Project acronym ALKAGE
Project Algebraic and Kähler geometry
Researcher (PI) Jean-Pierre, Raymond, Philippe Demailly
Host Institution (HI) UNIVERSITE GRENOBLE ALPES
Call Details Advanced Grant (AdG), PE1, ERC-2014-ADG
Summary The purpose of this project is to study basic questions in algebraic and Kähler geometry. It is well known that the structure of projective or Kähler manifolds is governed by positivity or negativity properties of the curvature tensor. However, many fundamental problems are still wide open. Since the mid 1980's, I have developed a large number of key concepts and results that have led to important progress in transcendental algebraic geometry. Let me mention the discovery of holomorphic Morse inequalities, systematic applications of L² estimates with singular hermitian metrics, and a much improved understanding of Monge-Ampère equations and of singularities of plurisuharmonic functions. My first goal will be to investigate the Green-Griffiths-Lang conjecture asserting that an entire curve drawn in a variety of general type is algebraically degenerate. The subject is intimately related to important questions concerning Diophantine equations, especially higher dimensional generalizations of Faltings' theorem - the so-called Vojta program. One can rely here on a breakthrough I made in 2010, showing that all such entire curves must satisfy algebraic differential equations. A second closely related area of research of this project is the analysis of the structure of projective or compact Kähler manifolds. It can be seen as a generalization of the classification theory of surfaces by Kodaira, and of the more recent results for dimension 3 (Kawamata, Kollár, Mori, Shokurov, ...) to other dimensions. My plan is to combine powerful recent results obtained on the duality of positive cohomology cones with an analysis of the instability of the tangent bundle, i.e. of the Harder-Narasimhan filtration. On these ground-breaking questions, I intend to go much further and to enhance my national and international collaborations. These subjects already attract many young researchers and postdocs throughout the world, and the grant could be used to create even stronger interactions.
Summary
The purpose of this project is to study basic questions in algebraic and Kähler geometry. It is well known that the structure of projective or Kähler manifolds is governed by positivity or negativity properties of the curvature tensor. However, many fundamental problems are still wide open. Since the mid 1980's, I have developed a large number of key concepts and results that have led to important progress in transcendental algebraic geometry. Let me mention the discovery of holomorphic Morse inequalities, systematic applications of L² estimates with singular hermitian metrics, and a much improved understanding of Monge-Ampère equations and of singularities of plurisuharmonic functions. My first goal will be to investigate the Green-Griffiths-Lang conjecture asserting that an entire curve drawn in a variety of general type is algebraically degenerate. The subject is intimately related to important questions concerning Diophantine equations, especially higher dimensional generalizations of Faltings' theorem - the so-called Vojta program. One can rely here on a breakthrough I made in 2010, showing that all such entire curves must satisfy algebraic differential equations. A second closely related area of research of this project is the analysis of the structure of projective or compact Kähler manifolds. It can be seen as a generalization of the classification theory of surfaces by Kodaira, and of the more recent results for dimension 3 (Kawamata, Kollár, Mori, Shokurov, ...) to other dimensions. My plan is to combine powerful recent results obtained on the duality of positive cohomology cones with an analysis of the instability of the tangent bundle, i.e. of the Harder-Narasimhan filtration. On these ground-breaking questions, I intend to go much further and to enhance my national and international collaborations. These subjects already attract many young researchers and postdocs throughout the world, and the grant could be used to create even stronger interactions.
Max ERC Funding
1 809 345 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym ALLEGRO
Project Active large-scale learning for visual recognition
Researcher (PI) Cordelia Schmid
Host Institution (HI) INSTITUT NATIONAL DE RECHERCHE ENINFORMATIQUE ET AUTOMATIQUE
Call Details Advanced Grant (AdG), PE6, ERC-2012-ADG_20120216
Summary A massive and ever growing amount of digital image and video content
is available today, on sites such as
Flickr and YouTube, in audiovisual archives such as those of BBC and
INA, and in personal collections. In most cases, it comes with
additional information, such as text, audio or other metadata, that forms a
rather sparse and noisy, yet rich and diverse source of annotation,
ideally suited to emerging weakly supervised and active machine
learning technology. The ALLEGRO project will take visual recognition
to the next level by using this largely untapped source of data to
automatically learn visual models. The main research objective of
our project is the development of new algorithms and computer software
capable of autonomously exploring evolving data collections, selecting
the relevant information, and determining the visual models most
appropriate for different object, scene, and activity categories. An
emphasis will be put on learning visual models from video, a
particularly rich source of information, and on the representation of
human activities, one of today's most challenging problems in computer
vision. Although this project addresses fundamental research
issues, it is expected to result in significant advances in
high-impact applications that range from visual mining of the Web and
automated annotation and organization of family photo and video albums
to large-scale information retrieval in television archives.
