Project acronym 321
Project from Cubic To Linear complexity in computational electromagnetics
Researcher (PI) Francesco Paolo ANDRIULLI
Host Institution (HI) POLITECNICO DI TORINO
Call Details Consolidator Grant (CoG), PE7, ERC-2016-COG
Summary Computational Electromagnetics (CEM) is the scientific field at the origin of all new modeling and simulation tools required by the constantly arising design challenges of emerging and future technologies in applied electromagnetics. As in many other technological fields, however, the trend in all emerging technologies in electromagnetic engineering is going towards miniaturized, higher density and multi-scale scenarios. Computationally speaking this translates in the steep increase of the number of degrees of freedom. Given that the design cost (the cost of a multi-right-hand side problem dominated by matrix inversion) can scale as badly as cubically with these degrees of freedom, this fact, as pointed out by many, will sensibly compromise the practical impact of CEM on future and emerging technologies.
For this reason, the CEM scientific community has been looking for years for a FFT-like paradigm shift: a dynamic fast direct solver providing a design cost that would scale only linearly with the degrees of freedom. Such a fast solver is considered today a Holy Grail of the discipline.
The Grand Challenge of 321 will be to tackle this Holy Grail in Computational Electromagnetics by investigating a dynamic Fast Direct Solver for Maxwell Problems that would run in a linear-instead-of-cubic complexity for an arbitrary number and configuration of degrees of freedom.
The failure of all previous attempts will be overcome by a game-changing transformation of the CEM classical problem that will leverage on a recent breakthrough of the PI. Starting from this, the project will investigate an entire new paradigm for impacting algorithms to achieve this grand challenge.
The impact of the FFT’s quadratic-to-linear paradigm shift shows how computational complexity reductions can be groundbreaking on applications. The cubic-to-linear paradigm shift, which the 321 project will aim for, will have such a rupturing impact on electromagnetic science and technology.
Summary
Computational Electromagnetics (CEM) is the scientific field at the origin of all new modeling and simulation tools required by the constantly arising design challenges of emerging and future technologies in applied electromagnetics. As in many other technological fields, however, the trend in all emerging technologies in electromagnetic engineering is going towards miniaturized, higher density and multi-scale scenarios. Computationally speaking this translates in the steep increase of the number of degrees of freedom. Given that the design cost (the cost of a multi-right-hand side problem dominated by matrix inversion) can scale as badly as cubically with these degrees of freedom, this fact, as pointed out by many, will sensibly compromise the practical impact of CEM on future and emerging technologies.
For this reason, the CEM scientific community has been looking for years for a FFT-like paradigm shift: a dynamic fast direct solver providing a design cost that would scale only linearly with the degrees of freedom. Such a fast solver is considered today a Holy Grail of the discipline.
The Grand Challenge of 321 will be to tackle this Holy Grail in Computational Electromagnetics by investigating a dynamic Fast Direct Solver for Maxwell Problems that would run in a linear-instead-of-cubic complexity for an arbitrary number and configuration of degrees of freedom.
The failure of all previous attempts will be overcome by a game-changing transformation of the CEM classical problem that will leverage on a recent breakthrough of the PI. Starting from this, the project will investigate an entire new paradigm for impacting algorithms to achieve this grand challenge.
The impact of the FFT’s quadratic-to-linear paradigm shift shows how computational complexity reductions can be groundbreaking on applications. The cubic-to-linear paradigm shift, which the 321 project will aim for, will have such a rupturing impact on electromagnetic science and technology.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym BENDER
Project BiogENesis and Degradation of Endoplasmic Reticulum proteins
Researcher (PI) Friedrich Förster
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Consolidator Grant (CoG), LS1, ERC-2016-COG
Summary The Endoplasmic Reticulum (ER) membrane in all eukaryotic cells has an intricate protein network that facilitates protein biogene-sis and homeostasis. The molecular complexity and sophisticated regulation of this machinery favours study-ing it in its native microenvironment by novel approaches. Cryo-electron tomography (CET) allows 3D im-aging of membrane-associated complexes in their native surrounding. Computational analysis of many sub-tomograms depicting the same type of macromolecule, a technology I pioneered, provides subnanometer resolution insights into different conformations of native complexes.
