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-OA-HISTO
Project Development of 3D Histopathological Grading of Osteoarthritis
Researcher (PI) Simo Jaakko Saarakkala
Host Institution (HI) OULUN YLIOPISTO
Country Finland
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 ACTAR TPC
Project Active Target and Time Projection Chamber
Researcher (PI) Gwen Grinyer
Host Institution (HI) GRAND ACCELERATEUR NATIONAL D'IONS LOURDS
Country France
Call Details Starting Grant (StG), PE2, ERC-2013-StG
Summary The active target and time projection chamber (ACTAR TPC) is a novel gas-filled detection system that will permit new studies into the structure and decays of the most exotic nuclei. The use of a gas volume that acts as a sensitive detection medium and as the reaction target itself (an “active target”) offers considerable advantages over traditional nuclear physics detectors and techniques. In high-energy physics, TPC detectors have found profitable applications but their use in nuclear physics has been limited. With the ACTAR TPC design, individual detection pad sizes of 2 mm are the smallest ever attempted in either discipline but is a requirement for high-efficiency and high-resolution nuclear spectroscopy. The corresponding large number of electronic channels (16000 from a surface of only 25×25 cm) requires new developments in high-density electronics and data-acquisition systems that are not yet available in the nuclear physics domain. New experiments in regions of the nuclear chart that cannot be presently contemplated will become feasible with ACTAR TPC.
Summary
The active target and time projection chamber (ACTAR TPC) is a novel gas-filled detection system that will permit new studies into the structure and decays of the most exotic nuclei. The use of a gas volume that acts as a sensitive detection medium and as the reaction target itself (an “active target”) offers considerable advantages over traditional nuclear physics detectors and techniques. In high-energy physics, TPC detectors have found profitable applications but their use in nuclear physics has been limited. With the ACTAR TPC design, individual detection pad sizes of 2 mm are the smallest ever attempted in either discipline but is a requirement for high-efficiency and high-resolution nuclear spectroscopy. The corresponding large number of electronic channels (16000 from a surface of only 25×25 cm) requires new developments in high-density electronics and data-acquisition systems that are not yet available in the nuclear physics domain. New experiments in regions of the nuclear chart that cannot be presently contemplated will become feasible with ACTAR TPC.
Max ERC Funding
1 290 000 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym ANTHROPOID
Project Great ape organoids to reconstruct uniquely human development
Researcher (PI) Jarrett CAMP
Host Institution (HI) INSTITUT FUR MOLEKULARE UND KLINISCHE OPHTHALMOLOGIE BASEL
Country Switzerland
Call Details Starting Grant (StG), LS2, ERC-2018-STG
Summary Humans diverged from our closest living relatives, chimpanzees and other great apes, 6-10 million years ago. Since this divergence, our ancestors acquired genetic changes that enhanced cognition, altered metabolism, and endowed our species with an adaptive capacity to colonize the entire planet and reshape the biosphere. Through genome comparisons between modern humans, Neandertals, chimpanzees and other apes we have identified genetic changes that likely contribute to innovations in human metabolic and cognitive physiology. However, it has been difficult to assess the functional effects of these genetic changes due to the lack of cell culture systems that recapitulate great ape organ complexity. Human and chimpanzee pluripotent stem cells (PSCs) can self-organize into three-dimensional (3D) tissues that recapitulate the morphology, function, and genetic programs controlling organ development. Our vision is to use organoids to study the changes that set modern humans apart from our closest evolutionary relatives as well as all other organisms on the planet. In ANTHROPOID we will generate a great ape developmental cell atlas using cortex, liver, and small intestine organoids. We will use single-cell transcriptomics and chromatin accessibility to identify cell type-specific features of transcriptome divergence at cellular resolution. We will dissect enhancer evolution using single-cell genomic screens and ancestralize human cells to resurrect pre-human cellular phenotypes. ANTHROPOID utilizes quantitative and state-of-the-art methods to explore exciting high-risk questions at multiple branches of the modern human lineage. This project is a ground breaking starting point to replay evolution and tackle the ancient question of what makes us uniquely human?
