Project acronym CITIZINGLOBAL
Project Citizens, Institutions and Globalization
Researcher (PI) Giacomo Antonio Maria PONZETTO
Host Institution (HI) Centre de Recerca en Economia Internacional (CREI)
Call Details Starting Grant (StG), SH1, ERC-2016-STG
Summary Globalization has brought the world economy unprecedented prosperity, but it poses governance challenges. It needs governments to provide the infrastructure for global economic integration and to refrain from destructive protectionism; yet it can engender popular discontent and a crisis of democracy. My proposal will study when trade- and productivity-enhancing policies enjoy democratic support; why voters may support instead inefficient surplus-reducing policies; and how political structure reacts to globalization.
Part A studies the puzzling popularity of protectionism and how lobbies can raise it by manipulating information. It will study empirically if greater transparency causes lower trade barriers. It will introduce salience theory to political economics and argue that voters overweight concentrated losses and disregard diffuse benefits. It will show that lobbies can raise protection by channeling information to insiders and advertising the plight of displaced workers.
Part B studies inefficient infrastructure policy and the ensuing spatial misallocation of economic activity. It will show that voters’ unequal knowledge lets local residents capture national policy. They disregard nationwide positive externalities, so investment in major cities is insufficient, but also nationwide taxes, so spending in low-density areas is excessive. It will argue that the fundamental attribution error causes voter opposition to growth-enhancing policies and efficient incentive schemes like congestion pricing.
Part C studies how the size of countries and international unions adapts to expanding trade opportunities. It will focus on three forces: cultural diversity, economies of scale and scope in government, and trade-reducing border effects. It will show they explain increasing country size in the 19th century; the rise and fall of colonial empires; and the recent emergence of regional and global economic unions, accompanied by a peaceful increase in the number of countries.
Summary
Globalization has brought the world economy unprecedented prosperity, but it poses governance challenges. It needs governments to provide the infrastructure for global economic integration and to refrain from destructive protectionism; yet it can engender popular discontent and a crisis of democracy. My proposal will study when trade- and productivity-enhancing policies enjoy democratic support; why voters may support instead inefficient surplus-reducing policies; and how political structure reacts to globalization.
Part A studies the puzzling popularity of protectionism and how lobbies can raise it by manipulating information. It will study empirically if greater transparency causes lower trade barriers. It will introduce salience theory to political economics and argue that voters overweight concentrated losses and disregard diffuse benefits. It will show that lobbies can raise protection by channeling information to insiders and advertising the plight of displaced workers.
Part B studies inefficient infrastructure policy and the ensuing spatial misallocation of economic activity. It will show that voters’ unequal knowledge lets local residents capture national policy. They disregard nationwide positive externalities, so investment in major cities is insufficient, but also nationwide taxes, so spending in low-density areas is excessive. It will argue that the fundamental attribution error causes voter opposition to growth-enhancing policies and efficient incentive schemes like congestion pricing.
Part C studies how the size of countries and international unions adapts to expanding trade opportunities. It will focus on three forces: cultural diversity, economies of scale and scope in government, and trade-reducing border effects. It will show they explain increasing country size in the 19th century; the rise and fall of colonial empires; and the recent emergence of regional and global economic unions, accompanied by a peaceful increase in the number of countries.
