Project acronym AISENS
Project New generation of high sensitive atom interferometers
Researcher (PI) Marco Fattori
Host Institution (HI) CONSIGLIO NAZIONALE DELLE RICERCHE
Call Details Starting Grant (StG), PE2, ERC-2010-StG_20091028
Summary Interferometers are fundamental tools for the study of nature laws and for the precise measurement and control of the physical world. In the last century, the scientific and technological progress has proceeded in parallel with a constant improvement of interferometric performances. For this reason, the challenge of conceiving and realizing new generations of interferometers with broader ranges of operation and with higher sensitivities is always open and actual.
Despite the introduction of laser devices has deeply improved the way of developing and performing interferometric measurements with light, the atomic matter wave analogous, i.e. the Bose-Einstein condensate (BEC), has not yet triggered any revolution in precision interferometry. However, thanks to recent improvements on the control of the quantum properties of ultra-cold atomic gases, and new original ideas on the creation and manipulation of quantum entangled particles, the field of atom interferometry is now mature to experience a big step forward.
The system I want to realize is a Mach-Zehnder spatial interferometer operating with trapped BECs. Undesired decoherence sources will be suppressed by implementing BECs with tunable interactions in ultra-stable optical potentials. Entangled states will be used to improve the sensitivity of the sensor beyond the standard quantum limit to ideally reach the ultimate, Heisenberg, limit set by quantum mechanics. The resulting apparatus will show unprecedented spatial resolution and will overcome state-of-the-art interferometers with cold (non condensed) atomic gases.
A successful completion of this project will lead to a new generation of interferometers for the immediate application to local inertial measurements with unprecedented resolution. In addition, we expect to develop experimental capabilities which might find application well beyond quantum interferometry and crucially contribute to the broader emerging field of quantum-enhanced technologies.
Summary
Interferometers are fundamental tools for the study of nature laws and for the precise measurement and control of the physical world. In the last century, the scientific and technological progress has proceeded in parallel with a constant improvement of interferometric performances. For this reason, the challenge of conceiving and realizing new generations of interferometers with broader ranges of operation and with higher sensitivities is always open and actual.
Despite the introduction of laser devices has deeply improved the way of developing and performing interferometric measurements with light, the atomic matter wave analogous, i.e. the Bose-Einstein condensate (BEC), has not yet triggered any revolution in precision interferometry. However, thanks to recent improvements on the control of the quantum properties of ultra-cold atomic gases, and new original ideas on the creation and manipulation of quantum entangled particles, the field of atom interferometry is now mature to experience a big step forward.
The system I want to realize is a Mach-Zehnder spatial interferometer operating with trapped BECs. Undesired decoherence sources will be suppressed by implementing BECs with tunable interactions in ultra-stable optical potentials. Entangled states will be used to improve the sensitivity of the sensor beyond the standard quantum limit to ideally reach the ultimate, Heisenberg, limit set by quantum mechanics. The resulting apparatus will show unprecedented spatial resolution and will overcome state-of-the-art interferometers with cold (non condensed) atomic gases.
A successful completion of this project will lead to a new generation of interferometers for the immediate application to local inertial measurements with unprecedented resolution. In addition, we expect to develop experimental capabilities which might find application well beyond quantum interferometry and crucially contribute to the broader emerging field of quantum-enhanced technologies.
Max ERC Funding
1 068 000 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym ALLQUANTUM
Project All-solid-state quantum electrodynamics in photonic crystals
Researcher (PI) Peter Lodahl
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE2, ERC-2010-StG_20091028
Summary In quantum electrodynamics a range of fundamental processes are driven by omnipresent vacuum fluctuations. Photonic crystals can control vacuum fluctuations and thereby the fundamental interaction between light and matter. We will conduct experiments on quantum dots in photonic crystals and observe novel quantum electrodynamics effects including fractional decay and the modified Lamb shift. Furthermore, photonic crystals will be explored for shielding sensitive quantum-superposition states against decoherence.
Defects in photonic crystals allow novel functionalities enabling nanocavities and waveguides. We will use the tight confinement of light in a nanocavity to entangle a quantum dot and a photon, and explore the scalability. Controlled ways of generating scalable and robust quantum entanglement is the essential missing link limiting quantum communication and quantum computing. A single quantum dot coupled to a slowly propagating mode in a photonic crystal waveguide will be used to induce large nonlinearities at the few-photon level.
