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 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 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
Project acronym BETAIMAGE
Project An in vivo imaging approach to understand pancreatic beta-cell signal-transduction
Researcher (PI) Per-Olof Berggren
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Advanced Grant (AdG), LS4, ERC-2013-ADG
Summary The challenge in cell physiology/pathology today is to translate in vitro findings to the living organism. We have developed a unique approach where signal-transduction can be investigated in vivo non-invasively, longitudinally at single cell resolution, using the anterior chamber of the eye as a natural body window for imaging. We will use this approach to understand how the universally important and highly complex signal Ca2+ is regulated in the pancreatic beta-cell, while localized in the vascularized and innervated islet of Langerhans, and how that affects the insulin secretory machinery in vivo. Engrafted islets in the eye take on identical innervation- and vascularization patterns as those in the pancreas and are proficient in regulating glucose homeostasis in the animal. Since the pancreatic islet constitutes a micro-organ, this imaging approach offers a seminal model system to understand Ca2+ signaling in individual cells at the organ level in real life. We will test the hypothesis that the Ca2+-signal has a key role in pancreatic beta-cell function and survival in vivo and that perturbation in the Ca2+-signal serves as a common denominator for beta-cell pathology associated with impaired glucose homeostasis and diabetes. Of special interest is how innervation impacts on Ca2+-dynamics and the integration of autocrine, paracrine and endocrine signals in fine-tuning the Ca2+-signal with regard to beta-cell function and survival. We aim to define key defects in the machinery regulating Ca2+-dynamics in association with the autoimmune reaction, inflammation and obesity eventually resulting in diabetes. Our imaging platform will be applied to clarify in vivo regulation of Ca2+-dynamics in both healthy and diabetic human beta-cells. To define novel drugable targets for treatment of diabetes, it is crucial to identify similarities and differences in the molecular machinery regulating the in vivo Ca2+-signal in the human and in the rodent beta-cell.
Summary
The challenge in cell physiology/pathology today is to translate in vitro findings to the living organism. We have developed a unique approach where signal-transduction can be investigated in vivo non-invasively, longitudinally at single cell resolution, using the anterior chamber of the eye as a natural body window for imaging. We will use this approach to understand how the universally important and highly complex signal Ca2+ is regulated in the pancreatic beta-cell, while localized in the vascularized and innervated islet of Langerhans, and how that affects the insulin secretory machinery in vivo. Engrafted islets in the eye take on identical innervation- and vascularization patterns as those in the pancreas and are proficient in regulating glucose homeostasis in the animal. Since the pancreatic islet constitutes a micro-organ, this imaging approach offers a seminal model system to understand Ca2+ signaling in individual cells at the organ level in real life. We will test the hypothesis that the Ca2+-signal has a key role in pancreatic beta-cell function and survival in vivo and that perturbation in the Ca2+-signal serves as a common denominator for beta-cell pathology associated with impaired glucose homeostasis and diabetes. Of special interest is how innervation impacts on Ca2+-dynamics and the integration of autocrine, paracrine and endocrine signals in fine-tuning the Ca2+-signal with regard to beta-cell function and survival. We aim to define key defects in the machinery regulating Ca2+-dynamics in association with the autoimmune reaction, inflammation and obesity eventually resulting in diabetes. Our imaging platform will be applied to clarify in vivo regulation of Ca2+-dynamics in both healthy and diabetic human beta-cells. To define novel drugable targets for treatment of diabetes, it is crucial to identify similarities and differences in the molecular machinery regulating the in vivo Ca2+-signal in the human and in the rodent beta-cell.
Max ERC Funding
2 499 590 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym CUSTOMER
Project Customizable Embedded Real-Time Systems: Challenges and Key Techniques
Researcher (PI) Yi WANG
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), PE6, ERC-2018-ADG
Summary Today, many industrial products are defined by software and therefore customizable: their functionalities implemented by software can be modified and extended by dynamic software updates on demand. This trend towards customizable products is rapidly expanding into all domains of IT, including Embedded Real-Time Systems (ERTS) deployed in Cyber-Physical Systems such as cars, medical devices etc. However, the current state-of-practice in safety-critical systems allows hardly any modifications once they are put in operation. The lack of techniques to preserve crucial safety conditions for customizable systems severely restricts the benefits of advances in software-defined systems engineering.