I propose to leverage CET of cellular and cell-free systems to reveal the molecular details of ER protein bio-genesis and homeostasis. In detail, I will study: (a) The structure of the ER translocon, the dynamic gateway for import of nascent proteins into the ER and their maturation. The largest component is the oligosaccharyl transferase complex. (b) Cotranslational ER import, N-glycosylation, chaperone-mediated stabilization and folding as well as oligomerization of established model substrate such a major histocompatibility complex (MHC) class I and II complexes. (c) The degradation of misfolded ER-residing proteins by the cytosolic 26S proteasome using cytomegalovirus-induced depletion of MHC class I as a model system. (d) The structural changes of the ER-bound translation machinery upon ER stress through IRE1-mediated degradation of mRNA that is specific for ER-targeted proteins. (e) The improved ‘in silico purification’ of different states of native macromolecules by maximum likelihood subtomogram classification and its application to a-d.
This project will be the blueprint for a new approach to structural biology of membrane-associated processes. It will contribute to our mechanistic understanding of viral immune evasion and glycosylation disorders as well as numerous diseases involving chronic ER stress including diabetes and neurodegenerative diseases.
Summary
The Endoplasmic Reticulum (ER) membrane in all eukaryotic cells has an intricate protein network that facilitates protein biogene-sis and homeostasis. The molecular complexity and sophisticated regulation of this machinery favours study-ing it in its native microenvironment by novel approaches. Cryo-electron tomography (CET) allows 3D im-aging of membrane-associated complexes in their native surrounding. Computational analysis of many sub-tomograms depicting the same type of macromolecule, a technology I pioneered, provides subnanometer resolution insights into different conformations of native complexes.
I propose to leverage CET of cellular and cell-free systems to reveal the molecular details of ER protein bio-genesis and homeostasis. In detail, I will study: (a) The structure of the ER translocon, the dynamic gateway for import of nascent proteins into the ER and their maturation. The largest component is the oligosaccharyl transferase complex. (b) Cotranslational ER import, N-glycosylation, chaperone-mediated stabilization and folding as well as oligomerization of established model substrate such a major histocompatibility complex (MHC) class I and II complexes. (c) The degradation of misfolded ER-residing proteins by the cytosolic 26S proteasome using cytomegalovirus-induced depletion of MHC class I as a model system. (d) The structural changes of the ER-bound translation machinery upon ER stress through IRE1-mediated degradation of mRNA that is specific for ER-targeted proteins. (e) The improved ‘in silico purification’ of different states of native macromolecules by maximum likelihood subtomogram classification and its application to a-d.
This project will be the blueprint for a new approach to structural biology of membrane-associated processes. It will contribute to our mechanistic understanding of viral immune evasion and glycosylation disorders as well as numerous diseases involving chronic ER stress including diabetes and neurodegenerative diseases.