Finally we will explore a novel route to enhanced light-matter interaction employing controlled disorder in photonic crystals. In disordered media multiple scattering of light takes place and can lead to the formation of Anderson-localized modes. We will explore cavity quantum electrodynamics in Anderson-localized random cavities considering disorder a resource and not a nuisance, which is the traditional view.
The main focus of the project will be on optical experiments, but fabrication of photonic crystals and detailed theory will be carried out as well. Several of the proposed experiments will constitute milestones in quantum optics and may pave the way for all-solid-state quantum communication with quantum dots in photonic crystals.
Summary
In quantum electrodynamics a range of fundamental processes are driven by omnipresent vacuum fluctuations. Photonic crystals can control vacuum fluctuations and thereby the fundamental interaction between light and matter. We will conduct experiments on quantum dots in photonic crystals and observe novel quantum electrodynamics effects including fractional decay and the modified Lamb shift. Furthermore, photonic crystals will be explored for shielding sensitive quantum-superposition states against decoherence.
Defects in photonic crystals allow novel functionalities enabling nanocavities and waveguides. We will use the tight confinement of light in a nanocavity to entangle a quantum dot and a photon, and explore the scalability. Controlled ways of generating scalable and robust quantum entanglement is the essential missing link limiting quantum communication and quantum computing. A single quantum dot coupled to a slowly propagating mode in a photonic crystal waveguide will be used to induce large nonlinearities at the few-photon level.
Finally we will explore a novel route to enhanced light-matter interaction employing controlled disorder in photonic crystals. In disordered media multiple scattering of light takes place and can lead to the formation of Anderson-localized modes. We will explore cavity quantum electrodynamics in Anderson-localized random cavities considering disorder a resource and not a nuisance, which is the traditional view.
The main focus of the project will be on optical experiments, but fabrication of photonic crystals and detailed theory will be carried out as well. Several of the proposed experiments will constitute milestones in quantum optics and may pave the way for all-solid-state quantum communication with quantum dots in photonic crystals.
Max ERC Funding
1 199 648 €
Duration
Start date: 2010-12-01, End date: 2015-11-30
Project acronym ALOGLADIS
Project From Anderson localization to Bose, Fermi and spin glasses in disordered ultracold gases
Researcher (PI) Laurent Sanchez-Palencia
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE2, ERC-2010-StG_20091028
Summary The field of disordered quantum gases is developing rapidly. Dramatic progress has been achieved recently and first experimental observation of one-dimensional Anderson localization (AL) of matterwaves has been reported using Bose-Einstein condensates in controlled disorder (in our group at Institut d'Optique and at LENS; Nature, 2008). This dramatic success results from joint theoretical and experimental efforts, we have contributed to. Most importantly, it opens unprecedented routes to pursue several outstanding challenges in the multidisciplinary field of disordered systems, which, after fifty years of Anderson localization, is more active than ever.
This theoretical project aims at further developing the emerging field of disordered quantum gases towards novel challenges. Our aim is twofold. First, we will propose and analyze schemes where experiments on ultracold atoms can address unsolved issues: AL in dimensions higher than one, effects of inter-atomic interactions on AL, strongly-correlated disordered gases and quantum simulators for spin systems (spin glasses). Second, by taking into account specific features of ultracold atoms, beyond standard toy-models, we will raise and study new questions which have not been addressed before (eg long-range correlations of speckle potentials, finite-size effects, controlled interactions). Both aspects would open new frontiers to disordered quantum gases and offer new possibilities to shed new light on highly debated issues.
Our main concerns are thus to (i) study situations relevant to experiments, (ii) develop new approaches, applicable to ultracold atoms, (iii) identify key observables, and (iv) propose new challenging experiments. In this project, we will benefit from the original situation of our theory team: It is independent but forms part of a larger group (lead by A. Aspect), which is a world-leader in experiments on disordered quantum gases, we have already developed close collaborative relationship with.
Summary
The field of disordered quantum gases is developing rapidly. Dramatic progress has been achieved recently and first experimental observation of one-dimensional Anderson localization (AL) of matterwaves has been reported using Bose-Einstein condensates in controlled disorder (in our group at Institut d'Optique and at LENS; Nature, 2008). This dramatic success results from joint theoretical and experimental efforts, we have contributed to. Most importantly, it opens unprecedented routes to pursue several outstanding challenges in the multidisciplinary field of disordered systems, which, after fifty years of Anderson localization, is more active than ever.
