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 APOLLO
Project Advanced Signal Processing Technologies for Wireless Powered Communications
Researcher (PI) Ioannis Krikidis
Host Institution (HI) UNIVERSITY OF CYPRUS
Call Details Consolidator Grant (CoG), PE7, ERC-2018-COG
Summary Wireless power transfer (WPT), pioneered by Tesla, is an idea at least as old as radio communications. However, on the one hand, due to health concerns and the large antenna dimensions required for transmission of high energy levels, until recently WPT has been limited mostly to very short distance applications. On the other hand, recent advances in silicon technology have significantly reduced the energy needs of electronic systems, making WPT over radio waves a potential source of energy for low power devices. Although WPT through radio waves has already found various short-range applications (such as the radio-frequency identification technology, healthcare monitoring etc.), its integration as a building block in the operation of wireless communications systems is still unexploited. On the other hand, conventional radio wave based information and energy transmissions have largely been designed separately. However, many applications can benefit from simultaneous wireless information and power transfer (SWIPT).
The overall objective of the APOLLO project is to study the integration of WPT/SWIPT technology into future wireless communication systems. Compared to past and current research efforts in this area, our technical approach is deeply interdisciplinary and more comprehensive, combining the expertise of wireless communications, control theory, information theory, optimization, and electronics/microwave engineering.
The key outcomes of the project include: 1) a rigorous and complete mathematical theory for WPT/SWIPT via information/communication/control theoretic studies; 2) new physical and cross-layer mechanisms that will enable the integration of WPT/SWIPT into future communication systems; 3) new network architectures that will fully exploit potential benefits of WPT/SWIPT; and 4) development of a proof-of-concept by implementing highly-efficient and multi-band metamaterial energy harvesting sensors for SWIPT.
Summary
Wireless power transfer (WPT), pioneered by Tesla, is an idea at least as old as radio communications. However, on the one hand, due to health concerns and the large antenna dimensions required for transmission of high energy levels, until recently WPT has been limited mostly to very short distance applications. On the other hand, recent advances in silicon technology have significantly reduced the energy needs of electronic systems, making WPT over radio waves a potential source of energy for low power devices. Although WPT through radio waves has already found various short-range applications (such as the radio-frequency identification technology, healthcare monitoring etc.), its integration as a building block in the operation of wireless communications systems is still unexploited. On the other hand, conventional radio wave based information and energy transmissions have largely been designed separately. However, many applications can benefit from simultaneous wireless information and power transfer (SWIPT).
The overall objective of the APOLLO project is to study the integration of WPT/SWIPT technology into future wireless communication systems. Compared to past and current research efforts in this area, our technical approach is deeply interdisciplinary and more comprehensive, combining the expertise of wireless communications, control theory, information theory, optimization, and electronics/microwave engineering.
The key outcomes of the project include: 1) a rigorous and complete mathematical theory for WPT/SWIPT via information/communication/control theoretic studies; 2) new physical and cross-layer mechanisms that will enable the integration of WPT/SWIPT into future communication systems; 3) new network architectures that will fully exploit potential benefits of WPT/SWIPT; and 4) development of a proof-of-concept by implementing highly-efficient and multi-band metamaterial energy harvesting sensors for SWIPT.
