Project acronym COHORT
Project The demography of skills and beliefs in Europe with a focus on cohort change
Researcher (PI) Vegard Fykse Skirbekk
Host Institution (HI) INTERNATIONALES INSTITUT FUER ANGEWANDTE SYSTEMANALYSE
Country Austria
Call Details Starting Grant (StG), SH3, ERC-2009-StG
Summary The central research theme of this proposal is the study of social change (skills, productivity, attitudes and beliefs) in Europe along cohort lines and as a function of changing age composition. Using demographic methods, age-specific and cohort-specific changes shall be quantitatively disentangled. The impact of migration flows as well as fertility differentials combined with intergenerational transmissions will be taken into account. It is expected that viewed together, these analyses will result in significant new insights and represent frontier research about likely social and economic challenges associated with ageing and demographic change in Europe and the appropriate policies for coping with them. Unlike projections of long-term economic growth or energy use, demographic forecasts tend to have comparatively low margins of error, even for forecasts half a century ahead. Traits that change systematically along age or cohort lines may therefore be projected with some degree of accuracy, which in turn can allow governments and individuals to better foresee and improve policies for predictable social change. The study will investigate two major topics, the first relating to human capital, skills, and work performance; the second relating to beliefs and attitudes in Europe. Understanding age variation in productivity and how to improve senior workers skills and capacities are paramount for ageing countries. Moreover, individual-level demographic behaviour can have aggregate level implications, including changing societal values and belief structures. The binding element is how such projections will improve one s capacity to foresee and hence develop more targeted policies that relate to ageing societies.
Summary
The central research theme of this proposal is the study of social change (skills, productivity, attitudes and beliefs) in Europe along cohort lines and as a function of changing age composition. Using demographic methods, age-specific and cohort-specific changes shall be quantitatively disentangled. The impact of migration flows as well as fertility differentials combined with intergenerational transmissions will be taken into account. It is expected that viewed together, these analyses will result in significant new insights and represent frontier research about likely social and economic challenges associated with ageing and demographic change in Europe and the appropriate policies for coping with them. Unlike projections of long-term economic growth or energy use, demographic forecasts tend to have comparatively low margins of error, even for forecasts half a century ahead. Traits that change systematically along age or cohort lines may therefore be projected with some degree of accuracy, which in turn can allow governments and individuals to better foresee and improve policies for predictable social change. The study will investigate two major topics, the first relating to human capital, skills, and work performance; the second relating to beliefs and attitudes in Europe. Understanding age variation in productivity and how to improve senior workers skills and capacities are paramount for ageing countries. Moreover, individual-level demographic behaviour can have aggregate level implications, including changing societal values and belief structures. The binding element is how such projections will improve one s capacity to foresee and hence develop more targeted policies that relate to ageing societies.
Max ERC Funding
981 415 €
Duration
Start date: 2009-10-01, End date: 2015-03-31
Project acronym DecentLivingEnergy
Project Energy and emissions thresholds for providing decent living standards to all
Researcher (PI) Narasimha Desirazu Rao
Host Institution (HI) INTERNATIONALES INSTITUT FUER ANGEWANDTE SYSTEMANALYSE
Country Austria
Call Details Starting Grant (StG), SH3, ERC-2014-STG
Summary There is confusion surrounding how poverty eradication will contribute to climate change. This is due to knowledge gaps related to the material basis of poverty, and the relationship between energy and human development. Addressing this issue rigorously requires bridging gaps between global justice, economics, energy systems analysis, and industrial ecology, and applying this knowledge to projections of anthropogenic greenhouse gases. This project will develop a body of knowledge that quantifies the energy needs and related climate change impacts for providing decent living standards to all. The research will address three questions: which goods and services, and with what characteristics, constitute ‘decent living standards’? What energy resources are required to provide these goods and services in different countries, and what impact will this energy use have on climate change? How do the constituents of decent living and their energy needs evolve as countries develop? The first task will operationalize basic needs views of human development and advance their empirical validity by discerning characteristics of basic goods in household consumption patterns. The second will quantify the energy needs (and climate-related emissions) for decent living constituents and reveal their dependence on culture, climate, technology, and other contextual conditions in countries. This will be done using lifecycle analysis and input-output analysis, and mapping energy to climate change using state-of-the-art energy-economy integrated assessment modelling tools for 5 emerging economies that face the challenges of eradicating poverty and mitigating climate change. The third task will shed light on path dependencies and trends in the evolution of basic goods and their energy intensity using empirical analysis. This research will identify opportunities to shift developing societies towards low-carbon pathways, and help quantify burden-sharing arrangements for climate mitigation.