Max ERC Funding
2 496 611 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym BiT
Project How the Human Brain Masters Time
Researcher (PI) Domenica Bueti
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Call Details Consolidator Grant (CoG), SH4, ERC-2015-CoG
Summary If you suddenly hear your song on the radio and spontaneously decide to burst into dance in your living room, you need to precisely time your movements if you do not want to find yourself on your bookshelf. Most of what we do or perceive depends on how accurately we represent the temporal properties of the environment however we cannot see or touch time. As such, time in the millisecond range is both a fundamental and elusive dimension of everyday experiences. Despite the obvious importance of time to information processing and to behavior in general, little is known yet about how the human brain process time. Existing approaches to the study of the neural mechanisms of time mainly focus on the identification of brain regions involved in temporal computations (‘where’ time is processed in the brain), whereas most computational models vary in their biological plausibility and do not always make clear testable predictions. BiT is a groundbreaking research program designed to challenge current models of time perception and to offer a new perspective in the study of the neural basis of time. The groundbreaking nature of BiT derives from the novelty of the questions asked (‘when’ and ‘how’ time is processed in the brain) and from addressing them using complementary but distinct research approaches (from human neuroimaging to brain stimulation techniques, from the investigation of the whole brain to the focus on specific brain regions). By testing a new biologically plausible hypothesis of temporal representation (via duration tuning and ‘chronotopy’) and by scrutinizing the functional properties and, for the first time, the temporal hierarchies of ‘putative’ time regions, BiT will offer a multifaceted knowledge of how the human brain represents time. This new knowledge will challenge our understanding of brain organization and function that typically lacks of a time angle and will impact our understanding of how the brain uses time information for perception and action
Summary
If you suddenly hear your song on the radio and spontaneously decide to burst into dance in your living room, you need to precisely time your movements if you do not want to find yourself on your bookshelf. Most of what we do or perceive depends on how accurately we represent the temporal properties of the environment however we cannot see or touch time. As such, time in the millisecond range is both a fundamental and elusive dimension of everyday experiences. Despite the obvious importance of time to information processing and to behavior in general, little is known yet about how the human brain process time. Existing approaches to the study of the neural mechanisms of time mainly focus on the identification of brain regions involved in temporal computations (‘where’ time is processed in the brain), whereas most computational models vary in their biological plausibility and do not always make clear testable predictions. BiT is a groundbreaking research program designed to challenge current models of time perception and to offer a new perspective in the study of the neural basis of time. The groundbreaking nature of BiT derives from the novelty of the questions asked (‘when’ and ‘how’ time is processed in the brain) and from addressing them using complementary but distinct research approaches (from human neuroimaging to brain stimulation techniques, from the investigation of the whole brain to the focus on specific brain regions). By testing a new biologically plausible hypothesis of temporal representation (via duration tuning and ‘chronotopy’) and by scrutinizing the functional properties and, for the first time, the temporal hierarchies of ‘putative’ time regions, BiT will offer a multifaceted knowledge of how the human brain represents time. This new knowledge will challenge our understanding of brain organization and function that typically lacks of a time angle and will impact our understanding of how the brain uses time information for perception and action
Max ERC Funding
1 670 830 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym BrightEyes
Project Multi-Parameter Live-Cell Observation of Biomolecular Processes with Single-Photon Detector Array
Researcher (PI) Giuseppe Vicidomini
Host Institution (HI) FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Call Details Consolidator Grant (CoG), PE7, ERC-2018-COG
Summary Fluorescence single-molecule (SM) detection techniques have the potential to provide insights into the complex functions, structures and interactions of individual, specifically labelled biomolecules. However, current SM techniques work properly only when the biomolecule is observed in controlled environments, e.g., immobilized on a glass surface. Observation of biomolecular processes in living (multi)cellular environments – which is fundamental for sound biological conclusion – always comes with a price, such as invasiveness, limitations in the accessible information and constraints in the spatial and temporal scales.
The overall objective of the BrightEyes project is to break the above limitations by creating a novel SM approach compatible with the state-of-the-art biomolecule-labelling protocols, able to track a biomolecule deep inside (multi)cellular environments – with temporal resolution in the microsecond scale, and with hundreds of micrometres tracking range – and simultaneously observe its structural changes, its nano- and micro-environments.
Specifically, by exploring a novel single-photon detectors array, the BrightEyes project will implement an optical system, able to continuously (i) track in real-time the biomolecule of interest from which to decode its dynamics and interactions; (ii) measure the nano-environment fluorescence spectroscopy properties, such as lifetime, photon-pair correlation and intensity, from which to extract the biochemical properties of the nano-environment, the structural properties of the biomolecule – via SM-FRET and anti-bunching – and the interactions of the biomolecule with other biomolecular species – via STED-FCS; (iii) visualize the sub-cellular structures within the micro-environment with sub-diffraction spatial resolution – via STED and image scanning microscopy.
This unique paradigm will enable unprecedented studies of biomolecular behaviours, interactions and self-organization at near-physiological conditions.
Summary
Fluorescence single-molecule (SM) detection techniques have the potential to provide insights into the complex functions, structures and interactions of individual, specifically labelled biomolecules. However, current SM techniques work properly only when the biomolecule is observed in controlled environments, e.g., immobilized on a glass surface. Observation of biomolecular processes in living (multi)cellular environments – which is fundamental for sound biological conclusion – always comes with a price, such as invasiveness, limitations in the accessible information and constraints in the spatial and temporal scales.
