Project acronym 2-3-AUT
Project Surfaces, 3-manifolds and automorphism groups
Researcher (PI) Nathalie Wahl
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), PE1, ERC-2009-StG
Summary The scientific goal of the proposal is to answer central questions related to diffeomorphism groups of manifolds of dimension 2 and 3, and to their deformation invariant analogs, the mapping class groups. While the classification of surfaces has been known for more than a century, their automorphism groups have yet to be fully understood. Even less is known about diffeomorphisms of 3-manifolds despite much interest, and the objects here have only been classified recently, by the breakthrough work of Perelman on the Poincar\'e and geometrization conjectures. In dimension 2, I will focus on the relationship between mapping class groups and topological conformal field theories, with applications to Hochschild homology. In dimension 3, I propose to compute the stable homology of classifying spaces of diffeomorphism groups and mapping class groups, as well as study the homotopy type of the space of diffeomorphisms. I propose moreover to establish homological stability theorems in the wider context of automorphism groups and more general families of groups. The project combines breakthrough methods from homotopy theory with methods from differential and geometric topology. The research team will consist of 3 PhD students, and 4 postdocs, which I will lead.
Summary
The scientific goal of the proposal is to answer central questions related to diffeomorphism groups of manifolds of dimension 2 and 3, and to their deformation invariant analogs, the mapping class groups. While the classification of surfaces has been known for more than a century, their automorphism groups have yet to be fully understood. Even less is known about diffeomorphisms of 3-manifolds despite much interest, and the objects here have only been classified recently, by the breakthrough work of Perelman on the Poincar\'e and geometrization conjectures. In dimension 2, I will focus on the relationship between mapping class groups and topological conformal field theories, with applications to Hochschild homology. In dimension 3, I propose to compute the stable homology of classifying spaces of diffeomorphism groups and mapping class groups, as well as study the homotopy type of the space of diffeomorphisms. I propose moreover to establish homological stability theorems in the wider context of automorphism groups and more general families of groups. The project combines breakthrough methods from homotopy theory with methods from differential and geometric topology. The research team will consist of 3 PhD students, and 4 postdocs, which I will lead.
Max ERC Funding
724 992 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym 2LIVEr
Project IL-2 gene therapy for chronic hepatitis B virus infection
Researcher (PI) Matteo IANNACONE
Host Institution (HI) OSPEDALE SAN RAFFAELE SRL
Country Italy
Call Details Proof of Concept (PoC), ERC-2020-PoC
Summary Hepatitis B virus (HBV) infections remain a major public health issue worldwide. Over 350 -400 million people are chronically infected by HBV, and about 1 million people die each year from the complications of this infection (cirrhosis and hepatocellular carcinoma) with a consequent hefty economic impact on national health systems. This led the World Health Organization to recognise HBV infection as a key priority and adopt the global health sector strategy to eliminate viral hepatitis, with a target of reducing new infections by 90% and mortality by 65% by 2030.
The risk of developing a chronic infection in healthy adults is due to a weaker, dysfunctional and narrowly focused CD8+ T cell response. Since the mechanisms underlying HBV persistence are not fully elucidated, current treatments (antiviral drugs and Interferon) aim to reduce the development of liver disease, while a definitive treatment for curing this infection is not yet available on the market.
Within the ERC Consolidator Grant 725038 “FATE”, we recently characterized the mechanisms behind the ineffective CD8+ T cell response towards HBV, demonstrating the potential efficacy of interleukin-2 (IL-2) – a cytokine – to reactivate it, thus achieving antiviral activity. This discovery, jointly with our proprietary third-generation, self-inactivating lentiviral vectors (LVs) that allow selective hepatocellular expression of IL-2, pave the way to single-dose gene therapy-based approach, a potential functional cure against chronic hepatitis B.
2LIVEr project intends to optimize and further validate our novel therapeutic approach from both a technical and commercial standpoint, moving from TRL3 to TRL4, thus fastening the roadmap towards the market.
