Project acronym 20SComplexity
Project An integrative approach to uncover the multilevel regulation of 20S proteasome degradation
Researcher (PI) Michal Sharon
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Country Israel
Call Details Starting Grant (StG), LS1, ERC-2014-STG
Summary For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route.
To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation:
Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome.
Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function.
Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach.
Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.
Summary
For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route.
To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation:
Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome.
Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function.
Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach.
Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym 3D-FIREFLUC
Project Taming the particle transport in magnetized plasmas via perturbative fields
Researcher (PI) Eleonora VIEZZER
Host Institution (HI) UNIVERSIDAD DE SEVILLA
Country Spain
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary Wave-particle interactions are ubiquitous in nature and play a fundamental role in astrophysical and fusion plasmas. In solar plasmas, magnetohydrodynamic (MHD) fluctuations are thought to be responsible for the heating of the solar corona and the generation of the solar wind. In magnetically confined fusion (MCF) devices, enhanced particle transport induced by MHD fluctuations can deteriorate the plasma confinement, and also endanger the device integrity. MCF devices are an ideal testbed to verify current models and develop mitigation / protection techniques.
The proposed project paves the way for providing active control techniques to tame the MHD induced particle transport in a fusion plasma. A solid understanding of the interaction between energetic particles and MHD instabilities in the presence of electric fields and plasma currents is required to develop such techniques. I will pursue this goal through innovative diagnosis techniques with unprecedented spatio-temporal resolution. Combined with state-of-the-art hybrid MHD codes, a deep insight into the underlying physics mechanism will be gained. The outcome of this research project will have a major impact for next-step MCF devices as I will provide ground-breaking control techniques for mitigating MHD induced particle transport in magnetized plasmas.
The project consists of 3 research lines which follow a bottom-up approach:
(1) Cutting-edge instrumentation, aiming at the new generation of energetic particle and edge current diagnostics.
(2) Unravel the dynamics of energetic particles, electric fields, edge currents and MHD fluctuations.
(3) From lab to space weather: The developed models will revolutionize our understanding of the observed particle acceleration and transport in the solar corona.
Based on this approach, the project represents a gateway between the fusion, astrophysics and space communities opening new avenues for a common basic understanding.
Summary
Wave-particle interactions are ubiquitous in nature and play a fundamental role in astrophysical and fusion plasmas. In solar plasmas, magnetohydrodynamic (MHD) fluctuations are thought to be responsible for the heating of the solar corona and the generation of the solar wind. In magnetically confined fusion (MCF) devices, enhanced particle transport induced by MHD fluctuations can deteriorate the plasma confinement, and also endanger the device integrity. MCF devices are an ideal testbed to verify current models and develop mitigation / protection techniques.
The proposed project paves the way for providing active control techniques to tame the MHD induced particle transport in a fusion plasma. A solid understanding of the interaction between energetic particles and MHD instabilities in the presence of electric fields and plasma currents is required to develop such techniques. I will pursue this goal through innovative diagnosis techniques with unprecedented spatio-temporal resolution. Combined with state-of-the-art hybrid MHD codes, a deep insight into the underlying physics mechanism will be gained. The outcome of this research project will have a major impact for next-step MCF devices as I will provide ground-breaking control techniques for mitigating MHD induced particle transport in magnetized plasmas.
The project consists of 3 research lines which follow a bottom-up approach:
(1) Cutting-edge instrumentation, aiming at the new generation of energetic particle and edge current diagnostics.
(2) Unravel the dynamics of energetic particles, electric fields, edge currents and MHD fluctuations.
(3) From lab to space weather: The developed models will revolutionize our understanding of the observed particle acceleration and transport in the solar corona.
Based on this approach, the project represents a gateway between the fusion, astrophysics and space communities opening new avenues for a common basic understanding.
Max ERC Funding
1 512 250 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym 3D-QUEST
Project 3D-Quantum Integrated Optical Simulation
Researcher (PI) Fabio Sciarrino
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Country Italy
Call Details Starting Grant (StG), PE2, ERC-2012-StG_20111012
Summary "Quantum information was born from the merging of classical information and quantum physics. Its main objective consists of understanding the quantum nature of information and learning how to process it by using physical systems which operate by following quantum mechanics laws. Quantum simulation is a fundamental instrument to investigate phenomena of quantum systems dynamics, such as quantum transport, particle localizations and energy transfer, quantum-to-classical transition, and even quantum improved computation, all tasks that are hard to simulate with classical approaches. Within this framework integrated photonic circuits have a strong potential to realize quantum information processing by optical systems.
