Project acronym ICC
Project Institutions in Consumer Credit
Researcher (PI) Daniel Alberto PARAVISINI MAGGI
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Call Details Consolidator Grant (CoG), SH1, ERC-2017-COG
Summary Whether (and why) the market for consumer credit is inefficient is still an open question with important implications for household well-being. The research in this proposal will study sources of inefficiencies in two burgeoning consumer credit institutions: high-cost credit and on-line marketplaces. Each institution serves borrowers on opposite ends of the wealth and credit risk spectrum. Thus, they provide an ideal laboratory for studying the wide range of economic frictions that shape the access and price of credit for households. Despite growing attention from academics and severe scrutiny by policymakers, the economic and social impact of both institutions are yet not well understood.
The first stream of projects in the proposal is aimed at providing new evidence on the trade-offs involved in the use of high-cost credit. High-cost credit, such as Payday loans, is often the only source of funding for poor households. Alleviating liquidity shortages with high-cost credit may have negative long term consequences for financial health, an effect often attributed to borrower self-control problems. In the first project of the stream I use data from a Payday lender in the U.K. to explore a new channel for this effect—reputation—that does not rely on borrower irrationality. The second project combines data from 21 police forces in the U.K. to evaluate the social consequences of high-cost credit through the lens of criminal behavior.
The second stream of projects characterizes previously unexplored sources of adverse selection in credit markets, with substantive positive and normative implications. Using data from the largest on-line marketplace in the U.S., I aim to demonstrate how asymmetric information distorts maturity choice, and how information gathering by the lender can drive away low-risk borrowers. The final project of this stream will use previously unavailable data to produce the first comprehensive characterization of on-line credit marketplaces worldwide.
Summary
Whether (and why) the market for consumer credit is inefficient is still an open question with important implications for household well-being. The research in this proposal will study sources of inefficiencies in two burgeoning consumer credit institutions: high-cost credit and on-line marketplaces. Each institution serves borrowers on opposite ends of the wealth and credit risk spectrum. Thus, they provide an ideal laboratory for studying the wide range of economic frictions that shape the access and price of credit for households. Despite growing attention from academics and severe scrutiny by policymakers, the economic and social impact of both institutions are yet not well understood.
The first stream of projects in the proposal is aimed at providing new evidence on the trade-offs involved in the use of high-cost credit. High-cost credit, such as Payday loans, is often the only source of funding for poor households. Alleviating liquidity shortages with high-cost credit may have negative long term consequences for financial health, an effect often attributed to borrower self-control problems. In the first project of the stream I use data from a Payday lender in the U.K. to explore a new channel for this effect—reputation—that does not rely on borrower irrationality. The second project combines data from 21 police forces in the U.K. to evaluate the social consequences of high-cost credit through the lens of criminal behavior.
The second stream of projects characterizes previously unexplored sources of adverse selection in credit markets, with substantive positive and normative implications. Using data from the largest on-line marketplace in the U.S., I aim to demonstrate how asymmetric information distorts maturity choice, and how information gathering by the lender can drive away low-risk borrowers. The final project of this stream will use previously unavailable data to produce the first comprehensive characterization of on-line credit marketplaces worldwide.
Max ERC Funding
1 017 851 €
Duration
Start date: 2018-08-01, End date: 2021-07-31
Project acronym IFDG
Project INNOVATION, FIRM DYNAMICS AND GROWTH: what do we learn from French firm-level data?
Researcher (PI) Philippe AGHION
Host Institution (HI) COLLEGE DE FRANCE
Call Details Advanced Grant (AdG), SH1, ERC-2017-ADG
Summary This research project will confort theory and data to deepen our understanding of the mechanisms and policies of innovation, and the relationship between innovation, growth and social mobility. The underlying framework is the Schumpeterian theory of economic growth, where: (i) growth is generated by innovative entrepreneurs; (ii) entrepreneurial investments respond to incentives that are themselves shaped by economic policies and institutions; (iii) new innovations involves creative destruction. This project will explore new extensions of the Schumpeterian growth paradigm together with new firm-level and individual datasets to analyze the following questions : (a) the measurement of productivity growth and the extent to which measured TFP growth factors is correctly accounting for new innovation; (b) the relashionship between innovation and trade and more specifically the causal links from export and import to innovation, and the main channels through wich export and import affect innovation; (c) the effect of fiscal and institutional changes on entrepreneurship: in particular, how recent changes in the French legislation on self-employement have affected individual incentives to become self-employed, and differently so for different social or regional groups of individuals; (d) the relationship between creative destruction, inequality, and wellbeing: in particular, how does creative destruction (mesured by job or firm turnover) impact on social mobility (e.g measured by the probability of making it to top income brackets conditional upon a low initial income or a low parental income) and health. This approach can shed new light on important aspects of the growth process such as: the middle income trap, secular stagnation, the recent rise in top income inequality, and firm dynamics. Moreover, the paradigm can be used to think (or rethink) about growth policy design.
