Project acronym 0MSPIN
Project Spintronics based on relativistic phenomena in systems with zero magnetic moment
Researcher (PI) Tomas Jungwirth
Host Institution (HI) FYZIKALNI USTAV AV CR V.V.I
Country Czechia
Call Details Advanced Grant (AdG), PE3, ERC-2010-AdG_20100224
Summary The 0MSPIN project consists of an extensive integrated theoretical, experimental and device development programme of research opening a radical new approach to spintronics. Spintronics has the potential to supersede existing storage and memory applications, and to provide alternatives to current CMOS technology. Ferromagnetic matels used in all current spintronics applications may make it impractical to realise the full potential of spintronics. Metals are unsuitable for transistor and information processing applications, for opto-electronics, or for high-density integration. The 0MSPIN project aims to remove the major road-block holding back the development of spintronics in a radical way: removing the ferromagnetic component from key active parts or from the whole of the spintronic devices. This approach is based on exploiting the combination of exchange and spin-orbit coupling phenomena and material systems with zero macroscopic moment. The goal of the 0MSPIN is to provide a new paradigm by which spintronics can enter the realms of conventional semiconductors in both fundamental condensed matter research and in information technologies. In the central part of the proposal, the research towards this goal is embedded within a materials science project whose aim is to introduce into physics and microelectronics an entirely new class of semiconductors. 0MSPIN seeks to exploit three classes of material systems: (1) Antiferromagnetic bi-metallic 3d-5d alloys (e.g. Mn2Au). (2) Antiferromagnetic I-II-V semiconductors (e.g. LiMnAs). (3) Non-magnetic spin-orbit coupled semiconductors with injected spin-polarized currents (e.g. 2D III-V structures). Proof of concept devices operating at high temperatures will be fabricated to show-case new functionalities offered by zero-moment systems for sensing and memory applications, information processing, and opto-electronics technologies.
Summary
The 0MSPIN project consists of an extensive integrated theoretical, experimental and device development programme of research opening a radical new approach to spintronics. Spintronics has the potential to supersede existing storage and memory applications, and to provide alternatives to current CMOS technology. Ferromagnetic matels used in all current spintronics applications may make it impractical to realise the full potential of spintronics. Metals are unsuitable for transistor and information processing applications, for opto-electronics, or for high-density integration. The 0MSPIN project aims to remove the major road-block holding back the development of spintronics in a radical way: removing the ferromagnetic component from key active parts or from the whole of the spintronic devices. This approach is based on exploiting the combination of exchange and spin-orbit coupling phenomena and material systems with zero macroscopic moment. The goal of the 0MSPIN is to provide a new paradigm by which spintronics can enter the realms of conventional semiconductors in both fundamental condensed matter research and in information technologies. In the central part of the proposal, the research towards this goal is embedded within a materials science project whose aim is to introduce into physics and microelectronics an entirely new class of semiconductors. 0MSPIN seeks to exploit three classes of material systems: (1) Antiferromagnetic bi-metallic 3d-5d alloys (e.g. Mn2Au). (2) Antiferromagnetic I-II-V semiconductors (e.g. LiMnAs). (3) Non-magnetic spin-orbit coupled semiconductors with injected spin-polarized currents (e.g. 2D III-V structures). Proof of concept devices operating at high temperatures will be fabricated to show-case new functionalities offered by zero-moment systems for sensing and memory applications, information processing, and opto-electronics technologies.
