Project acronym 1st-principles-discs
Project A First Principles Approach to Accretion Discs
Researcher (PI) Martin Elias Pessah
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE9, ERC-2012-StG_20111012
Summary Most celestial bodies, from planets, to stars, to black holes; gain mass during their lives by means of an accretion disc. Understanding the physical processes that determine the rate at which matter accretes and energy is radiated in these discs is vital for unraveling the formation, evolution, and fate of almost every type of object in the Universe. Despite the fact that magnetic fields have been known to be crucial in accretion discs since the early 90’s, the majority of astrophysical questions that depend on the details of how disc accretion proceeds are still being addressed using the “standard” accretion disc model (developed in the early 70’s), where magnetic fields do not play an explicit role. This has prevented us from fully exploring the astrophysical consequences and observational signatures of realistic accretion disc models, leading to a profound disconnect between observations (usually interpreted with the standard paradigm) and modern accretion disc theory and numerical simulations (where magnetic turbulence is crucial). The goal of this proposal is to use several complementary approaches in order to finally move beyond the standard paradigm. This program has two main objectives: 1) Develop the theoretical framework to incorporate magnetic fields, and the ensuing turbulence, into self-consistent accretion disc models, and investigate their observational implications. 2) Investigate transport and radiative processes in collision-less disc regions, where non-thermal radiation originates, by employing a kinetic particle description of the plasma. In order to achieve these goals, we will use, and build upon, state-of-the-art magnetohydrodynamic and particle-in-cell codes in conjunction with theoretical modeling. This framework will make it possible to address fundamental questions on stellar and planet formation, binary systems with a compact object, and supermassive black hole feedback in a way that has no counterpart within the standard paradigm.
Summary
Most celestial bodies, from planets, to stars, to black holes; gain mass during their lives by means of an accretion disc. Understanding the physical processes that determine the rate at which matter accretes and energy is radiated in these discs is vital for unraveling the formation, evolution, and fate of almost every type of object in the Universe. Despite the fact that magnetic fields have been known to be crucial in accretion discs since the early 90’s, the majority of astrophysical questions that depend on the details of how disc accretion proceeds are still being addressed using the “standard” accretion disc model (developed in the early 70’s), where magnetic fields do not play an explicit role. This has prevented us from fully exploring the astrophysical consequences and observational signatures of realistic accretion disc models, leading to a profound disconnect between observations (usually interpreted with the standard paradigm) and modern accretion disc theory and numerical simulations (where magnetic turbulence is crucial). The goal of this proposal is to use several complementary approaches in order to finally move beyond the standard paradigm. This program has two main objectives: 1) Develop the theoretical framework to incorporate magnetic fields, and the ensuing turbulence, into self-consistent accretion disc models, and investigate their observational implications. 2) Investigate transport and radiative processes in collision-less disc regions, where non-thermal radiation originates, by employing a kinetic particle description of the plasma. In order to achieve these goals, we will use, and build upon, state-of-the-art magnetohydrodynamic and particle-in-cell codes in conjunction with theoretical modeling. This framework will make it possible to address fundamental questions on stellar and planet formation, binary systems with a compact object, and supermassive black hole feedback in a way that has no counterpart within the standard paradigm.
Max ERC Funding
1 793 697 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym 2STEPPARKIN
Project A novel two-step model for neurodegeneration in Parkinson’s disease
Researcher (PI) Emi Nagoshi
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Starting Grant (StG), LS5, ERC-2012-StG_20111109
Summary Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Despite the advances in gene discovery associated with PD, the knowledge of the PD pathogenesis is largely limited to the involvement of these genes in the generic cell death pathways, and why degeneration is specific to DA neurons and why the degeneration is progressive remain enigmatic. Broad goal of our work is therefore to elucidate the mechanisms underlying specific and progressive DA neuron degeneration in PD. Our new Drosophila model of PD ⎯Fer2 gene loss-of-function mutation⎯ is unusually well suited to address these questions. Fer2 mutants exhibit specific and progressive death of brain DA neurons as well as severe locomotor defects and short life span. Strikingly, the death of DA neuron is initiated in a small cluster of Fer2-expressing DA neurons and subsequently propagates to Fer2-negative DA neurons. We therefore propose a novel two-step model of the neurodegeneration in PD: primary cell death occurs in a specific subset of dopamindegic neurons that are genetically defined, and subsequently the failure of the neuronal connectivity triggers and propagates secondary cell death to remaining DA neurons. In this research, we will test this hypothesis and investigate the underlying molecular mechanisms. This will be the first study to examine circuit-dependency in DA neuron degeneration. Our approach will use a combination of non-biased genomic techniques and candidate-based screening, in addition to the powerful Drosophila genetic toolbox. Furthermore, to test this hypothesis beyond the Drosophila model, we will establish new mouse models of PD that exhibit progressive DA neuron degeneration. Outcome of this research will likely revolutionize the understanding of PD pathogenesis and open an avenue toward the discovery of effective therapy strategies against PD.