Summary
Humans diverged from our closest living relatives, chimpanzees and other great apes, 6-10 million years ago. Since this divergence, our ancestors acquired genetic changes that enhanced cognition, altered metabolism, and endowed our species with an adaptive capacity to colonize the entire planet and reshape the biosphere. Through genome comparisons between modern humans, Neandertals, chimpanzees and other apes we have identified genetic changes that likely contribute to innovations in human metabolic and cognitive physiology. However, it has been difficult to assess the functional effects of these genetic changes due to the lack of cell culture systems that recapitulate great ape organ complexity. Human and chimpanzee pluripotent stem cells (PSCs) can self-organize into three-dimensional (3D) tissues that recapitulate the morphology, function, and genetic programs controlling organ development. Our vision is to use organoids to study the changes that set modern humans apart from our closest evolutionary relatives as well as all other organisms on the planet. In ANTHROPOID we will generate a great ape developmental cell atlas using cortex, liver, and small intestine organoids. We will use single-cell transcriptomics and chromatin accessibility to identify cell type-specific features of transcriptome divergence at cellular resolution. We will dissect enhancer evolution using single-cell genomic screens and ancestralize human cells to resurrect pre-human cellular phenotypes. ANTHROPOID utilizes quantitative and state-of-the-art methods to explore exciting high-risk questions at multiple branches of the modern human lineage. This project is a ground breaking starting point to replay evolution and tackle the ancient question of what makes us uniquely human?
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym ANTI-ATOM
Project Many-body theory of antimatter interactions with atoms, molecules and condensed matter
Researcher (PI) Dermot GREEN
Host Institution (HI) THE QUEEN'S UNIVERSITY OF BELFAST
Country United Kingdom
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary The ability of positrons to annihilate with electrons, producing characteristic gamma rays, gives them important use in medicine via positron-emission tomography (PET), diagnostics of industrially-important materials, and in elucidating astrophysical phenomena. Moreover, the fundamental interactions of positrons and positronium (Ps) with atoms, molecules and condensed matter are currently under intensive study in numerous international laboratories, to illuminate collision phenomena and perform precision tests of fundamental laws.
Proper interpretation and development of these costly and difficult experiments requires accurate calculations of low-energy positron and Ps interactions with normal matter. These systems, however, involve strong correlations, e.g., polarisation of the atom and virtual-Ps formation (where an atomic electron tunnels to the positron): they significantly effect positron- and Ps-atom/molecule interactions, e.g., enhancing annihilation rates by many orders of magnitude, and making the accurate description of these systems a challenging many-body problem. Current theoretical capability lags severely behind that of experiment. Major theoretical and computational developments are required to bridge the gap.
One powerful method, which accounts for the correlations in a natural, transparent and systematic way, is many-body theory (MBT). Building on my expertise in the field, I propose to develop new MBT to deliver unique and unrivalled capability in theory and computation of low-energy positron and Ps interactions with atoms, molecules, and condensed matter. The ambitious programme will provide the basic understanding required to interpret and develop the fundamental experiments, antimatter-based materials science techniques, and wider technologies, e.g., (PET), and more broadly, potentially revolutionary and generally applicable computational methodologies that promise to define a new level of high-precision in atomic-MBT calculations.
Summary
The ability of positrons to annihilate with electrons, producing characteristic gamma rays, gives them important use in medicine via positron-emission tomography (PET), diagnostics of industrially-important materials, and in elucidating astrophysical phenomena. Moreover, the fundamental interactions of positrons and positronium (Ps) with atoms, molecules and condensed matter are currently under intensive study in numerous international laboratories, to illuminate collision phenomena and perform precision tests of fundamental laws.
Proper interpretation and development of these costly and difficult experiments requires accurate calculations of low-energy positron and Ps interactions with normal matter. These systems, however, involve strong correlations, e.g., polarisation of the atom and virtual-Ps formation (where an atomic electron tunnels to the positron): they significantly effect positron- and Ps-atom/molecule interactions, e.g., enhancing annihilation rates by many orders of magnitude, and making the accurate description of these systems a challenging many-body problem. Current theoretical capability lags severely behind that of experiment. Major theoretical and computational developments are required to bridge the gap.
One powerful method, which accounts for the correlations in a natural, transparent and systematic way, is many-body theory (MBT). Building on my expertise in the field, I propose to develop new MBT to deliver unique and unrivalled capability in theory and computation of low-energy positron and Ps interactions with atoms, molecules, and condensed matter. The ambitious programme will provide the basic understanding required to interpret and develop the fundamental experiments, antimatter-based materials science techniques, and wider technologies, e.g., (PET), and more broadly, potentially revolutionary and generally applicable computational methodologies that promise to define a new level of high-precision in atomic-MBT calculations.
