Project acronym ASYMMEM
Project Lipid asymmetry: a cellular battery?
Researcher (PI) André NADLER
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Starting Grant (StG), LS3, ERC-2017-STG
Summary It is a basic textbook notion that the plasma membranes of virtually all organisms display an asymmetric lipid distribution between inner and outer leaflets far removed from thermodynamic equilibrium. As a fundamental biological principle, lipid asymmetry has been linked to numerous cellular processes. However, a clear mechanistic justification for the continued existence of lipid asymmetry throughout evolution has yet to be established. We propose here that lipid asymmetry serves as a store of potential energy that is used to fuel energy-intense membrane remodelling and signalling events for instance during membrane fusion and fission. This implies that rapid, local changes of trans-membrane lipid distribution rather than a continuously maintained out-of-equilibrium situation are crucial for cellular function. Consequently, new methods for quantifying the kinetics of lipid trans-bilayer movement are required, as traditional approaches are mostly suited for analysing quasi-steady-state conditions. Addressing this need, we will develop and employ novel photochemical lipid probes and lipid biosensors to quantify localized trans-bilayer lipid movement. We will use these tools for identifying yet unknown protein components of the lipid asymmetry regulating machinery and analyse their function with regard to membrane dynamics and signalling in cell motility. Focussing on cell motility enables targeted chemical and genetic perturbations while monitoring lipid dynamics on timescales and in membrane structures that are well suited for light microscopy. Ultimately, we aim to reconstitute lipid asymmetry as a driving force for membrane remodelling in vitro. We expect that our work will break new ground in explaining one of the least understood features of the plasma membrane and pave the way for a new, dynamic membrane model. Since the plasma membrane serves as the major signalling hub, this will have impact in almost every area of the life sciences.
Summary
It is a basic textbook notion that the plasma membranes of virtually all organisms display an asymmetric lipid distribution between inner and outer leaflets far removed from thermodynamic equilibrium. As a fundamental biological principle, lipid asymmetry has been linked to numerous cellular processes. However, a clear mechanistic justification for the continued existence of lipid asymmetry throughout evolution has yet to be established. We propose here that lipid asymmetry serves as a store of potential energy that is used to fuel energy-intense membrane remodelling and signalling events for instance during membrane fusion and fission. This implies that rapid, local changes of trans-membrane lipid distribution rather than a continuously maintained out-of-equilibrium situation are crucial for cellular function. Consequently, new methods for quantifying the kinetics of lipid trans-bilayer movement are required, as traditional approaches are mostly suited for analysing quasi-steady-state conditions. Addressing this need, we will develop and employ novel photochemical lipid probes and lipid biosensors to quantify localized trans-bilayer lipid movement. We will use these tools for identifying yet unknown protein components of the lipid asymmetry regulating machinery and analyse their function with regard to membrane dynamics and signalling in cell motility. Focussing on cell motility enables targeted chemical and genetic perturbations while monitoring lipid dynamics on timescales and in membrane structures that are well suited for light microscopy. Ultimately, we aim to reconstitute lipid asymmetry as a driving force for membrane remodelling in vitro. We expect that our work will break new ground in explaining one of the least understood features of the plasma membrane and pave the way for a new, dynamic membrane model. Since the plasma membrane serves as the major signalling hub, this will have impact in almost every area of the life sciences.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym BACTIN
Project Shaping the bacterial cell wall: the actin-like cytoskeleton, from single molecules to morphogenesis and antimicrobials
Researcher (PI) Rut CARBALLIDO LOPEZ
Host Institution (HI) INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE
Call Details Consolidator Grant (CoG), LS3, ERC-2017-COG
Summary One of the ultimate goals in cell biology is to understand how cells determine their shape. In bacteria, the cell wall and the actin-like (MreB) cytoskeleton are major determinants of cell shape. As a hallmark of microbial life, the external cell wall is the most conspicuous macromolecule expanding in concert with cell growth and one of the most prominent targets for antibiotics. Despite decades of study, the mechanism of cell wall morphogenesis remains poorly understood. In rod-shaped bacteria, actin-like MreB proteins assemble into disconnected membrane-associated structures (patches) that move processively around the cell periphery and are thought to control shape by spatiotemporally organizing macromolecular machineries that effect sidewall elongation. However, the ultrastructure of MreB assemblies and the mechanistic details underlying their morphogenetic function remain to be elucidated.
