Project acronym ABC
Project Targeting Multidrug Resistant Cancer
Researcher (PI) Gergely Szakacs
Host Institution (HI) TERMESZETTUDOMANYI KUTATOKOZPONT
Country Hungary
Call Details Starting Grant (StG), LS7, ERC-2010-StG_20091118
Summary Despite considerable advances in drug discovery, resistance to anticancer chemotherapy confounds the effective treatment of patients. Cancer cells can acquire broad cross-resistance to mechanistically and structurally unrelated drugs. P-glycoprotein (Pgp) actively extrudes many types of drugs from cancer cells, thereby conferring resistance to those agents. The central tenet of my work is that Pgp, a universally accepted biomarker of drug resistance, should in addition be considered as a molecular target of multidrug-resistant (MDR) cancer cells. Successful targeting of MDR cells would reduce the tumor burden and would also enable the elimination of ABC transporter-overexpressing cancer stem cells that are responsible for the replenishment of tumors. The proposed project is based on the following observations:
- First, by using a pharmacogenomic approach, I have revealed the hidden vulnerability of MDRcells (Szakács et al. 2004, Cancer Cell 6, 129-37);
- Second, I have identified a series of MDR-selective compounds with increased toxicity toPgp-expressing cells
(Turk et al.,Cancer Res, 2009. 69(21));
- Third, I have shown that MDR-selective compounds can be used to prevent theemergence of MDR (Ludwig, Szakács et al. 2006, Cancer Res 66, 4808-15);
- Fourth, we have generated initial pharmacophore models for cytotoxicity and MDR-selectivity (Hall et al. 2009, J Med Chem 52, 3191-3204).
I propose a comprehensive series of studies that will address thefollowing critical questions:
- First, what is the scope of MDR-selective compounds?
- Second, what is their mechanism of action?
- Third, what is the optimal therapeutic modality?
Extensive biological, pharmacological and bioinformatic analyses will be utilized to address four major specific aims. These aims address basic questions concerning the physiology of MDR ABC transporters in determining the mechanism of action of MDR-selective compounds, setting the stage for a fresh therapeutic approach that may eventually translate into improved patient care.
Summary
Despite considerable advances in drug discovery, resistance to anticancer chemotherapy confounds the effective treatment of patients. Cancer cells can acquire broad cross-resistance to mechanistically and structurally unrelated drugs. P-glycoprotein (Pgp) actively extrudes many types of drugs from cancer cells, thereby conferring resistance to those agents. The central tenet of my work is that Pgp, a universally accepted biomarker of drug resistance, should in addition be considered as a molecular target of multidrug-resistant (MDR) cancer cells. Successful targeting of MDR cells would reduce the tumor burden and would also enable the elimination of ABC transporter-overexpressing cancer stem cells that are responsible for the replenishment of tumors. The proposed project is based on the following observations:
- First, by using a pharmacogenomic approach, I have revealed the hidden vulnerability of MDRcells (Szakács et al. 2004, Cancer Cell 6, 129-37);
- Second, I have identified a series of MDR-selective compounds with increased toxicity toPgp-expressing cells
(Turk et al.,Cancer Res, 2009. 69(21));
- Third, I have shown that MDR-selective compounds can be used to prevent theemergence of MDR (Ludwig, Szakács et al. 2006, Cancer Res 66, 4808-15);
- Fourth, we have generated initial pharmacophore models for cytotoxicity and MDR-selectivity (Hall et al. 2009, J Med Chem 52, 3191-3204).
I propose a comprehensive series of studies that will address thefollowing critical questions:
- First, what is the scope of MDR-selective compounds?
- Second, what is their mechanism of action?
- Third, what is the optimal therapeutic modality?
Extensive biological, pharmacological and bioinformatic analyses will be utilized to address four major specific aims. These aims address basic questions concerning the physiology of MDR ABC transporters in determining the mechanism of action of MDR-selective compounds, setting the stage for a fresh therapeutic approach that may eventually translate into improved patient care.