Max ERC Funding
960 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym CLIMAHAL
Project Climate dimension of natural halogens in the Earth system: Past, present, future
Researcher (PI) Alfonso SAIZ LOPEZ
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Consolidator Grant (CoG), PE10, ERC-2016-COG
Summary Naturally-emitted very short-lived halogens (VSLH) have a profound impact on the chemistry and composition of the atmosphere, destroying greenhouse gases and altering aerosol production, which together can change the Earth´s radiative balance. Therefore, natural halogens possess leverage to influence climate, although their contribution to climate change is not well established and most climate models have yet to consider their effects. Also, there is increasing evidence that natural halogens i) impact on the air quality of coastal cities, ii) accelerates the atmospheric deposition of mercury (a toxic heavy metal) and iii) that their natural ocean and ice emissions are controlled by biological and photochemical mechanisms that may respond to climate changes. Motivated by the above, this project aims to quantify the so far unrecognized natural halogen-climate feedbacks and the impact of these feedbacks on global atmospheric oxidizing capacity (AOC) and radiative forcing (RF) across pre-industrial, present and future climates. Answering these questions is essential to predict if these climate-mediated feedbacks can reduce or amplify future climate change. To this end we will develop a multidisciplinary research approach using laboratory and field observations and models interactively that will allow us to peel apart the detailed physical processes behind the contribution of natural halogens to global climate change. Furthermore, the work plan also involves examining past-future climate impacts of natural halogens within a holistic Earth System model, where we will develop the multidirectional halogen interactions in the land-ocean-ice-biosphere-atmosphere coupled system. This will provide a breakthrough in our understanding of the importance of these natural processes for the composition and oxidation capacity of the Earth´s atmosphere and climate, both in the presence and absence of human influence.
Summary
Naturally-emitted very short-lived halogens (VSLH) have a profound impact on the chemistry and composition of the atmosphere, destroying greenhouse gases and altering aerosol production, which together can change the Earth´s radiative balance. Therefore, natural halogens possess leverage to influence climate, although their contribution to climate change is not well established and most climate models have yet to consider their effects. Also, there is increasing evidence that natural halogens i) impact on the air quality of coastal cities, ii) accelerates the atmospheric deposition of mercury (a toxic heavy metal) and iii) that their natural ocean and ice emissions are controlled by biological and photochemical mechanisms that may respond to climate changes. Motivated by the above, this project aims to quantify the so far unrecognized natural halogen-climate feedbacks and the impact of these feedbacks on global atmospheric oxidizing capacity (AOC) and radiative forcing (RF) across pre-industrial, present and future climates. Answering these questions is essential to predict if these climate-mediated feedbacks can reduce or amplify future climate change. To this end we will develop a multidisciplinary research approach using laboratory and field observations and models interactively that will allow us to peel apart the detailed physical processes behind the contribution of natural halogens to global climate change. Furthermore, the work plan also involves examining past-future climate impacts of natural halogens within a holistic Earth System model, where we will develop the multidirectional halogen interactions in the land-ocean-ice-biosphere-atmosphere coupled system. This will provide a breakthrough in our understanding of the importance of these natural processes for the composition and oxidation capacity of the Earth´s atmosphere and climate, both in the presence and absence of human influence.
Max ERC Funding
1 979 112 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym EDST
Project Economic Development and Structural Transformation
Researcher (PI) Maria Paula BUSTOS
Host Institution (HI) FUNDACION CENTRO DE ESTUDIOS MONETARIOS Y FINANCIEROS
Call Details Starting Grant (StG), SH1, ERC-2016-STG
Summary The early development literature documented that the growth path of most advanced economies was accompanied by a process of structural transformation. As economies develop, the share of agriculture in employment falls and workers migrate to cities to find employment in the industrial and service sectors [Clark (1940), Kuznets (1957)]. In the first industrialized countries, technical improvements in agriculture favoured the development of industry and services by releasing labour, increasing demand and raising profits to finance other activities. However, several scholars noted that the positive effects of agricultural productivity on economic development are no longer operative in open economies. In addition, there is a large theoretical literature highlighting how market failures can retard structural transformation in developing countries. In particular, financial frictions might constrain the reallocation of capital and thus retard the process of labour reallocation. In this project, we propose to contribute to our understanding of structural transformation by providing direct empirical evidence on the effects of exogenous shocks to local agricultural and manufacturing productivity on the reallocation of capital and labour across sectors, firms and space in Brazil. For this purpose, we construct the first data set that permits to jointly observe labour and credit flows across sectors and space. To exploit the spatial dimension of the capital allocation problem, we design a new empirical which exploits the geographical structure of bank branch networks. Similarly, we propose to study the spatial dimension of the labour allocation problem by exploiting differences in migration costs across regions due to transportation and social networks.
