Project acronym 5D Heart Patch
Project A Functional, Mature In vivo Human Ventricular Muscle Patch for Cardiomyopathy
Researcher (PI) Kenneth Randall Chien
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Advanced Grant (AdG), LS7, ERC-2016-ADG
Summary Developing new therapeutic strategies for heart regeneration is a major goal for cardiac biology and medicine. While cardiomyocytes can be generated from human pluripotent stem (hPSC) cells in vitro, it has proven difficult to use these cells to generate a large scale, mature human heart ventricular muscle graft on the injured heart in vivo. The central objective of this proposal is to optimize the generation of a large-scale pure, fully functional human ventricular muscle patch in vivo through the self-assembly of purified human ventricular progenitors and the localized expression of defined paracrine factors that drive their expansion, differentiation, vascularization, matrix formation, and maturation. Recently, we have found that purified hPSC-derived ventricular progenitors (HVPs) can self-assemble in vivo on the epicardial surface into a 3D vascularized, and functional ventricular patch with its own extracellular matrix via a cell autonomous pathway. A two-step protocol and FACS purification of HVP receptors can generate billions of pure HVPs- The current proposal will lead to the identification of defined paracrine pathways to enhance the survival, grafting/implantation, expansion, differentiation, matrix formation, vascularization and maturation of the graft in vivo. We will captalize on our unique HVP system and our novel modRNA technology to deliver therapeutic strategies by using the in vivo human ventricular muscle to model in vivo arrhythmogenic cardiomyopathy, and optimize the ability of the graft to compensate for the massive loss of functional muscle during ischemic cardiomyopathy and post-myocardial infarction. The studies will lead to new in vivo chimeric models of human cardiac disease and an experimental paradigm to optimize organ-on-organ cardiac tissue engineers of an in vivo, functional mature ventricular patch for cardiomyopathy
Summary
Developing new therapeutic strategies for heart regeneration is a major goal for cardiac biology and medicine. While cardiomyocytes can be generated from human pluripotent stem (hPSC) cells in vitro, it has proven difficult to use these cells to generate a large scale, mature human heart ventricular muscle graft on the injured heart in vivo. The central objective of this proposal is to optimize the generation of a large-scale pure, fully functional human ventricular muscle patch in vivo through the self-assembly of purified human ventricular progenitors and the localized expression of defined paracrine factors that drive their expansion, differentiation, vascularization, matrix formation, and maturation. Recently, we have found that purified hPSC-derived ventricular progenitors (HVPs) can self-assemble in vivo on the epicardial surface into a 3D vascularized, and functional ventricular patch with its own extracellular matrix via a cell autonomous pathway. A two-step protocol and FACS purification of HVP receptors can generate billions of pure HVPs- The current proposal will lead to the identification of defined paracrine pathways to enhance the survival, grafting/implantation, expansion, differentiation, matrix formation, vascularization and maturation of the graft in vivo. We will captalize on our unique HVP system and our novel modRNA technology to deliver therapeutic strategies by using the in vivo human ventricular muscle to model in vivo arrhythmogenic cardiomyopathy, and optimize the ability of the graft to compensate for the massive loss of functional muscle during ischemic cardiomyopathy and post-myocardial infarction. The studies will lead to new in vivo chimeric models of human cardiac disease and an experimental paradigm to optimize organ-on-organ cardiac tissue engineers of an in vivo, functional mature ventricular patch for cardiomyopathy
Max ERC Funding
2 149 228 €
Duration
Start date: 2017-12-01, End date: 2022-11-30
Project acronym ALK7
Project Metabolic control by the TGF-² superfamily receptor ALK7: A novel regulator of insulin secretion, fat accumulation and energy balance
Researcher (PI) Carlos Ibanez
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Advanced Grant (AdG), LS4, ERC-2008-AdG
Summary The aim of this proposal is to understand a novel regulatory signaling network controlling insulin secretion, fat accumulation and energy balance centered around selected components of the TGF-² signaling system, including Activins A and B, GDF-3 and their receptors ALK7 and ALK4. Recent results from my laboratory indicate that these molecules are part of paracrine signaling networks that control important functions in pancreatic islets and adipose tissue through feedback inhibition and feed-forward regulation. These discoveries have open up a new research area with important implications for the understanding of metabolic networks and the treatment of human metabolic syndromes, such as diabetes and obesity.