The aim of 3D-QUEST is to develop and implement quantum simulation by exploiting 3-dimensional integrated photonic circuits. 3D-QUEST is structured to demonstrate the potential of linear optics to implement a computational power beyond the one of a classical computer. Such ""hard-to-simulate"" scenario is disclosed when multiphoton-multimode platforms are realized. The 3D-QUEST research program will focus on three tasks of growing difficulty.
A-1. To simulate bosonic-fermionic dynamics with integrated optical systems acting on 2 photon entangled states.
A-2. To pave the way towards hard-to-simulate, scalable quantum linear optical circuits by investigating m-port interferometers acting on n-photon states with n>2.
A-3. To exploit 3-dimensional integrated structures for the observation of new quantum optical phenomena and for the quantum simulation of more complex scenarios.
3D-QUEST will exploit the potential of the femtosecond laser writing integrated waveguides. This technique will be adopted to realize 3-dimensional capabilities and high flexibility, bringing in this way the optical quantum simulation in to new regime."
Summary
"Quantum information was born from the merging of classical information and quantum physics. Its main objective consists of understanding the quantum nature of information and learning how to process it by using physical systems which operate by following quantum mechanics laws. Quantum simulation is a fundamental instrument to investigate phenomena of quantum systems dynamics, such as quantum transport, particle localizations and energy transfer, quantum-to-classical transition, and even quantum improved computation, all tasks that are hard to simulate with classical approaches. Within this framework integrated photonic circuits have a strong potential to realize quantum information processing by optical systems.
The aim of 3D-QUEST is to develop and implement quantum simulation by exploiting 3-dimensional integrated photonic circuits. 3D-QUEST is structured to demonstrate the potential of linear optics to implement a computational power beyond the one of a classical computer. Such ""hard-to-simulate"" scenario is disclosed when multiphoton-multimode platforms are realized. The 3D-QUEST research program will focus on three tasks of growing difficulty.
A-1. To simulate bosonic-fermionic dynamics with integrated optical systems acting on 2 photon entangled states.
A-2. To pave the way towards hard-to-simulate, scalable quantum linear optical circuits by investigating m-port interferometers acting on n-photon states with n>2.
A-3. To exploit 3-dimensional integrated structures for the observation of new quantum optical phenomena and for the quantum simulation of more complex scenarios.
3D-QUEST will exploit the potential of the femtosecond laser writing integrated waveguides. This technique will be adopted to realize 3-dimensional capabilities and high flexibility, bringing in this way the optical quantum simulation in to new regime."
Max ERC Funding
1 474 800 €
Duration
Start date: 2012-08-01, End date: 2017-07-31
Project acronym 3DCellPhase-
Project In situ Structural Analysis of Molecular Crowding and Phase Separation
Researcher (PI) Julia MAHAMID
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Country Germany
Call Details Starting Grant (StG), LS1, ERC-2017-STG
Summary This proposal brings together two fields in biology, namely the emerging field of phase-separated assemblies in cell biology and state-of-the-art cellular cryo-electron tomography, to advance our understanding on a fundamental, yet illusive, question: the molecular organization of the cytoplasm.
Eukaryotes organize their biochemical reactions into functionally distinct compartments. Intriguingly, many, if not most, cellular compartments are not membrane enclosed. Rather, they assemble dynamically by phase separation, typically triggered upon a specific event. Despite significant progress on reconstituting such liquid-like assemblies in vitro, we lack information as to whether these compartments in vivo are indeed amorphous liquids, or whether they exhibit structural features such as gels or fibers. My recent work on sample preparation of cells for cryo-electron tomography, including cryo-focused ion beam thinning, guided by 3D correlative fluorescence microscopy, shows that we can now prepare site-specific ‘electron-transparent windows’ in suitable eukaryotic systems, which allow direct examination of structural features of cellular compartments in their cellular context. Here, we will use these techniques to elucidate the structural principles and cytoplasmic environment driving the dynamic assembly of two phase-separated compartments: Stress granules, which are RNA bodies that form rapidly in the cytoplasm upon cellular stress, and centrosomes, which are sites of microtubule nucleation. We will combine these studies with a quantitative description of the crowded nature of cytoplasm and of its local variations, to provide a direct readout of the impact of excluded volume on molecular assembly in living cells. Taken together, these studies will provide fundamental insights into the structural basis by which cells form biochemical compartments.
Summary
This proposal brings together two fields in biology, namely the emerging field of phase-separated assemblies in cell biology and state-of-the-art cellular cryo-electron tomography, to advance our understanding on a fundamental, yet illusive, question: the molecular organization of the cytoplasm.