Summary
This research project will confort theory and data to deepen our understanding of the mechanisms and policies of innovation, and the relationship between innovation, growth and social mobility. The underlying framework is the Schumpeterian theory of economic growth, where: (i) growth is generated by innovative entrepreneurs; (ii) entrepreneurial investments respond to incentives that are themselves shaped by economic policies and institutions; (iii) new innovations involves creative destruction. This project will explore new extensions of the Schumpeterian growth paradigm together with new firm-level and individual datasets to analyze the following questions : (a) the measurement of productivity growth and the extent to which measured TFP growth factors is correctly accounting for new innovation; (b) the relashionship between innovation and trade and more specifically the causal links from export and import to innovation, and the main channels through wich export and import affect innovation; (c) the effect of fiscal and institutional changes on entrepreneurship: in particular, how recent changes in the French legislation on self-employement have affected individual incentives to become self-employed, and differently so for different social or regional groups of individuals; (d) the relationship between creative destruction, inequality, and wellbeing: in particular, how does creative destruction (mesured by job or firm turnover) impact on social mobility (e.g measured by the probability of making it to top income brackets conditional upon a low initial income or a low parental income) and health. This approach can shed new light on important aspects of the growth process such as: the middle income trap, secular stagnation, the recent rise in top income inequality, and firm dynamics. Moreover, the paradigm can be used to think (or rethink) about growth policy design.
Max ERC Funding
1 968 588 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym IL-22 AND IL-22BP
Project Identifying the immune and microbial network controlling the IL-22 – IL-22bp axis to open the doors for targeted therapies
Researcher (PI) Samuel Huber
Host Institution (HI) UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF
Call Details Starting Grant (StG), LS6, ERC-2013-StG
Summary Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer. One hypothesis is that the same factors important for wound healing, if left unchecked, also promote tumorigenesis. Tight control by a sensor of tissue damage should induce these factors to promote tissue repair, while limiting their activity to prevent development of cancer.
IL-22, a prototypical tissue repair factor, plays an important role in a wide variety of intestinal disease including infection, wound healing, colitis, and cancer. Indeed, IL-22 has protective and detrimental effects dependent on the milieu and disease suggesting that proper regulation is required. IL-22 expression is directly regulated, additionally a soluble IL-22 receptor (IL-22 binding protein; IL-22bp), can bind and neutralize IL-22. We reported recently that sensing of intestinal tissue damage and components of the microbiota via the NLRP3 or NLRP6 inflammasomes led to a down regulation of IL-22bp, thereby increasing bioavailability of IL-22. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumor development if not controlled by IL-22bp during the recovery phase.
Accordingly a spatial and temporal regulation of IL-22 is crucial. Hence, global administration or blockade of IL-22 is unlikely to be therapeutically beneficial. We are using several newly generated conditional knock-out (cCasp1-/-, cIL-18R-/-, cIL-18-/-, cIL-22R1-/-), knock-in (IL-22 BFP), and gnotobiotic mice, aiming to analyze the cellular and microbial network regulating the IL-22 – IL-22bp axis at a resolution previously unfeasible. Our results will provide novel insights into the network between microflora, epithelium, and immune system regulating tissue regeneration and tumor development, and can lead to therapies for potentially a wide variety of intestinal diseases, such as infection, colon cancer, IBD, or wound healing.
Summary
Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer. One hypothesis is that the same factors important for wound healing, if left unchecked, also promote tumorigenesis. Tight control by a sensor of tissue damage should induce these factors to promote tissue repair, while limiting their activity to prevent development of cancer.