To drive progress in this new research area beyond the state-of-the-art it is proposed to: i) Elucidate the molecular mechanisms by which Activins regulate Ca2+ influx and insulin secretion in pancreatic ²-cells; ii) Elucidate the molecular mechanisms underlying the effects of GDF-3 on adipocyte metabolism, turnover and fat accumulation; iii) Investigate the interplay between insulin levels and fat deposition in the development of insulin resistance using mutant mice lacking Activin B and GDF-3; iv) Investigate tissue-specific contributions of ALK7 and ALK4 signaling to metabolic control by generating and characterizing conditional mutant mice; v) Investigate the effects of specific and reversible inactivation of ALK7 and ALK4 on metabolic regulation using a novel chemical-genetic approach based on analog-sensitive alleles.
This is research of a high-gain/high-risk nature. It is posed to open unique opportunities for further exploration of complex metabolic networks. The development of drugs capable of enhancing insulin secretion, limiting fat accumulation and ameliorating diet-induced obesity by targeting components of the ALK7 signaling network will find a strong rationale in the results of the proposed work.
Summary
The aim of this proposal is to understand a novel regulatory signaling network controlling insulin secretion, fat accumulation and energy balance centered around selected components of the TGF-² signaling system, including Activins A and B, GDF-3 and their receptors ALK7 and ALK4. Recent results from my laboratory indicate that these molecules are part of paracrine signaling networks that control important functions in pancreatic islets and adipose tissue through feedback inhibition and feed-forward regulation. These discoveries have open up a new research area with important implications for the understanding of metabolic networks and the treatment of human metabolic syndromes, such as diabetes and obesity.
To drive progress in this new research area beyond the state-of-the-art it is proposed to: i) Elucidate the molecular mechanisms by which Activins regulate Ca2+ influx and insulin secretion in pancreatic ²-cells; ii) Elucidate the molecular mechanisms underlying the effects of GDF-3 on adipocyte metabolism, turnover and fat accumulation; iii) Investigate the interplay between insulin levels and fat deposition in the development of insulin resistance using mutant mice lacking Activin B and GDF-3; iv) Investigate tissue-specific contributions of ALK7 and ALK4 signaling to metabolic control by generating and characterizing conditional mutant mice; v) Investigate the effects of specific and reversible inactivation of ALK7 and ALK4 on metabolic regulation using a novel chemical-genetic approach based on analog-sensitive alleles.
This is research of a high-gain/high-risk nature. It is posed to open unique opportunities for further exploration of complex metabolic networks. The development of drugs capable of enhancing insulin secretion, limiting fat accumulation and ameliorating diet-induced obesity by targeting components of the ALK7 signaling network will find a strong rationale in the results of the proposed work.
Max ERC Funding
2 462 154 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym ALMA
Project Attosecond Control of Light and Matter
Researcher (PI) Anne L'huillier
Host Institution (HI) MAX IV Laboratory, Lund University
Country Sweden
Call Details Advanced Grant (AdG), PE2, ERC-2008-AdG
Summary Attosecond light pulses are generated when an intense laser interacts with a gas target. These pulses are not only short, enabling the study of electronic processes at their natural time scale, but also coherent. The vision of this proposal is to extend temporal coherent control concepts to a completely new regime of time and energy, combining (i) ultrashort pulses (ii) broadband excitation (iii) high photon energy, allowing scientists to reach not only valence but also inner shells in atoms and molecules, and, when needed, (iv) high spatial resolution. We want to explore how elementary electronic processes in atoms, molecules and more complex systems can be controlled by using well designed sequences of attosecond pulses. The research project proposed is organized into four parts: 1. Attosecond control of light leading to controlled sequences of attosecond pulses We will develop techniques to generate sequences of attosecond pulses with a variable number of pulses and controlled carrier-envelope-phase variation between consecutive pulses. 2. Attosecond control of electronic processes in atoms and molecules We will investigate the dynamics and coherence of phenomena induced by attosecond excitation of electron wave packets in various systems and we will explore how they can be controlled by a controlled sequence of ultrashort pulses. 3. Intense attosecond sources to reach the nonlinear regime We will optimize attosecond light sources in a systematic way, including amplification of the radiation by injecting a free electron laser. This will open up the possibility to develop nonlinear measurement and control schemes. 4. Attosecond control in more complex systems, including high spatial resolution We will develop ultrafast microscopy techniques, in order to obtain meaningful temporal information in surface and solid state physics. Two directions will be explored, digital in line microscopic holography and photoemission electron microscopy.
