of the problems rather than the symptoms. This project has the potential to change the way we think about treating gut disorders and how to develop peptide therapeutics, and it will pave the way towards the intriguing and longer-term goal of modulating the central nervous system via the gut-brain axis.
Max ERC Funding
1 487 396 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym HALODRUGSYN
Project Innovative Strategies towards Halogenated Organic Molecules: From Reaction Design to Application in Drug Synthesis
Researcher (PI) Thomas MAGAUER
Host Institution (HI) UNIVERSITAET INNSBRUCK
Call Details Starting Grant (StG), PE5, ERC-2016-STG
Summary Halogenated arenes and heteroarenes have become essential structural motifs of the pharmaceutical industry to create novel drugs against bacterial infections and cancer, and constitute highly valuable functional units in chemistry. Current methods for the installation of carbon-halogen bonds lack efficiency, selectivity, and practicability within the complex molecular setting of drug development processes. These restrictions prevent many potential drugs from being synthesized in a time- and cost-efficient manner.
In this project, I aim to address these challenges by engineering a highly elaborated synthetic toolbox that is equipped with novel transformations of unprecedented efficiency, selectivity and practicability. I will apply these transformations to the construction of novel antibiotics against resistant strains and more efficient chemotherapeutics to combat cancer.
The first objective is to establish innovative transformations that enable for the first time an efficient access to halogenated arenes. I will accomplish this goal by developing novel ring-expansion reactions and apply them to the first synthesis of the antibiotic salimabromide in order to address the acute problem of antibiotic resistance. Within the second part of this project, I will extend this unique synthetic platform to heteroarenes and establish a groundbreaking method based on carbon-fluorine bond activation. This will represent the first broadly applicable strategy to produce novel fluorinated heteroarene based anti-cancer drugs with unparalleled precision, efficiency and selectivity. Taken together, the realization of these strategies, all of which are unprecedented, provides for the first time a solution for the limitations associated with current methods. With my expertise in synthetic chemistry, which I have gained from my achievements in natural product synthesis, and an outstanding publication record in this research field, I am confident to accomplish these ambitious goals.
Summary
Halogenated arenes and heteroarenes have become essential structural motifs of the pharmaceutical industry to create novel drugs against bacterial infections and cancer, and constitute highly valuable functional units in chemistry. Current methods for the installation of carbon-halogen bonds lack efficiency, selectivity, and practicability within the complex molecular setting of drug development processes. These restrictions prevent many potential drugs from being synthesized in a time- and cost-efficient manner.
In this project, I aim to address these challenges by engineering a highly elaborated synthetic toolbox that is equipped with novel transformations of unprecedented efficiency, selectivity and practicability. I will apply these transformations to the construction of novel antibiotics against resistant strains and more efficient chemotherapeutics to combat cancer.
The first objective is to establish innovative transformations that enable for the first time an efficient access to halogenated arenes. I will accomplish this goal by developing novel ring-expansion reactions and apply them to the first synthesis of the antibiotic salimabromide in order to address the acute problem of antibiotic resistance. Within the second part of this project, I will extend this unique synthetic platform to heteroarenes and establish a groundbreaking method based on carbon-fluorine bond activation. This will represent the first broadly applicable strategy to produce novel fluorinated heteroarene based anti-cancer drugs with unparalleled precision, efficiency and selectivity. Taken together, the realization of these strategies, all of which are unprecedented, provides for the first time a solution for the limitations associated with current methods. With my expertise in synthetic chemistry, which I have gained from my achievements in natural product synthesis, and an outstanding publication record in this research field, I am confident to accomplish these ambitious goals.
Max ERC Funding
1 496 664 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym HOMOVIS
Project High-level Prior Models for Computer Vision
Researcher (PI) Thomas Pock
Host Institution (HI) TECHNISCHE UNIVERSITAET GRAZ
Call Details Starting Grant (StG), PE6, ERC-2014-STG
Summary Since more than 50 years, computer vision has been a very active research field but it is still far away from the abilities of the human visual system. This stunning performance of the human visual system can be mainly contributed to a highly efficient three-layer architecture: A low-level layer that sparsifies the visual information by detecting important image features such as image gradients, a mid-level layer that implements disocclusion and boundary completion processes and finally a high-level layer that is concerned with the recognition of objects.
Variational methods are certainly one of the most successful methods for low-level vision. However, it is very unlikely that these methods can be further improved without the integration of high-level prior models. Therefore, we propose a unified mathematical framework that allows for a natural integration of high-level priors into low-level variational models. In particular, we propose to represent images in a higher-dimensional space which is inspired by the architecture for the visual cortex. This space performs a decomposition of the image gradients into magnitude and direction and hence performs a lifting of the 2D image to a 3D space. This has several advantages: Firstly, the higher-dimensional embedding allows to implement mid-level tasks such as boundary completion and disocclusion processes in a very natural way. Secondly, the lifted space allows for an explicit access to the orientation and the magnitude of image gradients. In turn, distributions of gradient orientations – known to be highly effective for object detection – can be utilized as high-level priors. This inverts the bottom-up nature of object detectors and hence adds an efficient top-down process to low-level variational models.
The developed mathematical approaches will go significantly beyond traditional variational models for computer vision and hence will define a new state-of-the-art in the field.