The aim of this project is to combine ground-breaking light microscopy and spectroscopy techniques with cutting-edge genetic, biochemical and systems biology approaches available in the model rod-shaped bacterium Bacillus subtilis to elucidate how MreB and cell wall biosynthetic enzymes collectively act to build a cell. Within this context, new features of MreB assemblies will be determined in vivo and in vitro, and a “toolbox” of approaches to determine the modes of action of antibiotics targeting cell wall processes will be developed. Parameters measured by the different approaches will be used to refine a mathematical model aiming to quantitatively describe the features of bacterial cell wall growth. The long-term goals of BActin are to understand general principles of bacterial cell morphogenesis and to provide mechanistic templates and new reporters for the screening of novel antibiotics.
Summary
One of the ultimate goals in cell biology is to understand how cells determine their shape. In bacteria, the cell wall and the actin-like (MreB) cytoskeleton are major determinants of cell shape. As a hallmark of microbial life, the external cell wall is the most conspicuous macromolecule expanding in concert with cell growth and one of the most prominent targets for antibiotics. Despite decades of study, the mechanism of cell wall morphogenesis remains poorly understood. In rod-shaped bacteria, actin-like MreB proteins assemble into disconnected membrane-associated structures (patches) that move processively around the cell periphery and are thought to control shape by spatiotemporally organizing macromolecular machineries that effect sidewall elongation. However, the ultrastructure of MreB assemblies and the mechanistic details underlying their morphogenetic function remain to be elucidated.
The aim of this project is to combine ground-breaking light microscopy and spectroscopy techniques with cutting-edge genetic, biochemical and systems biology approaches available in the model rod-shaped bacterium Bacillus subtilis to elucidate how MreB and cell wall biosynthetic enzymes collectively act to build a cell. Within this context, new features of MreB assemblies will be determined in vivo and in vitro, and a “toolbox” of approaches to determine the modes of action of antibiotics targeting cell wall processes will be developed. Parameters measured by the different approaches will be used to refine a mathematical model aiming to quantitatively describe the features of bacterial cell wall growth. The long-term goals of BActin are to understand general principles of bacterial cell morphogenesis and to provide mechanistic templates and new reporters for the screening of novel antibiotics.
Max ERC Funding
1 902 195 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym BIGlobal
Project Firm Growth and Market Power in the Global Economy
Researcher (PI) Swati DHINGRA
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Call Details Starting Grant (StG), SH1, ERC-2017-STG
Summary According to the European Commission, to design effective policies for ensuring a “more dynamic, innovative and competitive” economy, it is essential to understand the decision-making process of firms as they differ a lot in terms of their capacities and policy responses (EC 2007). The objective of my future research is to provide such an analysis. BIGlobal will examine the sources of firm growth and market power to provide new insights into welfare and policy in a globalized world.
Much of analysis of the global economy is set in the paradigm of markets that allocate resources efficiently and there is little role for policy. But big firms dominate economic activity, especially across borders. How do firms grow and what is the effect of their market power on the welfare impact of globalization? This project will determine how firm decisions matter for the aggregate gains from globalization, the division of these gains across different individuals and their implications for policy design.
Over the next five years, I will incorporate richer firms behaviour in models of international trade to understand how trade and industrial policies impact the growth process, especially in less developed markets. The specific questions I will address include: how can trade and competition policy ensure consumers benefit from globalization when firms engaged in international trade have market power, how do domestic policies to encourage agribusiness firms affect the extent to which small farmers gain from trade, how do industrial policies affect firm growth through input linkages, and what is the impact of banking globalization on the growth of firms in the real sector.