Summary
Attosecond light pulses are generated when an intense laser interacts with a gas target. These pulses are not only short, enabling the study of electronic processes at their natural time scale, but also coherent. The vision of this proposal is to extend temporal coherent control concepts to a completely new regime of time and energy, combining (i) ultrashort pulses (ii) broadband excitation (iii) high photon energy, allowing scientists to reach not only valence but also inner shells in atoms and molecules, and, when needed, (iv) high spatial resolution. We want to explore how elementary electronic processes in atoms, molecules and more complex systems can be controlled by using well designed sequences of attosecond pulses. The research project proposed is organized into four parts: 1. Attosecond control of light leading to controlled sequences of attosecond pulses We will develop techniques to generate sequences of attosecond pulses with a variable number of pulses and controlled carrier-envelope-phase variation between consecutive pulses. 2. Attosecond control of electronic processes in atoms and molecules We will investigate the dynamics and coherence of phenomena induced by attosecond excitation of electron wave packets in various systems and we will explore how they can be controlled by a controlled sequence of ultrashort pulses. 3. Intense attosecond sources to reach the nonlinear regime We will optimize attosecond light sources in a systematic way, including amplification of the radiation by injecting a free electron laser. This will open up the possibility to develop nonlinear measurement and control schemes. 4. Attosecond control in more complex systems, including high spatial resolution We will develop ultrafast microscopy techniques, in order to obtain meaningful temporal information in surface and solid state physics. Two directions will be explored, digital in line microscopic holography and photoemission electron microscopy.
Max ERC Funding
2 250 000 €
Duration
Start date: 2008-12-01, End date: 2013-11-30
Project acronym AMIMOS
Project Agile MIMO Systems for Communications, Biomedicine, and Defense
Researcher (PI) Bjorn Ottersten
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Country Sweden
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary This proposal targets the emerging frontier research field of multiple-input multiple-output (MIMO) systems along with several innovative and somewhat unconventional applications of such systems. The use of arrays of transmitters and receivers will have a profound impact on future medical imaging/therapy systems, radar systems, and radio communication networks. Multiple transmitters provide a tremendous versatility and allow waveforms to be adapted temporally and spatially to environmental conditions. This is useful for individually tailored illumination of human tissue in biomedical imaging or ultrasound therapy. In radar systems, multiple transmit beams can be formed simultaneously via separate waveform designs allowing accurate target classification. In a wireless communication system, multiple communication signals can be directed to one or more users at the same time on the same frequency carrier. In addition, multiple receivers can be used in the above applications to provide increased detection performance, interference rejection, and improved estimation accuracy. The joint modelling, analysis, and design of these multidimensional transmit and receive schemes form the core of this research proposal. Ultimately, our research aims at developing the fundamental tools that will allow the design of wireless communication systems with an order-of-magnitude higher capacity at a lower cost than today; of ultrasound therapy systems maximizing delivered power while reducing treatment duration and unwanted illumination; and of distributed aperture multi-beam radars allowing more effective target location, identification, and classification. Europe has several successful industries that are active in biomedical imaging/therapy, radar systems, and wireless communications. The future success of these sectors critically depends on the ability to innovate and integrate new technology.
Summary
This proposal targets the emerging frontier research field of multiple-input multiple-output (MIMO) systems along with several innovative and somewhat unconventional applications of such systems. The use of arrays of transmitters and receivers will have a profound impact on future medical imaging/therapy systems, radar systems, and radio communication networks. Multiple transmitters provide a tremendous versatility and allow waveforms to be adapted temporally and spatially to environmental conditions. This is useful for individually tailored illumination of human tissue in biomedical imaging or ultrasound therapy. In radar systems, multiple transmit beams can be formed simultaneously via separate waveform designs allowing accurate target classification. In a wireless communication system, multiple communication signals can be directed to one or more users at the same time on the same frequency carrier. In addition, multiple receivers can be used in the above applications to provide increased detection performance, interference rejection, and improved estimation accuracy. The joint modelling, analysis, and design of these multidimensional transmit and receive schemes form the core of this research proposal. Ultimately, our research aims at developing the fundamental tools that will allow the design of wireless communication systems with an order-of-magnitude higher capacity at a lower cost than today; of ultrasound therapy systems maximizing delivered power while reducing treatment duration and unwanted illumination; and of distributed aperture multi-beam radars allowing more effective target location, identification, and classification. Europe has several successful industries that are active in biomedical imaging/therapy, radar systems, and wireless communications. The future success of these sectors critically depends on the ability to innovate and integrate new technology.