The overall objective of the BrightEyes project is to break the above limitations by creating a novel SM approach compatible with the state-of-the-art biomolecule-labelling protocols, able to track a biomolecule deep inside (multi)cellular environments – with temporal resolution in the microsecond scale, and with hundreds of micrometres tracking range – and simultaneously observe its structural changes, its nano- and micro-environments.
Specifically, by exploring a novel single-photon detectors array, the BrightEyes project will implement an optical system, able to continuously (i) track in real-time the biomolecule of interest from which to decode its dynamics and interactions; (ii) measure the nano-environment fluorescence spectroscopy properties, such as lifetime, photon-pair correlation and intensity, from which to extract the biochemical properties of the nano-environment, the structural properties of the biomolecule – via SM-FRET and anti-bunching – and the interactions of the biomolecule with other biomolecular species – via STED-FCS; (iii) visualize the sub-cellular structures within the micro-environment with sub-diffraction spatial resolution – via STED and image scanning microscopy.
This unique paradigm will enable unprecedented studies of biomolecular behaviours, interactions and self-organization at near-physiological conditions.
Max ERC Funding
1 861 250 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym CoAct
Project Communication in Action: Towards a model of Contextualized Action and Language Processing
Researcher (PI) Judith HOLLER
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Consolidator Grant (CoG), SH4, ERC-2017-COG
Summary Language is fundamental to human sociality. While the last century has given us many fundamental insights into how we use and understand it, core issues that we face when doing so within its natural environment—face-to-face conversation—remain untackled. When we speak we also send signals with our head, eyes, face, hands, torso, etc. How do we orchestrate and integrate all this information into meaningful messages? CoAct will lead to a new model with in situ language processing at its core, the Contextualized Action and Language (CoALa) processing model. The defining characteristic of in situ language is its multimodal nature. Moreover, the essence of language use is social action; that is, we use language to do things—we question, offer, decline etc. These social actions are embedded in conversational structure where one speaking turn follows another at a remarkable speed, with millisecond gaps between them. Conversation thus confronts us with a significant psycholinguistic challenge. While one could expect that the many co-speech bodily signals exacerbate this challenge, CoAct proposes that they actually play a key role in dealing with it. It tests this in three subprojects that combine methods from a variety of disciplines but focus on the social actions performed by questions and responses as a uniting theme: (1) ProdAct uses conversational corpora to investigate the multimodal architecture of social actions with the assumption that they differ in their ‘visual signatures’, (2) CompAct tests whether these bodily signatures contribute to social action comprehension, and if they do so early and rapidly, (3) IntAct investigates whether bodily signals play a facilitating role also when faced with the complex task of comprehending while planning a next social action. Thus, CoAct aims to advance current psycholinguistic theory by developing a new model of language processing based on an integrative framework uniting aspects from psychology , philosophy and sociology.
Summary
Language is fundamental to human sociality. While the last century has given us many fundamental insights into how we use and understand it, core issues that we face when doing so within its natural environment—face-to-face conversation—remain untackled. When we speak we also send signals with our head, eyes, face, hands, torso, etc. How do we orchestrate and integrate all this information into meaningful messages? CoAct will lead to a new model with in situ language processing at its core, the Contextualized Action and Language (CoALa) processing model. The defining characteristic of in situ language is its multimodal nature. Moreover, the essence of language use is social action; that is, we use language to do things—we question, offer, decline etc. These social actions are embedded in conversational structure where one speaking turn follows another at a remarkable speed, with millisecond gaps between them. Conversation thus confronts us with a significant psycholinguistic challenge. While one could expect that the many co-speech bodily signals exacerbate this challenge, CoAct proposes that they actually play a key role in dealing with it. It tests this in three subprojects that combine methods from a variety of disciplines but focus on the social actions performed by questions and responses as a uniting theme: (1) ProdAct uses conversational corpora to investigate the multimodal architecture of social actions with the assumption that they differ in their ‘visual signatures’, (2) CompAct tests whether these bodily signatures contribute to social action comprehension, and if they do so early and rapidly, (3) IntAct investigates whether bodily signals play a facilitating role also when faced with the complex task of comprehending while planning a next social action. Thus, CoAct aims to advance current psycholinguistic theory by developing a new model of language processing based on an integrative framework uniting aspects from psychology , philosophy and sociology.