Summary
The early development literature documented that the growth path of most advanced economies was accompanied by a process of structural transformation. As economies develop, the share of agriculture in employment falls and workers migrate to cities to find employment in the industrial and service sectors [Clark (1940), Kuznets (1957)]. In the first industrialized countries, technical improvements in agriculture favoured the development of industry and services by releasing labour, increasing demand and raising profits to finance other activities. However, several scholars noted that the positive effects of agricultural productivity on economic development are no longer operative in open economies. In addition, there is a large theoretical literature highlighting how market failures can retard structural transformation in developing countries. In particular, financial frictions might constrain the reallocation of capital and thus retard the process of labour reallocation. In this project, we propose to contribute to our understanding of structural transformation by providing direct empirical evidence on the effects of exogenous shocks to local agricultural and manufacturing productivity on the reallocation of capital and labour across sectors, firms and space in Brazil. For this purpose, we construct the first data set that permits to jointly observe labour and credit flows across sectors and space. To exploit the spatial dimension of the capital allocation problem, we design a new empirical which exploits the geographical structure of bank branch networks. Similarly, we propose to study the spatial dimension of the labour allocation problem by exploiting differences in migration costs across regions due to transportation and social networks.
Max ERC Funding
1 486 500 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym Evoland
Project Evolution of regulatory landscapes at multiple timescales
Researcher (PI) Jose Luis GOMEZ-SKARMETA
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), LS8, ERC-2016-ADG
Summary Evolution of animal morphology relies on changes in developmental programs that control body plans and organ shape. Such changes are thought to arise form alteration of the expression of functionally conserved developmental genes and their vast downstream networks. Although this hypothesis has a profound impact on the way we view animal evolution, final proof is still lacking. The hypothesis calls for evolution to take place mainly through modifications of cis-regulatory elements (CREs) controlling gene expression. However, these genomic regions are precisely those that we understand the least and, until recently, basic knowledge on how regulatory information is organized in the 3D genome or how to spatio-temporally assign CREs to their target genes was unknown.
The advent of next generation sequencing-based tools has made possible to identify genome-wide CREs and reveal how they are organized in the 3D genome. But this new knowledge has been largely ignored by most hypotheses on the evolution of gene expression, development and animal morphology. These new high-throughput methods have been mainly restricted to selected model organisms, and due to the lack of sequence conservation of CREs across lineages, we still have very limited information about the impact of CREs on animal morphology evolution.
By integrating in a systematic and phylogenetically driven manner the contribution of CREs and their 3D organization to animal morphology at different evolutionary scales, we will for the first time link evolution, regulatory information, genome 3D architecture and morphology. We will apply this strategy to study animal morphology along the evolution of deuterostome body plans, the generation of fin morphological diversity in vertebrates, and the recent phenotypic changes in fish adapted to cave environments.
Our proposal will make ground-breaking advances in our understanding of the global principles underlying the evolution of cis-regulatory DNA and animal form.
Summary
Evolution of animal morphology relies on changes in developmental programs that control body plans and organ shape. Such changes are thought to arise form alteration of the expression of functionally conserved developmental genes and their vast downstream networks. Although this hypothesis has a profound impact on the way we view animal evolution, final proof is still lacking. The hypothesis calls for evolution to take place mainly through modifications of cis-regulatory elements (CREs) controlling gene expression. However, these genomic regions are precisely those that we understand the least and, until recently, basic knowledge on how regulatory information is organized in the 3D genome or how to spatio-temporally assign CREs to their target genes was unknown.
The advent of next generation sequencing-based tools has made possible to identify genome-wide CREs and reveal how they are organized in the 3D genome. But this new knowledge has been largely ignored by most hypotheses on the evolution of gene expression, development and animal morphology. These new high-throughput methods have been mainly restricted to selected model organisms, and due to the lack of sequence conservation of CREs across lineages, we still have very limited information about the impact of CREs on animal morphology evolution.