Max ERC Funding
1 872 720 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym ANALYTICAL SOCIOLOGY
Project Analytical Sociology: Theoretical Developments and Empirical Research
Researcher (PI) Mats Peter Hedstroem
Host Institution (HI) LINKOPINGS UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), SH2, ERC-2012-ADG_20120411
Summary This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction.
One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link.
The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed.
Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.
Summary
This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction.
One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link.
The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed.
Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.
Max ERC Funding
1 745 098 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym ANGIOFAT
Project New mechanisms of angiogenesis modulators in switching between white and brown adipose tissues
Researcher (PI) Yihai Cao
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Advanced Grant (AdG), LS4, ERC-2009-AdG
Summary Understanding the molecular mechanisms underlying adipose blood vessel growth or regression opens new fundamentally insight into novel therapeutic options for the treatment of obesity and its related metabolic diseases such as type 2 diabetes and cancer. Unlike any other tissues in the body, the adipose tissue constantly experiences expansion and shrinkage throughout the adult life. Adipocytes in the white adipose tissue have the ability to switch into metabolically highly active brown-like adipocytes. Brown adipose tissue (BAT) contains significantly higher numbers of microvessels than white adipose tissue (WAT) in order to adopt the high rates of metabolism. Thus, an angiogenic phenotype has to be switched on during the transition from WAT into BAT. We have found that acclimation of mice in cold could induce transition from inguinal and epidedymal WAT into BAT by upregulation of angiogenic factor expression and down-regulations of angiogenesis inhibitors (Xue et al, Cell Metabolism, 2009). The transition from WAT into BAT is dependent on vascular endothelial growth factor (VEGF) that primarily targets on vascular endothelial cells via a tissue hypoxia-independent mechanism. VEGF blockade significantly alters adipose tissue metabolism. In another genetic model, we show similar findings that angiogenesis is crucial to mediate the transition from WAT into BAT (Xue et al, PNAS, 2008). Here we propose that the vascular tone determines the metabolic switch between WAT and BAT. Characterization of these novel angiogenic pathways may reveal new mechanisms underlying development of obesity- and metabolism-related disease complications and may define novel therapeutic targets. Thus, the benefit of this research proposal is enormous and is aimed to treat the most common and highly risk human health conditions in the modern time.
Summary
Understanding the molecular mechanisms underlying adipose blood vessel growth or regression opens new fundamentally insight into novel therapeutic options for the treatment of obesity and its related metabolic diseases such as type 2 diabetes and cancer. Unlike any other tissues in the body, the adipose tissue constantly experiences expansion and shrinkage throughout the adult life. Adipocytes in the white adipose tissue have the ability to switch into metabolically highly active brown-like adipocytes. Brown adipose tissue (BAT) contains significantly higher numbers of microvessels than white adipose tissue (WAT) in order to adopt the high rates of metabolism. Thus, an angiogenic phenotype has to be switched on during the transition from WAT into BAT. We have found that acclimation of mice in cold could induce transition from inguinal and epidedymal WAT into BAT by upregulation of angiogenic factor expression and down-regulations of angiogenesis inhibitors (Xue et al, Cell Metabolism, 2009). The transition from WAT into BAT is dependent on vascular endothelial growth factor (VEGF) that primarily targets on vascular endothelial cells via a tissue hypoxia-independent mechanism. VEGF blockade significantly alters adipose tissue metabolism. In another genetic model, we show similar findings that angiogenesis is crucial to mediate the transition from WAT into BAT (Xue et al, PNAS, 2008). Here we propose that the vascular tone determines the metabolic switch between WAT and BAT. Characterization of these novel angiogenic pathways may reveal new mechanisms underlying development of obesity- and metabolism-related disease complications and may define novel therapeutic targets. Thus, the benefit of this research proposal is enormous and is aimed to treat the most common and highly risk human health conditions in the modern time.