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Despite the advances in gene discovery associated with PD, the knowledge of the PD pathogenesis is largely limited to the involvement of these genes in the generic cell death pathways, and why degeneration is specific to DA neurons and why the degeneration is progressive remain enigmatic. Broad goal of our work is therefore to elucidate the mechanisms underlying specific and progressive DA neuron degeneration in PD. Our new Drosophila model of PD ⎯Fer2 gene loss-of-function mutation⎯ is unusually well suited to address these questions. Fer2 mutants exhibit specific and progressive death of brain DA neurons as well as severe locomotor defects and short life span. Strikingly, the death of DA neuron is initiated in a small cluster of Fer2-expressing DA neurons and subsequently propagates to Fer2-negative DA neurons. We therefore propose a novel two-step model of the neurodegeneration in PD: primary cell death occurs in a specific subset of dopamindegic neurons that are genetically defined, and subsequently the failure of the neuronal connectivity triggers and propagates secondary cell death to remaining DA neurons. In this research, we will test this hypothesis and investigate the underlying molecular mechanisms. This will be the first study to examine circuit-dependency in DA neuron degeneration. Our approach will use a combination of non-biased genomic techniques and candidate-based screening, in addition to the powerful Drosophila genetic toolbox. Furthermore, to test this hypothesis beyond the Drosophila model, we will establish new mouse models of PD that exhibit progressive DA neuron degeneration. Outcome of this research will likely revolutionize the understanding of PD pathogenesis and open an avenue toward the discovery of effective therapy strategies against PD.
Max ERC Funding
1 518 960 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym 3D-JOINT
Project 3D Bioprinting of JOINT Replacements
Researcher (PI) Johannes Jos Malda
Host Institution (HI) UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Call Details Consolidator Grant (CoG), LS7, ERC-2014-CoG
Summary The world has a significant medical challenge in repairing injured or diseased joints. Joint degeneration and its related pain is a major socio-economic burden that will increase over the next decade and is currently addressed by implanting a metal prosthesis. For the long term, the ideal solution to joint injury is to successfully regenerate rather than replace the damaged cartilage with synthetic implants. Recent advances in key technologies are now bringing this “holy grail” within reach; regenerative approaches, based on cell therapy, are already clinically available albeit only for smaller focal cartilage defects.
One of these key technologies is three-dimensional (3D) bio-printing, which provides a greatly controlled placement and organization of living constructs through the layer-by-layer deposition of materials and cells. These tissue constructs can be applied as tissue models for research and screening. However, the lack of biomechanical properties of these tissue constructs has hampered their application to the regeneration of damaged, degenerated or diseased tissue.
Having established a cartilage-focussed research laboratory in the University Medical Center Utrecht, I have addressed this biomechanical limitation of hydrogels through the use of hydrogel composites. Specifically, I have pioneered a 3D bio-printing technology that combines accurately printed small diameter thermoplast filaments with cell invasive hydrogels to form strong fibre-reinforced constructs. This, in combination with bioreactor technology, is the key to the generation of larger, complex tissue constructs with cartilage-like biomechanical resilience. With 3D-JOINT I will use my in-depth bio-printing and bioreactor knowledge and experience to develop a multi-phasic 3D-printed biological replacement of the joint.
Summary
The world has a significant medical challenge in repairing injured or diseased joints. Joint degeneration and its related pain is a major socio-economic burden that will increase over the next decade and is currently addressed by implanting a metal prosthesis. For the long term, the ideal solution to joint injury is to successfully regenerate rather than replace the damaged cartilage with synthetic implants. Recent advances in key technologies are now bringing this “holy grail” within reach; regenerative approaches, based on cell therapy, are already clinically available albeit only for smaller focal cartilage defects.