Summary
There is confusion surrounding how poverty eradication will contribute to climate change. This is due to knowledge gaps related to the material basis of poverty, and the relationship between energy and human development. Addressing this issue rigorously requires bridging gaps between global justice, economics, energy systems analysis, and industrial ecology, and applying this knowledge to projections of anthropogenic greenhouse gases. This project will develop a body of knowledge that quantifies the energy needs and related climate change impacts for providing decent living standards to all. The research will address three questions: which goods and services, and with what characteristics, constitute ‘decent living standards’? What energy resources are required to provide these goods and services in different countries, and what impact will this energy use have on climate change? How do the constituents of decent living and their energy needs evolve as countries develop? The first task will operationalize basic needs views of human development and advance their empirical validity by discerning characteristics of basic goods in household consumption patterns. The second will quantify the energy needs (and climate-related emissions) for decent living constituents and reveal their dependence on culture, climate, technology, and other contextual conditions in countries. This will be done using lifecycle analysis and input-output analysis, and mapping energy to climate change using state-of-the-art energy-economy integrated assessment modelling tools for 5 emerging economies that face the challenges of eradicating poverty and mitigating climate change. The third task will shed light on path dependencies and trends in the evolution of basic goods and their energy intensity using empirical analysis. This research will identify opportunities to shift developing societies towards low-carbon pathways, and help quantify burden-sharing arrangements for climate mitigation.
Max ERC Funding
869 722 €
Duration
Start date: 2015-06-01, End date: 2019-05-31
Project acronym EURREP
Project Fertility, reproduction and population change in 21st Century Europe
Researcher (PI) Tomas Sobotka
Host Institution (HI) OESTERREICHISCHE AKADEMIE DER WISSENSCHAFTEN
Country Austria
Call Details Starting Grant (StG), SH3, ERC-2011-StG_20101124
Summary This project will address key issues related to fertility and reproduction in 21st century Europe and their implications. We aim to expand our knowledge of contemporary reproductive behaviour, critically assess theoretical perspectives on fertility, develop new indicators for analyzing and projecting fertility and improve our understanding of fertility intentions.
Combining detailed databases, especially the expanding Human Fertility Database, as well as surveys, and theoretical perspectives, the research team will study contemporary fertility trends and their explanations. An emphasis will be put on analyzing and explaining very low fertility that became a matter of public concern in some countries.
We will review and confront the existing theories of fertility and examine their validity and premises at different levels of explanation. We will look how and under which circumstances they can illuminate observed fertility trends as well as the reversals in correlation between selected aggregate level-level indicators (female labour force participation, GDP level, marriage rates, etc.) and fertility.
Specific attention will be paid to studying systematically fertility intentions and desires of men and women in different settings and populations. Here the key issue is whether and why a systematic disagreement between intended and realized fertility exists at an aggregate level.
Finally, we aim to elaborate the indicators of fertility and population replacement. These will be used to assess long-term implications of contemporary fertility and migration patterns for population change and composition in different regions of Europe.
Summary
This project will address key issues related to fertility and reproduction in 21st century Europe and their implications. We aim to expand our knowledge of contemporary reproductive behaviour, critically assess theoretical perspectives on fertility, develop new indicators for analyzing and projecting fertility and improve our understanding of fertility intentions.
Combining detailed databases, especially the expanding Human Fertility Database, as well as surveys, and theoretical perspectives, the research team will study contemporary fertility trends and their explanations. An emphasis will be put on analyzing and explaining very low fertility that became a matter of public concern in some countries.