By integrating in a systematic and phylogenetically driven manner the contribution of CREs and their 3D organization to animal morphology at different evolutionary scales, we will for the first time link evolution, regulatory information, genome 3D architecture and morphology. We will apply this strategy to study animal morphology along the evolution of deuterostome body plans, the generation of fin morphological diversity in vertebrates, and the recent phenotypic changes in fish adapted to cave environments.
Our proposal will make ground-breaking advances in our understanding of the global principles underlying the evolution of cis-regulatory DNA and animal form.
Max ERC Funding
2 499 514 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym FunKeyGut
Project Illuminating Functional Networks and Keystone Species in the Gut
Researcher (PI) David Michael BERRY
Host Institution (HI) UNIVERSITAT WIEN
Call Details Starting Grant (StG), LS8, ERC-2016-STG
Summary We live in an intimate symbiosis with our gut microbiota, which provides us services such as vitamin production, breakdown of dietary compounds, and immune training. Sequencing-based approaches that have been applied to catalogue the gut microbiota have revealed intriguing discoveries associating the microbiome with diet and disease. The next outstanding challenge is to unravel the many activities and interactions that define gut microbiota function.
The gut microbiota is a diverse community of cooperating and competing microbes. These interactions form a network that links organisms with each other and their environment. Interactions in such a “functional network” are based partially, though not exclusively, on food webs. Certain “keystone species”, such as Rumonicoccus bromii, are thought to play a major role in these networks. Though some evidence exists for the presence of keystone species, their identity and activity remains largely unknown. As keystone species are vital to networks they are ideal targets for manipulating the gut microbiota to improve metabolic health and protect against enteropathogen infection.
Given the complexity of the gut microbiota, networks can only be elucidated directly in the native community. This project aims to identify functional networks and keystone species in the human gut using novel approaches that are uniquely and ideally suited for studying microbial activity in complex communities. Using state-of-the-art methods such as stable isotope labeling, Raman microspectroscopy, and secondary ion mass spectrometry (NanoSIMS) we will illuminate functional networks in situ. This will allow us to identify what factors shape gut microbiota activity, reveal important food webs, and ultimately use network knowledge to target the microbiota with prebiotic/probiotic treatments rationally designed to promote health.
Summary
We live in an intimate symbiosis with our gut microbiota, which provides us services such as vitamin production, breakdown of dietary compounds, and immune training. Sequencing-based approaches that have been applied to catalogue the gut microbiota have revealed intriguing discoveries associating the microbiome with diet and disease. The next outstanding challenge is to unravel the many activities and interactions that define gut microbiota function.
The gut microbiota is a diverse community of cooperating and competing microbes. These interactions form a network that links organisms with each other and their environment. Interactions in such a “functional network” are based partially, though not exclusively, on food webs. Certain “keystone species”, such as Rumonicoccus bromii, are thought to play a major role in these networks. Though some evidence exists for the presence of keystone species, their identity and activity remains largely unknown. As keystone species are vital to networks they are ideal targets for manipulating the gut microbiota to improve metabolic health and protect against enteropathogen infection.
Given the complexity of the gut microbiota, networks can only be elucidated directly in the native community. This project aims to identify functional networks and keystone species in the human gut using novel approaches that are uniquely and ideally suited for studying microbial activity in complex communities. Using state-of-the-art methods such as stable isotope labeling, Raman microspectroscopy, and secondary ion mass spectrometry (NanoSIMS) we will illuminate functional networks in situ. This will allow us to identify what factors shape gut microbiota activity, reveal important food webs, and ultimately use network knowledge to target the microbiota with prebiotic/probiotic treatments rationally designed to promote health.