Eukaryotes organize their biochemical reactions into functionally distinct compartments. Intriguingly, many, if not most, cellular compartments are not membrane enclosed. Rather, they assemble dynamically by phase separation, typically triggered upon a specific event. Despite significant progress on reconstituting such liquid-like assemblies in vitro, we lack information as to whether these compartments in vivo are indeed amorphous liquids, or whether they exhibit structural features such as gels or fibers. My recent work on sample preparation of cells for cryo-electron tomography, including cryo-focused ion beam thinning, guided by 3D correlative fluorescence microscopy, shows that we can now prepare site-specific ‘electron-transparent windows’ in suitable eukaryotic systems, which allow direct examination of structural features of cellular compartments in their cellular context. Here, we will use these techniques to elucidate the structural principles and cytoplasmic environment driving the dynamic assembly of two phase-separated compartments: Stress granules, which are RNA bodies that form rapidly in the cytoplasm upon cellular stress, and centrosomes, which are sites of microtubule nucleation. We will combine these studies with a quantitative description of the crowded nature of cytoplasm and of its local variations, to provide a direct readout of the impact of excluded volume on molecular assembly in living cells. Taken together, these studies will provide fundamental insights into the structural basis by which cells form biochemical compartments.
Max ERC Funding
1 228 125 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym 3DSPIN
Project 3-Dimensional Maps of the Spinning Nucleon
Researcher (PI) Alessandro Bacchetta
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PAVIA
Country Italy
Call Details Consolidator Grant (CoG), PE2, ERC-2014-CoG
Summary How does the inside of the proton look like? What generates its spin?
3DSPIN will deliver essential information to answer these questions at the frontier of subnuclear physics.
At present, we have detailed maps of the distribution of quarks and gluons in the nucleon in 1D (as a function of their momentum in a single direction). We also know that quark spins account for only about 1/3 of the spin of the nucleon.
3DSPIN will lead the way into a new stage of nucleon mapping, explore the distribution of quarks in full 3D momentum space and obtain unprecedented information on orbital angular momentum.
Goals
1. extract from experimental data the 3D distribution of quarks (in momentum space), as described by Transverse-Momentum Distributions (TMDs);
2. obtain from TMDs information on quark Orbital Angular Momentum (OAM).
Methodology
3DSPIN will implement state-of-the-art fitting procedures to analyze relevant experimental data and extract quark TMDs, similarly to global fits of standard parton distribution functions. Information about quark angular momentum will be obtained through assumptions based on theoretical considerations. The next five years represent an ideal time window to accomplish our goals, thanks to the wealth of expected data from deep-inelastic scattering experiments (COMPASS, Jefferson Lab), hadronic colliders (Fermilab, BNL, LHC), and electron-positron colliders (BELLE, BABAR). The PI has a strong reputation in this field. The group will operate in partnership with the Italian National Institute of Nuclear Physics and in close interaction with leading experts and experimental collaborations worldwide.
Impact
Mapping the 3D structure of chemical compounds has revolutionized chemistry. Similarly, mapping the 3D structure of the nucleon will have a deep impact on our understanding of the fundamental constituents of matter. We will open new perspectives on the dynamics of quarks and gluons and sharpen our view of high-energy processes involving nucleons.
Summary
How does the inside of the proton look like? What generates its spin?
3DSPIN will deliver essential information to answer these questions at the frontier of subnuclear physics.
At present, we have detailed maps of the distribution of quarks and gluons in the nucleon in 1D (as a function of their momentum in a single direction). We also know that quark spins account for only about 1/3 of the spin of the nucleon.
3DSPIN will lead the way into a new stage of nucleon mapping, explore the distribution of quarks in full 3D momentum space and obtain unprecedented information on orbital angular momentum.
Goals
1. extract from experimental data the 3D distribution of quarks (in momentum space), as described by Transverse-Momentum Distributions (TMDs);
2. obtain from TMDs information on quark Orbital Angular Momentum (OAM).
Methodology
3DSPIN will implement state-of-the-art fitting procedures to analyze relevant experimental data and extract quark TMDs, similarly to global fits of standard parton distribution functions. Information about quark angular momentum will be obtained through assumptions based on theoretical considerations. The next five years represent an ideal time window to accomplish our goals, thanks to the wealth of expected data from deep-inelastic scattering experiments (COMPASS, Jefferson Lab), hadronic colliders (Fermilab, BNL, LHC), and electron-positron colliders (BELLE, BABAR). The PI has a strong reputation in this field. The group will operate in partnership with the Italian National Institute of Nuclear Physics and in close interaction with leading experts and experimental collaborations worldwide.