Max ERC Funding
1 499 640 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym ATOMKI-PPROCESS
Project Nuclear reaction studies relevant to the astrophysical p-process nucleosynthesis
Researcher (PI) Gyoergy Gyuerky
Host Institution (HI) ATOMMAGKUTATO INTEZET
Country Hungary
Call Details Starting Grant (StG), PE2, ERC-2007-StG
Summary The astrophysical p-process, the stellar production mechanism of the heavy, proton rich isotopes (p-isotopes), is one of the least studied processes in nucleosynthesis. The astrophysical site(s) for the p-process could not yet be clearly identified. In order to reproduce the natural abundances of the p-isotopes, the p-process models must take into account a huge nuclear reaction network. A precise knowledge of the rate of the nuclear reactions in this network is essential for a reliable abundance calculation and for a clear assignment of the astrophysical site(s). For lack of experimental data the nuclear physics inputs for the reaction networks are based on statistical model calculations. These calculations are largely untested in the mass and energy range relevant to the p-process and the uncertainties in the reaction rate values result in a correspondingly uncertain prediction of the p-isotope abundances. Therefore, experiments aiming at the determination of reaction rates for the p-process are of great importance. In this project nuclear reaction cross section measurements will be carried out in the mass and energy range of p-process to check the reliability of the statistical model calculations and to put the p-process models on a more reliable base. The accelerators of the Institute of Nuclear Research in Debrecen, Hungary provide the necessary basis for such studies. The p-process model calculations are especially sensitive to the rates of reactions involving alpha particles and heavy nuclei. Because of technical difficulties, so far there are practically no experimental data available on such reactions and the uncertainty in these reaction rates is presently one of the biggest contributions to the uncertainty of p-isotope abundance calculations. With the help of the ERC grant the alpha-induced reaction cross sections can be measured on heavy isotopes for the first time, which could contribute to a better understanding of the astrophysical p-process.
Summary
The astrophysical p-process, the stellar production mechanism of the heavy, proton rich isotopes (p-isotopes), is one of the least studied processes in nucleosynthesis. The astrophysical site(s) for the p-process could not yet be clearly identified. In order to reproduce the natural abundances of the p-isotopes, the p-process models must take into account a huge nuclear reaction network. A precise knowledge of the rate of the nuclear reactions in this network is essential for a reliable abundance calculation and for a clear assignment of the astrophysical site(s). For lack of experimental data the nuclear physics inputs for the reaction networks are based on statistical model calculations. These calculations are largely untested in the mass and energy range relevant to the p-process and the uncertainties in the reaction rate values result in a correspondingly uncertain prediction of the p-isotope abundances. Therefore, experiments aiming at the determination of reaction rates for the p-process are of great importance. In this project nuclear reaction cross section measurements will be carried out in the mass and energy range of p-process to check the reliability of the statistical model calculations and to put the p-process models on a more reliable base. The accelerators of the Institute of Nuclear Research in Debrecen, Hungary provide the necessary basis for such studies. The p-process model calculations are especially sensitive to the rates of reactions involving alpha particles and heavy nuclei. Because of technical difficulties, so far there are practically no experimental data available on such reactions and the uncertainty in these reaction rates is presently one of the biggest contributions to the uncertainty of p-isotope abundance calculations. With the help of the ERC grant the alpha-induced reaction cross sections can be measured on heavy isotopes for the first time, which could contribute to a better understanding of the astrophysical p-process.