Each project will combine theoretical work with rich data from developing economies to expand the frontier of knowledge on trade and industrial policy, and to provide a basis for informed policymaking.
Summary
According to the European Commission, to design effective policies for ensuring a “more dynamic, innovative and competitive” economy, it is essential to understand the decision-making process of firms as they differ a lot in terms of their capacities and policy responses (EC 2007). The objective of my future research is to provide such an analysis. BIGlobal will examine the sources of firm growth and market power to provide new insights into welfare and policy in a globalized world.
Much of analysis of the global economy is set in the paradigm of markets that allocate resources efficiently and there is little role for policy. But big firms dominate economic activity, especially across borders. How do firms grow and what is the effect of their market power on the welfare impact of globalization? This project will determine how firm decisions matter for the aggregate gains from globalization, the division of these gains across different individuals and their implications for policy design.
Over the next five years, I will incorporate richer firms behaviour in models of international trade to understand how trade and industrial policies impact the growth process, especially in less developed markets. The specific questions I will address include: how can trade and competition policy ensure consumers benefit from globalization when firms engaged in international trade have market power, how do domestic policies to encourage agribusiness firms affect the extent to which small farmers gain from trade, how do industrial policies affect firm growth through input linkages, and what is the impact of banking globalization on the growth of firms in the real sector.
Each project will combine theoretical work with rich data from developing economies to expand the frontier of knowledge on trade and industrial policy, and to provide a basis for informed policymaking.
Max ERC Funding
1 313 103 €
Duration
Start date: 2017-12-01, End date: 2022-11-30
Project acronym BinD
Project Mitotic Bookmarking, Stem Cells and early Development
Researcher (PI) Pablo Navarro Gil
Host Institution (HI) INSTITUT PASTEUR
Call Details Consolidator Grant (CoG), LS3, ERC-2017-COG
Summary The goal of this proposal is to deliver a new theoretical framework to understand how transcription factors (TFs) sustain cell identity during developmental processes. Recognised as key drivers of cell fate acquisition, TFs are currently not considered to directly contribute to the mitotic inheritance of chromatin states. Instead, these are passively propagated through cell division by a variety of epigenetic marks. Recent discoveries, including by our lab, challenge this view: developmental TFs may impact the propagation of regulatory information from mother to daughter cells through a process known as mitotic bookmarking. This hypothesis, largely overlooked by mainstream epigenetic research during the last two decades, will be investigated in embryo-derived stem cells and during early mouse development. Indeed, these immature cell identities are largely independent from canonical epigenetic repression; hence, current models cannot account for their properties. We will comprehensively identify mitotic bookmarking factors in stem cells and early embryos, establish their function in stem cell self-renewal, cell fate acquisition and dissect how they contribute to chromatin regulation in mitosis. This will allow us to study the relationships between bookmarking factors and other mechanisms of epigenetic inheritance. To achieve this, unique techniques to modulate protein activity and histone modifications specifically in mitotic cells will be established. Thus, a mechanistic understanding of how mitosis influences gene regulation and of how mitotic bookmarking contributes to the propagation of immature cell identities will be delivered. Based on robust preliminary data, we anticipate the discovery of new functions for TFs in several genetic and epigenetic processes. This knowledge should have a wide impact on chromatin biology and cell fate studies as well as in other fields studying processes dominated by TFs and cell proliferation.