Impact
Mapping the 3D structure of chemical compounds has revolutionized chemistry. Similarly, mapping the 3D structure of the nucleon will have a deep impact on our understanding of the fundamental constituents of matter. We will open new perspectives on the dynamics of quarks and gluons and sharpen our view of high-energy processes involving nucleons.
Max ERC Funding
1 509 000 €
Duration
Start date: 2015-07-01, End date: 2020-12-31
Project acronym 3FLEX
Project Three-Component Fermi Gas Lattice Experiment
Researcher (PI) Selim Jochim
Host Institution (HI) RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Country Germany
Call Details Starting Grant (StG), PE2, ERC-2011-StG_20101014
Summary Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.
Summary
Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.
Max ERC Funding
1 469 040 €
Duration
Start date: 2011-08-01, End date: 2016-07-31
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 4DPHOTON
Project Beyond Light Imaging: High-Rate Single-Photon Detection in Four Dimensions
Researcher (PI) Massimiliano FIORINI
Host Institution (HI) ISTITUTO NAZIONALE DI FISICA NUCLEARE
Country Italy
Call Details Consolidator Grant (CoG), PE2, ERC-2018-COG
Summary Goal of the 4DPHOTON project is the development and construction of a photon imaging detector with unprecedented performance. The proposed device will be capable of detecting fluxes of single-photons up to one billion photons per second, over areas of several square centimetres, and will measure - for each photon - position and time simultaneously with resolutions better than ten microns and few tens of picoseconds, respectively. These figures of merit will open many important applications allowing significant advances in particle physics, life sciences or other emerging fields where excellent timing and position resolutions are simultaneously required.
Our goal will be achieved thanks to the use of an application-specific integrated circuit in 65 nm complementary metal-oxide-semiconductor (CMOS) technology, that will deliver a timing resolution of few tens of picoseconds at the pixel level, over few hundred thousand individually-active pixel channels, allowing very high rates of photons to be detected, and the corresponding information digitized and transferred to a processing unit.
As a result of the 4DPHOTON project we will remove the constraints that many light imaging applications have due to the lack of precise single-photon information on four dimensions (4D): the three spatial coordinates and time simultaneously. In particular, we will prove the performance of this detector in the field of particle physics, performing the reconstruction of Cherenkov photon rings with a timing resolution of ten picoseconds. With its excellent granularity, timing resolution, rate capability and compactness, this detector will represent a new paradigm for the realisation of future Ring Imaging Cherenkov detectors, capable of achieving high efficiency particle identification in environments with very high particle multiplicities, exploiting time-association of the photon hits.
Summary
Goal of the 4DPHOTON project is the development and construction of a photon imaging detector with unprecedented performance. The proposed device will be capable of detecting fluxes of single-photons up to one billion photons per second, over areas of several square centimetres, and will measure - for each photon - position and time simultaneously with resolutions better than ten microns and few tens of picoseconds, respectively. These figures of merit will open many important applications allowing significant advances in particle physics, life sciences or other emerging fields where excellent timing and position resolutions are simultaneously required.
Our goal will be achieved thanks to the use of an application-specific integrated circuit in 65 nm complementary metal-oxide-semiconductor (CMOS) technology, that will deliver a timing resolution of few tens of picoseconds at the pixel level, over few hundred thousand individually-active pixel channels, allowing very high rates of photons to be detected, and the corresponding information digitized and transferred to a processing unit.
As a result of the 4DPHOTON project we will remove the constraints that many light imaging applications have due to the lack of precise single-photon information on four dimensions (4D): the three spatial coordinates and time simultaneously. In particular, we will prove the performance of this detector in the field of particle physics, performing the reconstruction of Cherenkov photon rings with a timing resolution of ten picoseconds. With its excellent granularity, timing resolution, rate capability and compactness, this detector will represent a new paradigm for the realisation of future Ring Imaging Cherenkov detectors, capable of achieving high efficiency particle identification in environments with very high particle multiplicities, exploiting time-association of the photon hits.
Max ERC Funding
1 975 000 €
Duration
Start date: 2019-12-01, End date: 2024-11-30
Project acronym 4TH-NU-AVENUE
Project Search for a fourth neutrino with a PBq anti-neutrino source
Researcher (PI) Thierry Michel Rene Lasserre
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Country France
Call Details Starting Grant (StG), PE2, ERC-2012-StG_20111012
Summary Several observed anomalies in neutrino oscillation data can be explained by a hypothetical fourth neutrino separated from the three standard neutrinos by a squared mass difference of a few eV2. This hypothesis can be tested with a PBq (ten kilocurie scale) 144Ce antineutrino beta-source deployed at the center of a large low background liquid scintillator detector, such like Borexino, KamLAND, and SNO+. In particular, the compact size of such a source could yield an energy-dependent oscillating pattern in event spatial distribution that would unambiguously determine neutrino mass differences and mixing angles.