Summary
Hepatitis B virus (HBV) infections remain a major public health issue worldwide. Over 350 -400 million people are chronically infected by HBV, and about 1 million people die each year from the complications of this infection (cirrhosis and hepatocellular carcinoma) with a consequent hefty economic impact on national health systems. This led the World Health Organization to recognise HBV infection as a key priority and adopt the global health sector strategy to eliminate viral hepatitis, with a target of reducing new infections by 90% and mortality by 65% by 2030.
The risk of developing a chronic infection in healthy adults is due to a weaker, dysfunctional and narrowly focused CD8+ T cell response. Since the mechanisms underlying HBV persistence are not fully elucidated, current treatments (antiviral drugs and Interferon) aim to reduce the development of liver disease, while a definitive treatment for curing this infection is not yet available on the market.
Within the ERC Consolidator Grant 725038 “FATE”, we recently characterized the mechanisms behind the ineffective CD8+ T cell response towards HBV, demonstrating the potential efficacy of interleukin-2 (IL-2) – a cytokine – to reactivate it, thus achieving antiviral activity. This discovery, jointly with our proprietary third-generation, self-inactivating lentiviral vectors (LVs) that allow selective hepatocellular expression of IL-2, pave the way to single-dose gene therapy-based approach, a potential functional cure against chronic hepatitis B.
2LIVEr project intends to optimize and further validate our novel therapeutic approach from both a technical and commercial standpoint, moving from TRL3 to TRL4, thus fastening the roadmap towards the market.
Max ERC Funding
150 000 €
Duration
Start date: 2020-07-01, End date: 2021-12-31
Project acronym 3DALIGN
Project Enhancing the performance of 3D-printed organic thermoelectrics by electric field-assisted molecular alignment
Researcher (PI) Francisco Molina-Lopez
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Country Belgium
Call Details Starting Grant (StG), PE7, ERC-2020-STG
Summary Thermoelectrics (TEs) are important because they can convert heat directly into electrical energy and enable efficient heating/cooling. However, their popularization has been hindered by 1) their low efficiency (especially at room temperature), 2) the use of rare/toxic materials, and 3) the difficulty to process those materials. In 3DALIGN, I target a 3-in-1 solution to these challenges by using for the first time electric-field-assisted molecular alignment of 3D-printed TE polymers. High electrical/low thermal conductivity is required for efficient TEs, but both conductivities go hand in hand in traditional inorganic TE materials. This paradigm can shift for polymers, which possess complicated molecular structure. Despite their relatively low electrical conductivity, conducting polymers are appealing for TEs due to their much lower thermal conductivity than inorganic TE materials. Existing studies of organic TEs have focused on finding new materials, but no attention has been paid to molecular ordering, a known strategy to improve performance in organic transistors. I have recently developed a versatile method to induce molecular alignment in solution-processed polymers by using externally applied electric fields. In 3DALIGN, I propose to use this new method to boost the electrical conductivity of polymer TEs while inducing minimal alteration in their thermal conductivity. The high-risk of this goal is mitigated by other advantages of using polymer TEs: polymers are less toxic and more abundant than inorganic TE materials; and they are easy to 3D print, enabling a simple fabrication route for large-area through-plane TE structures that will lead to novel applications. In conclusion, this project will shed light in the relationship between molecular ordering and transport properties of organic electronic materials. If successful, it will also introduce a breakthrough in the performance and feasibility of TEs.