Max ERC Funding
2 000 000 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym CORNEA
Project Controlling evolutionary dynamics of networked autonomous agents
Researcher (PI) Ming CAO
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Call Details Consolidator Grant (CoG), PE7, ERC-2017-COG
Summary Large-scale technological, biological, economic, and social complex systems act as complex networks of interacting autonomous agents. Large numbers of interacting agents making self-interested decisions can result in highly complex, sometimes surprising, and often suboptimal, collective behaviors. Empowered by recent breakthroughs in data-driven cognitive learning technologies, networked agents collectively give rise to evolutionary dynamics that cannot be easily modeled, analysed and/or controlled using current systems and control theory. Consequently, there is an urgent need to develop new theoretical foundations to tackle the emerging challenging control problems associated with evolutionary dynamics for networked autonomous agents.
The aim of this project is to develop a rigorous theory for the control of evolutionary dynamics so that interacting autonomous agents can be guided to solve group tasks through the pursuit of individual goals in an evolutionary dynamical process. The theory will then be tested, validated and improved against experimental results using robotic fish.
To achieve the aim, I will: (1) develop a general formulation for stochastic evolutionary dynamics with control inputs, enabling the study on controllability and stabilizability for evolutionary processes; (2) introduce stochastic control Lyapunov functions to design control laws; (3) construct new classes of conditional strategies that may propagate controlled actions effectively from focal agents in multiple time scales; and (4) validate experimentally on tasks with unknown difficulties that require a group of robotic fish to evolve and adapt.
The project will result in a major advance from the conventional usage of evolutionary game theory with the systematic design to actively control evolutionary outcomes. The combination of theory with experimentation and the multi-disciplinary nature of the approach will lead to new applications of autonomous robotic systems.
Summary
Large-scale technological, biological, economic, and social complex systems act as complex networks of interacting autonomous agents. Large numbers of interacting agents making self-interested decisions can result in highly complex, sometimes surprising, and often suboptimal, collective behaviors. Empowered by recent breakthroughs in data-driven cognitive learning technologies, networked agents collectively give rise to evolutionary dynamics that cannot be easily modeled, analysed and/or controlled using current systems and control theory. Consequently, there is an urgent need to develop new theoretical foundations to tackle the emerging challenging control problems associated with evolutionary dynamics for networked autonomous agents.
The aim of this project is to develop a rigorous theory for the control of evolutionary dynamics so that interacting autonomous agents can be guided to solve group tasks through the pursuit of individual goals in an evolutionary dynamical process. The theory will then be tested, validated and improved against experimental results using robotic fish.
To achieve the aim, I will: (1) develop a general formulation for stochastic evolutionary dynamics with control inputs, enabling the study on controllability and stabilizability for evolutionary processes; (2) introduce stochastic control Lyapunov functions to design control laws; (3) construct new classes of conditional strategies that may propagate controlled actions effectively from focal agents in multiple time scales; and (4) validate experimentally on tasks with unknown difficulties that require a group of robotic fish to evolve and adapt.
The project will result in a major advance from the conventional usage of evolutionary game theory with the systematic design to actively control evolutionary outcomes. The combination of theory with experimentation and the multi-disciplinary nature of the approach will lead to new applications of autonomous robotic systems.
Max ERC Funding
1 998 933 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym DARE2APPROACH
Project Dare to Approach: A Neurocognitive Approach to Alleviating Persistent Avoidance in Anxiety Disorders
Researcher (PI) karin ROELOFS
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Consolidator Grant (CoG), SH4, ERC-2017-COG
Summary How did three soldiers override their initial freezing response to overpower an armed terrorist in the Thalys-train to Paris in 2015? This question is relevant for anyone aiming to optimize approach-avoidance (AA) decisions during threat. It is particularly relevant for patients with anxiety disorders whose persistent avoidance is key to the maintenance of their anxiety.
