Project acronym Brain circRNAs
Project Rounding the circle: Unravelling the biogenesis, function and mechanism of action of circRNAs in the Drosophila brain.
Researcher (PI) Sebastian Kadener
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Consolidator Grant (CoG), LS5, ERC-2014-CoG
Summary Tight regulation of RNA metabolism is essential for normal brain function. This includes co and post-transcriptional regulation, which are extremely prevalent in neurons. Recently, circular RNAs (circRNAs), a highly abundant new type of regulatory non-coding RNA have been found across the animal kingdom. Two of these RNAs have been shown to act as miRNA sponges but no function is known for the thousands of other circRNAs, indicating the existence of a widespread layer of previously unknown gene regulation.
The present proposal aims to comprehensively determine the role and mode of actions of circRNAs in gene expression and RNA metabolism in the fly brain. We will do so by studying their biogenesis, transport, and mechanism of action, as well as by determining the roles of circRNAs in neuronal function and behaviour. Briefly, we will: 1) identify factors involved in the biogenesis, localization, and stabilization of circRNAs; 2) determine neuro-developmental, molecular, neural and behavioural phenotypes associated with down or up regulation of specific circRNAs; 3) study the molecular mechanisms of action of circRNAs: identify circRNAs that work as miRNA sponges and determine whether circRNAs can encode proteins or act as signalling molecules and 4) perform mechanistic studies in order to determine cause-effect relationships between circRNA function and brain physiology and behaviour.
The present proposal will reveal the key pathways by which circRNAs control gene expression and influence neuronal function and behaviour. Therefore it will be one of the pioneer works in the study of this new and important area of research, which we predict will fundamentally transform the study of gene expression regulation in the brain
Summary
Tight regulation of RNA metabolism is essential for normal brain function. This includes co and post-transcriptional regulation, which are extremely prevalent in neurons. Recently, circular RNAs (circRNAs), a highly abundant new type of regulatory non-coding RNA have been found across the animal kingdom. Two of these RNAs have been shown to act as miRNA sponges but no function is known for the thousands of other circRNAs, indicating the existence of a widespread layer of previously unknown gene regulation.
The present proposal aims to comprehensively determine the role and mode of actions of circRNAs in gene expression and RNA metabolism in the fly brain. We will do so by studying their biogenesis, transport, and mechanism of action, as well as by determining the roles of circRNAs in neuronal function and behaviour. Briefly, we will: 1) identify factors involved in the biogenesis, localization, and stabilization of circRNAs; 2) determine neuro-developmental, molecular, neural and behavioural phenotypes associated with down or up regulation of specific circRNAs; 3) study the molecular mechanisms of action of circRNAs: identify circRNAs that work as miRNA sponges and determine whether circRNAs can encode proteins or act as signalling molecules and 4) perform mechanistic studies in order to determine cause-effect relationships between circRNA function and brain physiology and behaviour.
The present proposal will reveal the key pathways by which circRNAs control gene expression and influence neuronal function and behaviour. Therefore it will be one of the pioneer works in the study of this new and important area of research, which we predict will fundamentally transform the study of gene expression regulation in the brain
Max ERC Funding
1 971 750 €
Duration
Start date: 2016-02-01, End date: 2021-01-31
Project acronym CLC
Project Cryptography with Low Complexity
Researcher (PI) Benny Applebaum
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), PE6, ERC-2014-STG
Summary The efficiency of cryptographic constructions is a fundamental question. Theoretically, it is important to understand how much computational resources are needed to guarantee strong notions of security. Practically, highly efficient schemes are always desirable for real-world applications. More generally, the possibility of cryptography with low complexity has wide applications for problems in computational complexity, combinatorial optimization, and computational learning theory.