Summary
Thermoelectrics (TEs) are important because they can convert heat directly into electrical energy and enable efficient heating/cooling. However, their popularization has been hindered by 1) their low efficiency (especially at room temperature), 2) the use of rare/toxic materials, and 3) the difficulty to process those materials. In 3DALIGN, I target a 3-in-1 solution to these challenges by using for the first time electric-field-assisted molecular alignment of 3D-printed TE polymers. High electrical/low thermal conductivity is required for efficient TEs, but both conductivities go hand in hand in traditional inorganic TE materials. This paradigm can shift for polymers, which possess complicated molecular structure. Despite their relatively low electrical conductivity, conducting polymers are appealing for TEs due to their much lower thermal conductivity than inorganic TE materials. Existing studies of organic TEs have focused on finding new materials, but no attention has been paid to molecular ordering, a known strategy to improve performance in organic transistors. I have recently developed a versatile method to induce molecular alignment in solution-processed polymers by using externally applied electric fields. In 3DALIGN, I propose to use this new method to boost the electrical conductivity of polymer TEs while inducing minimal alteration in their thermal conductivity. The high-risk of this goal is mitigated by other advantages of using polymer TEs: polymers are less toxic and more abundant than inorganic TE materials; and they are easy to 3D print, enabling a simple fabrication route for large-area through-plane TE structures that will lead to novel applications. In conclusion, this project will shed light in the relationship between molecular ordering and transport properties of organic electronic materials. If successful, it will also introduce a breakthrough in the performance and feasibility of TEs.
Max ERC Funding
1 710 853 €
Duration
Start date: 2021-02-01, End date: 2026-01-31
Project acronym 3DX-FLASH
Project Probing MHz processes in 3D with X-ray microscopy
Researcher (PI) Pablo Villanueva Perez
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE4, ERC-2020-STG
Summary I aim to develop an X-ray imaging technique capable of filming processes in 3D, with a temporal resolution several orders of magnitude faster than up-to-date 3D X-ray imaging techniques.
The unique penetration power of X-rays allows us to study systems in their native environment. This property has led to the development of X-ray microtomography (µCT). µCT acquires 3D information, which determines the functionality and mechanical properties of nature, by rotating a sample with respect to the X-ray source. µCT is a crucial tool for several scientific disciplines such as physics, biology, and chemistry.
Over the last decade, µCT has become a technique capable of not only recording 3D information but also filming dynamical processes. Several breakthroughs have made this possible: i) intense X-ray sources (synchrotron light sources), ii) efficient and fast X-ray detectors, and iii) fast 3D reconstruction algorithms. Despite all of these developments, the acquisition protocols remain unchanged, i.e., the sample is only rotated faster. This fast rotation introduces forces which may alter the studied dynamics and ultimately limit the achievable temporal resolution.
My project is to establish an X-ray microscope that avoids the sample rotation, obtaining 3D information from a single X-ray flash by splitting it into nine-angularly resolved beams which illuminate the sample simultaneously. This approach, when implemented at intense X-ray sources such as synchrotron light sources and X-ray free-electron lasers, will allow the filming of natural processes with micrometer to nanometer resolution and resolve dynamics from microseconds to femtoseconds. To demonstrate its capabilities, I will study fundamental processes in cellulose fibers, a renewable biomaterial, which can replace fossil-based materials, such as plastics. This technique will open up the possibility to film dynamics in 3D to answer questions coming from industry and natural sciences at rates not accessible today.
Summary
I aim to develop an X-ray imaging technique capable of filming processes in 3D, with a temporal resolution several orders of magnitude faster than up-to-date 3D X-ray imaging techniques.
The unique penetration power of X-rays allows us to study systems in their native environment. This property has led to the development of X-ray microtomography (µCT). µCT acquires 3D information, which determines the functionality and mechanical properties of nature, by rotating a sample with respect to the X-ray source. µCT is a crucial tool for several scientific disciplines such as physics, biology, and chemistry.
Over the last decade, µCT has become a technique capable of not only recording 3D information but also filming dynamical processes. Several breakthroughs have made this possible: i) intense X-ray sources (synchrotron light sources), ii) efficient and fast X-ray detectors, and iii) fast 3D reconstruction algorithms. Despite all of these developments, the acquisition protocols remain unchanged, i.e., the sample is only rotated faster. This fast rotation introduces forces which may alter the studied dynamics and ultimately limit the achievable temporal resolution.