This theoretical project aims at further developing the emerging field of disordered quantum gases towards novel challenges. Our aim is twofold. First, we will propose and analyze schemes where experiments on ultracold atoms can address unsolved issues: AL in dimensions higher than one, effects of inter-atomic interactions on AL, strongly-correlated disordered gases and quantum simulators for spin systems (spin glasses). Second, by taking into account specific features of ultracold atoms, beyond standard toy-models, we will raise and study new questions which have not been addressed before (eg long-range correlations of speckle potentials, finite-size effects, controlled interactions). Both aspects would open new frontiers to disordered quantum gases and offer new possibilities to shed new light on highly debated issues.
Our main concerns are thus to (i) study situations relevant to experiments, (ii) develop new approaches, applicable to ultracold atoms, (iii) identify key observables, and (iv) propose new challenging experiments. In this project, we will benefit from the original situation of our theory team: It is independent but forms part of a larger group (lead by A. Aspect), which is a world-leader in experiments on disordered quantum gases, we have already developed close collaborative relationship with.
Max ERC Funding
985 200 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym ASYMMETRY
Project Measurement of CP violation in the B_s system at LHCb
Researcher (PI) Stephanie Hansmann-Menzemer
Host Institution (HI) RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Call Details Starting Grant (StG), PE2, ERC-2010-StG_20091028
Summary The Large Hadron collider (LHC) at CERN will be a milestone for the understanding of fundamental interactions and for the future of high energy
physics. Four large experiments at the LHC are complementarily addressing the question of the origin of our Universe by searching for so-called New Physics.
The world of particles and their interactions is nowadays described by the Standard Model. Up to now there is no single measurement from laboratory experiments which contradicts this theory. However, there are still many open questions, thus physicists are convinced that there is a more fundamental theory, which incorporates New Physics.
It is expected that at the LHC either New Physics beyond the Standard Model will be discovered or excluded up to very high energies, which would revolutionize the understanding of particle physics and require completely new experimental and theoretical concepts.
The LHCb (Large Hadron Collider beauty) experiment is dedicated to precision measurements of B hadrons (B hadrons are all particles containing a beauty quark).
The analysis proposed here is the measurement of asymmetries between B_s particles and anti-B_s particles at the LHCb experiment. Any New Physics model will change the rate of observable processes via additional quantum corrections. Particle antiparticle asymmetries are extremely sensitive to these corrections thus a very powerful tool for indirect searches for New Physics contributions. In the past, most of the ground-breaking findings in particle physics, such as the existence of the
charm quark and the existence of a third quark family, have first been observed in indirect searches.
First - still statistically limited - measurements of the asymmetry in the B_s system indicate a 2 sigma deviation from the Standard Model prediction. A precision measurement of this asymmetry is potentially the first observation for New Physics beyond the Standard Model at the LHC. If no hint for New Physics will be found, this measurement will severely restrict the range of potential New Physics models.
Summary
The Large Hadron collider (LHC) at CERN will be a milestone for the understanding of fundamental interactions and for the future of high energy
physics. Four large experiments at the LHC are complementarily addressing the question of the origin of our Universe by searching for so-called New Physics.
The world of particles and their interactions is nowadays described by the Standard Model. Up to now there is no single measurement from laboratory experiments which contradicts this theory. However, there are still many open questions, thus physicists are convinced that there is a more fundamental theory, which incorporates New Physics.
It is expected that at the LHC either New Physics beyond the Standard Model will be discovered or excluded up to very high energies, which would revolutionize the understanding of particle physics and require completely new experimental and theoretical concepts.
The LHCb (Large Hadron Collider beauty) experiment is dedicated to precision measurements of B hadrons (B hadrons are all particles containing a beauty quark).
The analysis proposed here is the measurement of asymmetries between B_s particles and anti-B_s particles at the LHCb experiment. Any New Physics model will change the rate of observable processes via additional quantum corrections. Particle antiparticle asymmetries are extremely sensitive to these corrections thus a very powerful tool for indirect searches for New Physics contributions. In the past, most of the ground-breaking findings in particle physics, such as the existence of the
charm quark and the existence of a third quark family, have first been observed in indirect searches.