In this proposal we aim to understand what are the minimal computational resources needed to perform basic cryptographic tasks. In a nutshell, we suggest to focus on three main objectives. First, we would like to get better understanding of the cryptographic hardness of random local functions. Such functions can be computed by highly-efficient circuits and their cryptographic hardness provides a strong and clean formulation for the conjectured average-case hardness of constraint satisfaction problems - a fundamental subject which lies at the core of the theory of computer science. Our second objective is to harness our insights into the hardness of local functions to improve the efficiency of basic cryptographic building blocks such as pseudorandom functions. Finally, our third objective is to expand our theoretical understanding of garbled circuits, study their limitations, and improve their efficiency.
The suggested project can bridge across different regions of computer science such as random combinatorial structures, cryptography, and circuit complexity. It is expected to impact central problems in cryptography, while enriching the general landscape of theoretical computer science.
Summary
The efficiency of cryptographic constructions is a fundamental question. Theoretically, it is important to understand how much computational resources are needed to guarantee strong notions of security. Practically, highly efficient schemes are always desirable for real-world applications. More generally, the possibility of cryptography with low complexity has wide applications for problems in computational complexity, combinatorial optimization, and computational learning theory.
In this proposal we aim to understand what are the minimal computational resources needed to perform basic cryptographic tasks. In a nutshell, we suggest to focus on three main objectives. First, we would like to get better understanding of the cryptographic hardness of random local functions. Such functions can be computed by highly-efficient circuits and their cryptographic hardness provides a strong and clean formulation for the conjectured average-case hardness of constraint satisfaction problems - a fundamental subject which lies at the core of the theory of computer science. Our second objective is to harness our insights into the hardness of local functions to improve the efficiency of basic cryptographic building blocks such as pseudorandom functions. Finally, our third objective is to expand our theoretical understanding of garbled circuits, study their limitations, and improve their efficiency.
The suggested project can bridge across different regions of computer science such as random combinatorial structures, cryptography, and circuit complexity. It is expected to impact central problems in cryptography, while enriching the general landscape of theoretical computer science.
Max ERC Funding
1 265 750 €
Duration
Start date: 2015-05-01, End date: 2021-04-30
Project acronym FOC
Project Foundations of Cryptographic Hardness
Researcher (PI) Iftach Ilan Haitner
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), PE6, ERC-2014-STG
Summary A fundamental research challenge in modern cryptography is understanding the necessary hardness assumptions required to build different cryptographic primitives. Attempts to answer this question have gained tremendous success in the last 20-30 years. Most notably, it was shown that many highly complicated primitives can be based on the mere existence of one-way functions (i.e., easy to compute and hard to invert), while other primitives cannot be based on such functions. This research has yielded fundamental tools and concepts such as randomness extractors and computational notions of entropy. Yet many of the most fundamental questions remain unanswered.
Our first goal is to answer the fundamental question of whether cryptography can be based on the assumption that P not equal NP. Our second and third goals are to build a more efficient symmetric-key cryptographic primitives from one-way functions, and to establish effective methods for security amplification of cryptographic primitives. Succeeding in the second and last goals is likely to have great bearing on the way that we construct the very basic cryptographic primitives. A positive answer for the first question will be considered a dramatic result in the cryptography and computational complexity communities.
To address these goals, it is very useful to understand the relationship between different types and quantities of cryptographic hardness. Such understanding typically involves defining and manipulating different types of computational entropy, and comprehending the power of security reductions. We believe that this research will yield new concepts and techniques, with ramification beyond the realm of foundational cryptography.
Summary
A fundamental research challenge in modern cryptography is understanding the necessary hardness assumptions required to build different cryptographic primitives. Attempts to answer this question have gained tremendous success in the last 20-30 years. Most notably, it was shown that many highly complicated primitives can be based on the mere existence of one-way functions (i.e., easy to compute and hard to invert), while other primitives cannot be based on such functions. This research has yielded fundamental tools and concepts such as randomness extractors and computational notions of entropy. Yet many of the most fundamental questions remain unanswered.