Max ERC Funding
750 000 €
Duration
Start date: 2008-07-01, End date: 2013-06-30
Project acronym Aware
Project Aiding Antibiotic Development with Deep Analysis of Resistance Evolution
Researcher (PI) Csaba PAL
Host Institution (HI) SZEGEDI BIOLOGIAI KUTATOKOZPONT
Country Hungary
Call Details Proof of Concept (PoC), ERC-2019-PoC
Summary The inappropriate use of antibiotics has rapidly accelerated antibiotic resistance evolution in pathogens, rendering several existing antibiotics ineffective. However, many pharmaceutical companies have discontinued their antibiotic research programs. This is foremost due to the rapid spread of multi-drug resistant bacteria, which makes the commercial success of new antimicrobial drugs unpredictable. Antibiotic developers do not have a toolset to appropriately test antibiotic candidates for resistance evolution. Specifically, in the early phase of drug development, researchers typically identify numerous lead molecules with antimicrobial activities. It would be imperative to estimate the rate of resistance evolution at this early stage of development to all lead candidates in order to choose those that are the least prone to resistance evolution. The applicant and his team developed a technology, they term DIvERGE. It enables the exploration of resistance in a manner that is more comprehensive and effective than any other currently used approach. In a nutshell, DIvERGE finds resistance mutations in antibiotic resistance genes at an unprecedentedly comprehensive manner . DIvERGE offers a unique opportunity for pharmaceutical companies to identify antimicrobial agents with potentially longer clinical efficacy at an early stage of drug development. Thus, the goal is simple and bold – to identify antibiotics that are less prone to resistance development. Here the team aims to commercialise the technology.
Summary
The inappropriate use of antibiotics has rapidly accelerated antibiotic resistance evolution in pathogens, rendering several existing antibiotics ineffective. However, many pharmaceutical companies have discontinued their antibiotic research programs. This is foremost due to the rapid spread of multi-drug resistant bacteria, which makes the commercial success of new antimicrobial drugs unpredictable. Antibiotic developers do not have a toolset to appropriately test antibiotic candidates for resistance evolution. Specifically, in the early phase of drug development, researchers typically identify numerous lead molecules with antimicrobial activities. It would be imperative to estimate the rate of resistance evolution at this early stage of development to all lead candidates in order to choose those that are the least prone to resistance evolution. The applicant and his team developed a technology, they term DIvERGE. It enables the exploration of resistance in a manner that is more comprehensive and effective than any other currently used approach. In a nutshell, DIvERGE finds resistance mutations in antibiotic resistance genes at an unprecedentedly comprehensive manner . DIvERGE offers a unique opportunity for pharmaceutical companies to identify antimicrobial agents with potentially longer clinical efficacy at an early stage of drug development. Thus, the goal is simple and bold – to identify antibiotics that are less prone to resistance development. Here the team aims to commercialise the technology.
Max ERC Funding
150 000 €
Duration
Start date: 2019-11-01, End date: 2021-10-31
Project acronym AZIDRUGS
Project Molecular tattooing: azidated compounds pave the path towards light-activated covalent inhibitors for drug development
Researcher (PI) Andras MaLNaSI-CSIZMADIA
Host Institution (HI) DRUGMOTIF KORLATOLT FELELOSSEGU TARSASAG
Country Hungary
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary Until now the greatest limitation in the application of bioactive compounds has been the inability of confining them specifically to single cells or subcellular components within the organism. Our recently synthesized photoactive forms of bioactive compounds solve this problem. We have developed effective chemical synthesis methods to attach an azide group to small drug-like molecules, which makes them photoactive. As a result, light irradiation can induce the covalent attachment of these molecules to their target enzymes. By controlling the timing and position of light irradiation it is possible to confine the effect of these molecules in time and space. It is important to emphasize that azidation is the smallest possible modification (adding 3 nitrogen atoms) that makes a compound photoactive and based on our experience it does not alter biological activities of most of the original compounds.
Azidated inhibitors give unprecedented freedom to researchers because the covalent compound-target formations allow them to address questions which could not have been addressed before. Three major advantages are obtained by using azidated compounds 1: determination of small molecule interactome becomes highly effective, especially, the weak interactions can be determined, which was not possible before 2: it improves the pharmacodynamic and pharmacokinetic properties of biological compounds as the covalent attachment prolongs their effect. 3: Recently, we showed that photoactivation can be initiated by two-photon excitation, thereby confining the effect to femtoliter volumes and well-controlled spatial locations. This feature provides unprecedented spatial and temporal control in localizing the effect of biological compounds in cellular and subcelluler level in in vivo experiments. By realizing the need for photoactive compounds, the PI has established Drugmotif Ltd., a spin-off company, which provides the customers with special azidated chemicals for high-tech research.