Max ERC Funding
1 938 000 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym 5HT-OPTOGENETICS
Project Optogenetic Analysis of Serotonin Function in the Mammalian Brain
Researcher (PI) Zachary Mainen
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Country Portugal
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Summary
Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Max ERC Funding
2 318 636 €
Duration
Start date: 2010-07-01, End date: 2015-12-31
Project acronym 5HTCircuits
Project Modulation of cortical circuits and predictive neural coding by serotonin
Researcher (PI) Zachary Mainen
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Country Portugal
Call Details Advanced Grant (AdG), LS5, ERC-2014-ADG
Summary Serotonin (5-HT) is a central neuromodulator and a major target of therapeutic psychoactive drugs, but relatively little is known about how it modulates information processing in neural circuits. The theory of predictive coding postulates that the brain combines raw bottom-up sensory information with top-down information from internal models to make perceptual inferences about the world. We hypothesize, based on preliminary data and prior literature, that a role of 5-HT in this process is to report prediction errors and promote the suppression and weakening of erroneous internal models. We propose that it does this by inhibiting top-down relative to bottom-up cortical information flow. To test this hypothesis, we propose a set of experiments in mice performing olfactory perceptual tasks. Our specific aims are: (1) We will test whether 5-HT neurons encode sensory prediction errors. (2) We will test their causal role in using predictive cues to guide perceptual decisions. (3) We will characterize how 5-HT influences the encoding of sensory information by neuronal populations in the olfactory cortex and identify the underlying circuitry. (4) Finally, we will map the effects of 5-HT across the whole brain and use this information to target further causal manipulations to specific 5-HT projections. We accomplish these aims using state-of-the-art optogenetic, electrophysiological and imaging techniques (including 9.4T small-animal functional magnetic resonance imaging) as well as psychophysical tasks amenable to quantitative analysis and computational theory. Together, these experiments will tackle multiple facets of an important general computational question, bringing to bear an array of cutting-edge technologies to address with unprecedented mechanistic detail how 5-HT impacts neural coding and perceptual decision-making.
Summary
Serotonin (5-HT) is a central neuromodulator and a major target of therapeutic psychoactive drugs, but relatively little is known about how it modulates information processing in neural circuits. The theory of predictive coding postulates that the brain combines raw bottom-up sensory information with top-down information from internal models to make perceptual inferences about the world. We hypothesize, based on preliminary data and prior literature, that a role of 5-HT in this process is to report prediction errors and promote the suppression and weakening of erroneous internal models. We propose that it does this by inhibiting top-down relative to bottom-up cortical information flow. To test this hypothesis, we propose a set of experiments in mice performing olfactory perceptual tasks. Our specific aims are: (1) We will test whether 5-HT neurons encode sensory prediction errors. (2) We will test their causal role in using predictive cues to guide perceptual decisions. (3) We will characterize how 5-HT influences the encoding of sensory information by neuronal populations in the olfactory cortex and identify the underlying circuitry. (4) Finally, we will map the effects of 5-HT across the whole brain and use this information to target further causal manipulations to specific 5-HT projections. We accomplish these aims using state-of-the-art optogenetic, electrophysiological and imaging techniques (including 9.4T small-animal functional magnetic resonance imaging) as well as psychophysical tasks amenable to quantitative analysis and computational theory. Together, these experiments will tackle multiple facets of an important general computational question, bringing to bear an array of cutting-edge technologies to address with unprecedented mechanistic detail how 5-HT impacts neural coding and perceptual decision-making.
Max ERC Funding
2 486 074 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym ACCELERATES
Project Acceleration in Extreme Shocks: from the microphysics to laboratory and astrophysics scenarios
Researcher (PI) Luis Miguel De Oliveira E Silva
Host Institution (HI) INSTITUTO SUPERIOR TECNICO
Country Portugal
Call Details Advanced Grant (AdG), PE2, ERC-2010-AdG_20100224
Summary What is the origin of cosmic rays, what are the dominant acceleration mechanisms in relativistic shocks, how do cosmic rays self-consistently influence the shock dynamics, how are relativistic collisionless shocks formed are longstanding scientific questions, closely tied to extreme plasma physics processes, and where a close interplay between the micro-instabilities and the global dynamics is critical.
Relativistic shocks are closely connected with the propagation of intense streams of particles pervasive in many astrophysical scenarios. The possibility of exciting shocks in the laboratory will also be available very soon with multi-PW lasers or intense relativistic particle beams.