We will review and confront the existing theories of fertility and examine their validity and premises at different levels of explanation. We will look how and under which circumstances they can illuminate observed fertility trends as well as the reversals in correlation between selected aggregate level-level indicators (female labour force participation, GDP level, marriage rates, etc.) and fertility.
Specific attention will be paid to studying systematically fertility intentions and desires of men and women in different settings and populations. Here the key issue is whether and why a systematic disagreement between intended and realized fertility exists at an aggregate level.
Finally, we aim to elaborate the indicators of fertility and population replacement. These will be used to assess long-term implications of contemporary fertility and migration patterns for population change and composition in different regions of Europe.
Max ERC Funding
1 271 342 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym GEL-SYS
Project Smart HydroGEL SYStems – From Bioinspired Design to Soft Electronics and Machines
Researcher (PI) Martin KALTENBRUNNER
Host Institution (HI) UNIVERSITAT LINZ
Country Austria
Call Details Starting Grant (StG), PE8, ERC-2017-STG
Summary Hydrogels evolved as versatile building blocks of life – we all are in essence gel-embodied soft machines. Drawing inspiration from the diversity found in living creatures, GEL-SYS will develop a set of concepts, materials approaches and design rules for wide ranging classes of soft, hydrogel-based electronic, ionic and photonic devices in three core aims.
Aim (A) will pursue a high level of complexity in soft, yet tough biomimetic devices and machines by introducing nature-inspired instant strong bonds between hydrogels and antagonistic materials – from soft and elastic to hard and brittle. Building on these newly developed interfaces, aim (B) will pursue biocompatible hydrogel electronics with iontronic transducers and large area multimodal sensor arrays for a new class of medical tools and health monitors. Aim (C) will foster the current soft revolution of robotics with self-sensing, transparent grippers not occluding objects and workspace. A soft robotic visual system with hydrogel-based adaptive optical elements and ultraflexible photosensor arrays will allow robots to see while grasping. Autonomous operation will be a central question in soft systems, tackled with tough stretchable batteries and energy harvesting from mechanical motion on small and large scales with soft membranes. GEL-SYS will use our experience on soft, “imperceptible” electronics and devices. By fusing this technology platform with tough hydrogels - nature’s most pluripotent ingredient of soft machines - we aim to create the next generation of bionic systems. The envisioned hybrids promise new discoveries in the nonlinear mechanical responses of soft systems, and may allow exploiting triggered elastic instabilities for unconventional locomotion. Exploring soft matter, intimately united with solid materials, will trigger novel concepts for medical equipment, healthcare, consumer electronics, energy harvesting from renewable sources and in robotics, with imminent impact on our society.
Summary
Hydrogels evolved as versatile building blocks of life – we all are in essence gel-embodied soft machines. Drawing inspiration from the diversity found in living creatures, GEL-SYS will develop a set of concepts, materials approaches and design rules for wide ranging classes of soft, hydrogel-based electronic, ionic and photonic devices in three core aims.
Aim (A) will pursue a high level of complexity in soft, yet tough biomimetic devices and machines by introducing nature-inspired instant strong bonds between hydrogels and antagonistic materials – from soft and elastic to hard and brittle. Building on these newly developed interfaces, aim (B) will pursue biocompatible hydrogel electronics with iontronic transducers and large area multimodal sensor arrays for a new class of medical tools and health monitors. Aim (C) will foster the current soft revolution of robotics with self-sensing, transparent grippers not occluding objects and workspace. A soft robotic visual system with hydrogel-based adaptive optical elements and ultraflexible photosensor arrays will allow robots to see while grasping. Autonomous operation will be a central question in soft systems, tackled with tough stretchable batteries and energy harvesting from mechanical motion on small and large scales with soft membranes. GEL-SYS will use our experience on soft, “imperceptible” electronics and devices. By fusing this technology platform with tough hydrogels - nature’s most pluripotent ingredient of soft machines - we aim to create the next generation of bionic systems. The envisioned hybrids promise new discoveries in the nonlinear mechanical responses of soft systems, and may allow exploiting triggered elastic instabilities for unconventional locomotion. Exploring soft matter, intimately united with solid materials, will trigger novel concepts for medical equipment, healthcare, consumer electronics, energy harvesting from renewable sources and in robotics, with imminent impact on our society.