The proposed program aims to perform the necessary research and developments to produce and deploy an intense antineutrino source in a large liquid scintillator detector. Our program will address the definition of the production process of the neutrino source as well as its experimental characterization, the detailed physics simulation of both signal and backgrounds, the complete design and the realization of the thick shielding, the preparation of the interfaces with the antineutrino detector, including the safety and security aspects.
Summary
Several observed anomalies in neutrino oscillation data can be explained by a hypothetical fourth neutrino separated from the three standard neutrinos by a squared mass difference of a few eV2. This hypothesis can be tested with a PBq (ten kilocurie scale) 144Ce antineutrino beta-source deployed at the center of a large low background liquid scintillator detector, such like Borexino, KamLAND, and SNO+. In particular, the compact size of such a source could yield an energy-dependent oscillating pattern in event spatial distribution that would unambiguously determine neutrino mass differences and mixing angles.
The proposed program aims to perform the necessary research and developments to produce and deploy an intense antineutrino source in a large liquid scintillator detector. Our program will address the definition of the production process of the neutrino source as well as its experimental characterization, the detailed physics simulation of both signal and backgrounds, the complete design and the realization of the thick shielding, the preparation of the interfaces with the antineutrino detector, including the safety and security aspects.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym AAMDDR
Project DNA damage response and genome stability: The role of ATM, ATR and the Mre11 complex
Researcher (PI) Vincenzo Costanzo
Host Institution (HI) CANCER RESEARCH UK LBG
Country United Kingdom
Call Details Starting Grant (StG), LS1, ERC-2007-StG
Summary Chromosomal DNA is continuously subjected to exogenous and endogenous damaging insults. In the presence of DNA damage cells activate a multi-faceted checkpoint response that delays cell cycle progression and promotes DNA repair. Failures in this response lead to genomic instability, the main feature of cancer cells. Several cancer-prone human syndromes including the Ataxia teleangiectasia (A-T), the A-T Like Disorder (ATLD) and the Seckel Syndrome reflect defects in the specific genes of the DNA damage response such as ATM, MRE11 and ATR. DNA damage response pathways are poorly understood at biochemical level in vertebrate organisms. We have established a cell-free system based on Xenopus laevis egg extract to study molecular events underlying DNA damage response. This is the first in vitro system that recapitulates different aspects of the DNA damage response in vertebrates. Using this system we propose to study the biochemistry of the ATM, ATR and the Mre11 complex dependent DNA damage response. In particular we will: 1) Dissect the signal transduction pathway that senses DNA damage and promotes cell cycle arrest and DNA damage repair; 2) Analyze at molecular level the role of ATM, ATR, Mre11 in chromosomal DNA replication and mitosis during normal and stressful conditions; 3) Identify substrates of the ATM and ATR dependent DNA damage response using an innovative screening procedure.
Summary
Chromosomal DNA is continuously subjected to exogenous and endogenous damaging insults. In the presence of DNA damage cells activate a multi-faceted checkpoint response that delays cell cycle progression and promotes DNA repair. Failures in this response lead to genomic instability, the main feature of cancer cells. Several cancer-prone human syndromes including the Ataxia teleangiectasia (A-T), the A-T Like Disorder (ATLD) and the Seckel Syndrome reflect defects in the specific genes of the DNA damage response such as ATM, MRE11 and ATR. DNA damage response pathways are poorly understood at biochemical level in vertebrate organisms. We have established a cell-free system based on Xenopus laevis egg extract to study molecular events underlying DNA damage response. This is the first in vitro system that recapitulates different aspects of the DNA damage response in vertebrates. Using this system we propose to study the biochemistry of the ATM, ATR and the Mre11 complex dependent DNA damage response. In particular we will: 1) Dissect the signal transduction pathway that senses DNA damage and promotes cell cycle arrest and DNA damage repair; 2) Analyze at molecular level the role of ATM, ATR, Mre11 in chromosomal DNA replication and mitosis during normal and stressful conditions; 3) Identify substrates of the ATM and ATR dependent DNA damage response using an innovative screening procedure.
Max ERC Funding
1 000 000 €
Duration
Start date: 2008-07-01, End date: 2013-06-30