Computational modeling is now established as a prominent research tool, by enabling the fully kinetic modeling of these systems for the first time. With the fast paced developments in high performance computing, the time is ripe for a focused research programme on simulation-based studies of relativistic shocks. This proposal therefore focuses on using self-consistent ab initio massively parallel simulations to study the physics of relativistic shocks, bridging the gap between the multidimensional microphysics of shock onset, formation, and propagation and the global system dynamics. Particular focus will be given to the shock acceleration mechanisms and the radiation signatures of the various physical processes, with the goal of solving some of the central questions in plasma/relativistic phenomena in astrophysics and in the laboratory, and opening new avenues between theoretical/massive computational studies, laboratory experiments and astrophysical observations.
Summary
What is the origin of cosmic rays, what are the dominant acceleration mechanisms in relativistic shocks, how do cosmic rays self-consistently influence the shock dynamics, how are relativistic collisionless shocks formed are longstanding scientific questions, closely tied to extreme plasma physics processes, and where a close interplay between the micro-instabilities and the global dynamics is critical.
Relativistic shocks are closely connected with the propagation of intense streams of particles pervasive in many astrophysical scenarios. The possibility of exciting shocks in the laboratory will also be available very soon with multi-PW lasers or intense relativistic particle beams.
Computational modeling is now established as a prominent research tool, by enabling the fully kinetic modeling of these systems for the first time. With the fast paced developments in high performance computing, the time is ripe for a focused research programme on simulation-based studies of relativistic shocks. This proposal therefore focuses on using self-consistent ab initio massively parallel simulations to study the physics of relativistic shocks, bridging the gap between the multidimensional microphysics of shock onset, formation, and propagation and the global system dynamics. Particular focus will be given to the shock acceleration mechanisms and the radiation signatures of the various physical processes, with the goal of solving some of the central questions in plasma/relativistic phenomena in astrophysics and in the laboratory, and opening new avenues between theoretical/massive computational studies, laboratory experiments and astrophysical observations.
Max ERC Funding
1 588 800 €
Duration
Start date: 2011-06-01, End date: 2016-07-31
Project acronym DAMAGECONTROL
Project Tissue Damage Control Regulates The Pathogenesis of Immune Mediated Inflammatory Diseases
Researcher (PI) Miguel Parreira Soares
Host Institution (HI) FUNDACAO CALOUSTE GULBENKIAN
Country Portugal
Call Details Advanced Grant (AdG), LS6, ERC-2011-ADG_20110310
Summary "We propose to study evolutionarily conserved stress-responsive protective mechanisms that limit the extent of tissue damage caused by pathogens or by the innate as well as adaptive immune response elicited by those pathogens, which, without a countervailing response would lead to irreversible tissue damage and disease. We refer to these protective mechanisms as “tissue damage control”, and will argue they are an essential component of immunity that allows the effector mechanisms involved in pathogen clearance to operate without causing disease. This proposal aims at identifying and characterizing the mechanism of action of stress-induced genetic programs conferring tissue damage control and to relate those to the pathogenesis of different immune mediated inflammatory diseases. We hypothesize that these genetic programs share as a common denominator their regulation by a restricted number of evolutionary conserved transcription factors that act as “master regulators” of different protective responses to specific forms of stress. We will use “loss” and “gain” of function approaches targeting these master regulators in mice to characterize their function and identify stress-responsive genes conferring tissue metabolic adaptation, cytoprotection and/or tissue regeneration, all of which are components of tissue damage control. Expression of these master regulators likely impacts the pathogenesis of immune mediated inflammatory conditions, as tested under this proposal for infectious as well as autoimmune-like diseases. This proposal should unveil an essential component of immunity that uncouples pathogen clearance from tissue damage and disease, namely tissue damage control, providing new therapeutic targets to suppress the pathogenesis of a broad range of immune mediated inflammatory diseases."