Max ERC Funding
1 318 419 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym ANYON
Project Engineering and exploring anyonic quantum gases
Researcher (PI) Christof WEITENBERG
Host Institution (HI) UNIVERSITAET HAMBURG
Country Germany
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary This project enters the experimental investigation of anyonic quantum gases. We will study anyons – conjectured particles with a statistical exchange phase anywhere between 0 and π – in different many-body systems. This progress will be enabled by a unique approach of bringing together artificial gauge fields and quantum gas microscopes for ultracold atoms.
Specifically, we will implement the 1D anyon Hubbard model via a lattice shaking protocol that imprints density-dependent Peierls phases. By engineering the statistical exchange phase, we can continuously tune between bosons and fermions and explore a statistically-induced quantum phase transition. We will monitor the continuous fermionization via the build-up of Friedel oscillations. Using state-of-the-art cold atom technology, we will thus open the physics of anyons to experimental research and address open questions related to their fractional exclusion statistics.
Secondly, we will create fractional quantum Hall systems in rapidly rotating microtraps. Using the quantum gas microscope, we will i) control the optical potentials at a level which allows approaching the centrifugal limit and ii) use small atom numbers equal to the inserted angular momentum quantum number. The strongly-correlated ground states such as the Laughlin state can be identified via their characteristic density correlations. Of particular interest are the quasihole excitations, whose predicted anyonic exchange statistics have not been directly observed to date. We will probe and test their statistics via the characteristic counting sequence in the excitation spectrum. Furthermore, we will test ideas to transfer anyonic properties of the excitations to a second tracer species. This approach will enable us to both probe the fractional exclusion statistics of the excitations and to create a 2D anyonic quantum gas.
In the long run, these techniques open a path to also study non-Abelian anyons with ultracold atoms.
Summary
This project enters the experimental investigation of anyonic quantum gases. We will study anyons – conjectured particles with a statistical exchange phase anywhere between 0 and π – in different many-body systems. This progress will be enabled by a unique approach of bringing together artificial gauge fields and quantum gas microscopes for ultracold atoms.
Specifically, we will implement the 1D anyon Hubbard model via a lattice shaking protocol that imprints density-dependent Peierls phases. By engineering the statistical exchange phase, we can continuously tune between bosons and fermions and explore a statistically-induced quantum phase transition. We will monitor the continuous fermionization via the build-up of Friedel oscillations. Using state-of-the-art cold atom technology, we will thus open the physics of anyons to experimental research and address open questions related to their fractional exclusion statistics.
Secondly, we will create fractional quantum Hall systems in rapidly rotating microtraps. Using the quantum gas microscope, we will i) control the optical potentials at a level which allows approaching the centrifugal limit and ii) use small atom numbers equal to the inserted angular momentum quantum number. The strongly-correlated ground states such as the Laughlin state can be identified via their characteristic density correlations. Of particular interest are the quasihole excitations, whose predicted anyonic exchange statistics have not been directly observed to date. We will probe and test their statistics via the characteristic counting sequence in the excitation spectrum. Furthermore, we will test ideas to transfer anyonic properties of the excitations to a second tracer species. This approach will enable us to both probe the fractional exclusion statistics of the excitations and to create a 2D anyonic quantum gas.
In the long run, these techniques open a path to also study non-Abelian anyons with ultracold atoms.
Max ERC Funding
1 497 500 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym APPLAUSE
Project Adolescent Precursors to Psychiatric Disorders – Learing from Analysis of User-Service Engagement
Researcher (PI) Sara Evans
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Country United Kingdom
Call Details Starting Grant (StG), LS7, ERC-2013-StG
Summary APPLAUSE’s aim is to produce a body of evidence that illustrates how young people with mental health problems currently interact with both formal mental health services and informal social and familial support structures. Careful analysis of data gathered in the UK and Brazil will allow formulation of globally relevant insights into mental health care delivery for young people, which will be presented internationally as a resource for future health care service design.
APPLAUSE will allow the collection of an important data set that does not currently exist in this field, and will look to other disciplines for innovative approaches to data analysis. Whist standard analysis may allow for snapshots of health service use, using innovative life course methods will allow us to to characterise patterns of complete service use of each individual participant’s experience of accessing mental health care and social support.