Max ERC Funding
1 930 625 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym ARS
Project Autonomous Robotic Surgery
Researcher (PI) Paolo FIORINI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI VERONA
Call Details Advanced Grant (AdG), PE7, ERC-2016-ADG
Summary The goal of the ARS project is the derivation of a unified framework for the autonomous execution of robotic tasks in challenging environments in which accurate performance and safety are of paramount importance. We have chosen surgery as the research scenario because of its importance, its intrinsic challenges, and the presence of three factors that make this project feasible and timely. In fact, we have recently concluded the I-SUR project demonstrating the feasibility of autonomous surgical actions, we have access to the first big data made available to researchers of clinical robotic surgeries, and we will be able to demonstrate the project results on the high performance surgical robot “da Vinci Research Kit”. The impact of autonomous robots on the workforce is a current subject of discussion, but surgical autonomy will be welcome by the medical personnel, e.g. to carry out simple intervention steps, react faster to unexpected events, or monitor the insurgence of fatigue. The framework for autonomous robotic surgery will include five main research objectives. The first will address the analysis of robotic surgery data set to extract action and knowledge models of the intervention. The second objective will focus on planning, which will consist of instantiating the intervention models to a patient specific anatomy. The third objective will address the design of the hybrid controllers for the discrete and continuous parts of the intervention. The fourth research objective will focus on real time reasoning to assess the intervention state and the overall surgical situation. Finally, the last research objective will address the verification, validation and benchmark of the autonomous surgical robotic capabilities. The research results to be achieved by ARS will contribute to paving the way towards enhancing autonomy and operational capabilities of service robots, with the ambitious goal of bridging the gap between robotic and human task execution capability.
Summary
The goal of the ARS project is the derivation of a unified framework for the autonomous execution of robotic tasks in challenging environments in which accurate performance and safety are of paramount importance. We have chosen surgery as the research scenario because of its importance, its intrinsic challenges, and the presence of three factors that make this project feasible and timely. In fact, we have recently concluded the I-SUR project demonstrating the feasibility of autonomous surgical actions, we have access to the first big data made available to researchers of clinical robotic surgeries, and we will be able to demonstrate the project results on the high performance surgical robot “da Vinci Research Kit”. The impact of autonomous robots on the workforce is a current subject of discussion, but surgical autonomy will be welcome by the medical personnel, e.g. to carry out simple intervention steps, react faster to unexpected events, or monitor the insurgence of fatigue. The framework for autonomous robotic surgery will include five main research objectives. The first will address the analysis of robotic surgery data set to extract action and knowledge models of the intervention. The second objective will focus on planning, which will consist of instantiating the intervention models to a patient specific anatomy. The third objective will address the design of the hybrid controllers for the discrete and continuous parts of the intervention. The fourth research objective will focus on real time reasoning to assess the intervention state and the overall surgical situation. Finally, the last research objective will address the verification, validation and benchmark of the autonomous surgical robotic capabilities. The research results to be achieved by ARS will contribute to paving the way towards enhancing autonomy and operational capabilities of service robots, with the ambitious goal of bridging the gap between robotic and human task execution capability.
Max ERC Funding
2 750 000 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym BACKUP
Project Unveiling the relationship between brain connectivity and function by integrated photonics
Researcher (PI) Lorenzo PAVESI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TRENTO
Call Details Advanced Grant (AdG), PE7, ERC-2017-ADG
Summary I will address the fundamental question of which is the role of neuron activity and plasticity in information elaboration and storage in the brain. I, together with an interdisciplinary team, will develop a hybrid neuro-morphic computing platform. Integrated photonic circuits will be interfaced to both electronic circuits and neuronal circuits (in vitro experiments) to emulate brain functions and develop schemes able to supplement (backup) neuronal functions. The photonic network is based on massive reconfigurable matrices of nonlinear nodes formed by microring resonators, which enter in regime of self-pulsing and chaos by positive optical feedback. These networks resemble human brain. I will push this analogy further by interfacing the photonic network with neurons making hybrid network. By using optogenetics, I will control the synaptic strengthen-ing and the neuron activity. Deep learning algorithms will model the biological network functionality, initial-ly within a separate artificial network and, then, in an integrated hybrid artificial-biological network.
My project aims at:
1. Developing a photonic integrated reservoir-computing network (RCN);
2. Developing dynamic memories in photonic integrated circuits using RCN;
3. Developing hybrid interfaces between a neuronal network and a photonic integrated circuit;
4. Developing a hybrid electronic, photonic and biological network that computes jointly;
5. Addressing neuronal network activity by photonic RCN to simulate in vitro memory storage and retrieval;
6. Elaborating the signal from RCN and neuronal circuits in order to cope with plastic changes in pathologi-cal brain conditions such as amnesia and epilepsy.