One of these key technologies is three-dimensional (3D) bio-printing, which provides a greatly controlled placement and organization of living constructs through the layer-by-layer deposition of materials and cells. These tissue constructs can be applied as tissue models for research and screening. However, the lack of biomechanical properties of these tissue constructs has hampered their application to the regeneration of damaged, degenerated or diseased tissue.
Having established a cartilage-focussed research laboratory in the University Medical Center Utrecht, I have addressed this biomechanical limitation of hydrogels through the use of hydrogel composites. Specifically, I have pioneered a 3D bio-printing technology that combines accurately printed small diameter thermoplast filaments with cell invasive hydrogels to form strong fibre-reinforced constructs. This, in combination with bioreactor technology, is the key to the generation of larger, complex tissue constructs with cartilage-like biomechanical resilience. With 3D-JOINT I will use my in-depth bio-printing and bioreactor knowledge and experience to develop a multi-phasic 3D-printed biological replacement of the joint.
Max ERC Funding
1 998 871 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym 3D-OA-HISTO
Project Development of 3D Histopathological Grading of Osteoarthritis
Researcher (PI) Simo Jaakko Saarakkala
Host Institution (HI) OULUN YLIOPISTO
Call Details Starting Grant (StG), LS7, ERC-2013-StG
Summary "Background: Osteoarthritis (OA) is a common musculoskeletal disease occurring worldwide. Despite extensive research, etiology of OA is still poorly understood. Histopathological grading (HPG) of 2D tissue sections is the gold standard reference method for determination of OA stage. However, traditional 2D-HPG is destructive and based only on subjective visual evaluation. These limitations induce bias to clinical in vitro OA diagnostics and basic research that both rely strongly on HPG.
Objectives: 1) To establish and validate the very first 3D-HPG of OA based on cutting-edge nano/micro-CT (Computed Tomography) technologies in vitro; 2) To use the established method to clarify the beginning phases of OA; and 3) To validate 3D-HPG of OA for in vivo use.
Methods: Several hundreds of human osteochondral samples from patients undergoing total knee arthroplasty will be collected. The samples will be imaged in vitro with nano/micro-CT and clinical high-end extremity CT devices using specific contrast-agents to quantify tissue constituents and structure in 3D in large volume. From this information, a novel 3D-HPG is developed with statistical classification algorithms. Finally, the developed novel 3D-HPG of OA will be applied clinically in vivo.
Significance: This is the very first study to establish 3D-HPG of OA pathology in vitro and in vivo. Furthermore, the developed technique hugely improves the understanding of the beginning phases of OA. Ultimately, the study will contribute for improving OA patients’ quality of life by slowing the disease progression, and for providing powerful tools to develop new OA therapies."
Summary
"Background: Osteoarthritis (OA) is a common musculoskeletal disease occurring worldwide. Despite extensive research, etiology of OA is still poorly understood. Histopathological grading (HPG) of 2D tissue sections is the gold standard reference method for determination of OA stage. However, traditional 2D-HPG is destructive and based only on subjective visual evaluation. These limitations induce bias to clinical in vitro OA diagnostics and basic research that both rely strongly on HPG.
Objectives: 1) To establish and validate the very first 3D-HPG of OA based on cutting-edge nano/micro-CT (Computed Tomography) technologies in vitro; 2) To use the established method to clarify the beginning phases of OA; and 3) To validate 3D-HPG of OA for in vivo use.
Methods: Several hundreds of human osteochondral samples from patients undergoing total knee arthroplasty will be collected. The samples will be imaged in vitro with nano/micro-CT and clinical high-end extremity CT devices using specific contrast-agents to quantify tissue constituents and structure in 3D in large volume. From this information, a novel 3D-HPG is developed with statistical classification algorithms. Finally, the developed novel 3D-HPG of OA will be applied clinically in vivo.
Significance: This is the very first study to establish 3D-HPG of OA pathology in vitro and in vivo. Furthermore, the developed technique hugely improves the understanding of the beginning phases of OA. Ultimately, the study will contribute for improving OA patients’ quality of life by slowing the disease progression, and for providing powerful tools to develop new OA therapies."