Summary
The goal of this proposal is to deliver a new theoretical framework to understand how transcription factors (TFs) sustain cell identity during developmental processes. Recognised as key drivers of cell fate acquisition, TFs are currently not considered to directly contribute to the mitotic inheritance of chromatin states. Instead, these are passively propagated through cell division by a variety of epigenetic marks. Recent discoveries, including by our lab, challenge this view: developmental TFs may impact the propagation of regulatory information from mother to daughter cells through a process known as mitotic bookmarking. This hypothesis, largely overlooked by mainstream epigenetic research during the last two decades, will be investigated in embryo-derived stem cells and during early mouse development. Indeed, these immature cell identities are largely independent from canonical epigenetic repression; hence, current models cannot account for their properties. We will comprehensively identify mitotic bookmarking factors in stem cells and early embryos, establish their function in stem cell self-renewal, cell fate acquisition and dissect how they contribute to chromatin regulation in mitosis. This will allow us to study the relationships between bookmarking factors and other mechanisms of epigenetic inheritance. To achieve this, unique techniques to modulate protein activity and histone modifications specifically in mitotic cells will be established. Thus, a mechanistic understanding of how mitosis influences gene regulation and of how mitotic bookmarking contributes to the propagation of immature cell identities will be delivered. Based on robust preliminary data, we anticipate the discovery of new functions for TFs in several genetic and epigenetic processes. This knowledge should have a wide impact on chromatin biology and cell fate studies as well as in other fields studying processes dominated by TFs and cell proliferation.
Max ERC Funding
1 900 844 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym BRIDGING
Project The function of membrane tethering in plant intercellular communication
Researcher (PI) Emmanuelle Maria Françoise Bayer
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), LS3, ERC-2017-COG
Summary Intercellular communication is critical for multicellularity. It coordinates the activities within individual cells to support the function of an organism as a whole. Plants have developed remarkable cellular machines -the Plasmodesmata (PD) pores- which interconnect every single cell within the plant body, establishing direct membrane and cytoplasmic continuity, a situation unique to plants. PD are indispensable for plant life. They control the flux of molecules between cells and are decisive for development, environmental adaptation and defence signalling. However, how PD integrate signalling to coordinate responses at a multicellular level remains unclear.
A striking feature of PD organisation, setting them apart from animal cell junctions, is a strand of endoplasmic reticulum (ER) running through the pore, tethered extremely tight (~10nm) to the plasma membrane (PM) by unidentified “spokes”. To date, the function of ER-PM contacts at PD remains a complete enigma. We don’t know how and why the two organelles come together at PD cellular junctions.
I recently proposed that ER-PM tethering is in fact central to PD function. In this project I will investigate the question of how integrated cellular responses benefit from organelle cross-talk at PD. The project integrates proteomic/bioinformatic approaches, biophysical/modelling methods and ultra-high resolution 3D imaging into molecular cell biology of plant cell-to-cell communication and will, for the first time, directly address the mechanism and function of ER-PM contacts at PD. We will pursue three complementary objectives to attain our goal: 1) Identify the mechanisms of PD membrane-tethering at the molecular level 2) Elucidate the dynamics and 3D architecture of ER-PM contact sites at PD 3) Uncover the function of ER-PM apposition for plant intercellular communication. Overall, the project will pioneer a radically new perspective on PD-mediated cell-to-cell communication, a fundamental aspect of plant biology
Summary
Intercellular communication is critical for multicellularity. It coordinates the activities within individual cells to support the function of an organism as a whole. Plants have developed remarkable cellular machines -the Plasmodesmata (PD) pores- which interconnect every single cell within the plant body, establishing direct membrane and cytoplasmic continuity, a situation unique to plants. PD are indispensable for plant life. They control the flux of molecules between cells and are decisive for development, environmental adaptation and defence signalling. However, how PD integrate signalling to coordinate responses at a multicellular level remains unclear.
A striking feature of PD organisation, setting them apart from animal cell junctions, is a strand of endoplasmic reticulum (ER) running through the pore, tethered extremely tight (~10nm) to the plasma membrane (PM) by unidentified “spokes”. To date, the function of ER-PM contacts at PD remains a complete enigma. We don’t know how and why the two organelles come together at PD cellular junctions.