Adolescence is a critical period in mental health development, which has been largely neglected by public health efforts. Psychiatric disorders rank as the primary cause of disability among individuals aged 10-24 years, worldwide. Moreover, many health risk behaviours emerge during adolescence and 70% of adult psychiatric disorders are preceded by mental health problems during adolescent years. However, delays to receiving care for psychiatric disorders, following disorder onset, avreage more than ten years and little is known about factors which impede access to and continuity of care among young people with mental health problems. APPLAUSE will analyse current access models, reports of individual experiences of positive and negative interactions with health care services and the culturally embedded social factors that impact on such access. Addressing this complex problem from a global perspective will advance the development of a more diverse and innovative set of strategies for improving earlier access to care.
Summary
APPLAUSE’s aim is to produce a body of evidence that illustrates how young people with mental health problems currently interact with both formal mental health services and informal social and familial support structures. Careful analysis of data gathered in the UK and Brazil will allow formulation of globally relevant insights into mental health care delivery for young people, which will be presented internationally as a resource for future health care service design.
APPLAUSE will allow the collection of an important data set that does not currently exist in this field, and will look to other disciplines for innovative approaches to data analysis. Whist standard analysis may allow for snapshots of health service use, using innovative life course methods will allow us to to characterise patterns of complete service use of each individual participant’s experience of accessing mental health care and social support.
Adolescence is a critical period in mental health development, which has been largely neglected by public health efforts. Psychiatric disorders rank as the primary cause of disability among individuals aged 10-24 years, worldwide. Moreover, many health risk behaviours emerge during adolescence and 70% of adult psychiatric disorders are preceded by mental health problems during adolescent years. However, delays to receiving care for psychiatric disorders, following disorder onset, avreage more than ten years and little is known about factors which impede access to and continuity of care among young people with mental health problems. APPLAUSE will analyse current access models, reports of individual experiences of positive and negative interactions with health care services and the culturally embedded social factors that impact on such access. Addressing this complex problem from a global perspective will advance the development of a more diverse and innovative set of strategies for improving earlier access to care.
Max ERC Funding
1 499 948 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym AxScale
Project Axions and relatives across different mass scales
Researcher (PI) Babette DoeBRICH
Host Institution (HI) EUROPEAN ORGANIZATION FOR NUCLEAR RESEARCH
Country Switzerland
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary Pseudoscalar QCD axions and axion-like Particles (ALPs) are an excellent candidate for Dark Matter or can act as a mediator particle for Dark Matter. Since the discovery of the Higgs boson, we know that fundamental scalars exist and it is timely to explore the Axion/ALP parameter space more intensively. A look at the allowed axion/ALP parameter space makes it clear that these might exist at low mass (below few eV), as (part of) Dark Matter. Alternatively they might exist at higher mass, above roughly the MeV scale, potentially as a Dark Matter mediator particle. AxScale explores parts of these different mass regions, with complementary techniques but with one research team.
Firstly, with RADES, it develops a novel concept for a filter-like cavity for the search of QCD axion Dark matter at a few tens of a micro-eV. Dark Matter Axions can be discovered by their resonant conversion in that cavity embedded in a strong magnetic field. The `classical axion window' has recently received much interest from cosmological model-building and I will implement a novel cavity concept that will allow to explore this Dark Matter parameter region.
Secondly, AxScale searches for axions and ALPs using the NA62 detector at CERN's SPS. Especially the mass region above a few MeV can be efficiently searched by the use of a proton fixed-target facility. During nominal data taking NA62 investigates a Kaon beam. NA62 can also run in a mode in which its primary proton beam is fully dumped. With the resulting high interaction rate, the existence of weakly coupled particles can be efficiently probed. Thus, searches for ALPs from Kaon decays as well as from production in dumped protons with NA62 are foreseen in AxScale. More generally, NA62 can look for a plethora of `Dark Sector' particles with recorded and future data. With the AxScale program I aim at maximizing the reach of NA62 for these new physics models.