CUSTOMER is to provide the missing paradigm and technology for building and updating ERTS after deployment – subject to stringent timing constraints, dynamic workloads, and limited resources on complex platforms. CUSTOMER explores research areas crossing two fields: Real-Time Computing and Formal Verification to develop the key techniques enabling (1) dynamic updates of ERTS in the field, (2) incremental updates over the products life time and (3) safe updates by verification to avoid updates that may compromise system safety.
CUSTOMER will develop a unified model-based framework supported with tools for the design, modelling, verification, deployment and update of ERTS, aiming at advancing the research fields by establishing the missing scientific foundation for multiprocessor real-time computing and providing the next generation of design tools with significantly enhanced capability and scalability increased by orders of magnitude compared with state-of-the-art tools e.g. UPPAAL.
Summary
Today, many industrial products are defined by software and therefore customizable: their functionalities implemented by software can be modified and extended by dynamic software updates on demand. This trend towards customizable products is rapidly expanding into all domains of IT, including Embedded Real-Time Systems (ERTS) deployed in Cyber-Physical Systems such as cars, medical devices etc. However, the current state-of-practice in safety-critical systems allows hardly any modifications once they are put in operation. The lack of techniques to preserve crucial safety conditions for customizable systems severely restricts the benefits of advances in software-defined systems engineering.
CUSTOMER is to provide the missing paradigm and technology for building and updating ERTS after deployment – subject to stringent timing constraints, dynamic workloads, and limited resources on complex platforms. CUSTOMER explores research areas crossing two fields: Real-Time Computing and Formal Verification to develop the key techniques enabling (1) dynamic updates of ERTS in the field, (2) incremental updates over the products life time and (3) safe updates by verification to avoid updates that may compromise system safety.
CUSTOMER will develop a unified model-based framework supported with tools for the design, modelling, verification, deployment and update of ERTS, aiming at advancing the research fields by establishing the missing scientific foundation for multiprocessor real-time computing and providing the next generation of design tools with significantly enhanced capability and scalability increased by orders of magnitude compared with state-of-the-art tools e.g. UPPAAL.
Max ERC Funding
2 499 894 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym DALDECS
Project Development and Application of Laser Diagnostic Techniques for Combustion Studies
Researcher (PI) Lars Eric Marcus Alden
Host Institution (HI) MAX IV Laboratory, Lund University
Country Sweden
Call Details Advanced Grant (AdG), PE8, ERC-2009-AdG
Summary This project is directed towards development of new laser diagnostic techniques and a deepened physical understanding of more established techniques, aiming at new insights in phenomena related to combustion processes. These non-intrusive techniques with high resolution in space and time, will be used for measurements of key parameters, species concentrations and temperatures. The techniques to be used are; Non-linear optical techniques, mainly Polarization spectroscopy, PS. PS will mainly be developed for sensitive detection with high spatial resolution of "new" species in the IR region, e.g. individual hydrocarbons, toxic species as well as alkali metal compounds. Multiplex measurements of these species and temperature will be developed as well as 2D visualization. Quantitative measurements with high precision and accuracy; Laser induced fluorescence and Rayleigh/Raman scattering will be developed for quantitative measurements of species concentration and 2D temperatures. Also a new technique will be developed for single ended experiments based on picosecond LIDAR. Advanced imaging techniques; New high speed (10-100 kHz) visualization techniques as well as 3D and even 4D visualization will be developed. In order to properly visualize dense sprays we will develop Ballistic Imaging as well as a new technique based on structured illumination of the area of interest for suppression of multiple scattering which normally cause blurring effects. All techniques developed above will be used for key studies of phenomena related to various combustion phenomena; turbulent combustion, multiphase conversion processes, e.g. spray combustion and gasification/pyrolysis of solid bio fuels. The techniques will also be applied for development and physical understanding of how combustion could be influenced by plasma/electrical assistance. Finally, the techniques will be prepared for applications in industrial combustion apparatus, e.g. furnaces, gasturbines and IC engines
Summary