Max ERC Funding
1 498 279 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym GLOBALMACRO
Project Global Production Networks and Macroeconomic Interdependence
Researcher (PI) Julian DI GIOVANNI
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Call Details Consolidator Grant (CoG), SH1, ERC-2016-COG
Summary Researchers and policymakers alike have highlighted the potential efficiency gains of a global production structure. However, such linkages also raise the possibility of risks. This proposal tackles both empirical and theoretical challenges in incorporating the microeconomic structure of trade and international production networks in the study of the propagation of shocks internationally, and their impact on macroeconomic interdependence. Using newly constructed micro-level datasets, I provide quantitative analysis of the importance of the linkages in multicountry general equilibrium models of trade. First, using firm export and imported-input linkages, I provide a novel model-based estimation strategy to identify the role of country and firm-level shocks, and the implications of these estimates for the transmission of shocks across borders. By using structural trade models to estimate shocks at the firm level and studying the implications for the transmission of shocks across borders, I help bridge the micro-macro nexus in international economics. Second, I take an even more granular focus by studying the role of firm-to-firm production linkages in transmitting shocks across countries. To do so, I exploit a novel matching procedure between a country’s administrative dataset and cross-country firm-level data. I further build on these data by adding in domestic bank-firm relationships. This strategy allows for the study of how financial shocks are exported abroad via firms’ trade and multinational linkages. Third, I incorporate the insights from the empirical work into a full-scale multicountry general equilibrium model of trade, which allows for firm-level heterogeneity and microeconomic and macroeconomics shocks. I use the model for a quantitative study of the cross-country transmission of the different shocks via trade. This allows me to perform counterfactuals and examine the impact of policies, such as how opening to trade impacts macroeconomic interdependence.
Summary
Researchers and policymakers alike have highlighted the potential efficiency gains of a global production structure. However, such linkages also raise the possibility of risks. This proposal tackles both empirical and theoretical challenges in incorporating the microeconomic structure of trade and international production networks in the study of the propagation of shocks internationally, and their impact on macroeconomic interdependence. Using newly constructed micro-level datasets, I provide quantitative analysis of the importance of the linkages in multicountry general equilibrium models of trade. First, using firm export and imported-input linkages, I provide a novel model-based estimation strategy to identify the role of country and firm-level shocks, and the implications of these estimates for the transmission of shocks across borders. By using structural trade models to estimate shocks at the firm level and studying the implications for the transmission of shocks across borders, I help bridge the micro-macro nexus in international economics. Second, I take an even more granular focus by studying the role of firm-to-firm production linkages in transmitting shocks across countries. To do so, I exploit a novel matching procedure between a country’s administrative dataset and cross-country firm-level data. I further build on these data by adding in domestic bank-firm relationships. This strategy allows for the study of how financial shocks are exported abroad via firms’ trade and multinational linkages. Third, I incorporate the insights from the empirical work into a full-scale multicountry general equilibrium model of trade, which allows for firm-level heterogeneity and microeconomic and macroeconomics shocks. I use the model for a quantitative study of the cross-country transmission of the different shocks via trade. This allows me to perform counterfactuals and examine the impact of policies, such as how opening to trade impacts macroeconomic interdependence.
Max ERC Funding
1 381 250 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym GlymphEye
Project The Ocular Glymphatic System
Researcher (PI) Maiken Nedergaard
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), LS5, ERC-2016-ADG
Summary The glymphatic system is a highly organized brain-wide mechanism by which fluid wastes are removed from the brain that was recently described by my team. The glymphatic system clears 65% of amyloid-beta from the normal adult brain. A rapidly evolving literature has shown that the major neurodegenerative diseases of the eye, macular degeneration and glaucoma, may also result from the toxicity of uncleared protein wastes, including amyloid-beta. Yet the eye, like the brain, has no traditional lymphatic vessels. In this application, I propose that two of the most significant causes of human visual loss, macular degeneration and glaucoma – previously thought of as both intractable and unrelated – are instead mechanistically allied disorders that not only share a common causal pathway, but may both be therapeutically modified by targeting dysregulation of the glymphatic pathway. As such, this proposal seeks to link the biology of a fundamentally new pathway for both metabolic substrate and waste transport in the adult brain, to diseases of the eye that have long been resistant to either understanding or treatment.