My project is to establish an X-ray microscope that avoids the sample rotation, obtaining 3D information from a single X-ray flash by splitting it into nine-angularly resolved beams which illuminate the sample simultaneously. This approach, when implemented at intense X-ray sources such as synchrotron light sources and X-ray free-electron lasers, will allow the filming of natural processes with micrometer to nanometer resolution and resolve dynamics from microseconds to femtoseconds. To demonstrate its capabilities, I will study fundamental processes in cellulose fibers, a renewable biomaterial, which can replace fossil-based materials, such as plastics. This technique will open up the possibility to film dynamics in 3D to answer questions coming from industry and natural sciences at rates not accessible today.
Max ERC Funding
1 999 213 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
Project acronym 3SPIN
Project Three Dimensional Spintronics
Researcher (PI) Russell Paul Cowburn
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Advanced Grant (AdG), PE3, ERC-2009-AdG
Summary Spintronics, in which both the spin and the charge of the electron are used, is one of the most exciting new disciplines to emerge from nanoscience. The 3SPIN project seeks to open a new research front within spintronics: namely 3-dimensional spintronics, in which magnetic nanostructures are formed into a 3-dimensional interacting network of unrivalled density and hence technological benefit. 3SPIN will explore early-stage science that could underpin 3-dimensional metallic spintronics. The thesis of the project is: that by careful control of the constituent nanostructure properties, a 3-dimensional medium can be created in which a large number of topological solitons can exist. Although hardly studied at all to date, these solitons should be stable at room temperature, extremely compact and easy to manipulate and propagate. This makes them potentially ideal candidates to form the basis of a new spintronics in which the soliton is the basic transport vector instead of electrical current. ¬3.5M of funding is requested to form a new team of 5 researchers who, over a period of 60 months, will perform computer simulations and experimental studies of solitons in 3-dimensional networks of magnetic nanostructures and develop a laboratory demonstrator 3-dimensional memory device using solitons to represent and store data. A high performance electron beam lithography system (cost 1M¬) will be purchased to allow state-of-the-art magnetic nanostructures to be fabricated with perfect control over their magnetic properties, thus allowing the ideal conditions for solitons to be created and controllably manipulated. Outputs from the project will be a complete understanding of the properties of these new objects and a road map charting the next steps for research in the field.
Summary
Spintronics, in which both the spin and the charge of the electron are used, is one of the most exciting new disciplines to emerge from nanoscience. The 3SPIN project seeks to open a new research front within spintronics: namely 3-dimensional spintronics, in which magnetic nanostructures are formed into a 3-dimensional interacting network of unrivalled density and hence technological benefit. 3SPIN will explore early-stage science that could underpin 3-dimensional metallic spintronics. The thesis of the project is: that by careful control of the constituent nanostructure properties, a 3-dimensional medium can be created in which a large number of topological solitons can exist. Although hardly studied at all to date, these solitons should be stable at room temperature, extremely compact and easy to manipulate and propagate. This makes them potentially ideal candidates to form the basis of a new spintronics in which the soliton is the basic transport vector instead of electrical current. ¬3.5M of funding is requested to form a new team of 5 researchers who, over a period of 60 months, will perform computer simulations and experimental studies of solitons in 3-dimensional networks of magnetic nanostructures and develop a laboratory demonstrator 3-dimensional memory device using solitons to represent and store data. A high performance electron beam lithography system (cost 1M¬) will be purchased to allow state-of-the-art magnetic nanostructures to be fabricated with perfect control over their magnetic properties, thus allowing the ideal conditions for solitons to be created and controllably manipulated. Outputs from the project will be a complete understanding of the properties of these new objects and a road map charting the next steps for research in the field.