Summary
"We propose to study evolutionarily conserved stress-responsive protective mechanisms that limit the extent of tissue damage caused by pathogens or by the innate as well as adaptive immune response elicited by those pathogens, which, without a countervailing response would lead to irreversible tissue damage and disease. We refer to these protective mechanisms as “tissue damage control”, and will argue they are an essential component of immunity that allows the effector mechanisms involved in pathogen clearance to operate without causing disease. This proposal aims at identifying and characterizing the mechanism of action of stress-induced genetic programs conferring tissue damage control and to relate those to the pathogenesis of different immune mediated inflammatory diseases. We hypothesize that these genetic programs share as a common denominator their regulation by a restricted number of evolutionary conserved transcription factors that act as “master regulators” of different protective responses to specific forms of stress. We will use “loss” and “gain” of function approaches targeting these master regulators in mice to characterize their function and identify stress-responsive genes conferring tissue metabolic adaptation, cytoprotection and/or tissue regeneration, all of which are components of tissue damage control. Expression of these master regulators likely impacts the pathogenesis of immune mediated inflammatory conditions, as tested under this proposal for infectious as well as autoimmune-like diseases. This proposal should unveil an essential component of immunity that uncouples pathogen clearance from tissue damage and disease, namely tissue damage control, providing new therapeutic targets to suppress the pathogenesis of a broad range of immune mediated inflammatory diseases."
Max ERC Funding
2 306 197 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym InPairs
Project In Silico Pair Plasmas: from ultra intense lasers to relativistic astrophysics in the laboratory
Researcher (PI) LuIs Miguel DE OLIVEIRA E SILVA
Host Institution (HI) INSTITUTO SUPERIOR TECNICO
Country Portugal
Call Details Advanced Grant (AdG), PE2, ERC-2015-AdG
Summary How do extreme electromagnetic fields modify the dynamics of matter? Will quantum electrodynamics effects be important at the focus of an ultra intense laser? How are the magnetospheres of compact stellar remnants formed, and can we capture the physics of these environments in the laboratory? These are all longstanding questions with an overarching connection to extreme plasma physics.
Electron-positron pair plasmas are pervasive in all these scenarios. Highly nonlinear phenomena such as QED processes, magnetogenesis, radiation, field dynamics in complex geometries, and particle acceleration, are all linked with the collective dynamics of pair plasmas through mechanisms that remain poorly understood.
Building on our state-of-the-art models, on the availability of enormous computational power, and on our recent transformative discoveries on ab initio modelling of plasmas under extreme conditions, the time is ripe to answer these questions in silico. InPairs aims to understand the multidimensional dynamics of electron-positron plasmas under extreme laboratory and astrophysical fields, to determine the signatures of the radiative processes on pair plasmas, and to identify the physics of the magnetospheres of compact stellar remnants, focusing on the electrodynamics of pulsars, that can be mimicked in laboratory experiments using ultra high intensity lasers and charged particle beams.
This proposal relies on massively parallel simulations to bridge the gap, for the first time, between the pair plasma creation mechanisms, the collective multidimensional microphysics, and their global dynamics in complex geometries associated with laboratory and astrophysical systems. Emphasis will be given to detectable signatures e.g. radiation and accelerated particles, with the ultimate goal of solving some of the central questions in extreme plasma physics, thus opening new connections between computational studies, laboratory experiments, and relativistic plasma astrophysics.
Summary
How do extreme electromagnetic fields modify the dynamics of matter? Will quantum electrodynamics effects be important at the focus of an ultra intense laser? How are the magnetospheres of compact stellar remnants formed, and can we capture the physics of these environments in the laboratory? These are all longstanding questions with an overarching connection to extreme plasma physics.
Electron-positron pair plasmas are pervasive in all these scenarios. Highly nonlinear phenomena such as QED processes, magnetogenesis, radiation, field dynamics in complex geometries, and particle acceleration, are all linked with the collective dynamics of pair plasmas through mechanisms that remain poorly understood.
Building on our state-of-the-art models, on the availability of enormous computational power, and on our recent transformative discoveries on ab initio modelling of plasmas under extreme conditions, the time is ripe to answer these questions in silico. InPairs aims to understand the multidimensional dynamics of electron-positron plasmas under extreme laboratory and astrophysical fields, to determine the signatures of the radiative processes on pair plasmas, and to identify the physics of the magnetospheres of compact stellar remnants, focusing on the electrodynamics of pulsars, that can be mimicked in laboratory experiments using ultra high intensity lasers and charged particle beams.