I recently proposed that ER-PM tethering is in fact central to PD function. In this project I will investigate the question of how integrated cellular responses benefit from organelle cross-talk at PD. The project integrates proteomic/bioinformatic approaches, biophysical/modelling methods and ultra-high resolution 3D imaging into molecular cell biology of plant cell-to-cell communication and will, for the first time, directly address the mechanism and function of ER-PM contacts at PD. We will pursue three complementary objectives to attain our goal: 1) Identify the mechanisms of PD membrane-tethering at the molecular level 2) Elucidate the dynamics and 3D architecture of ER-PM contact sites at PD 3) Uncover the function of ER-PM apposition for plant intercellular communication. Overall, the project will pioneer a radically new perspective on PD-mediated cell-to-cell communication, a fundamental aspect of plant biology
Max ERC Funding
1 999 840 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym CELL HORMONE
Project Bringing into focus the cellular dynamics of the plant growth hormone gibberellin
Researcher (PI) Alexander Morgan JONES
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS3, ERC-2017-STG
Summary During an organism’s development it must integrate internal and external information. An example in plants, whose development stretches across their lifetime, is the coordination between environmental stimuli and endogenous cues on regulating the key hormone gibberellin (GA). The present challenge is to understand how these diverse signals influence GA levels and how GA signalling leads to diverse GA responses. This challenge is deepened by a fundamental problem in hormone research: the specific responses directed by a given hormone often depend on the cell-type, timing, and amount of hormone accumulation, but hormone concentrations are most often assessed at the organism or tissue level. Our approach, based on a novel optogenetic biosensor, GA Perception Sensor 1 (GPS1), brings the goal of high-resolution quantification of GA in vivo within reach. In plants expressing GPS1, we observe gradients of GA in elongating root and shoot tissues. We now aim to understand how a series of independently tunable enzymatic and transport activities combine to articulate the GA gradients that we observe. We further aim to discover the mechanisms by which endogenous and environmental signals regulate these GA enzymes and transporters. Finally, we aim to understand how one of these signals, light, regulates GA patterns to influence dynamic cell growth and organ behavior. Our overarching goal is a systems level understanding of the signal integration upstream and growth programming downstream of GA. The groundbreaking aspect of this proposal is our focus at the cellular level, and we are uniquely positioned to carry out our multidisciplinary aims involving biosensor engineering, innovative imaging, and multiscale modelling. We anticipate that the discoveries stemming from this project will provide the detailed understanding necessary to make strategic interventions into GA dynamic patterning in crop plants for specific improvements in growth, development, and environmental responses.
Summary
During an organism’s development it must integrate internal and external information. An example in plants, whose development stretches across their lifetime, is the coordination between environmental stimuli and endogenous cues on regulating the key hormone gibberellin (GA). The present challenge is to understand how these diverse signals influence GA levels and how GA signalling leads to diverse GA responses. This challenge is deepened by a fundamental problem in hormone research: the specific responses directed by a given hormone often depend on the cell-type, timing, and amount of hormone accumulation, but hormone concentrations are most often assessed at the organism or tissue level. Our approach, based on a novel optogenetic biosensor, GA Perception Sensor 1 (GPS1), brings the goal of high-resolution quantification of GA in vivo within reach. In plants expressing GPS1, we observe gradients of GA in elongating root and shoot tissues. We now aim to understand how a series of independently tunable enzymatic and transport activities combine to articulate the GA gradients that we observe. We further aim to discover the mechanisms by which endogenous and environmental signals regulate these GA enzymes and transporters. Finally, we aim to understand how one of these signals, light, regulates GA patterns to influence dynamic cell growth and organ behavior. Our overarching goal is a systems level understanding of the signal integration upstream and growth programming downstream of GA. The groundbreaking aspect of this proposal is our focus at the cellular level, and we are uniquely positioned to carry out our multidisciplinary aims involving biosensor engineering, innovative imaging, and multiscale modelling. We anticipate that the discoveries stemming from this project will provide the detailed understanding necessary to make strategic interventions into GA dynamic patterning in crop plants for specific improvements in growth, development, and environmental responses.