First - still statistically limited - measurements of the asymmetry in the B_s system indicate a 2 sigma deviation from the Standard Model prediction. A precision measurement of this asymmetry is potentially the first observation for New Physics beyond the Standard Model at the LHC. If no hint for New Physics will be found, this measurement will severely restrict the range of potential New Physics models.
Max ERC Funding
1 059 240 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym ATTOELECTRONICS
Project Attoelectronics: Steering electrons in atoms and molecules with synthesized waveforms of light
Researcher (PI) Eleftherios Goulielmakis
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Starting Grant (StG), PE2, ERC-2010-StG_20091028
Summary In order for electronics to meet the ever raising demands for higher speeds of operation, the dimensions of its basic elements drop continuously. This miniaturization, that will soon meet the dimensions of a single molecule or an atom, calls for new approaches in electronics that take advantage, rather than confront the dominant at these scales quantum laws.
Electronics on the scale of atoms and molecules require fields that are able to trigger and to steer electrons at speeds comparable to their intrinsic dynamics, determined by the quantum mechanical laws. For the valence electrons of atoms and molecules, this motion is clocked in tens to thousands of attoseconds, (1 as =10-18 sec) implying the potential for executing basic electronic operations in the PHz regime and beyond. This is approximately ~1000000 times faster as compared to any contemporary technology.
To meet this challenging goal, this project will utilize conceptual and technological advances of attosecond science as its primary tools. First, pulses of light, the fields of which can be sculpted and characterized with attosecond accuracy, for triggering as well as for terminating the ultrafast electron motion in an atom or a molecule. Second, attosecond pulses in the extreme ultraviolet, which can probe and frame-freeze the created electron motion, with unprecedented resolution, and determine the direction and the magnitude of the created currents.
This project will interrogate the limits of the fastest electronic motion that light fields can trigger as well as terminate, a few hundreds of attoseconds later, in an atom or a molecule. In this way it aims to explore new routes of atomic and molecular scale electronic switching at PHz frequencies.
Summary
In order for electronics to meet the ever raising demands for higher speeds of operation, the dimensions of its basic elements drop continuously. This miniaturization, that will soon meet the dimensions of a single molecule or an atom, calls for new approaches in electronics that take advantage, rather than confront the dominant at these scales quantum laws.
Electronics on the scale of atoms and molecules require fields that are able to trigger and to steer electrons at speeds comparable to their intrinsic dynamics, determined by the quantum mechanical laws. For the valence electrons of atoms and molecules, this motion is clocked in tens to thousands of attoseconds, (1 as =10-18 sec) implying the potential for executing basic electronic operations in the PHz regime and beyond. This is approximately ~1000000 times faster as compared to any contemporary technology.
To meet this challenging goal, this project will utilize conceptual and technological advances of attosecond science as its primary tools. First, pulses of light, the fields of which can be sculpted and characterized with attosecond accuracy, for triggering as well as for terminating the ultrafast electron motion in an atom or a molecule. Second, attosecond pulses in the extreme ultraviolet, which can probe and frame-freeze the created electron motion, with unprecedented resolution, and determine the direction and the magnitude of the created currents.
This project will interrogate the limits of the fastest electronic motion that light fields can trigger as well as terminate, a few hundreds of attoseconds later, in an atom or a molecule. In this way it aims to explore new routes of atomic and molecular scale electronic switching at PHz frequencies.