The objectives: WP1: Define the cellular mechanisms that drive ocular glymphatic transport of Amyloid-beta using an ex vivo preparation of the optic nerve. WP2: Use magnetic resonance imaging (MRI) to establish the existence of ocular glymphatic transport in live animals. WP3: Determine whether the ocular glymphatic system, like the brain lymphatic system, is critically regulated by the sleep-wake cycle. WP4: Test the hypothesis that age-dependent macular degeneration is caused by a suppression of ocular glymphatic transport, with secondary accumulation of toxic protein products in and subjacent to the retinal pigment epithelium? WP5: Define the impact of increased intraocular pressure on glymphatic export of amyloid-beta, and test the hypothesis that the decrease in ocular glymphatic transport contributes to degeneration of retinal ganglion cells in glaucoma.
Summary
The glymphatic system is a highly organized brain-wide mechanism by which fluid wastes are removed from the brain that was recently described by my team. The glymphatic system clears 65% of amyloid-beta from the normal adult brain. A rapidly evolving literature has shown that the major neurodegenerative diseases of the eye, macular degeneration and glaucoma, may also result from the toxicity of uncleared protein wastes, including amyloid-beta. Yet the eye, like the brain, has no traditional lymphatic vessels. In this application, I propose that two of the most significant causes of human visual loss, macular degeneration and glaucoma – previously thought of as both intractable and unrelated – are instead mechanistically allied disorders that not only share a common causal pathway, but may both be therapeutically modified by targeting dysregulation of the glymphatic pathway. As such, this proposal seeks to link the biology of a fundamentally new pathway for both metabolic substrate and waste transport in the adult brain, to diseases of the eye that have long been resistant to either understanding or treatment.
The objectives: WP1: Define the cellular mechanisms that drive ocular glymphatic transport of Amyloid-beta using an ex vivo preparation of the optic nerve. WP2: Use magnetic resonance imaging (MRI) to establish the existence of ocular glymphatic transport in live animals. WP3: Determine whether the ocular glymphatic system, like the brain lymphatic system, is critically regulated by the sleep-wake cycle. WP4: Test the hypothesis that age-dependent macular degeneration is caused by a suppression of ocular glymphatic transport, with secondary accumulation of toxic protein products in and subjacent to the retinal pigment epithelium? WP5: Define the impact of increased intraocular pressure on glymphatic export of amyloid-beta, and test the hypothesis that the decrease in ocular glymphatic transport contributes to degeneration of retinal ganglion cells in glaucoma.
Max ERC Funding
2 176 250 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym IllegalPharma
Project Competitive Dynamics in the Informal Economy: The case of Illegal Pharmaceutical Drugs
Researcher (PI) LUIS FRANCISCO DIESTRE MARTIN
Host Institution (HI) INSTITUTO DE EMPRESA SL
Call Details Starting Grant (StG), SH1, ERC-2016-STG
Summary This project aims to develop a competitive dynamics theory of the informal economy, which is currently lacking in academic research. Specifically, this project will adopt an institutional theory perspective to better understand three fundamental outcomes in the informal economy: market entry (illegal businesses’ decision to be active in a specific niche), price competition (price differentials between legal and illegal products), and product quality (quality of products sold in illegal businesses). The main conceptual proposition suggested in this project is that selling products through illegal means may still be perceived as a legitimate activity. Building on this statement, it will be proposed that the degree in which actors perceive the sale of an illegal product as a more or less legitimate activity will influence (1) entrepreneurs’ decision to illegally enter such market, (2) consumers’ willingness to pay for such illegal product (i.e., price differential versus the legal version of the product) and (3) manufacturers’ motivation to keep quality standards for that illegal product. The empirical setting for this study will be the illegal sale of pharmaceutical drugs. The sale of illegal pharmaceuticals accounts for more than 10% of the medicines market and over €30 billion in annual earnings (World Health Organization, 2003). It represents one of the biggest challenges for societies in that, attending to the WHO’s Department of Essential Medicines and Health Products, anywhere from 100,000 to a million people die every year due to falsified drugs. Accordingly, this study aims to provide two main contributions: (1) an academic contribution by developing a radically new theory of the competitive dynamics in the informal economy, and (2) a practical contribution by providing a better understanding of the determinants of the informal economy that could help policy makers and regulators in their goal of fighting the trading of illegal medicines.