Max ERC Funding
1 499 975 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym Glue2Degrade
Project Therapeutic hijacking of E3 Ligases
Researcher (PI) Georg WINTER
Host Institution (HI) CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH
Country Austria
Call Details Starting Grant (StG), LS1, ERC-2019-STG
Summary Traditional drug design relies on inhibition of enzymes or receptors with accessible hydrophobic pockets. The concept of proteolysis targeting chimeras (PROTACs) promised to overcome this limitation. Following our discovery of the first PROTAC that induced selective protein degradation in vivo, this technology has seen a boost in academia and industry. Despite global research efforts, advances are so far incremental: (i) most focus is on degrading targets that can be liganded and are druggable with conventional inhibitors; (ii) currently, only 3 out of 600 E3 ligases can be exploited. Glue2Degrade aims to transform the pharmacologically targetable space of the proteome. The project is built on the hypothesis that molecular glues (MGs), non-chimeric small molecules that degrade target proteins by inducing cooperative binding to E3 ligases, are much more prevalent than anticipated. Lenalidomide and related immunomodulatory drugs (IMiDs) are prime examples of the potential of MGs. Without a specific targeting moiety, IMiDs induce cooperative binding of the E3 ligase CRBN to undruggable proteins like IKZF1/3, thereby inducing their degradation. However, no technologies exist to rationally develop MGs that hijack other E3 ligases. ERC-funding would allow us to address this limitation. Based on data generated in my laboratory, we will systematically identify novel MGs and their E3 ligases by innovating (i) phenotypic discovery strategies, and (ii) an orthogonal chemical genetics pipeline. To elucidate the mechanisms of novel MGs, we will (iii) conduct target identification via unbiased proteomics followed by (iv) chemical optimization and initial translational characterization. Glue2Degrade, if successful, will transform the engageable E3 space and identify novel MGs, thereby opening up the potential for therapeutic development of cell-, tissue-, and cancer-type specific chemical degraders for undruggable proteins.
Summary
Traditional drug design relies on inhibition of enzymes or receptors with accessible hydrophobic pockets. The concept of proteolysis targeting chimeras (PROTACs) promised to overcome this limitation. Following our discovery of the first PROTAC that induced selective protein degradation in vivo, this technology has seen a boost in academia and industry. Despite global research efforts, advances are so far incremental: (i) most focus is on degrading targets that can be liganded and are druggable with conventional inhibitors; (ii) currently, only 3 out of 600 E3 ligases can be exploited. Glue2Degrade aims to transform the pharmacologically targetable space of the proteome. The project is built on the hypothesis that molecular glues (MGs), non-chimeric small molecules that degrade target proteins by inducing cooperative binding to E3 ligases, are much more prevalent than anticipated. Lenalidomide and related immunomodulatory drugs (IMiDs) are prime examples of the potential of MGs. Without a specific targeting moiety, IMiDs induce cooperative binding of the E3 ligase CRBN to undruggable proteins like IKZF1/3, thereby inducing their degradation. However, no technologies exist to rationally develop MGs that hijack other E3 ligases. ERC-funding would allow us to address this limitation. Based on data generated in my laboratory, we will systematically identify novel MGs and their E3 ligases by innovating (i) phenotypic discovery strategies, and (ii) an orthogonal chemical genetics pipeline. To elucidate the mechanisms of novel MGs, we will (iii) conduct target identification via unbiased proteomics followed by (iv) chemical optimization and initial translational characterization. Glue2Degrade, if successful, will transform the engageable E3 space and identify novel MGs, thereby opening up the potential for therapeutic development of cell-, tissue-, and cancer-type specific chemical degraders for undruggable proteins.