Max ERC Funding
1 262 000 €
Duration
Start date: 2010-12-01, End date: 2016-11-30
Project acronym BETATOBETA
Project The molecular basis of pancreatic beta cell replication
Researcher (PI) Yuval Dor
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), LS4, ERC-2010-StG_20091118
Summary A fundamental challenge of pancreas biology is to understand and manipulate the determinants of beta cell mass. The homeostatic maintenance of adult beta cell mass relies largely on replication of differentiated beta cells, but the triggers and signaling pathways involved remain poorly understood. Here I propose to investigate the physiological and molecular mechanisms that control beta cell replication. First, novel transgenic mouse tools will be used to isolate live replicating beta cells and to examine the genetic program of beta cell replication in vivo. Information gained will provide insights into the molecular biology of cell division in vivo. Additionally, these experiments will address critical unresolved questions in beta cell biology, for example whether duplication involves transient dedifferentiation. Second, genetic and pharmacologic tools will be used to dissect the signaling pathways controlling the entry of beta cells to the cell division cycle, with emphasis on the roles of glucose and insulin, the key physiological input and output of beta cells. The expected outcome of these studies is a detailed molecular understanding of the homeostatic maintenance of beta cell mass, describing how beta cell function is linked to beta cell number in vivo. This may suggest new targets and concepts for pharmacologic intervention, towards the development of regenerative therapy strategies in diabetes. More generally, the experiments will shed light on one of the greatest mysteries of developmental biology, namely how organs achieve and maintain their correct size. A fundamental challenge of pancreas biology is to understand and manipulate the determinants of beta cell mass. The homeostatic maintenance of adult beta cell mass relies largely on replication of differentiated beta cells, but the triggers and signaling pathways involved remain poorly understood. Here I propose to investigate the physiological and molecular mechanisms that control beta cell replication. First, novel transgenic mouse tools will be used to isolate live replicating beta cells and to examine the genetic program of beta cell replication in vivo. Information gained will provide insights into the molecular biology of cell division in vivo. Additionally, these experiments will address critical unresolved questions in beta cell biology, for example whether duplication involves transient dedifferentiation. Second, genetic and pharmacologic tools will be used to dissect the signaling pathways controlling the entry of beta cells to the cell division cycle, with emphasis on the roles of glucose and insulin, the key physiological input and output of beta cells. The expected outcome of these studies is a detailed molecular understanding of the homeostatic maintenance of beta cell mass, describing how beta cell function is linked to beta cell number in vivo. This may suggest new targets and concepts for pharmacologic intervention, towards the development of regenerative therapy strategies in diabetes. More generally, the experiments will shed light on one of the greatest mysteries of developmental biology, namely how organs achieve and maintain their correct size.
Summary
A fundamental challenge of pancreas biology is to understand and manipulate the determinants of beta cell mass. The homeostatic maintenance of adult beta cell mass relies largely on replication of differentiated beta cells, but the triggers and signaling pathways involved remain poorly understood. Here I propose to investigate the physiological and molecular mechanisms that control beta cell replication. First, novel transgenic mouse tools will be used to isolate live replicating beta cells and to examine the genetic program of beta cell replication in vivo. Information gained will provide insights into the molecular biology of cell division in vivo. Additionally, these experiments will address critical unresolved questions in beta cell biology, for example whether duplication involves transient dedifferentiation. Second, genetic and pharmacologic tools will be used to dissect the signaling pathways controlling the entry of beta cells to the cell division cycle, with emphasis on the roles of glucose and insulin, the key physiological input and output of beta cells. The expected outcome of these studies is a detailed molecular understanding of the homeostatic maintenance of beta cell mass, describing how beta cell function is linked to beta cell number in vivo. This may suggest new targets and concepts for pharmacologic intervention, towards the development of regenerative therapy strategies in diabetes. More generally, the experiments will shed light on one of the greatest mysteries of developmental biology, namely how organs achieve and maintain their correct size. A fundamental challenge of pancreas biology is to understand and manipulate the determinants of beta cell mass. The homeostatic maintenance of adult beta cell mass relies largely on replication of differentiated beta cells, but the triggers and signaling pathways involved remain poorly understood. Here I propose to investigate the physiological and molecular mechanisms that control beta cell replication. First, novel transgenic mouse tools will be used to isolate live replicating beta cells and to examine the genetic program of beta cell replication in vivo. Information gained will provide insights into the molecular biology of cell division in vivo. Additionally, these experiments will address critical unresolved questions in beta cell biology, for example whether duplication involves transient dedifferentiation. Second, genetic and pharmacologic tools will be used to dissect the signaling pathways controlling the entry of beta cells to the cell division cycle, with emphasis on the roles of glucose and insulin, the key physiological input and output of beta cells. The expected outcome of these studies is a detailed molecular understanding of the homeostatic maintenance of beta cell mass, describing how beta cell function is linked to beta cell number in vivo. This may suggest new targets and concepts for pharmacologic intervention, towards the development of regenerative therapy strategies in diabetes. More generally, the experiments will shed light on one of the greatest mysteries of developmental biology, namely how organs achieve and maintain their correct size.