Summary
This project aims to develop a competitive dynamics theory of the informal economy, which is currently lacking in academic research. Specifically, this project will adopt an institutional theory perspective to better understand three fundamental outcomes in the informal economy: market entry (illegal businesses’ decision to be active in a specific niche), price competition (price differentials between legal and illegal products), and product quality (quality of products sold in illegal businesses). The main conceptual proposition suggested in this project is that selling products through illegal means may still be perceived as a legitimate activity. Building on this statement, it will be proposed that the degree in which actors perceive the sale of an illegal product as a more or less legitimate activity will influence (1) entrepreneurs’ decision to illegally enter such market, (2) consumers’ willingness to pay for such illegal product (i.e., price differential versus the legal version of the product) and (3) manufacturers’ motivation to keep quality standards for that illegal product. The empirical setting for this study will be the illegal sale of pharmaceutical drugs. The sale of illegal pharmaceuticals accounts for more than 10% of the medicines market and over €30 billion in annual earnings (World Health Organization, 2003). It represents one of the biggest challenges for societies in that, attending to the WHO’s Department of Essential Medicines and Health Products, anywhere from 100,000 to a million people die every year due to falsified drugs. Accordingly, this study aims to provide two main contributions: (1) an academic contribution by developing a radically new theory of the competitive dynamics in the informal economy, and (2) a practical contribution by providing a better understanding of the determinants of the informal economy that could help policy makers and regulators in their goal of fighting the trading of illegal medicines.
Max ERC Funding
1 374 185 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym LinPro
Project Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
Researcher (PI) Simon Hippenmeyer
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Consolidator Grant (CoG), LS5, ERC-2016-COG
Summary The cerebral cortex consists of an extraordinary number and great diversity of neurons. Yet, how the cortical entity, with all its functional neuronal circuits, arises from the neural stem cells (NSCs) in the developing neuroepithelium is a major unsolved question in Neuroscience. Radial glia progenitors (RGPs) are responsible for producing nearly all neocortical neurons and a certain fraction of cortical glia including astrocytes. Our recent efforts provide evidence for a high degree of non-stochasticity and thus deterministic nature of RGP behavior in the mammalian neocortex. However, the cellular and molecular mechanisms controlling RGP lineage progression through proliferation, neurogenesis and especially gliogenesis are unknown. In a pursuit to obtain definitive insights into these fundamental questions we assess RGP lineage progression at the unprecedented single cell resolution, using the unique genetic MADM (Mosaic Analysis with Double Markers) technology. MADM offers an unparalleled approach to visualize and concomitantly manipulate sparse clones and small subsets of genetically defined neurons. Within the scope of this project we will use multidisciplinary experimental approaches to establish a research program with the following major objectives: We will 1) Functionally dissect the relative contribution of cell-autonomous intrinsic signaling and cell-non-autonomous effects in RGP lineage progression; 2) Define the principles of lineage progression in human RGPs in situ using MADM technology in cerebral organoid system; 3) Decipher the logic of glia lineage progression in the neocortex. The ultimate goal of the proposed research is to establish a definitive quantitative framework and mechanistic model of lineage progression in cortical NSCs. As such, the proposed research shall precipitate into extensive conceptual progress regarding the fundamental cellular and molecular principles of cerebral cortex development.