Summary
A massive and ever growing amount of digital image and video content
is available today, on sites such as
Flickr and YouTube, in audiovisual archives such as those of BBC and
INA, and in personal collections. In most cases, it comes with
additional information, such as text, audio or other metadata, that forms a
rather sparse and noisy, yet rich and diverse source of annotation,
ideally suited to emerging weakly supervised and active machine
learning technology. The ALLEGRO project will take visual recognition
to the next level by using this largely untapped source of data to
automatically learn visual models. The main research objective of
our project is the development of new algorithms and computer software
capable of autonomously exploring evolving data collections, selecting
the relevant information, and determining the visual models most
appropriate for different object, scene, and activity categories. An
emphasis will be put on learning visual models from video, a
particularly rich source of information, and on the representation of
human activities, one of today's most challenging problems in computer
vision. Although this project addresses fundamental research
issues, it is expected to result in significant advances in
high-impact applications that range from visual mining of the Web and
automated annotation and organization of family photo and video albums
to large-scale information retrieval in television archives.
Max ERC Funding
2 493 322 €
Duration
Start date: 2013-04-01, End date: 2019-03-31
Project acronym ALMA
Project Attosecond Control of Light and Matter
Researcher (PI) Anne L'huillier
Host Institution (HI) LUNDS UNIVERSITET
Call Details Advanced Grant (AdG), PE2, ERC-2008-AdG
Summary Attosecond light pulses are generated when an intense laser interacts with a gas target. These pulses are not only short, enabling the study of electronic processes at their natural time scale, but also coherent. The vision of this proposal is to extend temporal coherent control concepts to a completely new regime of time and energy, combining (i) ultrashort pulses (ii) broadband excitation (iii) high photon energy, allowing scientists to reach not only valence but also inner shells in atoms and molecules, and, when needed, (iv) high spatial resolution. We want to explore how elementary electronic processes in atoms, molecules and more complex systems can be controlled by using well designed sequences of attosecond pulses. The research project proposed is organized into four parts: 1. Attosecond control of light leading to controlled sequences of attosecond pulses We will develop techniques to generate sequences of attosecond pulses with a variable number of pulses and controlled carrier-envelope-phase variation between consecutive pulses. 2. Attosecond control of electronic processes in atoms and molecules We will investigate the dynamics and coherence of phenomena induced by attosecond excitation of electron wave packets in various systems and we will explore how they can be controlled by a controlled sequence of ultrashort pulses. 3. Intense attosecond sources to reach the nonlinear regime We will optimize attosecond light sources in a systematic way, including amplification of the radiation by injecting a free electron laser. This will open up the possibility to develop nonlinear measurement and control schemes. 4. Attosecond control in more complex systems, including high spatial resolution We will develop ultrafast microscopy techniques, in order to obtain meaningful temporal information in surface and solid state physics. Two directions will be explored, digital in line microscopic holography and photoemission electron microscopy.