Max ERC Funding
1 445 000 €
Duration
Start date: 2010-09-01, End date: 2015-08-31
Project acronym CAPSEVO
Project Evolution of flower morphology: the selfing syndrome in Capsella
Researcher (PI) Michael Lenhard
Host Institution (HI) UNIVERSITAET POTSDAM
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary The change from reproduction by outbreeding to selfing is one of the most frequent evolutionary transitions in plants. This transition is generally accompanied by changes in flower morphology and function, termed the selfing syndrome, including a reduction in flower size and a more closed flower structure. While the loss of self-incompatibility is relatively well understood, little is known about the molecular basis of the associated morphological changes and their evolutionary history. We will address these problems using the species pair Capsella grandiflora (the ancestral outbreeder) and C. rubella (the derived selfing species) as a genetically tractable model. We have established recombinant inbred lines from a cross of C. grandiflora x C. rubella and mapped quantitative trait loci affecting flower size and flower opening. Using this resource, the proposal will address four objectives. (1) We will isolate causal genes underlying the variation in flower size and opening, by combining genetic mapping with next-generation sequencing. (2) We will characterize the developmental and molecular functions of the isolated genes in Capsella and Arabidopsis. (3) We will dissect the molecular basis of the different allelic effects of the causal genes to determine which kinds of mutations have led to the morphological changes. (4) Based on population-genetic analyses of the isolated genes, the evolutionary history of the morphological changes will be retraced. Together, these strands of investigation will provide a detailed understanding of general processes underlying morphological evolution in plants.
Summary
The change from reproduction by outbreeding to selfing is one of the most frequent evolutionary transitions in plants. This transition is generally accompanied by changes in flower morphology and function, termed the selfing syndrome, including a reduction in flower size and a more closed flower structure. While the loss of self-incompatibility is relatively well understood, little is known about the molecular basis of the associated morphological changes and their evolutionary history. We will address these problems using the species pair Capsella grandiflora (the ancestral outbreeder) and C. rubella (the derived selfing species) as a genetically tractable model. We have established recombinant inbred lines from a cross of C. grandiflora x C. rubella and mapped quantitative trait loci affecting flower size and flower opening. Using this resource, the proposal will address four objectives. (1) We will isolate causal genes underlying the variation in flower size and opening, by combining genetic mapping with next-generation sequencing. (2) We will characterize the developmental and molecular functions of the isolated genes in Capsella and Arabidopsis. (3) We will dissect the molecular basis of the different allelic effects of the causal genes to determine which kinds of mutations have led to the morphological changes. (4) Based on population-genetic analyses of the isolated genes, the evolutionary history of the morphological changes will be retraced. Together, these strands of investigation will provide a detailed understanding of general processes underlying morphological evolution in plants.
Max ERC Funding
1 480 826 €
Duration
Start date: 2010-12-01, End date: 2016-11-30
Project acronym CARDIO-IPS
Project Induced Pluripotent stem Cells: A Novel Strategy to Study Inherited Cardiac Disorders
Researcher (PI) Lior Gepstein
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), LS4, ERC-2010-StG_20091118
Summary The study of several genetic disorders is hampered by the lack of suitable in vitro human models. We hypothesize that the generation of patient-specific induced pluripotent stem cells (iPSCs) will allow the development of disease-specific in vitro models; yielding new pathophysiologic insights into several genetic disorders and offering a unique platform to test novel therapeutic strategies. In the current proposal we plan utilize this novel approach to establish human iPSC (hiPSC) lines for the study of a variety of inherited cardiac disorders. The specific disease states that will be studied were chosen to reflect abnormalities in a wide-array of different cardiomyocyte cellular processes.
These include mutations leading to:
(1) abnormal ion channel function (“channelopathies”), such as the long QT and Brugada syndromes;
(2) abnormal intracellular storage of unnecessary material, such as in the glycogen storage disease type IIb (Pompe’s disease); and
(3) abnormalities in cell-to-cell contacts, such as in the case of arrhythmogenic right ventricular cardiomyopathy-dysplasia (ARVC-D). The different hiPSC lines generated will be coaxed to differentiate into the cardiac lineage. Detailed molecular, structural, functional, and pharmacological studies will then be performed to characterize the phenotypic properties of the generated hiPSC-derived cardiomyocytes, with specific emphasis on their molecular, ultrastructural, electrophysiological, and Ca2+ handling properties.
These studies should provide new insights into the pathophysiological mechanisms underlying the different familial arrhythmogenic and cardiomyopathy disorders studied, may allow optimization of patient-specific therapies (personalized medicine), and may facilitate the development of novel therapeutic strategies.