IL-22, a prototypical tissue repair factor, plays an important role in a wide variety of intestinal disease including infection, wound healing, colitis, and cancer. Indeed, IL-22 has protective and detrimental effects dependent on the milieu and disease suggesting that proper regulation is required. IL-22 expression is directly regulated, additionally a soluble IL-22 receptor (IL-22 binding protein; IL-22bp), can bind and neutralize IL-22. We reported recently that sensing of intestinal tissue damage and components of the microbiota via the NLRP3 or NLRP6 inflammasomes led to a down regulation of IL-22bp, thereby increasing bioavailability of IL-22. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumor development if not controlled by IL-22bp during the recovery phase.
Accordingly a spatial and temporal regulation of IL-22 is crucial. Hence, global administration or blockade of IL-22 is unlikely to be therapeutically beneficial. We are using several newly generated conditional knock-out (cCasp1-/-, cIL-18R-/-, cIL-18-/-, cIL-22R1-/-), knock-in (IL-22 BFP), and gnotobiotic mice, aiming to analyze the cellular and microbial network regulating the IL-22 – IL-22bp axis at a resolution previously unfeasible. Our results will provide novel insights into the network between microflora, epithelium, and immune system regulating tissue regeneration and tumor development, and can lead to therapies for potentially a wide variety of intestinal diseases, such as infection, colon cancer, IBD, or wound healing.
Max ERC Funding
1 498 392 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
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 ImmProDynamics
Project Dissecting the interplay between the dynamics of immune responses and pathogen proliferation in vivo
Researcher (PI) Andreas J. Müller
Host Institution (HI) OTTO-VON-GUERICKE-UNIVERSITAET MAGDEBURG
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Pathogen proliferation has profound implications for its persistence, treatment strategies, and the induction and execution of protective immune responses. In vivo, pathogen proliferation rates are heterogenic, confronting the immune system with a variety of microbial physiological states. It is unknown if, and by what molecular mechanism, the immune response can distinguish these different states on a cellular level. Also, understanding the link between pathogen proliferation and immune cell dynamics could provide critical information on how infections can be controlled, and how to counteract pathogen persistence and antibiotic resistance. However, this question has never been addressed due to difficulties in studying the dynamics of immune cells and at the same time probing pathogen proliferation.
In this project, we will make use of a novel in vivo reporter system that I have developed, in order to determine the role of the pathogen's proliferation for its interaction with the immune system. Specifically, we will (1) determine the tissue niche in which the pathogen proliferates, (2) investigate the differential dynamics of phagocyte-pathogen- and of T cell-APC-interactions related to pathogen proliferation rate, (3) manipulate the relationship between pathogen proliferation and immune cell dynamics by using proliferation-deficient mutants and optogenetic pathogen inactivation, (4) identify signaling pathways that are differentially induced in cells infected by high versus low proliferating pathogens, and test their involvement in differential immune cell dynamics related to pathogen proliferation.
ImmProDynamics will for the first time provide insights into how cells of the immune system react to distinct pathogen proliferative states in vivo. This will greatly expand our knowledge of host-pathogen interactions, which will be critical for the design of efficient vaccines and antimicrobial therapy.
Summary
Pathogen proliferation has profound implications for its persistence, treatment strategies, and the induction and execution of protective immune responses. In vivo, pathogen proliferation rates are heterogenic, confronting the immune system with a variety of microbial physiological states. It is unknown if, and by what molecular mechanism, the immune response can distinguish these different states on a cellular level. Also, understanding the link between pathogen proliferation and immune cell dynamics could provide critical information on how infections can be controlled, and how to counteract pathogen persistence and antibiotic resistance. However, this question has never been addressed due to difficulties in studying the dynamics of immune cells and at the same time probing pathogen proliferation.
In this project, we will make use of a novel in vivo reporter system that I have developed, in order to determine the role of the pathogen's proliferation for its interaction with the immune system. Specifically, we will (1) determine the tissue niche in which the pathogen proliferates, (2) investigate the differential dynamics of phagocyte-pathogen- and of T cell-APC-interactions related to pathogen proliferation rate, (3) manipulate the relationship between pathogen proliferation and immune cell dynamics by using proliferation-deficient mutants and optogenetic pathogen inactivation, (4) identify signaling pathways that are differentially induced in cells infected by high versus low proliferating pathogens, and test their involvement in differential immune cell dynamics related to pathogen proliferation.