Summary
Attosecond light pulses are generated when an intense laser interacts with a gas target. These pulses are not only short, enabling the study of electronic processes at their natural time scale, but also coherent. The vision of this proposal is to extend temporal coherent control concepts to a completely new regime of time and energy, combining (i) ultrashort pulses (ii) broadband excitation (iii) high photon energy, allowing scientists to reach not only valence but also inner shells in atoms and molecules, and, when needed, (iv) high spatial resolution. We want to explore how elementary electronic processes in atoms, molecules and more complex systems can be controlled by using well designed sequences of attosecond pulses. The research project proposed is organized into four parts: 1. Attosecond control of light leading to controlled sequences of attosecond pulses We will develop techniques to generate sequences of attosecond pulses with a variable number of pulses and controlled carrier-envelope-phase variation between consecutive pulses. 2. Attosecond control of electronic processes in atoms and molecules We will investigate the dynamics and coherence of phenomena induced by attosecond excitation of electron wave packets in various systems and we will explore how they can be controlled by a controlled sequence of ultrashort pulses. 3. Intense attosecond sources to reach the nonlinear regime We will optimize attosecond light sources in a systematic way, including amplification of the radiation by injecting a free electron laser. This will open up the possibility to develop nonlinear measurement and control schemes. 4. Attosecond control in more complex systems, including high spatial resolution We will develop ultrafast microscopy techniques, in order to obtain meaningful temporal information in surface and solid state physics. Two directions will be explored, digital in line microscopic holography and photoemission electron microscopy.
Max ERC Funding
2 250 000 €
Duration
Start date: 2008-12-01, End date: 2013-11-30
Project acronym AlmaCrypt
Project Algorithmic and Mathematical Cryptology
Researcher (PI) Antoine Joux
Host Institution (HI) SORBONNE UNIVERSITE
Call Details Advanced Grant (AdG), PE6, ERC-2014-ADG
Summary Cryptology is a foundation of information security in the digital world. Today's internet is protected by a form of cryptography based on complexity theoretic hardness assumptions. Ideally, they should be strong to ensure security and versatile to offer a wide range of functionalities and allow efficient implementations. However, these assumptions are largely untested and internet security could be built on sand.
The main ambition of Almacrypt is to remedy this issue by challenging the assumptions through an advanced algorithmic analysis.
In particular, this proposal questions the two pillars of public-key encryption: factoring and discrete logarithms. Recently, the PI contributed to show that in some cases, the discrete logarithm problem is considerably weaker than previously assumed. A main objective is to ponder the security of other cases of the discrete logarithm problem, including elliptic curves, and of factoring. We will study the generalization of the recent techniques and search for new algorithmic options with comparable or better efficiency.
We will also study hardness assumptions based on codes and subset-sum, two candidates for post-quantum cryptography. We will consider the applicability of recent algorithmic and mathematical techniques to the resolution of the corresponding putative hard problems, refine the analysis of the algorithms and design new algorithm tools.
Cryptology is not limited to the above assumptions: other hard problems have been proposed to aim at post-quantum security and/or to offer extra functionalities. Should the security of these other assumptions become critical, they would be added to Almacrypt's scope. They could also serve to demonstrate other applications of our algorithmic progress.
In addition to its scientific goal, Almacrypt also aims at seeding a strengthened research community dedicated to algorithmic and mathematical cryptology.
--
Summary
Cryptology is a foundation of information security in the digital world. Today's internet is protected by a form of cryptography based on complexity theoretic hardness assumptions. Ideally, they should be strong to ensure security and versatile to offer a wide range of functionalities and allow efficient implementations. However, these assumptions are largely untested and internet security could be built on sand.
The main ambition of Almacrypt is to remedy this issue by challenging the assumptions through an advanced algorithmic analysis.
In particular, this proposal questions the two pillars of public-key encryption: factoring and discrete logarithms. Recently, the PI contributed to show that in some cases, the discrete logarithm problem is considerably weaker than previously assumed. A main objective is to ponder the security of other cases of the discrete logarithm problem, including elliptic curves, and of factoring. We will study the generalization of the recent techniques and search for new algorithmic options with comparable or better efficiency.
We will also study hardness assumptions based on codes and subset-sum, two candidates for post-quantum cryptography. We will consider the applicability of recent algorithmic and mathematical techniques to the resolution of the corresponding putative hard problems, refine the analysis of the algorithms and design new algorithm tools.
Cryptology is not limited to the above assumptions: other hard problems have been proposed to aim at post-quantum security and/or to offer extra functionalities. Should the security of these other assumptions become critical, they would be added to Almacrypt's scope. They could also serve to demonstrate other applications of our algorithmic progress.