This project is directed towards development of new laser diagnostic techniques and a deepened physical understanding of more established techniques, aiming at new insights in phenomena related to combustion processes. These non-intrusive techniques with high resolution in space and time, will be used for measurements of key parameters, species concentrations and temperatures. The techniques to be used are; Non-linear optical techniques, mainly Polarization spectroscopy, PS. PS will mainly be developed for sensitive detection with high spatial resolution of "new" species in the IR region, e.g. individual hydrocarbons, toxic species as well as alkali metal compounds. Multiplex measurements of these species and temperature will be developed as well as 2D visualization. Quantitative measurements with high precision and accuracy; Laser induced fluorescence and Rayleigh/Raman scattering will be developed for quantitative measurements of species concentration and 2D temperatures. Also a new technique will be developed for single ended experiments based on picosecond LIDAR. Advanced imaging techniques; New high speed (10-100 kHz) visualization techniques as well as 3D and even 4D visualization will be developed. In order to properly visualize dense sprays we will develop Ballistic Imaging as well as a new technique based on structured illumination of the area of interest for suppression of multiple scattering which normally cause blurring effects. All techniques developed above will be used for key studies of phenomena related to various combustion phenomena; turbulent combustion, multiphase conversion processes, e.g. spray combustion and gasification/pyrolysis of solid bio fuels. The techniques will also be applied for development and physical understanding of how combustion could be influenced by plasma/electrical assistance. Finally, the techniques will be prepared for applications in industrial combustion apparatus, e.g. furnaces, gasturbines and IC engines
Max ERC Funding
2 466 000 €
Duration
Start date: 2010-02-01, End date: 2015-01-31
Project acronym EcoImmuneCosts
Project Immunity in Ecology and Evolution: 'Hidden' costs of disease, immune function and their consequences for Darwinian fitness
Researcher (PI) Dennis Lennart HASSELQUIST
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), LS8, ERC-2016-ADG
Summary Eco-immunology targets one of the great challenges in biology and medicine - how the immune system has evolved to optimize protection and minimize immunopathology (incl. autoimmune) costs. A primary target of my proposal is to study low-virulent pathogens causing mild infections, which for long have been considered harmless. Recent research suggests that this notion is false and that seemingly harmless pathogens entail delayed (‘hidden’) fitness costs. However, the mechanisms mediating these costs are still unknown. I will experimentally test if accelerated telomere degradation is a causative mechanism through which small immune costs can accumulate and be translated into senescence and reduced Darwinian fitness. Another key target is immune costs, which may be ‘hidden’ because of sexually antagonistic effects, and I will study how this may affect immune gene variation, immune costs and Darwinian fitness. These aspects are central for advancing our understanding of the evolution of disease resistance and immune function, incl. immune over-reactions (autoimmunity).
My project exploits a comprehensive 32-year study of great reed warblers to analyze selection patterns in the wild (Fig. 1a), and uses established captive songbird set-ups to conduct carefully designed experiments. The exceptional quality of the long-term data set, together with cutting-edge techniques to measure and manipulate parasite infection, telomere length, oxidative stress and immune gene diversity, provides exciting opportunities to conduct research that previously was unfeasible, pushing the rapidly growing field of eco-immunology (Fig. 1b) to new frontiers. The work integrates theory and methods of evolutionary ecology, immunology and molecular biology, and has broad significance including for e.g. epidemiology and ageing research. I envision my research to change how we look upon causes, consequences (and precautions) of mild infectious, autoimmune and degenerative diseases.
Summary
Eco-immunology targets one of the great challenges in biology and medicine - how the immune system has evolved to optimize protection and minimize immunopathology (incl. autoimmune) costs. A primary target of my proposal is to study low-virulent pathogens causing mild infections, which for long have been considered harmless. Recent research suggests that this notion is false and that seemingly harmless pathogens entail delayed (‘hidden’) fitness costs. However, the mechanisms mediating these costs are still unknown. I will experimentally test if accelerated telomere degradation is a causative mechanism through which small immune costs can accumulate and be translated into senescence and reduced Darwinian fitness. Another key target is immune costs, which may be ‘hidden’ because of sexually antagonistic effects, and I will study how this may affect immune gene variation, immune costs and Darwinian fitness. These aspects are central for advancing our understanding of the evolution of disease resistance and immune function, incl. immune over-reactions (autoimmunity).