ImmProDynamics will for the first time provide insights into how cells of the immune system react to distinct pathogen proliferative states in vivo. This will greatly expand our knowledge of host-pathogen interactions, which will be critical for the design of efficient vaccines and antimicrobial therapy.
Max ERC Funding
1 499 525 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym IMMUNE CELL SWARMS
Project Innate Immune Cell Swarms: Integrating and Adapting Single Cell and Population Dynamics in Inflamed and Infected Tissues
Researcher (PI) Tim LÄMMERMANN
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Neutrophils are essential effector cells of the innate immune response. Intravital microscopy studies have recently changed our perspective on neutrophil tissue dynamics. They revealed swarm-like migration patterns in several models of inflammation and infection: Neutrophil populations show strikingly coordinated behavior with phases of highly directed chemotaxis and clustering at local sites of tissue damage. My previous work established that neutrophils self-amplify this swarming response by auto-signaling, which provided the first molecular basis for the collective nature of neutrophil swarms (Lämmermann et al., Nature 2013). However, we are still at the beginning of unraveling the molecular pathways behind this newly discovered phenomenon.
Most importantly, we completely lack insight into the signals and mechanisms that stop neutrophil swarms in the resolution phase of an immune response. Since excess neutrophil accumulations cause deleterious tissue destruction in many inflammatory diseases, novel insights into the mechanisms, which prevent extensive swarm aggregation, might be of considerable therapeutic value. In accord with this, our proposal follows three aims: (i) dissecting the cellular and molecular mechanisms that control the resolution phase of neutrophil swarming, (ii) establishing a conceptual framework of how swarming immune cells adapt their dynamics to changing inflammatory milieus, and (iii) developing an integrated view on how neutrophil swarms are controlled by secondary waves of myeloid cell swarms. To achieve our goals, we will combine targeted mouse genetics with live cell imaging of immune cell dynamics in living tissues and the use of innovative mimics of physiological environments.
Our future findings on innate immune cell swarms promise to (i) advance our knowledge on leukocyte navigation in complex inflammatory tissues and (ii) provide new avenues for the therapeutic modulation of tissue regeneration after inflammation and infection.
Summary
Neutrophils are essential effector cells of the innate immune response. Intravital microscopy studies have recently changed our perspective on neutrophil tissue dynamics. They revealed swarm-like migration patterns in several models of inflammation and infection: Neutrophil populations show strikingly coordinated behavior with phases of highly directed chemotaxis and clustering at local sites of tissue damage. My previous work established that neutrophils self-amplify this swarming response by auto-signaling, which provided the first molecular basis for the collective nature of neutrophil swarms (Lämmermann et al., Nature 2013). However, we are still at the beginning of unraveling the molecular pathways behind this newly discovered phenomenon.
Most importantly, we completely lack insight into the signals and mechanisms that stop neutrophil swarms in the resolution phase of an immune response. Since excess neutrophil accumulations cause deleterious tissue destruction in many inflammatory diseases, novel insights into the mechanisms, which prevent extensive swarm aggregation, might be of considerable therapeutic value. In accord with this, our proposal follows three aims: (i) dissecting the cellular and molecular mechanisms that control the resolution phase of neutrophil swarming, (ii) establishing a conceptual framework of how swarming immune cells adapt their dynamics to changing inflammatory milieus, and (iii) developing an integrated view on how neutrophil swarms are controlled by secondary waves of myeloid cell swarms. To achieve our goals, we will combine targeted mouse genetics with live cell imaging of immune cell dynamics in living tissues and the use of innovative mimics of physiological environments.