Summary
Until now the greatest limitation in the application of bioactive compounds has been the inability of confining them specifically to single cells or subcellular components within the organism. Our recently synthesized photoactive forms of bioactive compounds solve this problem. We have developed effective chemical synthesis methods to attach an azide group to small drug-like molecules, which makes them photoactive. As a result, light irradiation can induce the covalent attachment of these molecules to their target enzymes. By controlling the timing and position of light irradiation it is possible to confine the effect of these molecules in time and space. It is important to emphasize that azidation is the smallest possible modification (adding 3 nitrogen atoms) that makes a compound photoactive and based on our experience it does not alter biological activities of most of the original compounds.
Azidated inhibitors give unprecedented freedom to researchers because the covalent compound-target formations allow them to address questions which could not have been addressed before. Three major advantages are obtained by using azidated compounds 1: determination of small molecule interactome becomes highly effective, especially, the weak interactions can be determined, which was not possible before 2: it improves the pharmacodynamic and pharmacokinetic properties of biological compounds as the covalent attachment prolongs their effect. 3: Recently, we showed that photoactivation can be initiated by two-photon excitation, thereby confining the effect to femtoliter volumes and well-controlled spatial locations. This feature provides unprecedented spatial and temporal control in localizing the effect of biological compounds in cellular and subcelluler level in in vivo experiments. By realizing the need for photoactive compounds, the PI has established Drugmotif Ltd., a spin-off company, which provides the customers with special azidated chemicals for high-tech research.
Max ERC Funding
150 000 €
Duration
Start date: 2013-12-01, End date: 2014-11-30
Project acronym BEHAVIORAL THEORY
Project Behavioral Theory and Economic Applications
Researcher (PI) Botond Koszegi
Host Institution (HI) KOZEP-EUROPAI EGYETEM
Country Hungary
Call Details Starting Grant (StG), SH1, ERC-2012-StG_20111124
Summary "This proposal outlines projects to develop robust and portable theories studying the impact of psychological phenomena in economic settings. The proposed work falls in three broad research agendas.
My first main agenda is to formally model and economically apply a simple observation: that when people make decisions, they do not focus equally on all attributes of their available options, and overweight the attributes they focus on. I will build a set of portable models of focusing in attribute-based choice and risky choice based on the idea that a person focuses more on attributes in which her options differ more. I will also use the framework to develop novel, focus-based, theories of intertemporal choice and social preferences, as well as analyze the implications of focusing for product design, principal-agent relationships, and other economic questions.
My second main agenda is to explore some implications for market outcomes, welfare, and policy of the possibility that consumers misperceive certain aspects of products. I will investigate the circumstances that facilitate the profitable deception of consumers; firms' incentives for ""innovating"" deceptive products, including novel financial products aimed at exploiting investors; how firms' ability to distinguish naive and sophisticated consumers affects the consequences of deception; whether learning on the part of consumers will help them to avoid making mistakes; and how regulators and other observers can detect consumer mistakes from market data.
Two further projects apply the model of reference-dependent utility I have developed in earlier work to understand the pricing and advertising behavior of firms. I will also aim to disseminate some of my work, along with other cutting-edge research in psychology and economics, in a Journal of Economic Literature survey on ""Behavioral Contract Theory."""
Summary
"This proposal outlines projects to develop robust and portable theories studying the impact of psychological phenomena in economic settings. The proposed work falls in three broad research agendas.