The long-term vision is that hybrid neuromorphic photonic networks will (a) clarify the way brain thinks, (b) compute beyond von Neumann, and (c) control and supplement specific neuronal functions.
Summary
I will address the fundamental question of which is the role of neuron activity and plasticity in information elaboration and storage in the brain. I, together with an interdisciplinary team, will develop a hybrid neuro-morphic computing platform. Integrated photonic circuits will be interfaced to both electronic circuits and neuronal circuits (in vitro experiments) to emulate brain functions and develop schemes able to supplement (backup) neuronal functions. The photonic network is based on massive reconfigurable matrices of nonlinear nodes formed by microring resonators, which enter in regime of self-pulsing and chaos by positive optical feedback. These networks resemble human brain. I will push this analogy further by interfacing the photonic network with neurons making hybrid network. By using optogenetics, I will control the synaptic strengthen-ing and the neuron activity. Deep learning algorithms will model the biological network functionality, initial-ly within a separate artificial network and, then, in an integrated hybrid artificial-biological network.
My project aims at:
1. Developing a photonic integrated reservoir-computing network (RCN);
2. Developing dynamic memories in photonic integrated circuits using RCN;
3. Developing hybrid interfaces between a neuronal network and a photonic integrated circuit;
4. Developing a hybrid electronic, photonic and biological network that computes jointly;
5. Addressing neuronal network activity by photonic RCN to simulate in vitro memory storage and retrieval;
6. Elaborating the signal from RCN and neuronal circuits in order to cope with plastic changes in pathologi-cal brain conditions such as amnesia and epilepsy.
The long-term vision is that hybrid neuromorphic photonic networks will (a) clarify the way brain thinks, (b) compute beyond von Neumann, and (c) control and supplement specific neuronal functions.
Max ERC Funding
2 499 825 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym BONEPHAGY
Project Defining the role of the FGF – autophagy axis in bone physiology
Researcher (PI) Carmine SETTEMBRE
Host Institution (HI) FONDAZIONE TELETHON
Call Details Starting Grant (StG), LS4, ERC-2016-STG
Summary Autophagy is a fundamental cellular catabolic process deputed to the degradation and recycling of a variety of intracellular materials. Autophagy plays a significant role in multiple human physio-pathological processes and is now emerging as a critical regulator of skeletal development and homeostasis. We have discovered that during postnatal development in mice, the growth factor FGF18 induces autophagy in the chondrocyte cells of the growth plate to regulate the secretion of type II collagen, a major component of cartilaginous extracellular matrix. The FGF signaling pathways play crucial roles during skeletal development and maintenance and are deregulated in many skeletal disorders. Hence our findings may offer the unique opportunity to uncover new molecular mechanisms through which FGF pathways regulate skeletal development and maintenance and to identify new targets for the treatment of FGF-related skeletal disorders. In this grant application we propose to study the role played by the different FGF ligands and receptors on autophagy regulation and to investigate the physiological relevance of these findings in the context of skeletal growth, homeostasis and maintenance. We will also investigate the intracellular machinery that links FGF signalling pathways to the regulation of autophagy. In addition, we generated preliminary data showing an impairment of autophagy in chondrocyte models of Achondroplasia (ACH) and Thanathoporic dysplasia, two skeletal disorders caused by mutations in FGFR3. We propose to study the role of autophagy in the pathogenesis of FGFR3-related dwarfisms and explore the pharmacological modulation of autophagy as new therapeutic approach for achondroplasia. This application, which combines cell biology, mouse genetics and pharmacological approaches, has the potential to shed light on new mechanisms involved in organismal development and homeostasis, which could be targeted to treat bone and cartilage diseases.