Our future findings on innate immune cell swarms promise to (i) advance our knowledge on leukocyte navigation in complex inflammatory tissues and (ii) provide new avenues for the therapeutic modulation of tissue regeneration after inflammation and infection.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym IMMUNEDIVERSITY
Project Defining of human adaptive immune gene diversity and its impact on disease
Researcher (PI) Gunilla KARLSSON HEDESTAM
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Advanced Grant (AdG), LS6, ERC-2017-ADG
Summary Why do vaccines protect some people but not all? Why can some people develop potent neutralizing antibodies to infections, while others cannot? Why do some people develop immune-associated diseases such as allergy, rheumatoid arthritis, multiple sclerosis and diabetes over their lifetimes, when the body has evolved to tolerate self? The answer lies in the adaptive immune system. B and T lymphocytes of the adaptive system express highly polymorphic receptors that allow for the recognition of large numbers of antigens. Our research is now uncovering an enormous heterogeneity in the germline genes that encode our B and T cell receptors. This fact has not been well appreciated because of the high complexity of the genomic regions that encode these receptors, with the presence of large insertions and deletions, a high degree of repetitiveness and gene copy number variations, which cannot be adequately met with conventional whole genome sequencing approaches.
We have developed a state-of-the-art approach we call IgDiscover, which comprises novel molecular library preparation approaches, next generation immune repertoire sequencing, computational analysis and a software that allows rapid construction of personalized antibody gene databases encompassing the hundreds of germline gene segments that rearrange to make up each individual’s naïve B cell repertoire. Thus, IgDiscover offers new possibilities to define human genetic diversity in these loci. This proposal also describes our development of ImmuneDiscover, a high throughput approach enabling personalized immune-profiling of very large numbers of individuals (>1000), encompassing not only Ig genes but also T cell receptor genes and the genes encoding the human major histocompatibility complexes. Here, we will use IgDiscover and ImmuneDiscover to elucidate global diversity in adaptive immune genes and we will investigate potential associations between antibody germline genes and the development of rheumatoid arthritis.
Summary
Why do vaccines protect some people but not all? Why can some people develop potent neutralizing antibodies to infections, while others cannot? Why do some people develop immune-associated diseases such as allergy, rheumatoid arthritis, multiple sclerosis and diabetes over their lifetimes, when the body has evolved to tolerate self? The answer lies in the adaptive immune system. B and T lymphocytes of the adaptive system express highly polymorphic receptors that allow for the recognition of large numbers of antigens. Our research is now uncovering an enormous heterogeneity in the germline genes that encode our B and T cell receptors. This fact has not been well appreciated because of the high complexity of the genomic regions that encode these receptors, with the presence of large insertions and deletions, a high degree of repetitiveness and gene copy number variations, which cannot be adequately met with conventional whole genome sequencing approaches.
We have developed a state-of-the-art approach we call IgDiscover, which comprises novel molecular library preparation approaches, next generation immune repertoire sequencing, computational analysis and a software that allows rapid construction of personalized antibody gene databases encompassing the hundreds of germline gene segments that rearrange to make up each individual’s naïve B cell repertoire. Thus, IgDiscover offers new possibilities to define human genetic diversity in these loci. This proposal also describes our development of ImmuneDiscover, a high throughput approach enabling personalized immune-profiling of very large numbers of individuals (>1000), encompassing not only Ig genes but also T cell receptor genes and the genes encoding the human major histocompatibility complexes. Here, we will use IgDiscover and ImmuneDiscover to elucidate global diversity in adaptive immune genes and we will investigate potential associations between antibody germline genes and the development of rheumatoid arthritis.
Max ERC Funding
2 500 000 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
Project acronym INCA
Project Genetic and environmental factors that control inflammation-driven colon cancer
Researcher (PI) Fiona M Powrie
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), LS6, ERC-2013-ADG
Summary "The human gastrointestinal tract is colonized by an abundant and diverse bacterial microbiota that exist in a mutualistic relationship with the host that promotes intestinal health. Maladaptation in this host microbial dialogue leads to a deranged inflammatory response and inflammatory bowel disease (IBD) that can progress to colon cancer. The complex interplay between genetic and environmental factors and their impact on intestinal inflammation are starting to be deciphered in IBD, however little is known about how they influence the transition from colitis to cancer. We recently established a relevant model of bacteria-driven invasive colon cancer and have mapped both genetic and immune pathways that perpetuate disease. Genetic susceptibility maps to a 1.7mb region on chromosome 3 containing the candidate gene Alpk1, an alpha-kinase. This locus mediates its effects through the IL-23 driven innate lymphoid cell response and we have identified the cytokine IL-22 as a key player in driving the tumour cell response. We will use a multi-disciplinary approach to probe the interaction between genetics, microbial drivers and inflammatory pathways that promote colon cancer. BAC transgenics and cell-type specific knock-out mice will be used to establish the function of Alpk1 in bacteria driven colon cancer. In vivo models will be complemented by novel 3D colonic organoid and crypt cultures generated from epithelial stem cells from normal or tumor tissue allowing analysis of microbial and cytokine signals that influence intestinal epithelial cell and stem cell function. Deep sequencing combined with bacterial cell culture will identify changes in the intestinal microbiota that drive tumourigenesis. Results from mouse models will be translated to analysis of human colorectal cancer. These studies will uncover new pathways involved in bacterial interaction, intestinal inflammation and tumour formation that may offer new therapeutic targets in IBD and colon cancer."