Moreover, the concepts and methodological knowhow developed in the current project could be extended, in the future, to derive human disease-specific cell culture models for a plurality of genetic disorders; enabling translational research ranging from investigation of the most fundamental cellular mechanisms involved in human tissue formation and physiology through disease investigation and the development and testing of novel therapies that could potentially find their way to the bedside
Summary
The study of several genetic disorders is hampered by the lack of suitable in vitro human models. We hypothesize that the generation of patient-specific induced pluripotent stem cells (iPSCs) will allow the development of disease-specific in vitro models; yielding new pathophysiologic insights into several genetic disorders and offering a unique platform to test novel therapeutic strategies. In the current proposal we plan utilize this novel approach to establish human iPSC (hiPSC) lines for the study of a variety of inherited cardiac disorders. The specific disease states that will be studied were chosen to reflect abnormalities in a wide-array of different cardiomyocyte cellular processes.
These include mutations leading to:
(1) abnormal ion channel function (“channelopathies”), such as the long QT and Brugada syndromes;
(2) abnormal intracellular storage of unnecessary material, such as in the glycogen storage disease type IIb (Pompe’s disease); and
(3) abnormalities in cell-to-cell contacts, such as in the case of arrhythmogenic right ventricular cardiomyopathy-dysplasia (ARVC-D). The different hiPSC lines generated will be coaxed to differentiate into the cardiac lineage. Detailed molecular, structural, functional, and pharmacological studies will then be performed to characterize the phenotypic properties of the generated hiPSC-derived cardiomyocytes, with specific emphasis on their molecular, ultrastructural, electrophysiological, and Ca2+ handling properties.
These studies should provide new insights into the pathophysiological mechanisms underlying the different familial arrhythmogenic and cardiomyopathy disorders studied, may allow optimization of patient-specific therapies (personalized medicine), and may facilitate the development of novel therapeutic strategies.
Moreover, the concepts and methodological knowhow developed in the current project could be extended, in the future, to derive human disease-specific cell culture models for a plurality of genetic disorders; enabling translational research ranging from investigation of the most fundamental cellular mechanisms involved in human tissue formation and physiology through disease investigation and the development and testing of novel therapies that could potentially find their way to the bedside
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-03-01, End date: 2016-02-29
Project acronym CBSCS
Project Physiology of the adult carotid body stem cell niche
Researcher (PI) Ricardo Pardal
Host Institution (HI) UNIVERSIDAD DE SEVILLA
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary The discovery of adult neural stem cells (NSCs) has broaden our view of the physiological plasticity of the nervous system,
and has opened new perspectives on the possibility of tissue regeneration and repair in the brain. NSCs reside in specialized
niches in the adult mammalian nervous system, where they are exposed to specific paracrine signals regulating their
behavior. These neural progenitors are generally in a quiescent state within their niche, and they activate their proliferation
depending on tissue regenerative and growth needs. Understanding the mechanisms by which NSCs enter and exit the
quiescent state is crucial for the comprehension of the physiology of the adult nervous system. In this project we will study
the behavior of a specific subpopulation of adult neural stem cells recently described by our group in the carotid body (CB).
This small organ constitutes the most important chemosensor of the peripheral nervous system and has neuronal glomus
cells responsible for the chemosensing, and glia-like sustentacular cells which were thought to have just a supportive role.
We recently described that these sustentacular cells are dormant stem cells able to activate their proliferation in response to a
physiological stimulus like hypoxia, and to differentiate into new glomus cells necessary for the adaptation of the organ.
Due to our precise experimental control of the activation and deactivation of the CB neurogenic niche, we believe the CB is
an ideal model to study fundamental questions about adult neural stem cell physiology and the interaction with the niche. We
propose to study the cellular and molecular mechanisms by which these carotid body stem cells enter and exit the quiescent
state, which will help us understand the physiology of adult neurogenic niches. Likewise, understanding this neurogenic
process will improve the efficacy of using glomus cells for cell therapy against neurological disease, and might help us
understand some neural tumors.