Max ERC Funding
2 799 996 €
Duration
Start date: 2010-03-01, End date: 2016-02-29
Project acronym 4D IMAGING
Project Towards 4D Imaging of Fundamental Processes on the Atomic and Sub-Atomic Scale
Researcher (PI) Ferenc Krausz
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Country Germany
Call Details Advanced Grant (AdG), PE2, ERC-2009-AdG
Summary State-of-the-art microscopy and diffraction imaging provides insight into the atomic and sub-atomic structure of matter. They permit determination of the positions of atoms in a crystal lattice or in a molecule as well as the distribution of electrons inside atoms. State-of-the-art time-resolved spectroscopy with femtosecond and attosecond resolution provides access to dynamic changes in the atomic and electronic structure of matter. Our proposal aims at combining these two frontier techniques of XXI century science to make a long-standing dream of scientist come true: the direct observation of atoms and electrons in their natural state: in motion. Shifts in the atoms positions by tens to hundreds of picometers can make chemical bonds break apart or newly form, changing the structure and/or chemical composition of matter. Electronic motion on similar scales may result in the emission of light, or the initiation of processes that lead to a change in physical or chemical properties, or biological function. These motions happen within femtoseconds and attoseconds, respectively. To make them observable, we need a 4-dimensional (4D) imaging technique capable of recording freeze-frame snapshots of microscopic systems with picometer spatial resolution and femtosecond to attosecond exposure time. The motion can then be visualized by slow-motion replay of the freeze-frame shots. The goal of this project is to develop a 4D imaging technique that will ultimately offer picometer resolution is space and attosecond resolution in time.
Summary
State-of-the-art microscopy and diffraction imaging provides insight into the atomic and sub-atomic structure of matter. They permit determination of the positions of atoms in a crystal lattice or in a molecule as well as the distribution of electrons inside atoms. State-of-the-art time-resolved spectroscopy with femtosecond and attosecond resolution provides access to dynamic changes in the atomic and electronic structure of matter. Our proposal aims at combining these two frontier techniques of XXI century science to make a long-standing dream of scientist come true: the direct observation of atoms and electrons in their natural state: in motion. Shifts in the atoms positions by tens to hundreds of picometers can make chemical bonds break apart or newly form, changing the structure and/or chemical composition of matter. Electronic motion on similar scales may result in the emission of light, or the initiation of processes that lead to a change in physical or chemical properties, or biological function. These motions happen within femtoseconds and attoseconds, respectively. To make them observable, we need a 4-dimensional (4D) imaging technique capable of recording freeze-frame snapshots of microscopic systems with picometer spatial resolution and femtosecond to attosecond exposure time. The motion can then be visualized by slow-motion replay of the freeze-frame shots. The goal of this project is to develop a 4D imaging technique that will ultimately offer picometer resolution is space and attosecond resolution in time.
Max ERC Funding
2 500 000 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym 4D-BIOMAP
Project Biomechanical Stimulation based on 4D Printed Magneto-Active Polymers
Researcher (PI) DANIEL GARCIA GONZALEZ
Host Institution (HI) UNIVERSIDAD CARLOS III DE MADRID
Country Spain
Call Details Starting Grant (StG), PE8, ERC-2020-STG
Summary MAPs are polymer-based composites that respond to magnetic fields with large deformation or tuneable mechanical properties. I aim to apply heterogeneous 3D printed MAPs as modifiable substrates to support biological structures which can have their deformation state and stiffness controlled by the external application of magnetic stimuli. Such mechanical stimulation has an important role on biological structures leading to alterations in functional responses, morphological changes and activation of growth or healing processes. Current bottlenecks preventing progress in this field are a lack of: a) appropriate experimental methodologies to enable characterisation of the behaviour of these materials; b) fundamental theoretical underpinnings to support the design and application of these new materials. The first step is to undertake in depth characterisation and assessment of 4D printed MAPs to create a detailed understanding of the underlying physics controlling the interactions between the polymeric matrices and embedded magnetic particles during application of mechanical and/or magnetic loadings. I will then culture biological structures on the novel 4D printed MAPs to create a ‘designed’ biostructure with specified and controllable responses to a given magnetic stimulus. These novel biostructures will be assessed using three applications: a) astrocyte cellular networks, b) neuronal circuits and c) astrocyte-neuronal networks. The evaluation of cellular damage, morphological and physiological alterations will validate the performance of the new biostructures and also contribute new understanding to the effects of deformation and stiffness gradients during glial scarring on physiological functions of central nervous system cells. The resulting deep understanding of magneto-mechanics of MAPs and their further development for controllable stimulation devices, will enable the international consolidation of my research group within the mechanics and bioengineering fields.