Max ERC Funding
2 411 547 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym ASD
Project Atomistic Spin-Dynamics; Methodology and Applications
Researcher (PI) Olof Ragnar Eriksson
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), PE3, ERC-2009-AdG
Summary Our aim is to provide a theoretical framework for studies of dynamical aspects of magnetic materials and magnetisation reversal, which has potential for applications for magnetic data storage and magnetic memory devices. The project focuses on developing and using an atomistic spin dynamics simulation method. Our goal is to identify novel materials and device geometries with improved performance. The scientific questions which will be addressed concern the understanding of the fundamental temporal limit of magnetisation switching and reversal, and the mechanisms which govern this limit. The methodological developments concern the ability to, from first principles theory, calculate the interatomic exchange parameters of materials in general, in particular for correlated electron materials, via the use of dynamical mean-field theory. The theoretical development also involves an atomistic spin dynamics simulation method, which once it has been established, will be released as a public software package. The proposed theoretical research will be intimately connected to world-leading experimental efforts, especially in Europe where a leading activity in experimental studies of magnetisation dynamics has been established. The ambition with this project is to become world-leading in the theory of simulating spin-dynamics phenomena, and to promote education and training of young researchers. To achieve our goals we will build up an open and lively environment, where the advances in the theoretical knowledge of spin-dynamics phenomena will be used to address important questions in information technology. In this environment the next generation research leaders will be fostered and trained, thus ensuring that the society of tomorrow is equipped with the scientific competence to tackle the challenges of our future.
Summary
Our aim is to provide a theoretical framework for studies of dynamical aspects of magnetic materials and magnetisation reversal, which has potential for applications for magnetic data storage and magnetic memory devices. The project focuses on developing and using an atomistic spin dynamics simulation method. Our goal is to identify novel materials and device geometries with improved performance. The scientific questions which will be addressed concern the understanding of the fundamental temporal limit of magnetisation switching and reversal, and the mechanisms which govern this limit. The methodological developments concern the ability to, from first principles theory, calculate the interatomic exchange parameters of materials in general, in particular for correlated electron materials, via the use of dynamical mean-field theory. The theoretical development also involves an atomistic spin dynamics simulation method, which once it has been established, will be released as a public software package. The proposed theoretical research will be intimately connected to world-leading experimental efforts, especially in Europe where a leading activity in experimental studies of magnetisation dynamics has been established. The ambition with this project is to become world-leading in the theory of simulating spin-dynamics phenomena, and to promote education and training of young researchers. To achieve our goals we will build up an open and lively environment, where the advances in the theoretical knowledge of spin-dynamics phenomena will be used to address important questions in information technology. In this environment the next generation research leaders will be fostered and trained, thus ensuring that the society of tomorrow is equipped with the scientific competence to tackle the challenges of our future.
Max ERC Funding
2 130 000 €
Duration
Start date: 2010-01-01, End date: 2014-12-31
Project acronym AXION
Project Axions: From Heaven to Earth
Researcher (PI) Frank Wilczek
Host Institution (HI) STOCKHOLMS UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), PE2, ERC-2016-ADG
Summary Axions are hypothetical particles whose existence would solve two major problems: the strong P, T problem (a major blemish on the standard model); and the dark matter problem. It is a most important goal to either observe or rule out the existence of a cosmic axion background. It appears that decisive observations may be possible, but only after orchestrating insight from specialities ranging from quantum field theory and astrophysical modeling to ultra-low noise quantum measurement theory. Detailed predictions for the magnitude and structure of the cosmic axion background depend on cosmological and astrophysical modeling, which can be constrained by theoretical insight and numerical simulation. In parallel, we must optimize strategies for extracting accessible signals from that very weakly interacting source.
While the existence of axions as fundamental particles remains hypothetical, the equations governing how axions interact with electromagnetic fields also govern (with different parameters) how certain materials interact with electromagnetic fields. Thus those materials embody “emergent” axions. The equations have remarkable properties, which one can test in these materials, and possibly put to practical use.