My project exploits a comprehensive 32-year study of great reed warblers to analyze selection patterns in the wild (Fig. 1a), and uses established captive songbird set-ups to conduct carefully designed experiments. The exceptional quality of the long-term data set, together with cutting-edge techniques to measure and manipulate parasite infection, telomere length, oxidative stress and immune gene diversity, provides exciting opportunities to conduct research that previously was unfeasible, pushing the rapidly growing field of eco-immunology (Fig. 1b) to new frontiers. The work integrates theory and methods of evolutionary ecology, immunology and molecular biology, and has broad significance including for e.g. epidemiology and ageing research. I envision my research to change how we look upon causes, consequences (and precautions) of mild infectious, autoimmune and degenerative diseases.
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-08-01, End date: 2023-01-31
Project acronym ERA
Project Earth Resilience in the Anthropocene (ERA)Integrating non-linear biophysical and social determinantsof Earth-system stability for global sustainabilitythrough a novel community modelling platform
Researcher (PI) johan ROCKSTRoeM
Host Institution (HI) STOCKHOLMS UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), SH2, ERC-2016-ADG
Summary In 2015, the UN Sustainable Development Goals (SDGs) and the Paris Agreement on climate recognised the deteriorating resilience of the Earth system in the Anthropocene. Maintaining Earth in the interglacial state that enabled the world’s societies to evolve over the past 12,000 years will require industrialised societies to embark on global-scale social transformations. Otherwise, there is a real risk of crossing tipping points in the Earth system triggering abrupt and irreversible changes.
A critical gap is that although nonlinear social and biophysical dynamics are recognized, we remain trapped in linear thinking. Global modelling and analyses – despite much progress – do not adequately represent nonlinear processes and abrupt changes, and social responses to sustainable development are incremental.
The goal of this project is to fill this gap, by exploring the biophysical and social determinants of the Earth’s long-term stability, building up a novel community modelling platform for analysis of nonlinearity and abrupt shifts, and informing global sustainability policy processes. The project will investigate two hypotheses: 1) Interactions, feedbacks and tipping points in the biosphere could, even in the absence of continued high emissions from fossil-fuel burning, tip Earth into a new state, committing to global warming over 2C and possibly beyond 4C; and 2) Only nonlinear societal transformations that aggregate to the global scale can assure long-term stability of the Earth and keep it in a manageable interglacial state.
The five research tasks are Task 1: analysis of nonlinear biosphere dynamics governing Earth resilience. Task 2: integrating nonlinear dynamics in World-Earth models. Task 3: exploring tipping points in social systems for large-scale transformation. Task 4: backcasting pathways for achieving the SDGs. Task 5: integrating World-Earth dynamics into online learning and virtual-reality games, e.g. Planet3 and Minecraft.
Summary
In 2015, the UN Sustainable Development Goals (SDGs) and the Paris Agreement on climate recognised the deteriorating resilience of the Earth system in the Anthropocene. Maintaining Earth in the interglacial state that enabled the world’s societies to evolve over the past 12,000 years will require industrialised societies to embark on global-scale social transformations. Otherwise, there is a real risk of crossing tipping points in the Earth system triggering abrupt and irreversible changes.
A critical gap is that although nonlinear social and biophysical dynamics are recognized, we remain trapped in linear thinking. Global modelling and analyses – despite much progress – do not adequately represent nonlinear processes and abrupt changes, and social responses to sustainable development are incremental.
The goal of this project is to fill this gap, by exploring the biophysical and social determinants of the Earth’s long-term stability, building up a novel community modelling platform for analysis of nonlinearity and abrupt shifts, and informing global sustainability policy processes. The project will investigate two hypotheses: 1) Interactions, feedbacks and tipping points in the biosphere could, even in the absence of continued high emissions from fossil-fuel burning, tip Earth into a new state, committing to global warming over 2C and possibly beyond 4C; and 2) Only nonlinear societal transformations that aggregate to the global scale can assure long-term stability of the Earth and keep it in a manageable interglacial state.
The five research tasks are Task 1: analysis of nonlinear biosphere dynamics governing Earth resilience. Task 2: integrating nonlinear dynamics in World-Earth models. Task 3: exploring tipping points in social systems for large-scale transformation. Task 4: backcasting pathways for achieving the SDGs. Task 5: integrating World-Earth dynamics into online learning and virtual-reality games, e.g. Planet3 and Minecraft.
Max ERC Funding
2 492 834 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