Summary
Since more than 50 years, computer vision has been a very active research field but it is still far away from the abilities of the human visual system. This stunning performance of the human visual system can be mainly contributed to a highly efficient three-layer architecture: A low-level layer that sparsifies the visual information by detecting important image features such as image gradients, a mid-level layer that implements disocclusion and boundary completion processes and finally a high-level layer that is concerned with the recognition of objects.
Variational methods are certainly one of the most successful methods for low-level vision. However, it is very unlikely that these methods can be further improved without the integration of high-level prior models. Therefore, we propose a unified mathematical framework that allows for a natural integration of high-level priors into low-level variational models. In particular, we propose to represent images in a higher-dimensional space which is inspired by the architecture for the visual cortex. This space performs a decomposition of the image gradients into magnitude and direction and hence performs a lifting of the 2D image to a 3D space. This has several advantages: Firstly, the higher-dimensional embedding allows to implement mid-level tasks such as boundary completion and disocclusion processes in a very natural way. Secondly, the lifted space allows for an explicit access to the orientation and the magnitude of image gradients. In turn, distributions of gradient orientations – known to be highly effective for object detection – can be utilized as high-level priors. This inverts the bottom-up nature of object detectors and hence adds an efficient top-down process to low-level variational models.
The developed mathematical approaches will go significantly beyond traditional variational models for computer vision and hence will define a new state-of-the-art in the field.
Max ERC Funding
1 473 525 €
Duration
Start date: 2015-06-01, End date: 2020-05-31
Project acronym HYPROTIN
Project Hyperpolarized Nuclear Magnetic Resonance Spectroscopy for Time-Resolved Monitoring of Interactions of Intrinsically Disordered Breast-Cancer Proteins
Researcher (PI) Dennis Christian Benjamin Arthur KURZBACH
Host Institution (HI) UNIVERSITAT WIEN
Call Details Starting Grant (StG), PE4, ERC-2018-STG
Summary HYPROTIN proposes a pioneering research platform for hyperpolarized magnetic resonance of breast-cancer related proteins that will revolutionize our view on tumorigenesis at the atomic level, through bottom-up reconstitution of medicinal relevant interaction pathways involving the breast cancer susceptibility protein 1 (BRCA1).
The risk to develop a hereditary breast or ovarian cancer (HBOC) increases to 55-65 % upon mutation of the BRCA1 gene. Yet, little is known about the biochemistry of tumorigenesis, so that drugs directed towards molecular targets are not satisfactory. To date, mastectomy remains the only preventive treatment. This dramatic lack of knowledge is a consequence of BRCA1 being an intrinsically disordered protein (IDP). Recognizing the importance of IDPs has revolutionized structural biology in the last decade, but this also represents a huge experimental challenge. To date, nuclear magnetic resonance (NMR) is the only technique available to study IDPs at high resolution. However, several limits of the technique must be overcome. Its low sensitivity impedes investigations under biologically meaningful conditions, so that new approaches are required.
The HYPROTIN project aims to achieve two methodological goals: 1) Residue-resolved studies of the BRCA1 IDP under physiological conditions; and 2) real-time monitoring of BRCA1-ligand binding, thereby adding a time-resolved dimension to the NMR characterization of IDPs. This systematic approach will provide unprecedented insight into the BRCA1 interactome, provide medically relevant data and residue-resolved protein interaction kinetics. This will open a new knowledge base for rational drug design.
The project will employ cutting-edge equipment that is unique worldwide, and will represent the first facility in Europe suited for these ground-breaking experiments. The PI has unique interdisciplinary experience enabling the demanding hyperpolarization approach to IDPs.
Summary
HYPROTIN proposes a pioneering research platform for hyperpolarized magnetic resonance of breast-cancer related proteins that will revolutionize our view on tumorigenesis at the atomic level, through bottom-up reconstitution of medicinal relevant interaction pathways involving the breast cancer susceptibility protein 1 (BRCA1).
The risk to develop a hereditary breast or ovarian cancer (HBOC) increases to 55-65 % upon mutation of the BRCA1 gene. Yet, little is known about the biochemistry of tumorigenesis, so that drugs directed towards molecular targets are not satisfactory. To date, mastectomy remains the only preventive treatment. This dramatic lack of knowledge is a consequence of BRCA1 being an intrinsically disordered protein (IDP). Recognizing the importance of IDPs has revolutionized structural biology in the last decade, but this also represents a huge experimental challenge. To date, nuclear magnetic resonance (NMR) is the only technique available to study IDPs at high resolution. However, several limits of the technique must be overcome. Its low sensitivity impedes investigations under biologically meaningful conditions, so that new approaches are required.
The HYPROTIN project aims to achieve two methodological goals: 1) Residue-resolved studies of the BRCA1 IDP under physiological conditions; and 2) real-time monitoring of BRCA1-ligand binding, thereby adding a time-resolved dimension to the NMR characterization of IDPs. This systematic approach will provide unprecedented insight into the BRCA1 interactome, provide medically relevant data and residue-resolved protein interaction kinetics. This will open a new knowledge base for rational drug design.
The project will employ cutting-edge equipment that is unique worldwide, and will represent the first facility in Europe suited for these ground-breaking experiments. The PI has unique interdisciplinary experience enabling the demanding hyperpolarization approach to IDPs.
Max ERC Funding
1 990 728 €
Duration
Start date: 2019-03-01, End date: 2024-02-29