Our first goal is to answer the fundamental question of whether cryptography can be based on the assumption that P not equal NP. Our second and third goals are to build a more efficient symmetric-key cryptographic primitives from one-way functions, and to establish effective methods for security amplification of cryptographic primitives. Succeeding in the second and last goals is likely to have great bearing on the way that we construct the very basic cryptographic primitives. A positive answer for the first question will be considered a dramatic result in the cryptography and computational complexity communities.
To address these goals, it is very useful to understand the relationship between different types and quantities of cryptographic hardness. Such understanding typically involves defining and manipulating different types of computational entropy, and comprehending the power of security reductions. We believe that this research will yield new concepts and techniques, with ramification beyond the realm of foundational cryptography.
Max ERC Funding
1 239 838 €
Duration
Start date: 2015-03-01, End date: 2021-02-28
Project acronym Human Decisions
Project The Neural Determinants of Perceptual Decision Making in the Human Brain
Researcher (PI) Redmond O'connell
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary How do we make reliable decisions given sensory information that is often weak or ambiguous? Current theories center on a brain mechanism whereby sensory evidence is integrated over time into a “decision variable” which triggers the appropriate action upon reaching a criterion. Neural signals fitting this role have been identified in monkey electrophysiology but efforts to study the neural dynamics underpinning human decision making have been hampered by technical challenges associated with non-invasive recording. This proposal builds on a recent paradigm breakthrough made by the applicant that enables parallel tracking of discrete neural signals that can be unambiguously linked to the three key information processing stages necessary for simple perceptual decisions: sensory encoding, decision formation and motor preparation. Chief among these is a freely-evolving decision variable signal which builds at an evidence-dependent rate up to an action-triggering threshold and precisely determines the timing and accuracy of perceptual reports at the single-trial level. This provides an unprecedented neurophysiological window onto the distinct parameters of the human decision process such that the underlying mechanisms of several major behavioral phenomena can finally be investigated. This proposal seeks to develop a systems-level understanding of perceptual decision making in the human brain by tackling three core questions: 1) what are the neural adaptations that allow us to deal with speed pressure and variations in the reliability of the physically presented evidence? 2) What neural mechanism determines our subjective confidence in a decision? and 3) How does aging impact on the distinct neural components underpinning perceptual decision making? Each of the experiments described in this proposal will definitively test key predictions from prominent theoretical models using a combination of temporally precise neurophysiological measurement and psychophysical modelling.
Summary
How do we make reliable decisions given sensory information that is often weak or ambiguous? Current theories center on a brain mechanism whereby sensory evidence is integrated over time into a “decision variable” which triggers the appropriate action upon reaching a criterion. Neural signals fitting this role have been identified in monkey electrophysiology but efforts to study the neural dynamics underpinning human decision making have been hampered by technical challenges associated with non-invasive recording. This proposal builds on a recent paradigm breakthrough made by the applicant that enables parallel tracking of discrete neural signals that can be unambiguously linked to the three key information processing stages necessary for simple perceptual decisions: sensory encoding, decision formation and motor preparation. Chief among these is a freely-evolving decision variable signal which builds at an evidence-dependent rate up to an action-triggering threshold and precisely determines the timing and accuracy of perceptual reports at the single-trial level. This provides an unprecedented neurophysiological window onto the distinct parameters of the human decision process such that the underlying mechanisms of several major behavioral phenomena can finally be investigated. This proposal seeks to develop a systems-level understanding of perceptual decision making in the human brain by tackling three core questions: 1) what are the neural adaptations that allow us to deal with speed pressure and variations in the reliability of the physically presented evidence? 2) What neural mechanism determines our subjective confidence in a decision? and 3) How does aging impact on the distinct neural components underpinning perceptual decision making? Each of the experiments described in this proposal will definitively test key predictions from prominent theoretical models using a combination of temporally precise neurophysiological measurement and psychophysical modelling.