Computational psychiatry has made great progress in formalizing how we make (mal)adaptive decisions. Current models, however, largely ignore the transient psychophysiological state of the decision maker. Parasympathetic state and flexibility in switching between para- and sympathetic states are directly related to freezing, and are known to bias AA-decisions toward avoidance. The central aim of this research program is to forge a mechanistic understanding of how we compute AA-decisions on the basis of those psychophysiological states, and to identify alterations in anxiety patients in order to guide new personalized neurocognitive interventions into their persistent avoidance.
I will develop a neurocomputational model of AA-decisions that accounts for transient psychophysiological states, in order to define which decision parameters are altered in active and passive avoidance in anxiety. I will test causal premises of the model using state-of-the-art techniques, including pharmacological and electrophysiological interventions. Based on these insights I will for the first time apply personalized brain stimulation to anxiety patients.
Clinically, this project should open the way to effective intervention with fearful avoidance in anxiety disorders that rank among the most common, costly and persistent mental disorders. Theoretically, conceptualizing transient psychophysiological states as causal factor in AA-decision models is essential to understanding passive and active avoidance. Optimizing AA-decisions also holds broad societal relevance given currently increased fearful avoidance of outgroups.
Summary
How did three soldiers override their initial freezing response to overpower an armed terrorist in the Thalys-train to Paris in 2015? This question is relevant for anyone aiming to optimize approach-avoidance (AA) decisions during threat. It is particularly relevant for patients with anxiety disorders whose persistent avoidance is key to the maintenance of their anxiety.
Computational psychiatry has made great progress in formalizing how we make (mal)adaptive decisions. Current models, however, largely ignore the transient psychophysiological state of the decision maker. Parasympathetic state and flexibility in switching between para- and sympathetic states are directly related to freezing, and are known to bias AA-decisions toward avoidance. The central aim of this research program is to forge a mechanistic understanding of how we compute AA-decisions on the basis of those psychophysiological states, and to identify alterations in anxiety patients in order to guide new personalized neurocognitive interventions into their persistent avoidance.
I will develop a neurocomputational model of AA-decisions that accounts for transient psychophysiological states, in order to define which decision parameters are altered in active and passive avoidance in anxiety. I will test causal premises of the model using state-of-the-art techniques, including pharmacological and electrophysiological interventions. Based on these insights I will for the first time apply personalized brain stimulation to anxiety patients.
Clinically, this project should open the way to effective intervention with fearful avoidance in anxiety disorders that rank among the most common, costly and persistent mental disorders. Theoretically, conceptualizing transient psychophysiological states as causal factor in AA-decision models is essential to understanding passive and active avoidance. Optimizing AA-decisions also holds broad societal relevance given currently increased fearful avoidance of outgroups.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym DIDYMUS
Project MICROMACHINED OPTOMECHANICAL DEVICES: looking at cells, tissues, and organs ... with a gentle touch
Researcher (PI) Davide Iannuzzi
Host Institution (HI) STICHTING VU
Call Details Consolidator Grant (CoG), PE7, ERC-2013-CoG
Summary Every time we grab an object to look at its geometrical details or to feel if it is hard or soft, we are ineluctably confronted with the limits of our senses. Behind its appearances, the object may still hide information that, encrypted in its microscopic features, remains undetected to our macroscopic assessment. In life sciences, those limits are more than just frustrating: they are an obstacle to study and detect life threatening conditions. Many different instruments may overcome those limits, but the vast majority of them rely either on “sight” (optics) or “touch” (mechanics) separately. On the contrary, I believe that it is from the combination of those two “senses” that we have more chances to tackle the future challenges of cell biology, tissue engineering, and medical diagnosis.