My first main agenda is to formally model and economically apply a simple observation: that when people make decisions, they do not focus equally on all attributes of their available options, and overweight the attributes they focus on. I will build a set of portable models of focusing in attribute-based choice and risky choice based on the idea that a person focuses more on attributes in which her options differ more. I will also use the framework to develop novel, focus-based, theories of intertemporal choice and social preferences, as well as analyze the implications of focusing for product design, principal-agent relationships, and other economic questions.
My second main agenda is to explore some implications for market outcomes, welfare, and policy of the possibility that consumers misperceive certain aspects of products. I will investigate the circumstances that facilitate the profitable deception of consumers; firms' incentives for ""innovating"" deceptive products, including novel financial products aimed at exploiting investors; how firms' ability to distinguish naive and sophisticated consumers affects the consequences of deception; whether learning on the part of consumers will help them to avoid making mistakes; and how regulators and other observers can detect consumer mistakes from market data.
Two further projects apply the model of reference-dependent utility I have developed in earlier work to understand the pricing and advertising behavior of firms. I will also aim to disseminate some of my work, along with other cutting-edge research in psychology and economics, in a Journal of Economic Literature survey on ""Behavioral Contract Theory."""
Max ERC Funding
1 275 448 €
Duration
Start date: 2012-11-01, End date: 2018-10-31
Project acronym BRAINCANNABINOIDS
Project Understanding the molecular blueprint and functional complexity of the endocannabinoid metabolome in the brain
Researcher (PI) Istvan Katona
Host Institution (HI) KIRSERLETI ORVOSTUDOMANYI KUTATOINTEZET
Country Hungary
Call Details Starting Grant (StG), LS5, ERC-2009-StG
Summary We and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.
Summary
We and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.
Max ERC Funding
1 638 000 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym CholAminCo
Project Synergy and antagonism of cholinergic and dopaminergic systems in associative learning
Researcher (PI) Balazs Gyoergy HANGYA
Host Institution (HI) KIRSERLETI ORVOSTUDOMANYI KUTATOINTEZET
Country Hungary
Call Details Starting Grant (StG), LS5, ERC-2016-STG
Summary Neuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimer’s. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two “classical” neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.
Summary
Neuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimer’s. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two “classical” neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.
Max ERC Funding
1 499 463 €
Duration
Start date: 2017-05-01, End date: 2022-10-31
Project acronym COGTOM
Project Cognitive tomography of mental representations
Researcher (PI) Mate Miklos LENGYEL
Host Institution (HI) KOZEP-EUROPAI EGYETEM
Country Hungary
Call Details Consolidator Grant (CoG), SH4, ERC-2016-COG
Summary Internal models are fundamental to our understanding of how the mind constructs percepts, makes decisions, controls movements, and interacts with others. Yet, we lack principled quantitative methods to systematically estimate internal models from observable behaviour, and current approaches for discovering their mental representations remain heuristic and piecemeal. I propose to develop a set of novel 'doubly Bayesian' data analytical methods, using state-of-the-art Bayesian statistical and machine learning techniques to infer humans' internal models formalised as prior distributions in Bayesian models of cognition. This approach, cognitive tomography, takes a series of behavioural observations, each of which in itself may have very limited information content, and accumulates a detailed reconstruction of the internal model based on these observations. I also propose a set of stringent, quantifiable criteria which will be systematically applied at each step of the proposed work to rigorously assess the success of our approach. These methodological advances will allow us to track how the structured, task-general internal models that are so fundamental to humans' superior cognitive abilities, change over time as a result of decay, interference, and learning. We will apply cognitive tomography to a variety of experimental data sets, collected by our collaborators, in paradigms ranging from perceptual learning, through visual and motor structure learning, to social and concept learning. These analyses will allow us to conclusively and quantitatively test our central hypothesis that, rather than simply changing along a single 'memory strength' dimension, internal models typically change via complex and consistent patterns of transformations along multiple dimensions simultaneously. To facilitate the widespread use of our methods, we will release and support off-the-shelf usable implementations of our algorithms together with synthetic and real test data sets.