Summary
"The human gastrointestinal tract is colonized by an abundant and diverse bacterial microbiota that exist in a mutualistic relationship with the host that promotes intestinal health. Maladaptation in this host microbial dialogue leads to a deranged inflammatory response and inflammatory bowel disease (IBD) that can progress to colon cancer. The complex interplay between genetic and environmental factors and their impact on intestinal inflammation are starting to be deciphered in IBD, however little is known about how they influence the transition from colitis to cancer. We recently established a relevant model of bacteria-driven invasive colon cancer and have mapped both genetic and immune pathways that perpetuate disease. Genetic susceptibility maps to a 1.7mb region on chromosome 3 containing the candidate gene Alpk1, an alpha-kinase. This locus mediates its effects through the IL-23 driven innate lymphoid cell response and we have identified the cytokine IL-22 as a key player in driving the tumour cell response. We will use a multi-disciplinary approach to probe the interaction between genetics, microbial drivers and inflammatory pathways that promote colon cancer. BAC transgenics and cell-type specific knock-out mice will be used to establish the function of Alpk1 in bacteria driven colon cancer. In vivo models will be complemented by novel 3D colonic organoid and crypt cultures generated from epithelial stem cells from normal or tumor tissue allowing analysis of microbial and cytokine signals that influence intestinal epithelial cell and stem cell function. Deep sequencing combined with bacterial cell culture will identify changes in the intestinal microbiota that drive tumourigenesis. Results from mouse models will be translated to analysis of human colorectal cancer. These studies will uncover new pathways involved in bacterial interaction, intestinal inflammation and tumour formation that may offer new therapeutic targets in IBD and colon cancer."
Max ERC Funding
2 484 620 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym IneqPol
Project Inequality - Public Policy and Political Economy
Researcher (PI) Florian SCHEUER
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Starting Grant (StG), SH1, ERC-2017-STG
Summary Over the past decades, many developed countries have seen considerable increases in income and wealth inequality. Political and economic arguments for and against offsetting this rise in inequality have been put forward. This research program aims at informing this debate by developing new models that capture these trends and by analyzing their optimal policy implications, both theoretically and quantitatively. The goal is to bring together approaches from public economics, labor economics, macroeconomics, and political economy to explore whether rising inequality necessitates institutional responses and, if so, which ones.
This project will shed light on this question from the following three related angles: (1) The changing nature of labor markets and its implications for inequality and tax policy. This part will focus on technological progress (e.g. the replacement of routine tasks) and shifts in the sectoral composition of the economy (e.g. the rise of finance) and what this means for the taxation of labor incomes, profits, and the desirability of basic income policies. (2) The intergenerational dynamics of inequality and the design of tax and public spending policies to promote economic mobility. We will develop a normative framework for optimal policies that balance both equality of opportunity principles and efficient parental sorting based on preference heterogeneity over public spending (e.g. on schools). (3) Wealth inequality and its implications for the political economy of tax policy. This part will incorporate capital taxation into the analysis and explore how it can help promote political stability, both when equilibrium taxes depend on the distribution of wealth in society and, conversely, when political influence correlates with wealth.
This research project aims both to develop new theoretical tools and to implement them empirically, with an emphasis on the implications for the design of real-world tax policies.
Summary
Over the past decades, many developed countries have seen considerable increases in income and wealth inequality. Political and economic arguments for and against offsetting this rise in inequality have been put forward. This research program aims at informing this debate by developing new models that capture these trends and by analyzing their optimal policy implications, both theoretically and quantitatively. The goal is to bring together approaches from public economics, labor economics, macroeconomics, and political economy to explore whether rising inequality necessitates institutional responses and, if so, which ones.