Summary
Pseudoscalar QCD axions and axion-like Particles (ALPs) are an excellent candidate for Dark Matter or can act as a mediator particle for Dark Matter. Since the discovery of the Higgs boson, we know that fundamental scalars exist and it is timely to explore the Axion/ALP parameter space more intensively. A look at the allowed axion/ALP parameter space makes it clear that these might exist at low mass (below few eV), as (part of) Dark Matter. Alternatively they might exist at higher mass, above roughly the MeV scale, potentially as a Dark Matter mediator particle. AxScale explores parts of these different mass regions, with complementary techniques but with one research team.
Firstly, with RADES, it develops a novel concept for a filter-like cavity for the search of QCD axion Dark matter at a few tens of a micro-eV. Dark Matter Axions can be discovered by their resonant conversion in that cavity embedded in a strong magnetic field. The `classical axion window' has recently received much interest from cosmological model-building and I will implement a novel cavity concept that will allow to explore this Dark Matter parameter region.
Secondly, AxScale searches for axions and ALPs using the NA62 detector at CERN's SPS. Especially the mass region above a few MeV can be efficiently searched by the use of a proton fixed-target facility. During nominal data taking NA62 investigates a Kaon beam. NA62 can also run in a mode in which its primary proton beam is fully dumped. With the resulting high interaction rate, the existence of weakly coupled particles can be efficiently probed. Thus, searches for ALPs from Kaon decays as well as from production in dumped protons with NA62 are foreseen in AxScale. More generally, NA62 can look for a plethora of `Dark Sector' particles with recorded and future data. With the AxScale program I aim at maximizing the reach of NA62 for these new physics models.
Max ERC Funding
1 134 375 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym BacRafts
Project Architecture of bacterial lipid rafts; inhibition of virulence and antibiotic resistance using raft-disassembling small molecules
Researcher (PI) Daniel Lopez Serrano
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Country Spain
Call Details Starting Grant (StG), LS6, ERC-2013-StG
Summary Membranes of eukaryotic cells organize signal transduction proteins into microdomains or lipid rafts whose integrity is essential for numerous cellular processes. Lipid rafts has been considered a fundamental step to define the cellular complexity of eukaryotes, assuming that bacteria do not require such a sophisticated organization of their signaling networks. However, I have discovered that bacteria organize many signaling pathways in membrane microdomains similar to the eukaryotic lipid rafts. Perturbation of bacterial lipid rafts leads to a potent and simultaneous impairment of all raft-harbored signaling pathways. Consequently, the disassembly of lipid rafts in pathogens like Staphylococcus aureus generates a simultaneous inhibition of numerous infection-related processes that can be further explored to control bacterial infections. This unexpected sophistication in membrane organization is unprecedented in bacteria and hence, this proposal will explore the molecular basis of the assembly of bacterial lipid rafts and their role in the infection-related processes. These questions will be addressed in three main goals: First, I will elucidate the molecular components and the mechanism of assembly of bacterial lipid rafts using S. aureus as model organism. Second, I will dissect the molecular basis that links the functionality of the infection-related processes to the integrity of bacterial lipid rafts. Third, my collection of anti-raft small molecules that are able to disrupt lipid rafts will be tested as antimicrobial agents to prevent hospital-acquired infections, abrogate pre-existing infections and develop bacteria-free materials that can be used in clinical settings. I will use a number of molecular approaches in combination with cutting-edge techniques in flow cytometry, cell-imaging and transcriptomics to clarify the architecture and functionality of lipid rafts and demonstrate the feasibility of targeting lipid a new strategy for anti-microbial therapy.
Summary
Membranes of eukaryotic cells organize signal transduction proteins into microdomains or lipid rafts whose integrity is essential for numerous cellular processes. Lipid rafts has been considered a fundamental step to define the cellular complexity of eukaryotes, assuming that bacteria do not require such a sophisticated organization of their signaling networks. However, I have discovered that bacteria organize many signaling pathways in membrane microdomains similar to the eukaryotic lipid rafts. Perturbation of bacterial lipid rafts leads to a potent and simultaneous impairment of all raft-harbored signaling pathways. Consequently, the disassembly of lipid rafts in pathogens like Staphylococcus aureus generates a simultaneous inhibition of numerous infection-related processes that can be further explored to control bacterial infections. This unexpected sophistication in membrane organization is unprecedented in bacteria and hence, this proposal will explore the molecular basis of the assembly of bacterial lipid rafts and their role in the infection-related processes. These questions will be addressed in three main goals: First, I will elucidate the molecular components and the mechanism of assembly of bacterial lipid rafts using S. aureus as model organism. Second, I will dissect the molecular basis that links the functionality of the infection-related processes to the integrity of bacterial lipid rafts. Third, my collection of anti-raft small molecules that are able to disrupt lipid rafts will be tested as antimicrobial agents to prevent hospital-acquired infections, abrogate pre-existing infections and develop bacteria-free materials that can be used in clinical settings. I will use a number of molecular approaches in combination with cutting-edge techniques in flow cytometry, cell-imaging and transcriptomics to clarify the architecture and functionality of lipid rafts and demonstrate the feasibility of targeting lipid a new strategy for anti-microbial therapy.