Closely related to axions, mathematically, are anyons. Anyons are particle-like excitations that elude the familiar classification into bosons and fermions. Theoretical and numerical studies indicate that they are common emergent features of highly entangled states of matter in two dimensions. Recent work suggests the existence of states of matter, both natural and engineered, in which anyon dynamics is both important and experimentally accessible. Since the equations for anyons and axions are remarkably similar, and both have common, deep roots in symmetry and topology, it will be fruitful to consider them together.
Summary
Axions are hypothetical particles whose existence would solve two major problems: the strong P, T problem (a major blemish on the standard model); and the dark matter problem. It is a most important goal to either observe or rule out the existence of a cosmic axion background. It appears that decisive observations may be possible, but only after orchestrating insight from specialities ranging from quantum field theory and astrophysical modeling to ultra-low noise quantum measurement theory. Detailed predictions for the magnitude and structure of the cosmic axion background depend on cosmological and astrophysical modeling, which can be constrained by theoretical insight and numerical simulation. In parallel, we must optimize strategies for extracting accessible signals from that very weakly interacting source.
While the existence of axions as fundamental particles remains hypothetical, the equations governing how axions interact with electromagnetic fields also govern (with different parameters) how certain materials interact with electromagnetic fields. Thus those materials embody “emergent” axions. The equations have remarkable properties, which one can test in these materials, and possibly put to practical use.
Closely related to axions, mathematically, are anyons. Anyons are particle-like excitations that elude the familiar classification into bosons and fermions. Theoretical and numerical studies indicate that they are common emergent features of highly entangled states of matter in two dimensions. Recent work suggests the existence of states of matter, both natural and engineered, in which anyon dynamics is both important and experimentally accessible. Since the equations for anyons and axions are remarkably similar, and both have common, deep roots in symmetry and topology, it will be fruitful to consider them together.
Max ERC Funding
2 324 391 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym BATESON
Project Dissecting genotype-phenotype relationships using high-throughput genomics and carefully selected study populations
Researcher (PI) Leif Andersson
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), LS2, ERC-2011-ADG_20110310
Summary A major aim in genome research is to reveal how genetic variation affects phenotypic variation. Here I propose to use high-throughput genomics (whole genome sequencing, transcriptome and epigenome analysis) to screen carefully selected study populations where the chances are particularly favourable to obtain novel insight into genotype-phenotype relationships. The ambition is to take discoveries all the way from phenotypic characterization to the identification of the genes and the actual genetic variant causing a phenotypic effect and to understanding the underlying functional mechanisms. The program will involve a fish (the Atlantic herring), a bird (the domestic chicken) and a mammal (the European rabbit). The Atlantic herring will be studied because it provides unique opportunities to study the genetics of adaptation in a natural population and because of the possibilities to revolutionize the fishery management of this economically important marine fish. We will generate a draft assembly of the herring genome and then perform whole genome resequencing of different populations to reveal the population structure and the loci underlying genetic adaptation. The European rabbit is an excellent model for studying the genetics of speciation due to the presence of two distinct subspecies on the Iberian Peninsula. The domestication of the rabbit is also particularly interesting because it is a recent event (about 1500 years ago) and it is well established that domestication happened from the wild rabbit population in southern France. Finally, the domestic chicken provides excellent opportunities for in depth functional studies since it is both a domestic animal harbouring a rich genetic diversity and an experimental organism.
(BATESON is the acronym for this proposal because Bateson (1902) pioneered the study of genotype-phenotype relationships in animals and used the chicken for this work.)
Summary
A major aim in genome research is to reveal how genetic variation affects phenotypic variation. Here I propose to use high-throughput genomics (whole genome sequencing, transcriptome and epigenome analysis) to screen carefully selected study populations where the chances are particularly favourable to obtain novel insight into genotype-phenotype relationships. The ambition is to take discoveries all the way from phenotypic characterization to the identification of the genes and the actual genetic variant causing a phenotypic effect and to understanding the underlying functional mechanisms. The program will involve a fish (the Atlantic herring), a bird (the domestic chicken) and a mammal (the European rabbit). The Atlantic herring will be studied because it provides unique opportunities to study the genetics of adaptation in a natural population and because of the possibilities to revolutionize the fishery management of this economically important marine fish. We will generate a draft assembly of the herring genome and then perform whole genome resequencing of different populations to reveal the population structure and the loci underlying genetic adaptation. The European rabbit is an excellent model for studying the genetics of speciation due to the presence of two distinct subspecies on the Iberian Peninsula. The domestication of the rabbit is also particularly interesting because it is a recent event (about 1500 years ago) and it is well established that domestication happened from the wild rabbit population in southern France. Finally, the domestic chicken provides excellent opportunities for in depth functional studies since it is both a domestic animal harbouring a rich genetic diversity and an experimental organism.