Max ERC Funding
1 499 616 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym CoSpaDD
Project Competition for Space in Development and Diseases
Researcher (PI) Romain LEVAYER
Host Institution (HI) INSTITUT PASTEUR
Call Details Starting Grant (StG), LS3, ERC-2017-STG
Summary Developing tissues have a remarkable plasticity illustrated by their capacity to regenerate and form normal organs despite strong perturbations. This requires the adjustment of single cell behaviour to their neighbours and to tissue scale parameters. The modulation of cell growth and proliferation was suggested to be driven by mechanical inputs, however the mechanisms adjusting cell death are not well known. Recently it was shown that epithelial cells could be eliminated by spontaneous live-cell delamination following an increase of cell density. Studying cell delamination in the midline region of the Drosophila pupal notum, we confirmed that local tissue crowding is necessary and sufficient to drive cell elimination and found that Caspase 3 activation precedes and is required for cell delamination. This suggested that a yet unknown pathway is responsible for crowding sensing and activation of caspase, which does not involve already known mechanical sensing pathways. Moreover, we showed that fast growing clones in the notum could induce neighbouring cell elimination through crowding-induced death. This suggested that crowding-induced death could promote tissue invasion by pretumoural cells.
Here we will combine genetics, quantitative live imaging, statistics, laser perturbations and modelling to study crowding-induced death in Drosophila in order to: 1) find single cell deformations responsible for caspase activation; 2) find new pathways responsible for density sensing and apoptosis induction; 3) test their contribution to adult tissue homeostasis, morphogenesis and cell elimination coordination; 4) study the role of crowding induced death during competition between different cell types and tissue invasion 5) Explore theoretically the conditions required for efficient space competition between two cell populations.
This project will provide essential information for the understanding of epithelial homeostasis, mechanotransduction and tissue invasion by tumoural cells
Summary
Developing tissues have a remarkable plasticity illustrated by their capacity to regenerate and form normal organs despite strong perturbations. This requires the adjustment of single cell behaviour to their neighbours and to tissue scale parameters. The modulation of cell growth and proliferation was suggested to be driven by mechanical inputs, however the mechanisms adjusting cell death are not well known. Recently it was shown that epithelial cells could be eliminated by spontaneous live-cell delamination following an increase of cell density. Studying cell delamination in the midline region of the Drosophila pupal notum, we confirmed that local tissue crowding is necessary and sufficient to drive cell elimination and found that Caspase 3 activation precedes and is required for cell delamination. This suggested that a yet unknown pathway is responsible for crowding sensing and activation of caspase, which does not involve already known mechanical sensing pathways. Moreover, we showed that fast growing clones in the notum could induce neighbouring cell elimination through crowding-induced death. This suggested that crowding-induced death could promote tissue invasion by pretumoural cells.
Here we will combine genetics, quantitative live imaging, statistics, laser perturbations and modelling to study crowding-induced death in Drosophila in order to: 1) find single cell deformations responsible for caspase activation; 2) find new pathways responsible for density sensing and apoptosis induction; 3) test their contribution to adult tissue homeostasis, morphogenesis and cell elimination coordination; 4) study the role of crowding induced death during competition between different cell types and tissue invasion 5) Explore theoretically the conditions required for efficient space competition between two cell populations.
This project will provide essential information for the understanding of epithelial homeostasis, mechanotransduction and tissue invasion by tumoural cells
Max ERC Funding
1 489 147 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym DENOVO-P
Project De novo Development of Polarity in Plant Cells
Researcher (PI) Liam DOLAN
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), LS3, ERC-2017-ADG
Summary The polarity of the single cell from which many organisms develop determines the polarity of the body axis. However, the polarity of these single cells is often inherited. For example, zygote polarity is inherited from the polarized egg cell of Arabidopsis thaliana. By contrast, polarity is not pre-set in the spore cell that forms the Marchantia polymorpha (Marchantia) plant. An environmental cue – directional light – polarises the spore cell which, in turn, directs the formation of the first (apical-basal) axis and the fates of the two daughter cells formed when the spore cell divides. Using Marchantia, we will discover how cell polarity is established de novo in the developing spore cell and how this, in turn, directs the specification of the first major axis in the plant.