Max ERC Funding
1 331 340 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym HCPO
Project Hormonal cross-talk in plant organogenesis
Researcher (PI) Eva Benkova
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Country Austria
Call Details Starting Grant (StG), LS1, ERC-2007-StG
Summary Growth and development of plants are regulated by signalling substances such as hormones. In plants, interactions between hormonal pathways represent crucial factors that govern their action. As the molecular basis for such hormonal cross-talk remains largely unknown, we will investigate the underlying mechanisms with a special focus on regulation of postembryonic organogenesis. We consider lateral root formation in Arabidopsis as an ideally suited model system, because it encompasses fundamental aspects of plant growth and development, such as dedifferentiation, re-entry into the cell cycle, coordinated cell divisions and differentiation. Furthermore, in lateral root formation, these processes are controlled by multiple hormonal pathways. In our proposal, we will focus on four main research directions. 1. Convergence of hormonal pathways on transport-dependent auxin distribution upstream of lateral root formation. Here, we want to identify key points in which auxin and other signalling pathways converge during lateral root formation and the molecular components involved in the process. 2. Role of auxin-cytokinin interaction in lateral root formation. Molecular events involved in auxin-cytokinin regulated lateral root formation will be studied by transcriptome analysis. 3. Identification of components of hormonal cross-talk by genetic approaches. Using lateral root formation as a model, we will perform mutant screens that will specifically target interactions between selected hormonal pathways. The spectrum of identified molecular components will be further expanded by a chemical genomics approach. 4. Formulation of general models for hormonal regulation of organogenesis. The acquired knowledge on molecular networks and their mutual interactions will be used to mathematically model lateral root development and to extrapolate them also on other developmental situations.
Summary
Growth and development of plants are regulated by signalling substances such as hormones. In plants, interactions between hormonal pathways represent crucial factors that govern their action. As the molecular basis for such hormonal cross-talk remains largely unknown, we will investigate the underlying mechanisms with a special focus on regulation of postembryonic organogenesis. We consider lateral root formation in Arabidopsis as an ideally suited model system, because it encompasses fundamental aspects of plant growth and development, such as dedifferentiation, re-entry into the cell cycle, coordinated cell divisions and differentiation. Furthermore, in lateral root formation, these processes are controlled by multiple hormonal pathways. In our proposal, we will focus on four main research directions. 1. Convergence of hormonal pathways on transport-dependent auxin distribution upstream of lateral root formation. Here, we want to identify key points in which auxin and other signalling pathways converge during lateral root formation and the molecular components involved in the process. 2. Role of auxin-cytokinin interaction in lateral root formation. Molecular events involved in auxin-cytokinin regulated lateral root formation will be studied by transcriptome analysis. 3. Identification of components of hormonal cross-talk by genetic approaches. Using lateral root formation as a model, we will perform mutant screens that will specifically target interactions between selected hormonal pathways. The spectrum of identified molecular components will be further expanded by a chemical genomics approach. 4. Formulation of general models for hormonal regulation of organogenesis. The acquired knowledge on molecular networks and their mutual interactions will be used to mathematically model lateral root development and to extrapolate them also on other developmental situations.
Max ERC Funding
1 300 000 €
Duration
Start date: 2008-07-01, End date: 2014-03-31
Project acronym HEMOX
Project The male-female health-mortality paradox
Researcher (PI) Marc Luy
Host Institution (HI) OESTERREICHISCHE AKADEMIE DER WISSENSCHAFTEN
Country Austria
Call Details Starting Grant (StG), SH3, ERC-2010-StG_20091209
Summary "From the 1960s to the 1980s a common wisdom about differences between males and females in health and mortality emerged which was summarised by the well-known phrase ""women are sicker, but men die quicker"". Recently this wisdom has been increasingly questioned. Nevertheless, the general idea of a paradoxical relationship between health and mortality among women and men persists until today. The purpose of this project is to decisively advance the understanding of the paradox by demonstrating that the reverse relationship between sex on the one side and health and mortality on the other is not as paradoxical as it seems. We hypothesise that two factors are mainly responsible for causing this intuitive contradiction. First, the overall reversal in sex morbidity and sex mortality differentials occurs because conditions that figure importantly in morbidity are not very important in mortality, and vice versa. Second, it is very likely that longevity is directly related to the absolute number of life years in ill health. Thus, women show higher morbidity rates not because they are female but because they are the sex with higher life expectancy. We will test these hypotheses in a ""natural experiment"" by analysing the relationship between health and mortality among Catholic nuns and monks from Austria and Germany in comparison to women and men of the general population. Cloister studies have a long scientific tradition and provided path-breaking knowledge for human medicine and demography, including the applicant s research during the last decade. This project follows the line of this tradition and will investigate the male-female health-mortality paradox in a longitudinal setting that is as close as one can get to an ideal long-term experiment in humans."