In addition to its scientific goal, Almacrypt also aims at seeding a strengthened research community dedicated to algorithmic and mathematical cryptology.
--
Max ERC Funding
2 403 125 €
Duration
Start date: 2016-01-01, End date: 2021-12-31
Project acronym ALOGLADIS
Project From Anderson localization to Bose, Fermi and spin glasses in disordered ultracold gases
Researcher (PI) Laurent Sanchez-Palencia
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE2, ERC-2010-StG_20091028
Summary The field of disordered quantum gases is developing rapidly. Dramatic progress has been achieved recently and first experimental observation of one-dimensional Anderson localization (AL) of matterwaves has been reported using Bose-Einstein condensates in controlled disorder (in our group at Institut d'Optique and at LENS; Nature, 2008). This dramatic success results from joint theoretical and experimental efforts, we have contributed to. Most importantly, it opens unprecedented routes to pursue several outstanding challenges in the multidisciplinary field of disordered systems, which, after fifty years of Anderson localization, is more active than ever.
This theoretical project aims at further developing the emerging field of disordered quantum gases towards novel challenges. Our aim is twofold. First, we will propose and analyze schemes where experiments on ultracold atoms can address unsolved issues: AL in dimensions higher than one, effects of inter-atomic interactions on AL, strongly-correlated disordered gases and quantum simulators for spin systems (spin glasses). Second, by taking into account specific features of ultracold atoms, beyond standard toy-models, we will raise and study new questions which have not been addressed before (eg long-range correlations of speckle potentials, finite-size effects, controlled interactions). Both aspects would open new frontiers to disordered quantum gases and offer new possibilities to shed new light on highly debated issues.
Our main concerns are thus to (i) study situations relevant to experiments, (ii) develop new approaches, applicable to ultracold atoms, (iii) identify key observables, and (iv) propose new challenging experiments. In this project, we will benefit from the original situation of our theory team: It is independent but forms part of a larger group (lead by A. Aspect), which is a world-leader in experiments on disordered quantum gases, we have already developed close collaborative relationship with.
Summary
The field of disordered quantum gases is developing rapidly. Dramatic progress has been achieved recently and first experimental observation of one-dimensional Anderson localization (AL) of matterwaves has been reported using Bose-Einstein condensates in controlled disorder (in our group at Institut d'Optique and at LENS; Nature, 2008). This dramatic success results from joint theoretical and experimental efforts, we have contributed to. Most importantly, it opens unprecedented routes to pursue several outstanding challenges in the multidisciplinary field of disordered systems, which, after fifty years of Anderson localization, is more active than ever.
This theoretical project aims at further developing the emerging field of disordered quantum gases towards novel challenges. Our aim is twofold. First, we will propose and analyze schemes where experiments on ultracold atoms can address unsolved issues: AL in dimensions higher than one, effects of inter-atomic interactions on AL, strongly-correlated disordered gases and quantum simulators for spin systems (spin glasses). Second, by taking into account specific features of ultracold atoms, beyond standard toy-models, we will raise and study new questions which have not been addressed before (eg long-range correlations of speckle potentials, finite-size effects, controlled interactions). Both aspects would open new frontiers to disordered quantum gases and offer new possibilities to shed new light on highly debated issues.
Our main concerns are thus to (i) study situations relevant to experiments, (ii) develop new approaches, applicable to ultracold atoms, (iii) identify key observables, and (iv) propose new challenging experiments. In this project, we will benefit from the original situation of our theory team: It is independent but forms part of a larger group (lead by A. Aspect), which is a world-leader in experiments on disordered quantum gases, we have already developed close collaborative relationship with.
Max ERC Funding
985 200 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym ALPAM
Project Atomic-Level Physics of Advanced Materials
Researcher (PI) Börje Johansson
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Advanced Grant (AdG), PE5, ERC-2008-AdG
Summary Most of the technological materials have been developed by very expensive and cumbersome trial and error methods. On the other hand, computer based theoretical design of advanced materials is an area where rapid and extensive developments are taking place. Within my group new theoretical tools have now been established which are extremely well suited to the study of complex materials. In this approach basic quantum mechanical theories are used to describe fundamental properties of alloys and compounds. The utilization of such calculations to investigate possible optimizations of certain key properties represents a major departure from the traditional design philosophy. The purpose of my project is to build up a new competence in the field of computer-aided simulations of advanced materials. The main goal will be to achieve a deep understanding of the behaviour of complex metallic systems under equilibrium and non-equilibrium conditions at the atomic level by studying their electronic, magnetic and atomic structure using the most modern and advanced computational methods. This will enable us to establish a set of materials parameters and composition-structure-property relations that are needed for materials optimization.