Summary
MAPs are polymer-based composites that respond to magnetic fields with large deformation or tuneable mechanical properties. I aim to apply heterogeneous 3D printed MAPs as modifiable substrates to support biological structures which can have their deformation state and stiffness controlled by the external application of magnetic stimuli. Such mechanical stimulation has an important role on biological structures leading to alterations in functional responses, morphological changes and activation of growth or healing processes. Current bottlenecks preventing progress in this field are a lack of: a) appropriate experimental methodologies to enable characterisation of the behaviour of these materials; b) fundamental theoretical underpinnings to support the design and application of these new materials. The first step is to undertake in depth characterisation and assessment of 4D printed MAPs to create a detailed understanding of the underlying physics controlling the interactions between the polymeric matrices and embedded magnetic particles during application of mechanical and/or magnetic loadings. I will then culture biological structures on the novel 4D printed MAPs to create a ‘designed’ biostructure with specified and controllable responses to a given magnetic stimulus. These novel biostructures will be assessed using three applications: a) astrocyte cellular networks, b) neuronal circuits and c) astrocyte-neuronal networks. The evaluation of cellular damage, morphological and physiological alterations will validate the performance of the new biostructures and also contribute new understanding to the effects of deformation and stiffness gradients during glial scarring on physiological functions of central nervous system cells. The resulting deep understanding of magneto-mechanics of MAPs and their further development for controllable stimulation devices, will enable the international consolidation of my research group within the mechanics and bioengineering fields.
Max ERC Funding
1 499 625 €
Duration
Start date: 2021-01-01, End date: 2025-12-31
Project acronym 5HT-OPTOGENETICS
Project Optogenetic Analysis of Serotonin Function in the Mammalian Brain
Researcher (PI) Zachary Mainen
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Country Portugal
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Summary
Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Max ERC Funding
2 318 636 €
Duration
Start date: 2010-07-01, End date: 2015-12-31
Project acronym AARTFAAC
Project Amsterdam-ASTRON Radio Transient Facility And Analysis Centre: Probing the Extremes of Astrophysics
Researcher (PI) Ralph Antoine Marie Joseph Wijers
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Advanced Grant (AdG), PE9, ERC-2009-AdG
Summary Some of the most extreme tests of physical law come from its manifestations in the behaviour of black holes and neutron stars, and as such these objects should be used as fundamental physics labs. Due to advances in both theoretical work and observational techniques, I have a major opportunity now to significantly push this agenda forward and get better answers to questions like: How are black holes born? How can energy be extracted from black holes? What is the origin of magnetic fields and cosmic rays in jets and shocks? Is their primary energy stream hadronic or magnetic? I propose to do this by exploiting the advent of wide-field radio astronomy: extreme objects are very rare and usually transient, so not only must one survey large areas of sky, but also must one do this often. I propose to form and shape a group that will use the LOFAR wide-field radio telescope to hunt for these extreme transients and systematically collect enough well-documented examples of the behaviour of each type of transient. Furthermore, I propose to expand LOFAR with a true 24/7 all-sky monitor to catch and study even the rarest of events. Next, I will use my experience in gamma-ray burst followup to conduct a vigorous multi-wavelength programme of study of these objects, to constrain their physics from as many angles as possible. This will eventually include results from multi-messenger astrophysics, in which we use neutrinos, gravity waves, and other non-electromagnetic messengers as extra diagnostics of the physics of these sources. Finally, I will build on my experience in modelling accretion phenomena and relativistic explosions to develop a theoretical framework for these phenomena and constrain the resulting models with the rich data sets we obtain.