Summary
Internal models are fundamental to our understanding of how the mind constructs percepts, makes decisions, controls movements, and interacts with others. Yet, we lack principled quantitative methods to systematically estimate internal models from observable behaviour, and current approaches for discovering their mental representations remain heuristic and piecemeal. I propose to develop a set of novel 'doubly Bayesian' data analytical methods, using state-of-the-art Bayesian statistical and machine learning techniques to infer humans' internal models formalised as prior distributions in Bayesian models of cognition. This approach, cognitive tomography, takes a series of behavioural observations, each of which in itself may have very limited information content, and accumulates a detailed reconstruction of the internal model based on these observations. I also propose a set of stringent, quantifiable criteria which will be systematically applied at each step of the proposed work to rigorously assess the success of our approach. These methodological advances will allow us to track how the structured, task-general internal models that are so fundamental to humans' superior cognitive abilities, change over time as a result of decay, interference, and learning. We will apply cognitive tomography to a variety of experimental data sets, collected by our collaborators, in paradigms ranging from perceptual learning, through visual and motor structure learning, to social and concept learning. These analyses will allow us to conclusively and quantitatively test our central hypothesis that, rather than simply changing along a single 'memory strength' dimension, internal models typically change via complex and consistent patterns of transformations along multiple dimensions simultaneously. To facilitate the widespread use of our methods, we will release and support off-the-shelf usable implementations of our algorithms together with synthetic and real test data sets.
Max ERC Funding
1 179 462 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym COLLMOT
Project Complex structure and dynamics of collective motion
Researcher (PI) Tamas Vicsek
Host Institution (HI) EOTVOS LORAND TUDOMANYEGYETEM
Country Hungary
Call Details Advanced Grant (AdG), PE3, ERC-2008-AdG
Summary Collective behaviour is a widespread phenomenon in nature and technology making it a very important subject to study in various contexts. The main goal we intend to achieve in our multidisciplinary research is the identification and documentation of new unifying principles describing the essential aspects of collective motion, being one of the most relevant and spectacular manifestations of collective behaviour. We shall carry out novel type of experiments, design models that are both simple and realistic enough to reproduce the observations and develop concepts for a better interpretation of the complexity of systems consisting of many organisms and such non-living objects as interacting robots. We plan to study systems ranging from cultures of migrating tissue cells through flocks of birds to collectively moving devices. The interrelation of these systems will be considered in order to deepen the understanding of the main patterns of group motion in both living and non-living systems by learning about the similar phenomena in the two domains of nature. Thus, we plan to understand the essential ingredients of flocking of birds by building collectively moving unmanned aerial vehicles while, in turn, high resolution spatiotemporal GPS data of pigeon flocks will be used to make helpful conclusions for the best designs for swarms of robots. In particular, we shall construct and build a set of vehicles that will be capable, for the first time, to exhibit flocking behaviour in the three-dimensional space. The methods we shall adopt will range from approaches used in statistical physics and network theory to various new techniques in cell biology and collective robotics. All this will be based on numerous prior results (both ours and others) published in leading interdisciplinary journals. The planned research will have the potential of leading to ground breaking results with significant implications in various fields of science and technology.
Summary
Collective behaviour is a widespread phenomenon in nature and technology making it a very important subject to study in various contexts. The main goal we intend to achieve in our multidisciplinary research is the identification and documentation of new unifying principles describing the essential aspects of collective motion, being one of the most relevant and spectacular manifestations of collective behaviour. We shall carry out novel type of experiments, design models that are both simple and realistic enough to reproduce the observations and develop concepts for a better interpretation of the complexity of systems consisting of many organisms and such non-living objects as interacting robots. We plan to study systems ranging from cultures of migrating tissue cells through flocks of birds to collectively moving devices. The interrelation of these systems will be considered in order to deepen the understanding of the main patterns of group motion in both living and non-living systems by learning about the similar phenomena in the two domains of nature. Thus, we plan to understand the essential ingredients of flocking of birds by building collectively moving unmanned aerial vehicles while, in turn, high resolution spatiotemporal GPS data of pigeon flocks will be used to make helpful conclusions for the best designs for swarms of robots. In particular, we shall construct and build a set of vehicles that will be capable, for the first time, to exhibit flocking behaviour in the three-dimensional space. The methods we shall adopt will range from approaches used in statistical physics and network theory to various new techniques in cell biology and collective robotics. All this will be based on numerous prior results (both ours and others) published in leading interdisciplinary journals. The planned research will have the potential of leading to ground breaking results with significant implications in various fields of science and technology.