Max ERC Funding
1 382 643 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym JCR
Project Judicial Conflict Resolution: Examining Hybrids of Non-adversarial Justice
Researcher (PI) Michal Alberstein
Host Institution (HI) BAR ILAN UNIVERSITY
Call Details Consolidator Grant (CoG), SH2, ERC-2014-CoG
Summary In the past few decades, the role of judges has changed dramatically and its nature has remained largely unexplored. To date, most cases settle or reach plea-bargaining, and the greater part of judges’ time is spent on managing cases and encouraging parties to reach consensual solutions. Adjudication based on formal rules is a rare phenomenon which judges mostly avoid.
The hypothesis underlying JCR is that the various Conflict Resolution methods which are used outside the courtroom, as alternatives to adjudication, could have a strong and positive influence, both theoretical and practical, on judicial activities inside the courts. Judicial activities may be conceptualised along the lines of generic modes of conflict resolution such as mediation and arbitration. Judicial conflict resolution activity is performed in the shadow of authority and in tension with it, and crosses the boundaries between criminal and civil conflicts. It can be evaluated, studied and improved through criteria which go beyond the prevalent search for efficiency in court administration.
Empirically, JCR will study judicial activities in promoting settlements comparatively from a quantitative and qualitative perspective, by using statistical analysis, in-depth interviews, mapping and framing legal resources, court observations and narrative analysis. Theoretically, JCR will develop a conflict resolution jurisprudence, which prioritises consent over coercion as a leading value for the administration of justice. Prescriptively, JCR will promote a participatory endeavour to build training programs for judges that implement the research findings regarding the judicial role. Following such findings, JCR will also consider generating recommendations to change legal rules, codes of ethics, measures of evaluation, and policy framings. JCR will increase accountability and access to justice by introducing coherence into a mainstream activity of processing legal conflicts.
Summary
In the past few decades, the role of judges has changed dramatically and its nature has remained largely unexplored. To date, most cases settle or reach plea-bargaining, and the greater part of judges’ time is spent on managing cases and encouraging parties to reach consensual solutions. Adjudication based on formal rules is a rare phenomenon which judges mostly avoid.
The hypothesis underlying JCR is that the various Conflict Resolution methods which are used outside the courtroom, as alternatives to adjudication, could have a strong and positive influence, both theoretical and practical, on judicial activities inside the courts. Judicial activities may be conceptualised along the lines of generic modes of conflict resolution such as mediation and arbitration. Judicial conflict resolution activity is performed in the shadow of authority and in tension with it, and crosses the boundaries between criminal and civil conflicts. It can be evaluated, studied and improved through criteria which go beyond the prevalent search for efficiency in court administration.
Empirically, JCR will study judicial activities in promoting settlements comparatively from a quantitative and qualitative perspective, by using statistical analysis, in-depth interviews, mapping and framing legal resources, court observations and narrative analysis. Theoretically, JCR will develop a conflict resolution jurisprudence, which prioritises consent over coercion as a leading value for the administration of justice. Prescriptively, JCR will promote a participatory endeavour to build training programs for judges that implement the research findings regarding the judicial role. Following such findings, JCR will also consider generating recommendations to change legal rules, codes of ethics, measures of evaluation, and policy framings. JCR will increase accountability and access to justice by introducing coherence into a mainstream activity of processing legal conflicts.
Max ERC Funding
1 272 534 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym lightMaterInt
Project Exploiting light and material interaction
Researcher (PI) Anat Levin Keslassy
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), PE6, ERC-2014-STG
Summary The interaction between light and material leads to beautiful visual phenomena that greatly enrich our perception of the world. The ability to measure and model light scattering is central to almost any field of science. However, light transport in rich scenes is a complex process involving a long sequence of scattering events. Computationally modeling, reproducing and acquiring the processes generated so easily by Mother Nature is an extremely challenging task. While several computational models have been proposed, they are all making various simplifying assumptions that cannot capture the full complexity of light transport processes in nature. In the proposed research, we suggest new measurement strategies and new inference algorithms that will allow us to infer more information on light and material interaction.