The research will be focused on fundamental technological properties related to defects in advanced metallic alloys (high-performance steels, superalloys, and refractory, energy related and geochemical materials) and alloy phases (solid solutions, intermetallic compounds), which will be studied by means of parameter free atomistic simulations combined with continuum modelling. As a first example, we will study the Fe-Cr system, which is of great interest to industry as well as in connection to nuclear waste. The Fe-Cr-Ni system will form another large group of materials under the aegis of this project. Special emphasis will also be placed on those Fe-alloys which exist under extreme conditions and are possible candidates for the Earth core.
Summary
Most of the technological materials have been developed by very expensive and cumbersome trial and error methods. On the other hand, computer based theoretical design of advanced materials is an area where rapid and extensive developments are taking place. Within my group new theoretical tools have now been established which are extremely well suited to the study of complex materials. In this approach basic quantum mechanical theories are used to describe fundamental properties of alloys and compounds. The utilization of such calculations to investigate possible optimizations of certain key properties represents a major departure from the traditional design philosophy. The purpose of my project is to build up a new competence in the field of computer-aided simulations of advanced materials. The main goal will be to achieve a deep understanding of the behaviour of complex metallic systems under equilibrium and non-equilibrium conditions at the atomic level by studying their electronic, magnetic and atomic structure using the most modern and advanced computational methods. This will enable us to establish a set of materials parameters and composition-structure-property relations that are needed for materials optimization.
The research will be focused on fundamental technological properties related to defects in advanced metallic alloys (high-performance steels, superalloys, and refractory, energy related and geochemical materials) and alloy phases (solid solutions, intermetallic compounds), which will be studied by means of parameter free atomistic simulations combined with continuum modelling. As a first example, we will study the Fe-Cr system, which is of great interest to industry as well as in connection to nuclear waste. The Fe-Cr-Ni system will form another large group of materials under the aegis of this project. Special emphasis will also be placed on those Fe-alloys which exist under extreme conditions and are possible candidates for the Earth core.
Max ERC Funding
2 000 000 €
Duration
Start date: 2009-03-01, End date: 2014-02-28
Project acronym AltCheM
Project In vivo functional screens to decipher mechanisms of stochastically- and mutationally-induced chemoresistance in Acute Myeloid Leukemia
Researcher (PI) Alexandre PUISSANT
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Starting Grant (StG), LS4, ERC-2017-STG
Summary Acute Myeloid Leukemia (AML), the most common leukemia diagnosed in adults, represents the paradigm of resistance to front-line therapies in hematology. Indeed, AML is so genetically complex that only few targeted therapies are currently tested in this disease and chemotherapy remains the only standard treatment for AML since the past four decades. Despite an initial sustained remission achieved by chemotherapeutic agents, almost all patients relapse with a chemoresistant minimal residual disease (MRD). The goal of my proposal is to characterize the still poorly understood biological mechanisms underlying persistence and emergence of MRD.
MRD is the consequence of the re-expansion of leukemia-initiating cells that are intrinsically more resistant to chemotherapy. This cell fraction may be stochastically more prone to survive front-line therapy regardless of their mutational status (the stochastic model), or genetically predetermined to resist by virtue of a collection of chemoprotective mutations (the mutational model).
I have already generated in mice, by consecutive rounds of chemotherapy, a stochastic MLL-AF9-driven chemoresistance model that I examined by RNA-sequencing. I will pursue the comprehensive cell autonomous and cell non-autonomous characterization of this chemoresistant AML disease using whole-exome and ChIP-sequencing.