Summary
Autophagy is a fundamental cellular catabolic process deputed to the degradation and recycling of a variety of intracellular materials. Autophagy plays a significant role in multiple human physio-pathological processes and is now emerging as a critical regulator of skeletal development and homeostasis. We have discovered that during postnatal development in mice, the growth factor FGF18 induces autophagy in the chondrocyte cells of the growth plate to regulate the secretion of type II collagen, a major component of cartilaginous extracellular matrix. The FGF signaling pathways play crucial roles during skeletal development and maintenance and are deregulated in many skeletal disorders. Hence our findings may offer the unique opportunity to uncover new molecular mechanisms through which FGF pathways regulate skeletal development and maintenance and to identify new targets for the treatment of FGF-related skeletal disorders. In this grant application we propose to study the role played by the different FGF ligands and receptors on autophagy regulation and to investigate the physiological relevance of these findings in the context of skeletal growth, homeostasis and maintenance. We will also investigate the intracellular machinery that links FGF signalling pathways to the regulation of autophagy. In addition, we generated preliminary data showing an impairment of autophagy in chondrocyte models of Achondroplasia (ACH) and Thanathoporic dysplasia, two skeletal disorders caused by mutations in FGFR3. We propose to study the role of autophagy in the pathogenesis of FGFR3-related dwarfisms and explore the pharmacological modulation of autophagy as new therapeutic approach for achondroplasia. This application, which combines cell biology, mouse genetics and pharmacological approaches, has the potential to shed light on new mechanisms involved in organismal development and homeostasis, which could be targeted to treat bone and cartilage diseases.
Max ERC Funding
1 586 430 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
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 CAPABLE
Project Composite integrated photonic platform by femtosecond laser micromachining
Researcher (PI) Roberto OSELLAME
Host Institution (HI) CONSIGLIO NAZIONALE DELLE RICERCHE
Call Details Advanced Grant (AdG), PE7, ERC-2016-ADG
Summary The quantum technology revolution promises a transformational impact on the society and economics worldwide. It will enable breakthrough advancements in such diverse fields as secure communications, computing, metrology, and imaging. Quantum photonics, which recently received an incredible boost by the use of integrated optical circuits, is an excellent technological platform to enable such revolution, as it already plays a relevant role in many of the above applications. However, some major technical roadblocks needs to be overcome. Currently, the various components required for a complete quantum photonic system are produced on very different materials by dedicated fabrication technologies, as no single material is able to fulfil all the requirements for single-photon generation, manipulation, storage and detection. This project proposes a new hybrid approach for integrated quantum photonic systems based on femtosecond laser microfabrication (FLM), enabling the innovative miniaturization of various components on different materials, but with a single tool and with very favourable integration capabilities.
This project will mainly focus on two major breakthroughs: the first one will be increasing the complexity achievable in the photonic platform and demonstrating unprecedented quantum computation capability; the second one will be the integration in the platform of multiple single-photon quantum memories and their interconnection.
Achievement of these goals will only be possible by taking full advantage of the unique features of FLM, from the possibility to machine very different materials, to the 3D capabilities in waveguide writing and selective material removal.
The successful demonstration and functional validation of this hybrid, integrated photonic platform will represent a significant leap for photonic microsystems in quantum computing and quantum communications.
Summary
The quantum technology revolution promises a transformational impact on the society and economics worldwide. It will enable breakthrough advancements in such diverse fields as secure communications, computing, metrology, and imaging. Quantum photonics, which recently received an incredible boost by the use of integrated optical circuits, is an excellent technological platform to enable such revolution, as it already plays a relevant role in many of the above applications. However, some major technical roadblocks needs to be overcome. Currently, the various components required for a complete quantum photonic system are produced on very different materials by dedicated fabrication technologies, as no single material is able to fulfil all the requirements for single-photon generation, manipulation, storage and detection. This project proposes a new hybrid approach for integrated quantum photonic systems based on femtosecond laser microfabrication (FLM), enabling the innovative miniaturization of various components on different materials, but with a single tool and with very favourable integration capabilities.