Summary
The cerebral cortex consists of an extraordinary number and great diversity of neurons. Yet, how the cortical entity, with all its functional neuronal circuits, arises from the neural stem cells (NSCs) in the developing neuroepithelium is a major unsolved question in Neuroscience. Radial glia progenitors (RGPs) are responsible for producing nearly all neocortical neurons and a certain fraction of cortical glia including astrocytes. Our recent efforts provide evidence for a high degree of non-stochasticity and thus deterministic nature of RGP behavior in the mammalian neocortex. However, the cellular and molecular mechanisms controlling RGP lineage progression through proliferation, neurogenesis and especially gliogenesis are unknown. In a pursuit to obtain definitive insights into these fundamental questions we assess RGP lineage progression at the unprecedented single cell resolution, using the unique genetic MADM (Mosaic Analysis with Double Markers) technology. MADM offers an unparalleled approach to visualize and concomitantly manipulate sparse clones and small subsets of genetically defined neurons. Within the scope of this project we will use multidisciplinary experimental approaches to establish a research program with the following major objectives: We will 1) Functionally dissect the relative contribution of cell-autonomous intrinsic signaling and cell-non-autonomous effects in RGP lineage progression; 2) Define the principles of lineage progression in human RGPs in situ using MADM technology in cerebral organoid system; 3) Decipher the logic of glia lineage progression in the neocortex. The ultimate goal of the proposed research is to establish a definitive quantitative framework and mechanistic model of lineage progression in cortical NSCs. As such, the proposed research shall precipitate into extensive conceptual progress regarding the fundamental cellular and molecular principles of cerebral cortex development.
Max ERC Funding
1 996 030 €
Duration
Start date: 2017-12-01, End date: 2022-11-30
Project acronym MICROGLIA-CIRCUIT
Project Microglia action towards neuronal circuit formation and function in health and disease
Researcher (PI) Sandra Siegert
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Starting Grant (StG), LS5, ERC-2016-STG
Summary Constructing a neuronal circuit requires a firework of developmental events: First, the desired cell types have to be generated and wired correctly. Random propagating burst of action potentials among neighboring cells are shaping the functional maturation of these cell types, which later will be activity-dependent refined. Microglia are exposed to this environment from the beginning and show throughout development a morphological “activated”, phagocytic state. However, microglia have been proven to be involved in synapse refinement, which leads to the question how do microglia know when to alter neuronal circuit elements during development without inducing circuit malfunction? This is a fundamental question because the microglia activation state during development is intriguingly similar to the activation state in neurodegenerative diseases. To address this question, I use the retina as a model and propose the following three aims: First, we will reveal how the functional and gene regulatory network of microglia are altered when they are exposed to the neuronal activity-dependent environment and identify neuronal-imposed developmental checkpoints. We will study whether alteration of microglia function in this system will impact circuit formation and function. Second, we will examine microglia dynamics upon sequential removal of neuronal cell types in disease conditions and investigate whether functional restoration of cell types using optogenetic techniques resets microglia function. Third, we will establish the role of healthy and diseased microglia in human retinal circuit formation by reprogramming microglia and 3D-retinoids from healthy and diseased human iPS cells. I predict that my findings provide crucial insights into the functional impact of microglia upon both normal development and function, as well as how their actions may lead to disease phenotypes in situations of neurodegenerative diseases.
Summary
Constructing a neuronal circuit requires a firework of developmental events: First, the desired cell types have to be generated and wired correctly. Random propagating burst of action potentials among neighboring cells are shaping the functional maturation of these cell types, which later will be activity-dependent refined. Microglia are exposed to this environment from the beginning and show throughout development a morphological “activated”, phagocytic state. However, microglia have been proven to be involved in synapse refinement, which leads to the question how do microglia know when to alter neuronal circuit elements during development without inducing circuit malfunction? This is a fundamental question because the microglia activation state during development is intriguingly similar to the activation state in neurodegenerative diseases. To address this question, I use the retina as a model and propose the following three aims: First, we will reveal how the functional and gene regulatory network of microglia are altered when they are exposed to the neuronal activity-dependent environment and identify neuronal-imposed developmental checkpoints. We will study whether alteration of microglia function in this system will impact circuit formation and function. Second, we will examine microglia dynamics upon sequential removal of neuronal cell types in disease conditions and investigate whether functional restoration of cell types using optogenetic techniques resets microglia function. Third, we will establish the role of healthy and diseased microglia in human retinal circuit formation by reprogramming microglia and 3D-retinoids from healthy and diseased human iPS cells. I predict that my findings provide crucial insights into the functional impact of microglia upon both normal development and function, as well as how their actions may lead to disease phenotypes in situations of neurodegenerative diseases.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