Max ERC Funding
1 500 000 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym 3DBrainStrom
Project Brain metastases: Deciphering tumor-stroma interactions in three dimensions for the rational design of nanomedicines
Researcher (PI) Ronit Satchi Fainaro
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Advanced Grant (AdG), LS7, ERC-2018-ADG
Summary Brain metastases represent a major therapeutic challenge. Despite significant breakthroughs in targeted therapies, survival rates of patients with brain metastases remain poor. Nowadays, discovery, development and evaluation of new therapies are performed on human cancer cells grown in 2D on rigid plastic plates followed by in vivo testing in immunodeficient mice. These experimental settings are lacking and constitute a fundamental hurdle for the translation of preclinical discoveries into clinical practice. We propose to establish 3D-printed models of brain metastases (Aim 1), which include brain extracellular matrix, stroma and serum containing immune cells flowing in functional tumor vessels. Our unique models better capture the clinical physio-mechanical tissue properties, signaling pathways, hemodynamics and drug responsiveness. Using our 3D-printed models, we aim to develop two new fronts for identifying novel clinically-relevant molecular drivers (Aim 2) followed by the development of precision nanomedicines (Aim 3). We will exploit our vast experience in anticancer nanomedicines to design three therapeutic approaches that target various cellular compartments involved in brain metastases: 1) Prevention of brain metastatic colonization using targeted nano-vaccines, which elicit antitumor immune response; 2) Intervention of tumor-brain stroma cells crosstalk when brain micrometastases establish; 3) Regression of macrometastatic disease by selectively targeting tumor cells. These approaches will materialize using our libraries of polymeric nanocarriers that selectively accumulate in tumors.
This project will result in a paradigm shift by generating new preclinical cancer models that will bridge the translational gap in cancer therapeutics. The insights and tumor-stroma-targeted nanomedicines developed here will pave the way for prediction of patient outcome, revolutionizing our perception of tumor modelling and consequently the way we prevent and treat cancer.
Summary
Brain metastases represent a major therapeutic challenge. Despite significant breakthroughs in targeted therapies, survival rates of patients with brain metastases remain poor. Nowadays, discovery, development and evaluation of new therapies are performed on human cancer cells grown in 2D on rigid plastic plates followed by in vivo testing in immunodeficient mice. These experimental settings are lacking and constitute a fundamental hurdle for the translation of preclinical discoveries into clinical practice. We propose to establish 3D-printed models of brain metastases (Aim 1), which include brain extracellular matrix, stroma and serum containing immune cells flowing in functional tumor vessels. Our unique models better capture the clinical physio-mechanical tissue properties, signaling pathways, hemodynamics and drug responsiveness. Using our 3D-printed models, we aim to develop two new fronts for identifying novel clinically-relevant molecular drivers (Aim 2) followed by the development of precision nanomedicines (Aim 3). We will exploit our vast experience in anticancer nanomedicines to design three therapeutic approaches that target various cellular compartments involved in brain metastases: 1) Prevention of brain metastatic colonization using targeted nano-vaccines, which elicit antitumor immune response; 2) Intervention of tumor-brain stroma cells crosstalk when brain micrometastases establish; 3) Regression of macrometastatic disease by selectively targeting tumor cells. These approaches will materialize using our libraries of polymeric nanocarriers that selectively accumulate in tumors.
This project will result in a paradigm shift by generating new preclinical cancer models that will bridge the translational gap in cancer therapeutics. The insights and tumor-stroma-targeted nanomedicines developed here will pave the way for prediction of patient outcome, revolutionizing our perception of tumor modelling and consequently the way we prevent and treat cancer.
Max ERC Funding
2 353 125 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym 3DICE
Project 3D Interstellar Chemo-physical Evolution
Researcher (PI) Valentine Wakelam
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE9, ERC-2013-StG
Summary At the end of their life, stars spread their inner material into the diffuse interstellar medium. This diffuse medium gets locally denser and form dark clouds (also called dense or molecular clouds) whose innermost part is shielded from the external UV field by the dust, allowing for molecules to grow and get more complex. Gravitational collapse occurs inside these dense clouds, forming protostars and their surrounding disks, and eventually planetary systems like (or unlike) our solar system. The formation and evolution of molecules, minerals, ices and organics from the diffuse medium to planetary bodies, their alteration or preservation throughout this cosmic chemical history set the initial conditions for building planets, atmospheres and possibly the first bricks of life. The current view of interstellar chemistry is based on fragmental works on key steps of the sequence that are observed. The objective of this proposal is to follow the fractionation of the elements between the gas-phase and the interstellar grains, from the most diffuse medium to protoplanetary disks, in order to constrain the chemical composition of the material in which planets are formed. The potential outcome of this project is to get a consistent and more accurate description of the chemical evolution of interstellar matter. To achieve this objective, I will improve our chemical model by adding new processes on grain surfaces relevant under the diffuse medium conditions. This upgraded gas-grain model will be coupled to 3D dynamical models of the formation of dense clouds from diffuse medium and of protoplanetary disks from dense clouds. The computed chemical composition will also be used with 3D radiative transfer codes to study the chemical tracers of the physics of protoplanetary disk formation. The robustness of the model predictions will be studied with sensitivity analyses. Finally, model results will be confronted to observations to address some of the current challenges.