Specifically, the research will focus on the following tasks: (i) Acquiring internal sub-scattering, and recovering the volumetric structure of partially translucent objects using transient imaging data; (ii) Acquiring external illumination from its reflection on diffused objects; (iii) Exploiting illumination for developing digital light sensitive displays, capable of presenting 3D scenes with spatially varying reflectance properties.
As light scattering is such a fundamental phenomenon, our envisioned new tools have applications in almost any field of science, from astronomy to microscopy, and in medicine. We plan to push the bound on the penetration depth of medical imaging devices, and allow chemists to infer more information on material decomposition through scattering. In earth science we can infer aerosol density from the scattering of sunlight in the atmosphere and ocean, a central challenge in any study of climate and pollution. In addition, we will pursue new technological developments such as light sensitive displays, offering a novel form of immersive visual experience, and new technologies of coded security cameras.
Summary
The interaction between light and material leads to beautiful visual phenomena that greatly enrich our perception of the world. The ability to measure and model light scattering is central to almost any field of science. However, light transport in rich scenes is a complex process involving a long sequence of scattering events. Computationally modeling, reproducing and acquiring the processes generated so easily by Mother Nature is an extremely challenging task. While several computational models have been proposed, they are all making various simplifying assumptions that cannot capture the full complexity of light transport processes in nature. In the proposed research, we suggest new measurement strategies and new inference algorithms that will allow us to infer more information on light and material interaction.
Specifically, the research will focus on the following tasks: (i) Acquiring internal sub-scattering, and recovering the volumetric structure of partially translucent objects using transient imaging data; (ii) Acquiring external illumination from its reflection on diffused objects; (iii) Exploiting illumination for developing digital light sensitive displays, capable of presenting 3D scenes with spatially varying reflectance properties.
As light scattering is such a fundamental phenomenon, our envisioned new tools have applications in almost any field of science, from astronomy to microscopy, and in medicine. We plan to push the bound on the penetration depth of medical imaging devices, and allow chemists to infer more information on material decomposition through scattering. In earth science we can infer aerosol density from the scattering of sunlight in the atmosphere and ocean, a central challenge in any study of climate and pollution. In addition, we will pursue new technological developments such as light sensitive displays, offering a novel form of immersive visual experience, and new technologies of coded security cameras.
Max ERC Funding
1 999 825 €
Duration
Start date: 2015-12-01, End date: 2021-08-31
Project acronym MultiScaleNeurovasc
Project Quantifying the structure-function of the neurovascular interface: from micro-circuits to large-scale functional organization
Researcher (PI) Pablo Blinder
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary Neuronal computations in the brain require a high metabolic budget yet the brain has extremely limited resources; calling for an on-demand, robust supply system to deliver nutrients to active regions. In most cases, neuronal activity results in an increase in blood flow to the active area, a phenomenon called functional hyperaemia. This coupling between neuronal and vascular activtuy underpins the mechanism enabling fMRI to map neuronal activity based on vascular dynamics; further, malfunction of the cellular players involved in coupling is now considered to play a key role in otherwise classically defined neurodegenerative diseases. We lack a concise description of the inner workings of this mechanism and a thorough quantitative description of the neuro-gila-vascular interface; issues that are best addressed by an investigation into the cellular mechanisms, the temporal dynamics and multi-scale spatial organization governing neurovascular coupling. My long-term goal is to provide a unified theory to encapsulate our knowledge on neurovascular coupling. Here, I hypothesize that functional hyperaemia results from the constant integration of vasoactive cues with region-dependent coupling emerging from different neuro-glia-vascular microcircuits, nuances in afferent wiring into vascular contractile elements and/or neuronal activity patterns. I will test this hypothesis with a multi-faceted correlative approach combining: two-photon awake imaging of cellular and vascular dynamics to obtain physiological data unaffected by anaesthetics; super-resolution structural imaging of intact volumes to map the fine details of micro-circuit structure; array-tomography to map in situ the neurovascular signalling machinery and novel optogenic tools to manipulate several of its specific components. I expect to offer a revolutionary mechanistic insight into one of the most basic and fundamental physiological processes behind the structure and function of the brain.