Inspired by this tantalizing perspective, and supported by a technology that I have brought from blackboard to market, I have now designed a scientific program to breach into the microscopic scale via an unbeaten path. The program develops along three projects addressing the three most relevant scales in life sciences: cells, tissues, and organs. In the first project, I will design and test a new optomechanical probe to investigate how a prolonged mechanical load on a brain cell of a living animal may trigger alterations in its Central Nervous System. With the second project, I will develop an optomechanical tactile instrument that can assess how subsurface tissues deform in response to a mechanical stroke – a study that may change the way physicians look at tissue classification. For the third project, I will deliver an acousto-optical gas trace sensors so compact that can penetrate inside the lungs of an adult patient, where it could be used for early detection of pulmonary life threatening diseases. Each project represents an opportunity to open an entire new field, where optics and micromechanics are combined to extend our senses well beyond their natural limits.
Summary
Every time we grab an object to look at its geometrical details or to feel if it is hard or soft, we are ineluctably confronted with the limits of our senses. Behind its appearances, the object may still hide information that, encrypted in its microscopic features, remains undetected to our macroscopic assessment. In life sciences, those limits are more than just frustrating: they are an obstacle to study and detect life threatening conditions. Many different instruments may overcome those limits, but the vast majority of them rely either on “sight” (optics) or “touch” (mechanics) separately. On the contrary, I believe that it is from the combination of those two “senses” that we have more chances to tackle the future challenges of cell biology, tissue engineering, and medical diagnosis.
Inspired by this tantalizing perspective, and supported by a technology that I have brought from blackboard to market, I have now designed a scientific program to breach into the microscopic scale via an unbeaten path. The program develops along three projects addressing the three most relevant scales in life sciences: cells, tissues, and organs. In the first project, I will design and test a new optomechanical probe to investigate how a prolonged mechanical load on a brain cell of a living animal may trigger alterations in its Central Nervous System. With the second project, I will develop an optomechanical tactile instrument that can assess how subsurface tissues deform in response to a mechanical stroke – a study that may change the way physicians look at tissue classification. For the third project, I will deliver an acousto-optical gas trace sensors so compact that can penetrate inside the lungs of an adult patient, where it could be used for early detection of pulmonary life threatening diseases. Each project represents an opportunity to open an entire new field, where optics and micromechanics are combined to extend our senses well beyond their natural limits.
Max ERC Funding
1 999 221 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym DNAMEREP
Project The role of essential DNA metabolism genes in vertebrate chromosome replication
Researcher (PI) Vincenzo Costanzo
Host Institution (HI) IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE
Call Details Consolidator Grant (CoG), LS1, ERC-2013-CoG
Summary "Faithful chromosomal DNA replication is essential to maintain genome stability. A number of DNA metabolism genes are involved at different levels in DNA replication. These factors are thought to facilitate the establishment of replication origins, assist the replication of chromatin regions with repetitive DNA, coordinate the repair of DNA molecules resulting from aberrant DNA replication events or protect replication forks in the presence of DNA lesions that impair their progression. Some DNA metabolism genes are present mainly in higher eukaryotes, suggesting the existence of more complex repair and replication mechanisms in organisms with complex genomes. The impact on cell survival of many DNA metabolism genes has so far precluded in depth molecular analysis. The use of cell free extracts able to recapitulate cell cycle events might help overcoming survival issues and facilitate these studies. The Xenopus laevis egg cell free extract represents an ideal system to study replication-associated functions of essential genes in vertebrate organisms. We will take advantage of this system together with innovative imaging and proteomic based experimental approaches that we are currently developing to characterize the molecular function of some essential DNA metabolism genes. In particular, we will characterize DNA metabolism genes involved in the assembly and distribution of replication origins in vertebrate cells, elucidate molecular mechanisms underlying the role of essential homologous recombination and fork protection proteins in chromosomal DNA replication, and finally identify and characterize factors required for faithful replication of specific vertebrate genomic regions.
The results of these studies will provide groundbreaking information on several aspects of vertebrate genome metabolism and will allow long-awaited understanding of the function of a number of vertebrate essential DNA metabolism genes involved in the duplication of large and complex genomes."
