Project acronym ACHILLES-HEEL
Project Crop resistance improvement by mining natural and induced variation in host accessibility factors
Researcher (PI) Sebastian Schornack
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS9, ERC-2014-STG
Summary Increasing crop yield to feed the world is a grand challenge of the 21st century but it is hampered by diseases caused by filamentous plant pathogens. The arms race between pathogen and plant demands constant adjustment of crop germplasm to tackle emerging pathogen races with new virulence features. To date, most crop disease resistance has relied on specific resistance genes that are effective only against a subset of races. We cannot solely rely on classical resistance genes to keep ahead of the pathogens. There is an urgent need to develop approaches based on knowledge of the pathogen’s Achilles heel: core plant processes that are required for pathogen colonization.
Our hypothesis is that disease resistance based on manipulation of host accessibility processes has a higher probability for durability, and is best identified using a broad host-range pathogen. I will employ the filamentous pathogen Phytophthora palmivora to mine plant alleles and unravel host processes providing microbial access in roots and leaves of monocot and dicot plants.
In Aim 1 I will utilize plant symbiosis mutants and allelic variation to elucidate general mechanisms of colonization by filamentous microbes. Importantly, allelic variation will be studied in economically relevant barley and wheat to allow immediate translation into breeding programs.
In Aim 2 I will perform a comparative study of microbial colonization in monocot and dicot roots and leaves. Transcriptional profiling of pathogen and plant will highlight common and contrasting principles and illustrate the impact of differential plant anatomies.
We will challenge our findings by testing beneficial fungi to assess commonalities and differences between mutualist and pathogen colonization. We will use genetics, cell biology and genomics to find suitable resistance alleles highly relevant to crop production and global food security. At the completion of the project, I expect to have a set of genes for resistance breeding.
Summary
Increasing crop yield to feed the world is a grand challenge of the 21st century but it is hampered by diseases caused by filamentous plant pathogens. The arms race between pathogen and plant demands constant adjustment of crop germplasm to tackle emerging pathogen races with new virulence features. To date, most crop disease resistance has relied on specific resistance genes that are effective only against a subset of races. We cannot solely rely on classical resistance genes to keep ahead of the pathogens. There is an urgent need to develop approaches based on knowledge of the pathogen’s Achilles heel: core plant processes that are required for pathogen colonization.
Our hypothesis is that disease resistance based on manipulation of host accessibility processes has a higher probability for durability, and is best identified using a broad host-range pathogen. I will employ the filamentous pathogen Phytophthora palmivora to mine plant alleles and unravel host processes providing microbial access in roots and leaves of monocot and dicot plants.
In Aim 1 I will utilize plant symbiosis mutants and allelic variation to elucidate general mechanisms of colonization by filamentous microbes. Importantly, allelic variation will be studied in economically relevant barley and wheat to allow immediate translation into breeding programs.
In Aim 2 I will perform a comparative study of microbial colonization in monocot and dicot roots and leaves. Transcriptional profiling of pathogen and plant will highlight common and contrasting principles and illustrate the impact of differential plant anatomies.
We will challenge our findings by testing beneficial fungi to assess commonalities and differences between mutualist and pathogen colonization. We will use genetics, cell biology and genomics to find suitable resistance alleles highly relevant to crop production and global food security. At the completion of the project, I expect to have a set of genes for resistance breeding.
Max ERC Funding
1 991 054 €
Duration
Start date: 2015-09-01, End date: 2021-08-31
Project acronym ADaPTIVE
Project Analysing Diversity with a Phenomic approach: Trends in Vertebrate Evolution
Researcher (PI) Anjali Goswami
Host Institution (HI) NATURAL HISTORY MUSEUM
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary What processes shape vertebrate diversity through deep time? Approaches to this question can focus on many different factors, from life history and ecology to large-scale environmental change and extinction. To date, the majority of studies on the evolution of vertebrate diversity have focused on relatively simple metrics, specifically taxon counts or univariate measures, such as body size. However, multivariate morphological data provides a more complete picture of evolutionary and palaeoecological change. Morphological data can also bridge deep-time palaeobiological analyses with studies of the genetic and developmental factors that shape variation and must also influence large-scale patterns of evolutionary change. Thus, accurately reconstructing the patterns and processes underlying evolution requires an approach that can fully represent an organism’s phenome, the sum total of their observable traits.