Summary
Neuronal computations in the brain require a high metabolic budget yet the brain has extremely limited resources; calling for an on-demand, robust supply system to deliver nutrients to active regions. In most cases, neuronal activity results in an increase in blood flow to the active area, a phenomenon called functional hyperaemia. This coupling between neuronal and vascular activtuy underpins the mechanism enabling fMRI to map neuronal activity based on vascular dynamics; further, malfunction of the cellular players involved in coupling is now considered to play a key role in otherwise classically defined neurodegenerative diseases. We lack a concise description of the inner workings of this mechanism and a thorough quantitative description of the neuro-gila-vascular interface; issues that are best addressed by an investigation into the cellular mechanisms, the temporal dynamics and multi-scale spatial organization governing neurovascular coupling. My long-term goal is to provide a unified theory to encapsulate our knowledge on neurovascular coupling. Here, I hypothesize that functional hyperaemia results from the constant integration of vasoactive cues with region-dependent coupling emerging from different neuro-glia-vascular microcircuits, nuances in afferent wiring into vascular contractile elements and/or neuronal activity patterns. I will test this hypothesis with a multi-faceted correlative approach combining: two-photon awake imaging of cellular and vascular dynamics to obtain physiological data unaffected by anaesthetics; super-resolution structural imaging of intact volumes to map the fine details of micro-circuit structure; array-tomography to map in situ the neurovascular signalling machinery and novel optogenic tools to manipulate several of its specific components. I expect to offer a revolutionary mechanistic insight into one of the most basic and fundamental physiological processes behind the structure and function of the brain.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-06-01, End date: 2020-05-31
Project acronym NeurogenesisCode
Project Deciphering the role of adult neurogenesis in hippocampal memory codes by optically imaging neuronal activity in freely behaving mice
Researcher (PI) Yaniv Ziv
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary The hippocampal dentate gyrus (DG) is one of the few areas in the adult mammalian brain that exhibits neurogenesis, the continuous generation of new neurons. Much evidence indicates that adult neurogenesis contributes to hippocampal-dependent cognition, but the nature of this contribution remains elusive. I envisioned that the clearest path towards understanding the function of adult neurogenesis would be to reveal the changes that occur in the coding properties of DG neurons throughout their development, and the changes that these neurons impose on neural codes generated by the hippocampus. The study of such coding dynamics requires longitudinal recordings of neuronal ensembles in both the DG and CA1 over periods of weeks, since this is the timescale on which new DG neurons mature. Until recently, however, it has been technically impossible to obtain such data. This urgent need drove me to develop a new method, which allows for the optical recording of Ca2+ dynamics from up to 1,200 of the same genetically defined neurons in the hippocampus of freely behaving mice for periods of months. Here, I propose to combine this method with established tools for manipulation of neurogenesis rates or newborn neuron activity, to determine how neurogenesis contributes to coding dynamics in downstream CA1 while mice repeatedly explore familiar environments or preform a long-term memory task. Furthermore, we will establish time-lapse imaging of Ca2+ dynamics in populations of newborn DG neurons while mice perform tasks that engage the DG, and find how newborn neuron coding properties evolve as a function of their maturation. Our work will advance the understanding of how the hippocampus supports long-term memory by resolving fundamental questions that pertain to a nearly unexplored facet of memory: how memory codes change with time, while their behavioral manifestations persist.