This proposal relies on massively parallel simulations to bridge the gap, for the first time, between the pair plasma creation mechanisms, the collective multidimensional microphysics, and their global dynamics in complex geometries associated with laboratory and astrophysical systems. Emphasis will be given to detectable signatures e.g. radiation and accelerated particles, with the ultimate goal of solving some of the central questions in extreme plasma physics, thus opening new connections between computational studies, laboratory experiments, and relativistic plasma astrophysics.
Max ERC Funding
1 951 124 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym StAdvInn
Project Strengthening adaptive immunity via innate immunity: enhancing the CD8 T cell response by using the NKG2D ligand expressed in a herpesvirus vector
Researcher (PI) Stipan Jonjic
Host Institution (HI) SVEUCILISTE U RIJECI, MEDICINSKI FAKULTET
Country Croatia
Call Details Advanced Grant (AdG), LS6, ERC-2012-ADG_20120314
Summary CD8+ T cells play a key role in the control of infections by intracellular pathogens. Recently, several top-notch studies provided ample evidence that NK cells are important in the regulation of CD8+ T cell response. NKG2D is an activating NK cell receptor which plays a role in the adaptive immune response by co-stimulating CD8+ T cells. Due to unique pattern of immune response, live attenuated CMVs are attractive candidates as vaccine vectors for a number of clinically relevant infections. The main idea behind this project stems from our preliminary data which suggest that a recombinant CMV vector expressing NKG2D ligand has a tremendous potential for subverting viral immunoevasion and boosting the efficiency of CD8 T cell response.
During the project we plan to systematically investigate the impact of all major innate immunity players on the CD8+ T cell response. A special focus will be given in obtaining new knowledge on the maintenance of memory CD8+ T cells during latent infection. This study will also provide novel insights on the role of NKG2D in both NK and T cell immunity. In order to test our hypothesis in vivo, we will employ state-of-the-art technology used in herpesvirus genetics coupled with high-end immune monitoring. Ultimately, we will translate our results to a human CMV vector, in order to gauge the impact of NKG2D signaling on immune response in a humanized mouse model.
We believe that the significance of the proposed study is enormous since stimulating CD8+ T cells has been widely recognized as a method of choice for vaccine development. There are relatively large number of pathogens for which the immunity acquired post-infection does not fully shelter against re-infection and disease. Therefore, we are in a desperate need for vaccines which offer superior protection compared to the one following natural infection. This study will provide groundbreaking information which will set the stage for the development of new vaccines and vaccine vectors.
Summary
CD8+ T cells play a key role in the control of infections by intracellular pathogens. Recently, several top-notch studies provided ample evidence that NK cells are important in the regulation of CD8+ T cell response. NKG2D is an activating NK cell receptor which plays a role in the adaptive immune response by co-stimulating CD8+ T cells. Due to unique pattern of immune response, live attenuated CMVs are attractive candidates as vaccine vectors for a number of clinically relevant infections. The main idea behind this project stems from our preliminary data which suggest that a recombinant CMV vector expressing NKG2D ligand has a tremendous potential for subverting viral immunoevasion and boosting the efficiency of CD8 T cell response.
During the project we plan to systematically investigate the impact of all major innate immunity players on the CD8+ T cell response. A special focus will be given in obtaining new knowledge on the maintenance of memory CD8+ T cells during latent infection. This study will also provide novel insights on the role of NKG2D in both NK and T cell immunity. In order to test our hypothesis in vivo, we will employ state-of-the-art technology used in herpesvirus genetics coupled with high-end immune monitoring. Ultimately, we will translate our results to a human CMV vector, in order to gauge the impact of NKG2D signaling on immune response in a humanized mouse model.
We believe that the significance of the proposed study is enormous since stimulating CD8+ T cells has been widely recognized as a method of choice for vaccine development. There are relatively large number of pathogens for which the immunity acquired post-infection does not fully shelter against re-infection and disease. Therefore, we are in a desperate need for vaccines which offer superior protection compared to the one following natural infection. This study will provide groundbreaking information which will set the stage for the development of new vaccines and vaccine vectors.
Max ERC Funding
1 754 897 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