Recent advances in imaging and data analysis allow large-scale study of phenomic evolution. In this project, I propose to quantitatively analyse the deep-time evolutionary diversity of tetrapods (amphibians, reptiles, birds, and mammals). Specifically, I will apply and extend new imaging, morphometric, and analytical tools to construct a multivariate phenomic dataset for living and extinct tetrapods from 3-D scans. I will use these data to rigorously compare extinction selectivity, timing, pace, and shape of adaptive radiations, and ecomorphological response to large-scale climatic shifts across all tetrapod clades. To do so, I will quantify morphological diversity (disparity) and rates of evolution spanning over 300 million years of tetrapod history. I will further analyse the evolution of phenotypic integration by quantifying not just the traits themselves, but changes in the relationships among traits, which reflect the genetic, developmental, and functional interactions that shape variation, the raw material for natural selection.
Summary
What processes shape vertebrate diversity through deep time? Approaches to this question can focus on many different factors, from life history and ecology to large-scale environmental change and extinction. To date, the majority of studies on the evolution of vertebrate diversity have focused on relatively simple metrics, specifically taxon counts or univariate measures, such as body size. However, multivariate morphological data provides a more complete picture of evolutionary and palaeoecological change. Morphological data can also bridge deep-time palaeobiological analyses with studies of the genetic and developmental factors that shape variation and must also influence large-scale patterns of evolutionary change. Thus, accurately reconstructing the patterns and processes underlying evolution requires an approach that can fully represent an organism’s phenome, the sum total of their observable traits.
Recent advances in imaging and data analysis allow large-scale study of phenomic evolution. In this project, I propose to quantitatively analyse the deep-time evolutionary diversity of tetrapods (amphibians, reptiles, birds, and mammals). Specifically, I will apply and extend new imaging, morphometric, and analytical tools to construct a multivariate phenomic dataset for living and extinct tetrapods from 3-D scans. I will use these data to rigorously compare extinction selectivity, timing, pace, and shape of adaptive radiations, and ecomorphological response to large-scale climatic shifts across all tetrapod clades. To do so, I will quantify morphological diversity (disparity) and rates of evolution spanning over 300 million years of tetrapod history. I will further analyse the evolution of phenotypic integration by quantifying not just the traits themselves, but changes in the relationships among traits, which reflect the genetic, developmental, and functional interactions that shape variation, the raw material for natural selection.
Max ERC Funding
1 482 818 €
Duration
Start date: 2015-06-01, End date: 2020-05-31
Project acronym BeeDanceGap
Project Honeybee communication: animal social learning at the height of social complexity
Researcher (PI) Ellouise Leadbeater
Host Institution (HI) ROYAL HOLLOWAY AND BEDFORD NEW COLLEGE
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary Learning from others is fundamental to ecological success across the animal kingdom, but a key theme to emerge from recent research is that individuals respond differently to social information. Understanding this diversity is an imposing challenge, because it is hard to replicate the overwhelming complexity of free-living groups within controlled laboratory conditions. Yet here I propose that one of the most complex social models that we know of— the sophisticated eusocial societies of honeybees— offer unrivaled and yet unrecognized potential to study social information flow through a natural group. The honeybee “dance language” is one of the most celebrated communication systems in the animal world, and central to a powerful information network that drives our most high-profile pollinator to food, but bee colonies are uniquely tractable for two reasons. Firstly, next-generation transcriptomics could allow us to delve deep into this complexity at the molecular level, on a scale that is simply not available in vertebrate social systems. I propose to track information flow through a natural group using brain gene expression profiles, to understand how dances elicit learning in the bee brain. Secondly, although bee foraging ranges are vast and diverse, social learning takes place in one centralized location (the hive). The social sciences now offer powerful new tools to analyze social networks, and I will use a cutting-edge network-based modelling approach to understand how the importance of social learning mechanisms shifts with ecology. In the face of global pollinator decline, understanding the contribution of foraging drivers to colony success has never been more pressing, but the importance of the dance language reaches far beyond food security concerns. This research integrates proximate and ultimate perspectives to produce a comprehensive, multi-disciplinary program; a high-risk, high-gain journey into new territory for understanding animal communication.