Summary
The hippocampal dentate gyrus (DG) is one of the few areas in the adult mammalian brain that exhibits neurogenesis, the continuous generation of new neurons. Much evidence indicates that adult neurogenesis contributes to hippocampal-dependent cognition, but the nature of this contribution remains elusive. I envisioned that the clearest path towards understanding the function of adult neurogenesis would be to reveal the changes that occur in the coding properties of DG neurons throughout their development, and the changes that these neurons impose on neural codes generated by the hippocampus. The study of such coding dynamics requires longitudinal recordings of neuronal ensembles in both the DG and CA1 over periods of weeks, since this is the timescale on which new DG neurons mature. Until recently, however, it has been technically impossible to obtain such data. This urgent need drove me to develop a new method, which allows for the optical recording of Ca2+ dynamics from up to 1,200 of the same genetically defined neurons in the hippocampus of freely behaving mice for periods of months. Here, I propose to combine this method with established tools for manipulation of neurogenesis rates or newborn neuron activity, to determine how neurogenesis contributes to coding dynamics in downstream CA1 while mice repeatedly explore familiar environments or preform a long-term memory task. Furthermore, we will establish time-lapse imaging of Ca2+ dynamics in populations of newborn DG neurons while mice perform tasks that engage the DG, and find how newborn neuron coding properties evolve as a function of their maturation. Our work will advance the understanding of how the hippocampus supports long-term memory by resolving fundamental questions that pertain to a nearly unexplored facet of memory: how memory codes change with time, while their behavioral manifestations persist.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym SynChI
Project Striatal cholinergic cell assemblies in movement disorders
Researcher (PI) Joshua Avi Goldberg
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Consolidator Grant (CoG), LS5, ERC-2014-CoG
Summary Pathological neuronal synchrony is the hallmark of many neurological disorders, including Parkinson’s disease (PD) and Huntington’s disease (HD), which further share deficits in cholinergic signaling. Moreover, recent findings have underscored the therapeutic relevance of the synchrony among striatal cholinergic interneurons (ChI) that orchestrate this signaling. They have shown that excessively synchronous ChI discharge induces di-synaptic release of dopamine, GABA and glutamate. Here, I propose to elucidate how ChI synchronization is generated under normal and pathological conditions and thereby identify novel therapeutic targets to treat PD and HD. This study has only very recently become feasible with the advent of powerful tools that I have mastered to explore ChI synchrony.
We will employ a combination of cutting-edge in vitro and in vivo techniques to simultaneously record a far larger population of pre-identified ChIs than is currently possible. We will express GCaMP6, a genetically encoded calcium indicator (GECI), exclusively in ChIs, and use multiphoton microscopy to image calcium transients from several ChIs simultaneously in conjunction with intracellular recording from individual ChIs in acute brain slices and in anesthetized mice. Additionally, we will use endoscopic GECI imaging in freely-moving classically conditioned mice. We will employ modern analyses that reveal low-dimensional structures in large neuronal datasets to quantify synchrony (1) during on-going activity; (2) during optogenetic activation of afferents; and (3), in the freely-moving mice, while presenting conditioned cues. Finally, we will study the origins of pathological synchrony in PD and HD mouse models and explore means to correct this condition. This comprehensive approach should explain the pathological ChI synchrony observed in PD; identify novel targets to treat PD and HD; and create a general methodology to study pathological synchrony in many other neurological disorders.
Summary
Pathological neuronal synchrony is the hallmark of many neurological disorders, including Parkinson’s disease (PD) and Huntington’s disease (HD), which further share deficits in cholinergic signaling. Moreover, recent findings have underscored the therapeutic relevance of the synchrony among striatal cholinergic interneurons (ChI) that orchestrate this signaling. They have shown that excessively synchronous ChI discharge induces di-synaptic release of dopamine, GABA and glutamate. Here, I propose to elucidate how ChI synchronization is generated under normal and pathological conditions and thereby identify novel therapeutic targets to treat PD and HD. This study has only very recently become feasible with the advent of powerful tools that I have mastered to explore ChI synchrony.