Summary
At the end of their life, stars spread their inner material into the diffuse interstellar medium. This diffuse medium gets locally denser and form dark clouds (also called dense or molecular clouds) whose innermost part is shielded from the external UV field by the dust, allowing for molecules to grow and get more complex. Gravitational collapse occurs inside these dense clouds, forming protostars and their surrounding disks, and eventually planetary systems like (or unlike) our solar system. The formation and evolution of molecules, minerals, ices and organics from the diffuse medium to planetary bodies, their alteration or preservation throughout this cosmic chemical history set the initial conditions for building planets, atmospheres and possibly the first bricks of life. The current view of interstellar chemistry is based on fragmental works on key steps of the sequence that are observed. The objective of this proposal is to follow the fractionation of the elements between the gas-phase and the interstellar grains, from the most diffuse medium to protoplanetary disks, in order to constrain the chemical composition of the material in which planets are formed. The potential outcome of this project is to get a consistent and more accurate description of the chemical evolution of interstellar matter. To achieve this objective, I will improve our chemical model by adding new processes on grain surfaces relevant under the diffuse medium conditions. This upgraded gas-grain model will be coupled to 3D dynamical models of the formation of dense clouds from diffuse medium and of protoplanetary disks from dense clouds. The computed chemical composition will also be used with 3D radiative transfer codes to study the chemical tracers of the physics of protoplanetary disk formation. The robustness of the model predictions will be studied with sensitivity analyses. Finally, model results will be confronted to observations to address some of the current challenges.
Max ERC Funding
1 166 231 €
Duration
Start date: 2013-09-01, End date: 2018-08-31
Project acronym 3Ps
Project 3Ps
Plastic-Antibodies, Plasmonics and Photovoltaic-Cells: on-site screening of cancer biomarkers made possible
Researcher (PI) Maria Goreti Ferreira Sales
Host Institution (HI) INSTITUTO SUPERIOR DE ENGENHARIA DO PORTO
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
Summary This project presents a new concept for the detection, diagnosis and monitoring of cancer biomarker patterns in point-of-care. The device under development will make use of the selectivity of the plastic antibodies as sensing materials and the interference they will play on the normal operation of a photovoltaic cell.
Plastic antibodies will be designed by surface imprinting procedures. Self-assembled monolayer and molecular imprinting techniques will be merged in this process because they allow the self-assembly of nanostructured materials on a “bottom-up” nanofabrication approach. A dye-sensitized solar cell will be used as photovoltaic cell. It includes a liquid interface in the cell circuit, which allows the introduction of the sample (also in liquid phase) without disturbing the normal cell operation. Furthermore, it works well with rather low cost materials and requires mild and easy processing conditions. The cell will be equipped with plasmonic structures to enhance light absorption and cell efficiency.
The device under development will be easily operated by any clinician or patient. It will require ambient light and a regular multimeter. Eye detection will be also tried out.
Summary
This project presents a new concept for the detection, diagnosis and monitoring of cancer biomarker patterns in point-of-care. The device under development will make use of the selectivity of the plastic antibodies as sensing materials and the interference they will play on the normal operation of a photovoltaic cell.
Plastic antibodies will be designed by surface imprinting procedures. Self-assembled monolayer and molecular imprinting techniques will be merged in this process because they allow the self-assembly of nanostructured materials on a “bottom-up” nanofabrication approach. A dye-sensitized solar cell will be used as photovoltaic cell. It includes a liquid interface in the cell circuit, which allows the introduction of the sample (also in liquid phase) without disturbing the normal cell operation. Furthermore, it works well with rather low cost materials and requires mild and easy processing conditions. The cell will be equipped with plasmonic structures to enhance light absorption and cell efficiency.