Summary
"From the 1960s to the 1980s a common wisdom about differences between males and females in health and mortality emerged which was summarised by the well-known phrase ""women are sicker, but men die quicker"". Recently this wisdom has been increasingly questioned. Nevertheless, the general idea of a paradoxical relationship between health and mortality among women and men persists until today. The purpose of this project is to decisively advance the understanding of the paradox by demonstrating that the reverse relationship between sex on the one side and health and mortality on the other is not as paradoxical as it seems. We hypothesise that two factors are mainly responsible for causing this intuitive contradiction. First, the overall reversal in sex morbidity and sex mortality differentials occurs because conditions that figure importantly in morbidity are not very important in mortality, and vice versa. Second, it is very likely that longevity is directly related to the absolute number of life years in ill health. Thus, women show higher morbidity rates not because they are female but because they are the sex with higher life expectancy. We will test these hypotheses in a ""natural experiment"" by analysing the relationship between health and mortality among Catholic nuns and monks from Austria and Germany in comparison to women and men of the general population. Cloister studies have a long scientific tradition and provided path-breaking knowledge for human medicine and demography, including the applicant s research during the last decade. This project follows the line of this tradition and will investigate the male-female health-mortality paradox in a longitudinal setting that is as close as one can get to an ideal long-term experiment in humans."
Max ERC Funding
999 999 €
Duration
Start date: 2011-04-01, End date: 2016-09-30
Project acronym KINETOCORE
Project Molecular Dissection of the Kinetochore – Microtubule Interface
Researcher (PI) Stefan Westermann
Host Institution (HI) FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Country Austria
Call Details Starting Grant (StG), LS1, ERC-2007-StG
Summary The ability of spindle microtubules of to interact dynamically with centromeric chromatin is a critical feature of chromosome segregation and ensures the faithful distribution of genetic material. Errors in this process lead to abnormal chromosome numbers and are a hallmark of cancer and birth defects. The kinetochore is the key cell division organelle that enables high fidelity transmission of genetic information by coupling chromosomes to the plus-ends of spindle microtubules during mitosis and meiosis. Despite its cytological description more than a century ago, little information is available on kinetochore function at a molecular level. Here, I propose to dissect the molecular mechanisms of kinetochore function using the budding yeast Saccharomyces cerevisiae as a model system. My previous work has demonstrated that fundamental aspects of kinetochore organization are conserved throughout evolution. I will use a combination of biochemistry, electron microscopy, in-vitro assays with static and dynamic microtubule substrates as well as yeast cell biology to address fundamental questions of kinetochore function. Specifically, my experiments aim to elucidate 1) the mechanism of phospho-regulation at the kinetochore-microtubule interface 2) the roles of plus-end tracking proteins in chromosome segregation 3) the roles of kinetochore subcomplexes in connecting microtubules and centromeres. Successful completion of the project will help to move the kinetochore field towards a detailed understanding of the molecular mechanisms of chromosome segregation and can open up new perspectives for analyzing the functions of this complex macromolecular machine.