To establish a mutationally-induced chemoresistant mouse model, I will conduct an innovative in vivo screen using pooled mutant open reading frame and shRNA libraries in order to predict which combinations of mutations, among those already known in AML, actively promote chemoresistance.
Finally, by combining genomic profiling and in vivo shRNA screening experiments, I will decipher the molecular mechanisms and identify the functional effectors of these two modes of resistance. Ultimately, I will then be able to firmly establish the fundamental relevance of the stochastic and/or the mutational model of chemoresistance for MRD genesis.
Summary
Acute Myeloid Leukemia (AML), the most common leukemia diagnosed in adults, represents the paradigm of resistance to front-line therapies in hematology. Indeed, AML is so genetically complex that only few targeted therapies are currently tested in this disease and chemotherapy remains the only standard treatment for AML since the past four decades. Despite an initial sustained remission achieved by chemotherapeutic agents, almost all patients relapse with a chemoresistant minimal residual disease (MRD). The goal of my proposal is to characterize the still poorly understood biological mechanisms underlying persistence and emergence of MRD.
MRD is the consequence of the re-expansion of leukemia-initiating cells that are intrinsically more resistant to chemotherapy. This cell fraction may be stochastically more prone to survive front-line therapy regardless of their mutational status (the stochastic model), or genetically predetermined to resist by virtue of a collection of chemoprotective mutations (the mutational model).
I have already generated in mice, by consecutive rounds of chemotherapy, a stochastic MLL-AF9-driven chemoresistance model that I examined by RNA-sequencing. I will pursue the comprehensive cell autonomous and cell non-autonomous characterization of this chemoresistant AML disease using whole-exome and ChIP-sequencing.
To establish a mutationally-induced chemoresistant mouse model, I will conduct an innovative in vivo screen using pooled mutant open reading frame and shRNA libraries in order to predict which combinations of mutations, among those already known in AML, actively promote chemoresistance.
Finally, by combining genomic profiling and in vivo shRNA screening experiments, I will decipher the molecular mechanisms and identify the functional effectors of these two modes of resistance. Ultimately, I will then be able to firmly establish the fundamental relevance of the stochastic and/or the mutational model of chemoresistance for MRD genesis.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym aLzINK
Project Alzheimer's disease and Zinc: the missing link ?
Researcher (PI) Christelle Sandrine Florence HUREAU-SABATER
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE5, ERC-2014-STG
Summary Alzheimer's disease (AD) is one of the most serious diseases mankind is now facing as its social and economical impacts are increasing fastly. AD is very complex and the amyloid-β (Aβ) peptide as well as metallic ions (mainly copper and zinc) have been linked to its aetiology. While the deleterious impact of Cu is widely acknowledged, intervention of Zn is certain but still needs to be figured out.
The main objective of the present proposal, which is strongly anchored in the bio-inorganic chemistry field at interface with spectroscopy and biochemistry, is to design, synthesize and study new drug candidates (ligands L) capable of (i) targeting Cu(II) bound to Aβ within the synaptic cleft, where Zn is co-localized and ultimately to develop Zn-driven Cu(II) removal from Aβ and (ii) disrupting the aberrant Cu(II)-Aβ interactions involved in ROS production and Aβ aggregation, two deleterious events in AD. The drug candidates will thus have high Cu(II) over Zn selectively to preserve the crucial physiological role of Zn in the neurotransmission process. Zn is always underestimated (if not completely neglected) in current therapeutic approaches targeting Cu(II) despite the known interference of Zn with Cu(II) binding.
To reach this objective, it is absolutely necessary to first understand the metal ions trafficking issues in presence of Aβ alone at a molecular level (i.e. without the drug candidates).This includes: (i) determination of Zn binding site to Aβ, impact on Aβ aggregation and cell toxicity, (ii) determination of the mutual influence of Zn and Cu to their coordination to Aβ, impact on Aβ aggregation, ROS production and cell toxicity.
Methods used will span from organic synthesis to studies of neuronal model cells, with a major contribution of a wide panel of spectroscopic techniques including NMR, EPR, mass spectrometry, fluorescence, UV-Vis, circular-dichroism, X-ray absorption spectroscopy...