Summary
The discovery of adult neural stem cells (NSCs) has broaden our view of the physiological plasticity of the nervous system,
and has opened new perspectives on the possibility of tissue regeneration and repair in the brain. NSCs reside in specialized
niches in the adult mammalian nervous system, where they are exposed to specific paracrine signals regulating their
behavior. These neural progenitors are generally in a quiescent state within their niche, and they activate their proliferation
depending on tissue regenerative and growth needs. Understanding the mechanisms by which NSCs enter and exit the
quiescent state is crucial for the comprehension of the physiology of the adult nervous system. In this project we will study
the behavior of a specific subpopulation of adult neural stem cells recently described by our group in the carotid body (CB).
This small organ constitutes the most important chemosensor of the peripheral nervous system and has neuronal glomus
cells responsible for the chemosensing, and glia-like sustentacular cells which were thought to have just a supportive role.
We recently described that these sustentacular cells are dormant stem cells able to activate their proliferation in response to a
physiological stimulus like hypoxia, and to differentiate into new glomus cells necessary for the adaptation of the organ.
Due to our precise experimental control of the activation and deactivation of the CB neurogenic niche, we believe the CB is
an ideal model to study fundamental questions about adult neural stem cell physiology and the interaction with the niche. We
propose to study the cellular and molecular mechanisms by which these carotid body stem cells enter and exit the quiescent
state, which will help us understand the physiology of adult neurogenic niches. Likewise, understanding this neurogenic
process will improve the efficacy of using glomus cells for cell therapy against neurological disease, and might help us
understand some neural tumors.
Max ERC Funding
1 476 000 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym CENTRIOLSTRUCTNUMBER
Project Control of Centriole Structure And Number
Researcher (PI) Monica Bettencourt Carvalho Dias
Host Institution (HI) FUNDACAO CALOUSTE GULBENKIAN
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary Centrioles are essential for the formation of several microtubule organizing structures including cilia, flagella and centrosomes. These structures are involved in a variety of functions, from cell motility to division. Centrosome defects are seen in many cancers, while abnormalities in cilia and flagella can lead to a variety of human diseases, such as polycystic kidney disease. The molecular mechanisms regulating centriole biogenesis have only recently started to be unravelled, opening new ways to answer a wide range of questions that have fascinated biologists for more than a century. In this grant we are asking two fundamental questions that are central to human disease: how is centriole structure and number established and regulated in the eukaryotic cell? To address these questions we propose to identify new molecular players, and to test the role of these and known players in the context of specific mechanistic hypothesis, using in vitro and in vivo models. We propose to develop novel assays for centriole structure and regulation in order to address mechanistic problems not accessible with today s assays. In our search for novel components we will use a multidisciplinary approach combining bioinformatics with high throughput screening. The use of in vitro systems will permit the quantitative dissection of molecular mechanisms, while the study of those mechanisms in Drosophila will allow us to understand them at the whole organism level. Furthermore, this analysis, together with studies in human tissue culture cells, will allow us to understand the consequences of misregulation of these fundamental centriole properties for human disease, such as ciliopathies and cancer. My group is already collaborating with medical doctors in the study of centriole aberrations in human disease (cancer and ciliopathies), which will be invaluable to bringing the results of this study to the translational level.
Summary
Centrioles are essential for the formation of several microtubule organizing structures including cilia, flagella and centrosomes. These structures are involved in a variety of functions, from cell motility to division. Centrosome defects are seen in many cancers, while abnormalities in cilia and flagella can lead to a variety of human diseases, such as polycystic kidney disease. The molecular mechanisms regulating centriole biogenesis have only recently started to be unravelled, opening new ways to answer a wide range of questions that have fascinated biologists for more than a century. In this grant we are asking two fundamental questions that are central to human disease: how is centriole structure and number established and regulated in the eukaryotic cell? To address these questions we propose to identify new molecular players, and to test the role of these and known players in the context of specific mechanistic hypothesis, using in vitro and in vivo models. We propose to develop novel assays for centriole structure and regulation in order to address mechanistic problems not accessible with today s assays. In our search for novel components we will use a multidisciplinary approach combining bioinformatics with high throughput screening. The use of in vitro systems will permit the quantitative dissection of molecular mechanisms, while the study of those mechanisms in Drosophila will allow us to understand them at the whole organism level. Furthermore, this analysis, together with studies in human tissue culture cells, will allow us to understand the consequences of misregulation of these fundamental centriole properties for human disease, such as ciliopathies and cancer. My group is already collaborating with medical doctors in the study of centriole aberrations in human disease (cancer and ciliopathies), which will be invaluable to bringing the results of this study to the translational level.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-01-01, End date: 2016-12-31