Summary
The ability of spindle microtubules of to interact dynamically with centromeric chromatin is a critical feature of chromosome segregation and ensures the faithful distribution of genetic material. Errors in this process lead to abnormal chromosome numbers and are a hallmark of cancer and birth defects. The kinetochore is the key cell division organelle that enables high fidelity transmission of genetic information by coupling chromosomes to the plus-ends of spindle microtubules during mitosis and meiosis. Despite its cytological description more than a century ago, little information is available on kinetochore function at a molecular level. Here, I propose to dissect the molecular mechanisms of kinetochore function using the budding yeast Saccharomyces cerevisiae as a model system. My previous work has demonstrated that fundamental aspects of kinetochore organization are conserved throughout evolution. I will use a combination of biochemistry, electron microscopy, in-vitro assays with static and dynamic microtubule substrates as well as yeast cell biology to address fundamental questions of kinetochore function. Specifically, my experiments aim to elucidate 1) the mechanism of phospho-regulation at the kinetochore-microtubule interface 2) the roles of plus-end tracking proteins in chromosome segregation 3) the roles of kinetochore subcomplexes in connecting microtubules and centromeres. Successful completion of the project will help to move the kinetochore field towards a detailed understanding of the molecular mechanisms of chromosome segregation and can open up new perspectives for analyzing the functions of this complex macromolecular machine.
Max ERC Funding
900 000 €
Duration
Start date: 2008-10-01, End date: 2013-09-30
Project acronym LEBMEC
Project Laser-engineered Biomimetic Matrices with Embedded Cells
Researcher (PI) Aleksandr Ovsianikov
Host Institution (HI) TECHNISCHE UNIVERSITAET WIEN
Country Austria
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary Traditional 2D cell culture systems used in biology do not accurately reproduce the 3D structure, function, or physiology of living tissue. Resulting behaviour and responses of cells are substantially different from those observed within natural extracellular matrices (ECM). The early designs of 3D cell-culture matrices focused on their bulk properties, while disregarding individual cell environment. However, recent findings indicate that the role of the ECM extends beyond a simple structural support to regulation of cell and tissue function. So far the mechanisms of this regulation are not fully understood, due to technical limitations of available research tools, diversity of tissues and complexity of cell-matrix interactions.
The main goal of this project is to develop a versatile and straightforward method, enabling systematic studies of cell-matrix interactions. 3D CAD matrices will be produced by femtosecond laser-induced polymerization of hydrogels with cells in them. Cell embedment results in a tissue-like intimate cell-matrix contact and appropriate cell densities right from the start.
A unique advantage of the LeBMEC is its capability to alter on demand a multitude of individual properties of produced 3D matrices, including: geometry, stiffness, and cell adhesion properties. It allows us systematically reconstruct and identify the key biomimetic properties of the ECM in vitro. The particular focus of this project is on the role of local mechanical properties of produced hydrogel constructs. It is known that, stem cells on soft 2D substrates differentiate into neurons, stiffer substrates induce bone cells, and intermediate ones result in myoblasts. With LeBMEC, a controlled distribution of site-specific stiffness within the same hydrogel matrix can be achieved in 3D. This way, by rational design of cell-culture matrices initially embedding only stem cells, for realisation of precisely defined 3D multi-tissue constructs, is possible for the first time.
Summary
Traditional 2D cell culture systems used in biology do not accurately reproduce the 3D structure, function, or physiology of living tissue. Resulting behaviour and responses of cells are substantially different from those observed within natural extracellular matrices (ECM). The early designs of 3D cell-culture matrices focused on their bulk properties, while disregarding individual cell environment. However, recent findings indicate that the role of the ECM extends beyond a simple structural support to regulation of cell and tissue function. So far the mechanisms of this regulation are not fully understood, due to technical limitations of available research tools, diversity of tissues and complexity of cell-matrix interactions.
The main goal of this project is to develop a versatile and straightforward method, enabling systematic studies of cell-matrix interactions. 3D CAD matrices will be produced by femtosecond laser-induced polymerization of hydrogels with cells in them. Cell embedment results in a tissue-like intimate cell-matrix contact and appropriate cell densities right from the start.