Max ERC Funding
1 493 126 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym BIO-IRT
Project Biologically individualized, model-based radiotherapy on the basis of multi-parametric molecular tumour profiling
Researcher (PI) Daniela Thorwarth
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Country Germany
Call Details Starting Grant (StG), LS7, ERC-2013-StG
Summary High precision radiotherapy (RT) allows extremely flexible tumour treatments achieving highly conformal radiation doses while sparing surrounding organs at risk. Nevertheless, failure rates of up to 50% are reported for head and neck cancer (HNC) due to radiation resistance induced by pathophysiologic factors such as hypoxia and other clinical factors as HPV-status, stage and tumour volume.
This project aims at developing a multi-parametric model for individualized RT (iRT) dose prescriptions in HNC based on biological markers and functional PET/MR imaging. This project goes far beyond current research standards and clinical practice as it aims for establishing hypoxia PET and f-MRI as well as biological markers in HNC as a role model for a novel concept from anatomy-based to biologically iRT.
During this project, a multi-parametric model will be developed on a preclinical basis that combines biological markers such as different oncogenes and hypoxia gene classifier with functional PET/MR imaging, such as FMISO PET in combination with different f-MRI techniques, like DW-, DCE- and BOLD-MRI in addition to MR spectroscopy. The ultimate goal of this project is a multi-parametric model to predict therapy outcome and guide iRT.
In a second part, a clinical study will be carried out to validate the preclinical model in patients. Based on the most informative radiobiological and imaging parameters as identified during the pre-clinical phase, biological markers and advanced PET/MR imaging will be evaluated in terms of their potential for iRT dose prescription.
Successful development of a model for biologically iRT prescription on the basis of multi-parametric molecular profiling would provide a unique basis for personalized cancer treatment. A validated multi-parametric model for RT outcome would represent a paradigm shift from anatomy-based to biologically iRT concepts with the ultimate goal of improving cancer cure rates.
Summary
High precision radiotherapy (RT) allows extremely flexible tumour treatments achieving highly conformal radiation doses while sparing surrounding organs at risk. Nevertheless, failure rates of up to 50% are reported for head and neck cancer (HNC) due to radiation resistance induced by pathophysiologic factors such as hypoxia and other clinical factors as HPV-status, stage and tumour volume.
This project aims at developing a multi-parametric model for individualized RT (iRT) dose prescriptions in HNC based on biological markers and functional PET/MR imaging. This project goes far beyond current research standards and clinical practice as it aims for establishing hypoxia PET and f-MRI as well as biological markers in HNC as a role model for a novel concept from anatomy-based to biologically iRT.
During this project, a multi-parametric model will be developed on a preclinical basis that combines biological markers such as different oncogenes and hypoxia gene classifier with functional PET/MR imaging, such as FMISO PET in combination with different f-MRI techniques, like DW-, DCE- and BOLD-MRI in addition to MR spectroscopy. The ultimate goal of this project is a multi-parametric model to predict therapy outcome and guide iRT.
In a second part, a clinical study will be carried out to validate the preclinical model in patients. Based on the most informative radiobiological and imaging parameters as identified during the pre-clinical phase, biological markers and advanced PET/MR imaging will be evaluated in terms of their potential for iRT dose prescription.
Successful development of a model for biologically iRT prescription on the basis of multi-parametric molecular profiling would provide a unique basis for personalized cancer treatment. A validated multi-parametric model for RT outcome would represent a paradigm shift from anatomy-based to biologically iRT concepts with the ultimate goal of improving cancer cure rates.
Max ERC Funding
1 370 799 €
Duration
Start date: 2014-01-01, End date: 2018-12-31