Max ERC Funding
1 248 000 €
Duration
Start date: 2009-03-01, End date: 2015-02-28
Project acronym COOPAIRENT
Project Cooper pairs as a source of entanglement
Researcher (PI) Szabolcs Csonka
Host Institution (HI) BUDAPESTI MUSZAKI ES GAZDASAGTUDOMANYI EGYETEM
Country Hungary
Call Details Starting Grant (StG), PE3, ERC-2010-StG_20091028
Summary Entanglement and non-locality are spectacular fundamentals of quantum mechanics and basic resources of future quantum computation algorithms. Electronic entanglement has attracted increasing attention during the last years. The electron spin as a purely quantum mechanical two level system has been put forward as a promising candidate for storing quantum information in solid state. Recently, great progress has been achieved in manipulation and read-out of quantum dot based spin Qubits. However, electron spin is also suitable to transfer quantum information, since mobile electrons can be coherently transmitted in a solid state device preserving the spin information. Thus, electron spin could provide a general platform for on-chip quantum computation and information processing.
Although several theoretical concepts have been worked out to address spin entangled mobile electrons, the absence of an entangler device has not allowed their realization so far. The aim of the present proposal is to overcome this experimental challenge and explore the entanglement of spatially separated electron pairs. Superconductors provide a natural source of entanglement, because their ground-state is composed of Cooper pairs in a spin-singlet state. However, the splitting of the Cooper pairs into separate electrons has to be enforced, which has been very recently realized by the applicant in two quantum dot Y-junction. This Y-junction will be used as a central building block to split Cooper pairs in a controlled fashion and the non-local nature of spin and charge correlations will be addressed in various device configurations.
Our research project will lead to a fundamental understanding of the production, manipulation and detection of spin entangled mobile electron pairs, thus it will significantly extend the frontiers of quantum coherence and opens a new horizon in the field of on-chip quantum information technologies.
Summary
Entanglement and non-locality are spectacular fundamentals of quantum mechanics and basic resources of future quantum computation algorithms. Electronic entanglement has attracted increasing attention during the last years. The electron spin as a purely quantum mechanical two level system has been put forward as a promising candidate for storing quantum information in solid state. Recently, great progress has been achieved in manipulation and read-out of quantum dot based spin Qubits. However, electron spin is also suitable to transfer quantum information, since mobile electrons can be coherently transmitted in a solid state device preserving the spin information. Thus, electron spin could provide a general platform for on-chip quantum computation and information processing.
Although several theoretical concepts have been worked out to address spin entangled mobile electrons, the absence of an entangler device has not allowed their realization so far. The aim of the present proposal is to overcome this experimental challenge and explore the entanglement of spatially separated electron pairs. Superconductors provide a natural source of entanglement, because their ground-state is composed of Cooper pairs in a spin-singlet state. However, the splitting of the Cooper pairs into separate electrons has to be enforced, which has been very recently realized by the applicant in two quantum dot Y-junction. This Y-junction will be used as a central building block to split Cooper pairs in a controlled fashion and the non-local nature of spin and charge correlations will be addressed in various device configurations.
Our research project will lead to a fundamental understanding of the production, manipulation and detection of spin entangled mobile electron pairs, thus it will significantly extend the frontiers of quantum coherence and opens a new horizon in the field of on-chip quantum information technologies.
Max ERC Funding
1 496 112 €
Duration
Start date: 2011-02-01, End date: 2016-10-31