The device under development will be easily operated by any clinician or patient. It will require ambient light and a regular multimeter. Eye detection will be also tried out.
Max ERC Funding
998 584 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym 4D-PET
Project Innovative PET scanner for dynamic imaging
Researcher (PI) José María BENLLOCH BAVIERA
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), LS7, ERC-2015-AdG
Summary The main objective of 4D-PET is to develop an innovative whole-body PET scanner based in a new detector concept that stores 3D position and time of every single gamma interaction with unprecedented resolution. The combination of scanner geometrical design and high timing resolution will enable developing a full sequence of all gamma-ray interactions inside the scanner, including Compton interactions, like in a 3D movie. 4D-PET fully exploits Time Of Flight (TOF) information to obtain a better image quality and to increase scanner sensitivity, through the inclusion in the image formation of all Compton events occurring inside the detector, which are always rejected in state-of-the-art PET scanners. The new PET design will radically improve state-of-the-art PET performance features, overcoming limitations of current PET technology and opening up new diagnostic venues and very valuable physiological information
Summary
The main objective of 4D-PET is to develop an innovative whole-body PET scanner based in a new detector concept that stores 3D position and time of every single gamma interaction with unprecedented resolution. The combination of scanner geometrical design and high timing resolution will enable developing a full sequence of all gamma-ray interactions inside the scanner, including Compton interactions, like in a 3D movie. 4D-PET fully exploits Time Of Flight (TOF) information to obtain a better image quality and to increase scanner sensitivity, through the inclusion in the image formation of all Compton events occurring inside the detector, which are always rejected in state-of-the-art PET scanners. The new PET design will radically improve state-of-the-art PET performance features, overcoming limitations of current PET technology and opening up new diagnostic venues and very valuable physiological information
Max ERC Funding
2 048 386 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym 4PI-SKY
Project 4 pi sky: Extreme Astrophysics with Revolutionary Radio Telescopes
Researcher (PI) Robert Philip Fender
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), PE9, ERC-2010-AdG_20100224
Summary Extreme astrophysical events such as relativistic flows, cataclysmic explosions and black hole accretion are one of the key areas for astrophysics in the 21st century. The extremes of physics experienced in these environments are beyond anything achievable in any laboratory on Earth, and provide a unique glimpse at the laws of physics operating in extraordinary regimes. All of these events are associated with transient radio emission, a tracer both of the acceleration of particles to relativistic energies, and coherent emitting regions with huge effective temperatures. By studying radio bursts from these phenomena we can pinpoint the sources of explosive events, understand the budget of kinetic feedback by explosive events in the ambient medium, and probe the physical state of the universe back to the epoch of reionisation, less than a billion years after the big bang. In seeking to push back the frontiers of extreme astrophysics, I will use a trio of revolutionary new radio telescopes, LOFAR, ASKAP and MeerKAT, pathfinders for the Square Kilometre Array, and all facilities in which I have a major role in the search for transients. I will build an infrastructure which transforms their combined operations for the discovery, classification and reporting of transient astrophysical events, over the whole sky, making them much more than the sum of their parts. This will include development of environments for the coordinated handling of extreme astrophysical events, in real time, via automated systems, as well as novel techniques for the detection of these events in a sea of noise. I will furthermore augment this program by buying in as a major partner to a rapid-response robotic optical telescope, and by cementing my relationship with an orbiting X-ray facility. This multiwavelength dimension will secure the astrophysical interpretation of our observational results and help to revolutionise high-energy astrophysics via a strong scientific exploitation program.
Summary
Extreme astrophysical events such as relativistic flows, cataclysmic explosions and black hole accretion are one of the key areas for astrophysics in the 21st century. The extremes of physics experienced in these environments are beyond anything achievable in any laboratory on Earth, and provide a unique glimpse at the laws of physics operating in extraordinary regimes. All of these events are associated with transient radio emission, a tracer both of the acceleration of particles to relativistic energies, and coherent emitting regions with huge effective temperatures. By studying radio bursts from these phenomena we can pinpoint the sources of explosive events, understand the budget of kinetic feedback by explosive events in the ambient medium, and probe the physical state of the universe back to the epoch of reionisation, less than a billion years after the big bang. In seeking to push back the frontiers of extreme astrophysics, I will use a trio of revolutionary new radio telescopes, LOFAR, ASKAP and MeerKAT, pathfinders for the Square Kilometre Array, and all facilities in which I have a major role in the search for transients. I will build an infrastructure which transforms their combined operations for the discovery, classification and reporting of transient astrophysical events, over the whole sky, making them much more than the sum of their parts. This will include development of environments for the coordinated handling of extreme astrophysical events, in real time, via automated systems, as well as novel techniques for the detection of these events in a sea of noise. I will furthermore augment this program by buying in as a major partner to a rapid-response robotic optical telescope, and by cementing my relationship with an orbiting X-ray facility. This multiwavelength dimension will secure the astrophysical interpretation of our observational results and help to revolutionise high-energy astrophysics via a strong scientific exploitation program.