We will employ a combination of cutting-edge in vitro and in vivo techniques to simultaneously record a far larger population of pre-identified ChIs than is currently possible. We will express GCaMP6, a genetically encoded calcium indicator (GECI), exclusively in ChIs, and use multiphoton microscopy to image calcium transients from several ChIs simultaneously in conjunction with intracellular recording from individual ChIs in acute brain slices and in anesthetized mice. Additionally, we will use endoscopic GECI imaging in freely-moving classically conditioned mice. We will employ modern analyses that reveal low-dimensional structures in large neuronal datasets to quantify synchrony (1) during on-going activity; (2) during optogenetic activation of afferents; and (3), in the freely-moving mice, while presenting conditioned cues. Finally, we will study the origins of pathological synchrony in PD and HD mouse models and explore means to correct this condition. This comprehensive approach should explain the pathological ChI synchrony observed in PD; identify novel targets to treat PD and HD; and create a general methodology to study pathological synchrony in many other neurological disorders.
Max ERC Funding
2 000 000 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym SYNTECH
Project Synthesis Technologies for Reactive Systems Software Engineers
Researcher (PI) Shahar Maoz
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), PE6, ERC-2014-STG
Summary The design and development of open reactive systems, which compute by reacting to ongoing stimuli from their environment, and include, for example, mobile applications running on smart phone devices, web-based applications, industrial robotic systems, embedded software running on chips inside cars and aircraft, etc., is a complex and challenging task. Despite advancement from low-level assembly languages to higher-level languages with powerful abstraction mechanisms, and the use of automated testing and formal verification, reactive systems software development is still a mostly manual and error-prone iterative activity of coding and debugging.
A fundamentally different alternative approach to reactive systems development is synthesis, the automatic creation of correct-by-construction software from its specification. Synthesis has the potential to transform the way open reactive systems software is developed, making the process more effective and productive, and making its results more reliable and usable. However, while important advancements have been recently made on the algorithmic aspects of synthesis, no work has yet taken advantage of these achievements to change software engineering practices from “program centric” to “specification centric”. No effective end-to-end means to use synthesis are available to engineers, and the potential revolutionary impact of synthesis on the engineering of reactive systems software is far from being fully explored.
The proposal targets four objectives: a new, rich specification language, tailored for synthesis and for use by software engineers; a set of new methods for specification centric development; tool implementations in ‘killer app’ application domains; and systematic evaluation with engineers.
The research aims to unleash and evaluate the potential of synthesis to revolutionize reactive systems software development and to open the way for new directions in software engineering research and practice.
Summary
The design and development of open reactive systems, which compute by reacting to ongoing stimuli from their environment, and include, for example, mobile applications running on smart phone devices, web-based applications, industrial robotic systems, embedded software running on chips inside cars and aircraft, etc., is a complex and challenging task. Despite advancement from low-level assembly languages to higher-level languages with powerful abstraction mechanisms, and the use of automated testing and formal verification, reactive systems software development is still a mostly manual and error-prone iterative activity of coding and debugging.
A fundamentally different alternative approach to reactive systems development is synthesis, the automatic creation of correct-by-construction software from its specification. Synthesis has the potential to transform the way open reactive systems software is developed, making the process more effective and productive, and making its results more reliable and usable. However, while important advancements have been recently made on the algorithmic aspects of synthesis, no work has yet taken advantage of these achievements to change software engineering practices from “program centric” to “specification centric”. No effective end-to-end means to use synthesis are available to engineers, and the potential revolutionary impact of synthesis on the engineering of reactive systems software is far from being fully explored.
The proposal targets four objectives: a new, rich specification language, tailored for synthesis and for use by software engineers; a set of new methods for specification centric development; tool implementations in ‘killer app’ application domains; and systematic evaluation with engineers.
The research aims to unleash and evaluate the potential of synthesis to revolutionize reactive systems software development and to open the way for new directions in software engineering research and practice.
Max ERC Funding
1 477 000 €
Duration
Start date: 2015-04-01, End date: 2020-09-30