This project will mainly focus on two major breakthroughs: the first one will be increasing the complexity achievable in the photonic platform and demonstrating unprecedented quantum computation capability; the second one will be the integration in the platform of multiple single-photon quantum memories and their interconnection.
Achievement of these goals will only be possible by taking full advantage of the unique features of FLM, from the possibility to machine very different materials, to the 3D capabilities in waveguide writing and selective material removal.
The successful demonstration and functional validation of this hybrid, integrated photonic platform will represent a significant leap for photonic microsystems in quantum computing and quantum communications.
Max ERC Funding
2 381 875 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym CARDIOEPIGEN
Project Epigenetics and microRNAs in Myocardial Function and Disease
Researcher (PI) Gianluigi Condorelli
Host Institution (HI) HUMANITAS MIRASOLE SPA
Call Details Advanced Grant (AdG), LS4, ERC-2011-ADG_20110310
Summary Heart failure (HF) is the ultimate outcome of many cardiovascular diseases. Re-expression of fetal genes in the adult heart contributes to development of HF. Two mechanisms involved in the control of gene expression are epigenetics and microRNAs (miRs). We propose a project on epigenetic and miR-mediated mechanisms leading to HF.
Epigenetics refers to heritable modification of DNA and histones that does not modify the genetic code. Depending on the type of modification and on the site affected, these chemical changes up- or down-regulate transcription of specific genes. Despite it being a major player in gene regulation, epigenetics has been only partly investigated in HF. miRs are regulatory RNAs that target mRNAs for inhibition. Dysregulation of the cardiac miR signature occurs in HF. miR expression may itself be under epigenetic control, constituting a miR-epigenetic regulatory network. To our knowledge, this possibility has not been studied yet.
Our specific hypothesis is that the profile of DNA/histone methylation and the cross-talk between epigenetic enzymes and miRs have fundamental roles in defining the characteristics of cells during cardiac development and that the dysregulation of these processes determines the deleterious nature of the stressed heart’s gene programme. We will test this first through a genome-wide study of DNA/histone methylation to generate maps of the main methylation modifications occurring in the genome of cardiac cells treated with a pro-hypertrophy regulator and of a HF model. We will then investigate the role of epigenetic enzymes deemed important in HF, through the generation and study of knockout mice models. Finally, we will test the possible therapeutic potential of modulating epigenetic genes.
We hope to further understand the pathological mechanisms leading to HF and to generate data instrumental to the development of diagnostic and therapeutic strategies for this disease.
Summary
Heart failure (HF) is the ultimate outcome of many cardiovascular diseases. Re-expression of fetal genes in the adult heart contributes to development of HF. Two mechanisms involved in the control of gene expression are epigenetics and microRNAs (miRs). We propose a project on epigenetic and miR-mediated mechanisms leading to HF.
Epigenetics refers to heritable modification of DNA and histones that does not modify the genetic code. Depending on the type of modification and on the site affected, these chemical changes up- or down-regulate transcription of specific genes. Despite it being a major player in gene regulation, epigenetics has been only partly investigated in HF. miRs are regulatory RNAs that target mRNAs for inhibition. Dysregulation of the cardiac miR signature occurs in HF. miR expression may itself be under epigenetic control, constituting a miR-epigenetic regulatory network. To our knowledge, this possibility has not been studied yet.
Our specific hypothesis is that the profile of DNA/histone methylation and the cross-talk between epigenetic enzymes and miRs have fundamental roles in defining the characteristics of cells during cardiac development and that the dysregulation of these processes determines the deleterious nature of the stressed heart’s gene programme. We will test this first through a genome-wide study of DNA/histone methylation to generate maps of the main methylation modifications occurring in the genome of cardiac cells treated with a pro-hypertrophy regulator and of a HF model. We will then investigate the role of epigenetic enzymes deemed important in HF, through the generation and study of knockout mice models. Finally, we will test the possible therapeutic potential of modulating epigenetic genes.