This project will shed light on this question from the following three related angles: (1) The changing nature of labor markets and its implications for inequality and tax policy. This part will focus on technological progress (e.g. the replacement of routine tasks) and shifts in the sectoral composition of the economy (e.g. the rise of finance) and what this means for the taxation of labor incomes, profits, and the desirability of basic income policies. (2) The intergenerational dynamics of inequality and the design of tax and public spending policies to promote economic mobility. We will develop a normative framework for optimal policies that balance both equality of opportunity principles and efficient parental sorting based on preference heterogeneity over public spending (e.g. on schools). (3) Wealth inequality and its implications for the political economy of tax policy. This part will incorporate capital taxation into the analysis and explore how it can help promote political stability, both when equilibrium taxes depend on the distribution of wealth in society and, conversely, when political influence correlates with wealth.
This research project aims both to develop new theoretical tools and to implement them empirically, with an emphasis on the implications for the design of real-world tax policies.
Max ERC Funding
1 008 665 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym INFINHET
Project Within and across countries heterogeneity in international finance
Researcher (PI) Nicolas Mathieu Georges Coeurdacier
Host Institution (HI) FONDATION NATIONALE DES SCIENCES POLITIQUES
Call Details Starting Grant (StG), SH1, ERC-2013-StG
Summary Financial globalization has led to a large increase in capital flows together with increasing global imbalances. Understanding how investors structure their international portfolios and how such decisions interact with the real side of the economy has become a critical macro issue. Recently, policy makers have been advocating the understanding of capital flows and global imbalances as a necessary step to analyze the roots of the last financial crisis and its international transmission. Another important evolution is the larger role played by fast growing emerging markets. The world is getting more asymmetric as they feature very different characteristics compared to developed countries.
INFINHET aims at developing new dynamic multi-country macro-models to better account for the heterogeneity across agents and across countries in order to answer age-old questions in international macro such as the benefits from financial integration, the adjustment of global imbalances, the dynamics of exchange rates and asset prices, international financial contagion, the international dimension of tax policies.
The first part of INFINHET deals with new methods for dynamic stochastic models with heterogeneous agents/countries. Applications include normative questions regarding the welfare impact of policies in open economies and positive questions regarding the dynamics of asset prices and capital flows. The second part focuses on long-term issues in multi-country overlapping generations models. It analyzes the importance of asymmetries between countries on macroeconomic outcomes in a globalized world. Besides differences in growth and demographics, asymmetries in financial institutions, insurance mechanisms and welfare states are emphasized, with a particular focus on the specificities of China. The theoretical predictions will be tested empirically. This will require the development of panel data based on cross-country aggregates and the use of micro data based on individuals.
Summary
Financial globalization has led to a large increase in capital flows together with increasing global imbalances. Understanding how investors structure their international portfolios and how such decisions interact with the real side of the economy has become a critical macro issue. Recently, policy makers have been advocating the understanding of capital flows and global imbalances as a necessary step to analyze the roots of the last financial crisis and its international transmission. Another important evolution is the larger role played by fast growing emerging markets. The world is getting more asymmetric as they feature very different characteristics compared to developed countries.
INFINHET aims at developing new dynamic multi-country macro-models to better account for the heterogeneity across agents and across countries in order to answer age-old questions in international macro such as the benefits from financial integration, the adjustment of global imbalances, the dynamics of exchange rates and asset prices, international financial contagion, the international dimension of tax policies.
The first part of INFINHET deals with new methods for dynamic stochastic models with heterogeneous agents/countries. Applications include normative questions regarding the welfare impact of policies in open economies and positive questions regarding the dynamics of asset prices and capital flows. The second part focuses on long-term issues in multi-country overlapping generations models. It analyzes the importance of asymmetries between countries on macroeconomic outcomes in a globalized world. Besides differences in growth and demographics, asymmetries in financial institutions, insurance mechanisms and welfare states are emphasized, with a particular focus on the specificities of China. The theoretical predictions will be tested empirically. This will require the development of panel data based on cross-country aggregates and the use of micro data based on individuals.
Max ERC Funding
1 176 938 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