The proposed research is feasible because of the unique characteristics of the Marchantia system:
1. Isolated single apolar cells become polarized allowing us to exploit the real-time imaging with experimental manipulation of polarising cues at each stage of development.
2. Haploid genetics can be exploited to carry out genetic screens of unprecedented depth and we can identify mutant genes using a fully annotated genome sequence.
3. Gene expression can be measured with high temporal resolution during polarization.
We propose to:
1. Describe the cellular and morphogenetic events that occur as the spore cell polarizes, divides asymmetrically to form cells at either end of the apical-basal axis.
2. Define the mechanism underpinning the de novo establishment of polarity using a combination of forward and reverse genetics and determine if this mechanism is conserved among land plants.
3. Determine the role of auxin in transmitting spore cell polarity to the cells at both ends of the apical-basal axis.
This will describe, for the first time, the molecular mechanism controlling the de novo polarization of a single cell that develops into a plant.
Summary
The polarity of the single cell from which many organisms develop determines the polarity of the body axis. However, the polarity of these single cells is often inherited. For example, zygote polarity is inherited from the polarized egg cell of Arabidopsis thaliana. By contrast, polarity is not pre-set in the spore cell that forms the Marchantia polymorpha (Marchantia) plant. An environmental cue – directional light – polarises the spore cell which, in turn, directs the formation of the first (apical-basal) axis and the fates of the two daughter cells formed when the spore cell divides. Using Marchantia, we will discover how cell polarity is established de novo in the developing spore cell and how this, in turn, directs the specification of the first major axis in the plant.
The proposed research is feasible because of the unique characteristics of the Marchantia system:
1. Isolated single apolar cells become polarized allowing us to exploit the real-time imaging with experimental manipulation of polarising cues at each stage of development.
2. Haploid genetics can be exploited to carry out genetic screens of unprecedented depth and we can identify mutant genes using a fully annotated genome sequence.
3. Gene expression can be measured with high temporal resolution during polarization.
We propose to:
1. Describe the cellular and morphogenetic events that occur as the spore cell polarizes, divides asymmetrically to form cells at either end of the apical-basal axis.
2. Define the mechanism underpinning the de novo establishment of polarity using a combination of forward and reverse genetics and determine if this mechanism is conserved among land plants.
3. Determine the role of auxin in transmitting spore cell polarity to the cells at both ends of the apical-basal axis.
This will describe, for the first time, the molecular mechanism controlling the de novo polarization of a single cell that develops into a plant.
Max ERC Funding
2 499 224 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym EMBED
Project Embedded Markets and the Economy
Researcher (PI) Matthew ELLIOTT
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), SH1, ERC-2017-STG
Summary EMBED takes a microeconomic approach to investigating the macroeconomic implications of market transactions being embedded in social relationships. Sociologists and economists have documented the importance of relationships for mediating trade in a wide range of market settings. EMBED seeks to investigate the implications of this for the economy as a whole.
Ethnographic work suggests that relationships foster common understandings which limit opportunistic behaviour. Subproject 1 will develop a first relational contacting theory of networked markets to capture this, and test these predictions using data from the Bundesbank. Formally modelling dynamic business-relationships, these relationships can be viewed as social capital. We will investigate whether this social capital is destroyed by economic shocks, and if so how long it takes to rebuild.
Subproject 2 will run a field experiment. We will intervene in a networked market to create new relationships in a variety of ways. The varying success of these approaches will help us better understand the role of relationships in markets. Moreover, as a result we’ll get exogenous variation in the market structure that will help identity the affects relationships have on market outcomes.
Subproject 3 will explore frictions in the clearing of networked markets. As the data requirements to empirically test between different theories are extremely demanding, laboratory experiments will be run. Breaking convention, these experiments will be protocol-free, although interactions will be closely monitored. This will create a more level playing field for testing different theories while also creating scope for the market to develop efficiency enhancing norms.
Subproject 4 will examine firm level multi-sourcing and production technology decisions, and how these feed into the creation of supply chains. The fragility of these supply chains will be investigated and equilibrium supply chains compared across countries.