Summary
Alzheimer's disease (AD) is one of the most serious diseases mankind is now facing as its social and economical impacts are increasing fastly. AD is very complex and the amyloid-β (Aβ) peptide as well as metallic ions (mainly copper and zinc) have been linked to its aetiology. While the deleterious impact of Cu is widely acknowledged, intervention of Zn is certain but still needs to be figured out.
The main objective of the present proposal, which is strongly anchored in the bio-inorganic chemistry field at interface with spectroscopy and biochemistry, is to design, synthesize and study new drug candidates (ligands L) capable of (i) targeting Cu(II) bound to Aβ within the synaptic cleft, where Zn is co-localized and ultimately to develop Zn-driven Cu(II) removal from Aβ and (ii) disrupting the aberrant Cu(II)-Aβ interactions involved in ROS production and Aβ aggregation, two deleterious events in AD. The drug candidates will thus have high Cu(II) over Zn selectively to preserve the crucial physiological role of Zn in the neurotransmission process. Zn is always underestimated (if not completely neglected) in current therapeutic approaches targeting Cu(II) despite the known interference of Zn with Cu(II) binding.
To reach this objective, it is absolutely necessary to first understand the metal ions trafficking issues in presence of Aβ alone at a molecular level (i.e. without the drug candidates).This includes: (i) determination of Zn binding site to Aβ, impact on Aβ aggregation and cell toxicity, (ii) determination of the mutual influence of Zn and Cu to their coordination to Aβ, impact on Aβ aggregation, ROS production and cell toxicity.
Methods used will span from organic synthesis to studies of neuronal model cells, with a major contribution of a wide panel of spectroscopic techniques including NMR, EPR, mass spectrometry, fluorescence, UV-Vis, circular-dichroism, X-ray absorption spectroscopy...
Max ERC Funding
1 499 948 €
Duration
Start date: 2015-03-01, End date: 2020-02-29
Project acronym AMIMOS
Project Agile MIMO Systems for Communications, Biomedicine, and Defense
Researcher (PI) Bjorn Ottersten
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary This proposal targets the emerging frontier research field of multiple-input multiple-output (MIMO) systems along with several innovative and somewhat unconventional applications of such systems. The use of arrays of transmitters and receivers will have a profound impact on future medical imaging/therapy systems, radar systems, and radio communication networks. Multiple transmitters provide a tremendous versatility and allow waveforms to be adapted temporally and spatially to environmental conditions. This is useful for individually tailored illumination of human tissue in biomedical imaging or ultrasound therapy. In radar systems, multiple transmit beams can be formed simultaneously via separate waveform designs allowing accurate target classification. In a wireless communication system, multiple communication signals can be directed to one or more users at the same time on the same frequency carrier. In addition, multiple receivers can be used in the above applications to provide increased detection performance, interference rejection, and improved estimation accuracy. The joint modelling, analysis, and design of these multidimensional transmit and receive schemes form the core of this research proposal. Ultimately, our research aims at developing the fundamental tools that will allow the design of wireless communication systems with an order-of-magnitude higher capacity at a lower cost than today; of ultrasound therapy systems maximizing delivered power while reducing treatment duration and unwanted illumination; and of distributed aperture multi-beam radars allowing more effective target location, identification, and classification. Europe has several successful industries that are active in biomedical imaging/therapy, radar systems, and wireless communications. The future success of these sectors critically depends on the ability to innovate and integrate new technology.
Summary
This proposal targets the emerging frontier research field of multiple-input multiple-output (MIMO) systems along with several innovative and somewhat unconventional applications of such systems. The use of arrays of transmitters and receivers will have a profound impact on future medical imaging/therapy systems, radar systems, and radio communication networks. Multiple transmitters provide a tremendous versatility and allow waveforms to be adapted temporally and spatially to environmental conditions. This is useful for individually tailored illumination of human tissue in biomedical imaging or ultrasound therapy. In radar systems, multiple transmit beams can be formed simultaneously via separate waveform designs allowing accurate target classification. In a wireless communication system, multiple communication signals can be directed to one or more users at the same time on the same frequency carrier. In addition, multiple receivers can be used in the above applications to provide increased detection performance, interference rejection, and improved estimation accuracy. The joint modelling, analysis, and design of these multidimensional transmit and receive schemes form the core of this research proposal. Ultimately, our research aims at developing the fundamental tools that will allow the design of wireless communication systems with an order-of-magnitude higher capacity at a lower cost than today; of ultrasound therapy systems maximizing delivered power while reducing treatment duration and unwanted illumination; and of distributed aperture multi-beam radars allowing more effective target location, identification, and classification. Europe has several successful industries that are active in biomedical imaging/therapy, radar systems, and wireless communications. The future success of these sectors critically depends on the ability to innovate and integrate new technology.