We hope to further understand the pathological mechanisms leading to HF and to generate data instrumental to the development of diagnostic and therapeutic strategies for this disease.
Max ERC Funding
2 500 000 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym CentSatRegFunc
Project Dissecting the function and regulation of centriolar satellites: key regulators of the centrosome/cilium complex
Researcher (PI) Elif Nur Firat Karalar
Host Institution (HI) KOC UNIVERSITY
Call Details Starting Grant (StG), LS3, ERC-2015-STG
Summary Centrosomes are the main microtubule-organizing centers of animal cells. They influence the morphology of the microtubule cytoskeleton and function as the base of primary cilium, a nexus for important signaling pathways. Structural and functional defects in centrosome/cilium complex cause a variety of human diseases including cancer, ciliopathies and microcephaly. To understand the relationship between human diseases and centrosome/cilium abnormalities, it is essential to elucidate the biogenesis of centrosome/cilium complex and the control mechanisms that regulate their structure and function. To tackle these fundamental problems, we will dissect the function and regulation of centriolar satellites, the array of granules that localize around the centrosome/cilium complex in mammalian cells. Only recently interest in the satellites has grown because mutations affecting satellite components were shown to cause ciliopathies, microcephaly and schizophrenia.
Remarkably, many centrosome/cilium proteins localize to these structures and we lack understanding of when, why and how these proteins localize to satellites. The central hypothesis of this grant is that satellites ensure proper centrosome/cilium complex structure and function by acting as transit paths for modification, assembly, storage, stability and trafficking of centrosome/cilium proteins. In Aim 1, we will identify the nature of regulatory and molecular relationship between satellites and the centrosome/cilium complex. In Aim 2, we will elucidate the role of satellites in proteostasis of centrosome/cilium proteins. In Aim 3, we will investigate the functional significance of satellite-localization of centrosome/cilium proteins during processes that go awry in human disease. Using a multidisciplinary approach, the proposed research will expand our knowledge of the spatiotemporal regulation of the centrosome/cilium complex and provide new insights into pathogenesis of ciliopathies and primary microcephaly.
Summary
Centrosomes are the main microtubule-organizing centers of animal cells. They influence the morphology of the microtubule cytoskeleton and function as the base of primary cilium, a nexus for important signaling pathways. Structural and functional defects in centrosome/cilium complex cause a variety of human diseases including cancer, ciliopathies and microcephaly. To understand the relationship between human diseases and centrosome/cilium abnormalities, it is essential to elucidate the biogenesis of centrosome/cilium complex and the control mechanisms that regulate their structure and function. To tackle these fundamental problems, we will dissect the function and regulation of centriolar satellites, the array of granules that localize around the centrosome/cilium complex in mammalian cells. Only recently interest in the satellites has grown because mutations affecting satellite components were shown to cause ciliopathies, microcephaly and schizophrenia.
Remarkably, many centrosome/cilium proteins localize to these structures and we lack understanding of when, why and how these proteins localize to satellites. The central hypothesis of this grant is that satellites ensure proper centrosome/cilium complex structure and function by acting as transit paths for modification, assembly, storage, stability and trafficking of centrosome/cilium proteins. In Aim 1, we will identify the nature of regulatory and molecular relationship between satellites and the centrosome/cilium complex. In Aim 2, we will elucidate the role of satellites in proteostasis of centrosome/cilium proteins. In Aim 3, we will investigate the functional significance of satellite-localization of centrosome/cilium proteins during processes that go awry in human disease. Using a multidisciplinary approach, the proposed research will expand our knowledge of the spatiotemporal regulation of the centrosome/cilium complex and provide new insights into pathogenesis of ciliopathies and primary microcephaly.
Max ERC Funding
1 499 819 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym COGSYSTEMS
Project Understanding actions and intentions of others
Researcher (PI) Giacomo Rizzolatti
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PARMA
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.
Summary
How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.
Max ERC Funding
1 992 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