Summary
EMBED takes a microeconomic approach to investigating the macroeconomic implications of market transactions being embedded in social relationships. Sociologists and economists have documented the importance of relationships for mediating trade in a wide range of market settings. EMBED seeks to investigate the implications of this for the economy as a whole.
Ethnographic work suggests that relationships foster common understandings which limit opportunistic behaviour. Subproject 1 will develop a first relational contacting theory of networked markets to capture this, and test these predictions using data from the Bundesbank. Formally modelling dynamic business-relationships, these relationships can be viewed as social capital. We will investigate whether this social capital is destroyed by economic shocks, and if so how long it takes to rebuild.
Subproject 2 will run a field experiment. We will intervene in a networked market to create new relationships in a variety of ways. The varying success of these approaches will help us better understand the role of relationships in markets. Moreover, as a result we’ll get exogenous variation in the market structure that will help identity the affects relationships have on market outcomes.
Subproject 3 will explore frictions in the clearing of networked markets. As the data requirements to empirically test between different theories are extremely demanding, laboratory experiments will be run. Breaking convention, these experiments will be protocol-free, although interactions will be closely monitored. This will create a more level playing field for testing different theories while also creating scope for the market to develop efficiency enhancing norms.
Subproject 4 will examine firm level multi-sourcing and production technology decisions, and how these feed into the creation of supply chains. The fragility of these supply chains will be investigated and equilibrium supply chains compared across countries.
Max ERC Funding
1 449 106 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym EMPCONSFIN
Project Empirical Analyses of Markets for Consumer Financial Products and their Effects
Researcher (PI) Alessandro GAVAZZA
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Call Details Consolidator Grant (CoG), SH1, ERC-2017-COG
Summary This proposal presents three broad projects on information frictions in households' credit markets and on the
consequences of these frictions for durable good markets. Specifically, an influential theoretical literature in
information economics has shown that borrowing constraints can arise in equilibrium when borrowers and
lenders have asymmetric information about borrowers' risks. Hence, the first project aims to provide the first
empirical analyses of markets (i.e., demand and supply) with asymmetric information and nonexclusive
trades---i.e., markets in which households can purchase multiple insurance contracts, such as in life
insurance markets, or can open multiple credit lines, such as in credit card markets. The second project aims
to study recent regulations of fees and prices in markets for consumer financial products, such as mortgages,
that could have the unintended consequences of increasing households' cost of credit and, thus, of tightening
their borrowing constraints. Finally, the third project aims to study the role of borrowing constraints in
durable goods markets, with a special focus on car markets during the Great Recession.
All these projects aim to develop and estimate structural models using data from different markets. I further
plan to use the estimated structural parameters to perform counterfactual policy analyses in each of the
specific markets analyzed in these projects.
Summary
This proposal presents three broad projects on information frictions in households' credit markets and on the
consequences of these frictions for durable good markets. Specifically, an influential theoretical literature in
information economics has shown that borrowing constraints can arise in equilibrium when borrowers and
lenders have asymmetric information about borrowers' risks. Hence, the first project aims to provide the first
empirical analyses of markets (i.e., demand and supply) with asymmetric information and nonexclusive
trades---i.e., markets in which households can purchase multiple insurance contracts, such as in life
insurance markets, or can open multiple credit lines, such as in credit card markets. The second project aims
to study recent regulations of fees and prices in markets for consumer financial products, such as mortgages,
that could have the unintended consequences of increasing households' cost of credit and, thus, of tightening
their borrowing constraints. Finally, the third project aims to study the role of borrowing constraints in
durable goods markets, with a special focus on car markets during the Great Recession.
All these projects aim to develop and estimate structural models using data from different markets. I further
plan to use the estimated structural parameters to perform counterfactual policy analyses in each of the
specific markets analyzed in these projects.
Max ERC Funding
1 550 945 €
Duration
Start date: 2018-06-01, End date: 2023-05-31