Summary
Some of the most extreme tests of physical law come from its manifestations in the behaviour of black holes and neutron stars, and as such these objects should be used as fundamental physics labs. Due to advances in both theoretical work and observational techniques, I have a major opportunity now to significantly push this agenda forward and get better answers to questions like: How are black holes born? How can energy be extracted from black holes? What is the origin of magnetic fields and cosmic rays in jets and shocks? Is their primary energy stream hadronic or magnetic? I propose to do this by exploiting the advent of wide-field radio astronomy: extreme objects are very rare and usually transient, so not only must one survey large areas of sky, but also must one do this often. I propose to form and shape a group that will use the LOFAR wide-field radio telescope to hunt for these extreme transients and systematically collect enough well-documented examples of the behaviour of each type of transient. Furthermore, I propose to expand LOFAR with a true 24/7 all-sky monitor to catch and study even the rarest of events. Next, I will use my experience in gamma-ray burst followup to conduct a vigorous multi-wavelength programme of study of these objects, to constrain their physics from as many angles as possible. This will eventually include results from multi-messenger astrophysics, in which we use neutrinos, gravity waves, and other non-electromagnetic messengers as extra diagnostics of the physics of these sources. Finally, I will build on my experience in modelling accretion phenomena and relativistic explosions to develop a theoretical framework for these phenomena and constrain the resulting models with the rich data sets we obtain.
Max ERC Funding
3 499 128 €
Duration
Start date: 2010-10-01, End date: 2016-09-30
Project acronym AAV-FACTORY
Project Synthetic Viral Nanosystem for Highly Efficient AAV Manufacturing for Gene Therapy
Researcher (PI) Imre Berger
Host Institution (HI) UNIVERSITY OF BRISTOL
Country United Kingdom
Call Details Proof of Concept (PoC), ERC-2020-PoC
Summary Gene therapy is one of the most innovative and fastest growing fields in the pharmaceutical industry. The first approved gene therapy utilized a recombinant AAV vector (rAAV), and dozens of additional rAAVs for gene therapy are presently in clinical trials. rAAV gene therapy drugs have been priced in the region of € 500’000 and above, which is partially a result of them being manufactured by highly complex processes combining multiple components, requiring 5-7 separate GMP production runs. We intend to introduce the first scalable, single-virus rAAV production platform to resolve this bottleneck. The resulting significant reduction of manufacturing complexity will both lower the price of future rAAV gene therapies, and also deliver additional, currently unaddressed or unaffordable rAAV treatments for genetic diseases into the clinic by providing scientists operating at the laboratory R&D stage with more user friendly and productive tools. The proposed project also develops for PoC purposes an rAAV gene therapy candidate to treat the devastating childhood congenital disease known as steroid resistant nephrotic syndrome SRNS.
Summary
Gene therapy is one of the most innovative and fastest growing fields in the pharmaceutical industry. The first approved gene therapy utilized a recombinant AAV vector (rAAV), and dozens of additional rAAVs for gene therapy are presently in clinical trials. rAAV gene therapy drugs have been priced in the region of € 500’000 and above, which is partially a result of them being manufactured by highly complex processes combining multiple components, requiring 5-7 separate GMP production runs. We intend to introduce the first scalable, single-virus rAAV production platform to resolve this bottleneck. The resulting significant reduction of manufacturing complexity will both lower the price of future rAAV gene therapies, and also deliver additional, currently unaddressed or unaffordable rAAV treatments for genetic diseases into the clinic by providing scientists operating at the laboratory R&D stage with more user friendly and productive tools. The proposed project also develops for PoC purposes an rAAV gene therapy candidate to treat the devastating childhood congenital disease known as steroid resistant nephrotic syndrome SRNS.
Max ERC Funding
150 000 €
Duration
Start date: 2021-02-01, End date: 2022-07-31