Max ERC Funding
2 999 847 €
Duration
Start date: 2011-07-01, End date: 2017-06-30
Project acronym 5D Heart Patch
Project A Functional, Mature In vivo Human Ventricular Muscle Patch for Cardiomyopathy
Researcher (PI) Kenneth Randall Chien
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Advanced Grant (AdG), LS7, ERC-2016-ADG
Summary Developing new therapeutic strategies for heart regeneration is a major goal for cardiac biology and medicine. While cardiomyocytes can be generated from human pluripotent stem (hPSC) cells in vitro, it has proven difficult to use these cells to generate a large scale, mature human heart ventricular muscle graft on the injured heart in vivo. The central objective of this proposal is to optimize the generation of a large-scale pure, fully functional human ventricular muscle patch in vivo through the self-assembly of purified human ventricular progenitors and the localized expression of defined paracrine factors that drive their expansion, differentiation, vascularization, matrix formation, and maturation. Recently, we have found that purified hPSC-derived ventricular progenitors (HVPs) can self-assemble in vivo on the epicardial surface into a 3D vascularized, and functional ventricular patch with its own extracellular matrix via a cell autonomous pathway. A two-step protocol and FACS purification of HVP receptors can generate billions of pure HVPs- The current proposal will lead to the identification of defined paracrine pathways to enhance the survival, grafting/implantation, expansion, differentiation, matrix formation, vascularization and maturation of the graft in vivo. We will captalize on our unique HVP system and our novel modRNA technology to deliver therapeutic strategies by using the in vivo human ventricular muscle to model in vivo arrhythmogenic cardiomyopathy, and optimize the ability of the graft to compensate for the massive loss of functional muscle during ischemic cardiomyopathy and post-myocardial infarction. The studies will lead to new in vivo chimeric models of human cardiac disease and an experimental paradigm to optimize organ-on-organ cardiac tissue engineers of an in vivo, functional mature ventricular patch for cardiomyopathy
Summary
Developing new therapeutic strategies for heart regeneration is a major goal for cardiac biology and medicine. While cardiomyocytes can be generated from human pluripotent stem (hPSC) cells in vitro, it has proven difficult to use these cells to generate a large scale, mature human heart ventricular muscle graft on the injured heart in vivo. The central objective of this proposal is to optimize the generation of a large-scale pure, fully functional human ventricular muscle patch in vivo through the self-assembly of purified human ventricular progenitors and the localized expression of defined paracrine factors that drive their expansion, differentiation, vascularization, matrix formation, and maturation. Recently, we have found that purified hPSC-derived ventricular progenitors (HVPs) can self-assemble in vivo on the epicardial surface into a 3D vascularized, and functional ventricular patch with its own extracellular matrix via a cell autonomous pathway. A two-step protocol and FACS purification of HVP receptors can generate billions of pure HVPs- The current proposal will lead to the identification of defined paracrine pathways to enhance the survival, grafting/implantation, expansion, differentiation, matrix formation, vascularization and maturation of the graft in vivo. We will captalize on our unique HVP system and our novel modRNA technology to deliver therapeutic strategies by using the in vivo human ventricular muscle to model in vivo arrhythmogenic cardiomyopathy, and optimize the ability of the graft to compensate for the massive loss of functional muscle during ischemic cardiomyopathy and post-myocardial infarction. The studies will lead to new in vivo chimeric models of human cardiac disease and an experimental paradigm to optimize organ-on-organ cardiac tissue engineers of an in vivo, functional mature ventricular patch for cardiomyopathy
Max ERC Funding
2 149 228 €
Duration
Start date: 2017-12-01, End date: 2022-11-30