Max ERC Funding
1 872 720 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym AMPERE
Project Accounting for Metallicity, Polarization of the Electrolyte, and Redox reactions in computational Electrochemistry
Researcher (PI) Mathieu Eric Salanne
Host Institution (HI) SORBONNE UNIVERSITE
Call Details Consolidator Grant (CoG), PE4, ERC-2017-COG
Summary Applied electrochemistry plays a key role in many technologies, such as batteries, fuel cells, supercapacitors or solar cells. It is therefore at the core of many research programs all over the world. Yet, fundamental electrochemical investigations remain scarce. In particular, electrochemistry is among the fields for which the gap between theory and experiment is the largest. From the computational point of view, there is no molecular dynamics (MD) software devoted to the simulation of electrochemical systems while other fields such as biochemistry (GROMACS) or material science (LAMMPS) have dedicated tools. This is due to the difficulty of accounting for complex effects arising from (i) the degree of metallicity of the electrode (i.e. from semimetals to perfect conductors), (ii) the mutual polarization occurring at the electrode/electrolyte interface and (iii) the redox reactivity through explicit electron transfers. Current understanding therefore relies on standard theories that derive from an inaccurate molecular-scale picture. My objective is to fill this gap by introducing a whole set of new methods for simulating electrochemical systems. They will be provided to the computational electrochemistry community as a cutting-edge MD software adapted to supercomputers. First applications will aim at the discovery of new electrolytes for energy storage. Here I will focus on (1) ‘‘water-in-salts’’ to understand why these revolutionary liquids enable much higher voltage than conventional solutions (2) redox reactions inside a nanoporous electrode to support the development of future capacitive energy storage devices. These selected applications are timely and rely on collaborations with leading experimental partners. The results are expected to shed an unprecedented light on the importance of polarization effects on the structure and the reactivity of electrode/electrolyte interfaces, establishing MD as a prominent tool for solving complex electrochemistry problems.
Summary
Applied electrochemistry plays a key role in many technologies, such as batteries, fuel cells, supercapacitors or solar cells. It is therefore at the core of many research programs all over the world. Yet, fundamental electrochemical investigations remain scarce. In particular, electrochemistry is among the fields for which the gap between theory and experiment is the largest. From the computational point of view, there is no molecular dynamics (MD) software devoted to the simulation of electrochemical systems while other fields such as biochemistry (GROMACS) or material science (LAMMPS) have dedicated tools. This is due to the difficulty of accounting for complex effects arising from (i) the degree of metallicity of the electrode (i.e. from semimetals to perfect conductors), (ii) the mutual polarization occurring at the electrode/electrolyte interface and (iii) the redox reactivity through explicit electron transfers. Current understanding therefore relies on standard theories that derive from an inaccurate molecular-scale picture. My objective is to fill this gap by introducing a whole set of new methods for simulating electrochemical systems. They will be provided to the computational electrochemistry community as a cutting-edge MD software adapted to supercomputers. First applications will aim at the discovery of new electrolytes for energy storage. Here I will focus on (1) ‘‘water-in-salts’’ to understand why these revolutionary liquids enable much higher voltage than conventional solutions (2) redox reactions inside a nanoporous electrode to support the development of future capacitive energy storage devices. These selected applications are timely and rely on collaborations with leading experimental partners. The results are expected to shed an unprecedented light on the importance of polarization effects on the structure and the reactivity of electrode/electrolyte interfaces, establishing MD as a prominent tool for solving complex electrochemistry problems.
Max ERC Funding
1 588 769 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