(BATESON is the acronym for this proposal because Bateson (1902) pioneered the study of genotype-phenotype relationships in animals and used the chicken for this work.)
Max ERC Funding
2 300 000 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym BBBARRIER
Project Mechanisms of regulation of the blood-brain barrier; towards opening and closing the barrier on demand
Researcher (PI) Bjoern Christer Betsholtz
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), LS4, ERC-2011-ADG_20110310
Summary In the bone-enclosed CNS, increased vascular permeability may cause life-threatening tissue swelling, and/or ischemia and inflammation which compromise tissue repair after trauma or stroke. The brain vasculature possesses several unique features collectively named the blood-brain barrier (BBB) in which passive permeability is almost completely abolished and replaced by a complex of specific transport mechanisms. The BBB is necessary to uphold the specific milieu necessary for neuronal function. Whereas breakdown of the BBB is part of many CNS diseases, including stroke, neuroinflammation, trauma and neurodegenerative disorders, its molecular mechanisms and consequences are unclear and debated. Conversely, the intact BBB is a huge obstacle for drug delivery to the brain. Research on the BBB therefore has two seemingly opposing aims: 1) to seal a damaged BBB and protect the brain from toxic blood products, and 2) to open the BBB “on demand” for drug delivery. A major problem in the BBB field has been the lack of in vivo animal models for molecular and functional studies. So far, available in vitro models are not recapitulating the in vivo BBB. Our recent work on mouse models lacking pericytes, a BBB-associated cell type, demonstrates a specific role for pericytes in the development and regulation of the mammalian BBB. These animal models are the first ones showing a general and significant BBB impairment in adulthood, and as such they provide a unique opportunity to address molecular mechanisms of BBB disruption in disease and in drug transport across the BBB. Importantly, the new models and tools that we have developed allow us to search for relevant druggable mechanisms and molecular targets in the BBB. The long-term goals of this proposal are to develop molecular strategies and tools to open and close the BBB “on demand” for drug delivery to the CNS, and to explore the importance and mechanisms of BBB dysfunction in neurodegenerative diseases and stroke.
Summary
In the bone-enclosed CNS, increased vascular permeability may cause life-threatening tissue swelling, and/or ischemia and inflammation which compromise tissue repair after trauma or stroke. The brain vasculature possesses several unique features collectively named the blood-brain barrier (BBB) in which passive permeability is almost completely abolished and replaced by a complex of specific transport mechanisms. The BBB is necessary to uphold the specific milieu necessary for neuronal function. Whereas breakdown of the BBB is part of many CNS diseases, including stroke, neuroinflammation, trauma and neurodegenerative disorders, its molecular mechanisms and consequences are unclear and debated. Conversely, the intact BBB is a huge obstacle for drug delivery to the brain. Research on the BBB therefore has two seemingly opposing aims: 1) to seal a damaged BBB and protect the brain from toxic blood products, and 2) to open the BBB “on demand” for drug delivery. A major problem in the BBB field has been the lack of in vivo animal models for molecular and functional studies. So far, available in vitro models are not recapitulating the in vivo BBB. Our recent work on mouse models lacking pericytes, a BBB-associated cell type, demonstrates a specific role for pericytes in the development and regulation of the mammalian BBB. These animal models are the first ones showing a general and significant BBB impairment in adulthood, and as such they provide a unique opportunity to address molecular mechanisms of BBB disruption in disease and in drug transport across the BBB. Importantly, the new models and tools that we have developed allow us to search for relevant druggable mechanisms and molecular targets in the BBB. The long-term goals of this proposal are to develop molecular strategies and tools to open and close the BBB “on demand” for drug delivery to the CNS, and to explore the importance and mechanisms of BBB dysfunction in neurodegenerative diseases and stroke.
Max ERC Funding
2 499 427 €
Duration
Start date: 2012-08-01, End date: 2017-07-31