Summary
"Faithful chromosomal DNA replication is essential to maintain genome stability. A number of DNA metabolism genes are involved at different levels in DNA replication. These factors are thought to facilitate the establishment of replication origins, assist the replication of chromatin regions with repetitive DNA, coordinate the repair of DNA molecules resulting from aberrant DNA replication events or protect replication forks in the presence of DNA lesions that impair their progression. Some DNA metabolism genes are present mainly in higher eukaryotes, suggesting the existence of more complex repair and replication mechanisms in organisms with complex genomes. The impact on cell survival of many DNA metabolism genes has so far precluded in depth molecular analysis. The use of cell free extracts able to recapitulate cell cycle events might help overcoming survival issues and facilitate these studies. The Xenopus laevis egg cell free extract represents an ideal system to study replication-associated functions of essential genes in vertebrate organisms. We will take advantage of this system together with innovative imaging and proteomic based experimental approaches that we are currently developing to characterize the molecular function of some essential DNA metabolism genes. In particular, we will characterize DNA metabolism genes involved in the assembly and distribution of replication origins in vertebrate cells, elucidate molecular mechanisms underlying the role of essential homologous recombination and fork protection proteins in chromosomal DNA replication, and finally identify and characterize factors required for faithful replication of specific vertebrate genomic regions.
The results of these studies will provide groundbreaking information on several aspects of vertebrate genome metabolism and will allow long-awaited understanding of the function of a number of vertebrate essential DNA metabolism genes involved in the duplication of large and complex genomes."
Max ERC Funding
1 999 800 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym DREAM
Project Distributed dynamic REpresentations for diAlogue Management
Researcher (PI) Raquel FERNANDEZ Rovira
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Consolidator Grant (CoG), SH4, ERC-2018-COG
Summary Our ability to communicate using language in conversation is considered the hallmark of human intelligence. Yet, while holding a dialogue is effortless for most of us, modelling this basic human skill by computational means has proven extremely difficult. In DREAM, I address this challenge by establishing a new computational model of a dialogue agent that can learn to take part in conversation directly from data about language use. DREAM stands at the crossroads of the symbolic and the sub-symbolic traditions regarding the nature of human cognitive processing and, by extension, its computational modelling. My model is grounded in linguistic theories of dialogue, rooted in the symbolic tradition, but exploits recent advances in computational learning that allow the agent to learn the representations that it manipulates, which are distributed and sub-symbolic, directly from experience. This is an original approach that constitutes a paradigm shift in dialogue modelling --- from predefined symbolic representations to automatic representation learning --- that will break new scientific ground in Computational Linguistics, Linguistics, and Artificial Intelligence. The DREAM agent will be implemented as an artificial neural network system and trained with task-oriented conversations where the participants have a well-defined end goal. The agent will be able to integrate linguistic and perceptual information and will be endowed with the capability to dynamically track both speaker commitments and partner-specific conventions, leading to more human-like and effective communication. Besides providing a breakthrough in our capacity to build sophisticated conversational agents, DREAM will have substantial impact on our scientific understanding of human language use, thanks to its emphasis on theory-driven hypotheses and model analysis.
Summary
Our ability to communicate using language in conversation is considered the hallmark of human intelligence. Yet, while holding a dialogue is effortless for most of us, modelling this basic human skill by computational means has proven extremely difficult. In DREAM, I address this challenge by establishing a new computational model of a dialogue agent that can learn to take part in conversation directly from data about language use. DREAM stands at the crossroads of the symbolic and the sub-symbolic traditions regarding the nature of human cognitive processing and, by extension, its computational modelling. My model is grounded in linguistic theories of dialogue, rooted in the symbolic tradition, but exploits recent advances in computational learning that allow the agent to learn the representations that it manipulates, which are distributed and sub-symbolic, directly from experience. This is an original approach that constitutes a paradigm shift in dialogue modelling --- from predefined symbolic representations to automatic representation learning --- that will break new scientific ground in Computational Linguistics, Linguistics, and Artificial Intelligence. The DREAM agent will be implemented as an artificial neural network system and trained with task-oriented conversations where the participants have a well-defined end goal. The agent will be able to integrate linguistic and perceptual information and will be endowed with the capability to dynamically track both speaker commitments and partner-specific conventions, leading to more human-like and effective communication. Besides providing a breakthrough in our capacity to build sophisticated conversational agents, DREAM will have substantial impact on our scientific understanding of human language use, thanks to its emphasis on theory-driven hypotheses and model analysis.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