A unique advantage of the LeBMEC is its capability to alter on demand a multitude of individual properties of produced 3D matrices, including: geometry, stiffness, and cell adhesion properties. It allows us systematically reconstruct and identify the key biomimetic properties of the ECM in vitro. The particular focus of this project is on the role of local mechanical properties of produced hydrogel constructs. It is known that, stem cells on soft 2D substrates differentiate into neurons, stiffer substrates induce bone cells, and intermediate ones result in myoblasts. With LeBMEC, a controlled distribution of site-specific stiffness within the same hydrogel matrix can be achieved in 3D. This way, by rational design of cell-culture matrices initially embedding only stem cells, for realisation of precisely defined 3D multi-tissue constructs, is possible for the first time.
Max ERC Funding
1 440 594 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym LUISE
Project An integrated socioecological approach to land-use intensity: Analyzing and mapping biophysical stocks/flows and their socioeconomic drivers
Researcher (PI) Karlheinz Erb
Host Institution (HI) UNIVERSITAET KLAGENFURT
Country Austria
Call Details Starting Grant (StG), SH3, ERC-2010-StG_20091209
Summary Land-use intensity is an essential aspect of the human use of terrestrial ecosystems. In the course of history, intensification of land use allowed to overcome Malthusian traps and supported population growth and im-proved diets. It can be anticipated that intensification will become even more decisive in the future, in the light of a growing world population, surges in biofuel consumption, and the simultaneous mandate to protect the world’s forests. Despite its importance, there is a lack of comprehensive, consistent, systematic, and spa-tially explicit metrics of land-use intensity. In consequence, the causal understanding of the factors, mecha-nisms, determinants and constraints underlying land intensification is unsatisfactory. This is due to the main-stream in land use research that predominantly operates with nominal scales, subdividing the Earth’s surface into discrete land cover units. This hampers the analysis of gradual changes, in particular those which are not related to changes in land cover. Intensification leads exactly to such changes. The overall goal of LUISE is the conceptualization and quantification of land use intensity and to contribute to an improved causal under-standing of land intensification. By applying and significantly extending existing methods of the material and energy flow analysis framework (MEFA), the full cycle of land intensification will be studied: Socioeco-nomic inputs to ecosystems, structural changes within ecosystems, changes in outputs of ecosystems to soci-ety, and the underlying socioeconomic constraints, feedbacks, and thresholds, from top-down macro perspec-tives as well as applying bottom-up approaches. The anticipated new empirical results and insights can allow further conceptualizations and quantifications of land modifications (land change without land cover change), and improve the understanding of the dynamic and complex interplay of society and nature that shapes spatial patterns as well as changes of land systems over time.
Summary
Land-use intensity is an essential aspect of the human use of terrestrial ecosystems. In the course of history, intensification of land use allowed to overcome Malthusian traps and supported population growth and im-proved diets. It can be anticipated that intensification will become even more decisive in the future, in the light of a growing world population, surges in biofuel consumption, and the simultaneous mandate to protect the world’s forests. Despite its importance, there is a lack of comprehensive, consistent, systematic, and spa-tially explicit metrics of land-use intensity. In consequence, the causal understanding of the factors, mecha-nisms, determinants and constraints underlying land intensification is unsatisfactory. This is due to the main-stream in land use research that predominantly operates with nominal scales, subdividing the Earth’s surface into discrete land cover units. This hampers the analysis of gradual changes, in particular those which are not related to changes in land cover. Intensification leads exactly to such changes. The overall goal of LUISE is the conceptualization and quantification of land use intensity and to contribute to an improved causal under-standing of land intensification. By applying and significantly extending existing methods of the material and energy flow analysis framework (MEFA), the full cycle of land intensification will be studied: Socioeco-nomic inputs to ecosystems, structural changes within ecosystems, changes in outputs of ecosystems to soci-ety, and the underlying socioeconomic constraints, feedbacks, and thresholds, from top-down macro perspec-tives as well as applying bottom-up approaches. The anticipated new empirical results and insights can allow further conceptualizations and quantifications of land modifications (land change without land cover change), and improve the understanding of the dynamic and complex interplay of society and nature that shapes spatial patterns as well as changes of land systems over time.
Max ERC Funding
887 121 €
Duration
Start date: 2010-10-01, End date: 2016-06-30