Summary
Learning from others is fundamental to ecological success across the animal kingdom, but a key theme to emerge from recent research is that individuals respond differently to social information. Understanding this diversity is an imposing challenge, because it is hard to replicate the overwhelming complexity of free-living groups within controlled laboratory conditions. Yet here I propose that one of the most complex social models that we know of— the sophisticated eusocial societies of honeybees— offer unrivaled and yet unrecognized potential to study social information flow through a natural group. The honeybee “dance language” is one of the most celebrated communication systems in the animal world, and central to a powerful information network that drives our most high-profile pollinator to food, but bee colonies are uniquely tractable for two reasons. Firstly, next-generation transcriptomics could allow us to delve deep into this complexity at the molecular level, on a scale that is simply not available in vertebrate social systems. I propose to track information flow through a natural group using brain gene expression profiles, to understand how dances elicit learning in the bee brain. Secondly, although bee foraging ranges are vast and diverse, social learning takes place in one centralized location (the hive). The social sciences now offer powerful new tools to analyze social networks, and I will use a cutting-edge network-based modelling approach to understand how the importance of social learning mechanisms shifts with ecology. In the face of global pollinator decline, understanding the contribution of foraging drivers to colony success has never been more pressing, but the importance of the dance language reaches far beyond food security concerns. This research integrates proximate and ultimate perspectives to produce a comprehensive, multi-disciplinary program; a high-risk, high-gain journey into new territory for understanding animal communication.
Max ERC Funding
1 422 010 €
Duration
Start date: 2016-02-01, End date: 2021-01-31
Project acronym CHIME
Project The Role of Cortico-Hippocampal Interactions during Memory Encoding
Researcher (PI) Daniel (Ari) Bendor
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary This research proposal’s goal is to investigate the role of cortico-hippocampal interactions during the encoding and consolidation of a memory. Current memory consolidation models postulate that memory storage in our brains occurs by a dynamic process- a recent episodic experience is initially encoded in the hippocampus, and during off-line states such as sleep, the encoded memory is gradually transferred to neocortex for long-term storage. One potential neural mechanism by which this could occur is replay, a phenomenon where neural activity patterns in the hippocampus evoked by a previous experience reactivate spontaneously during non-REM sleep, leading to coordinated cortical reactivation. While previous work suggests that hippocampal replay is important for encoding new memories, how memory consolidation is accomplished through cortico-hippocampal interactions is not well understood.
This research project has three major aims- 1) examine how cortical feedback influences which spatial trajectory is replayed by the hippocampus, 2) investigate how the hippocampal replay of a behavioural episode modifies cortical circuits, 3) measure the causal role of cortico-hippocampal interactions in consolidating memories. We will record ensemble activity from freely moving rats during an auditory-spatial association task and during post-behavioural sleep sessions. We will focus our ensemble recordings on two brain regions: 1) the dorsal CA1 region of the hippocampus, where the phenomenon of sleep replay has been most extensively examined, and 2) auditory cortex, a region of the brain critical for both auditory perception and long-term memory storage. This work will use behavioral and molecular-genetic techniques in combination with large-scale electrophysiological recordings, to help elucidate the role of cortico-hippocampal interactions in memory encoding and consolidation.
Summary
This research proposal’s goal is to investigate the role of cortico-hippocampal interactions during the encoding and consolidation of a memory. Current memory consolidation models postulate that memory storage in our brains occurs by a dynamic process- a recent episodic experience is initially encoded in the hippocampus, and during off-line states such as sleep, the encoded memory is gradually transferred to neocortex for long-term storage. One potential neural mechanism by which this could occur is replay, a phenomenon where neural activity patterns in the hippocampus evoked by a previous experience reactivate spontaneously during non-REM sleep, leading to coordinated cortical reactivation. While previous work suggests that hippocampal replay is important for encoding new memories, how memory consolidation is accomplished through cortico-hippocampal interactions is not well understood.
This research project has three major aims- 1) examine how cortical feedback influences which spatial trajectory is replayed by the hippocampus, 2) investigate how the hippocampal replay of a behavioural episode modifies cortical circuits, 3) measure the causal role of cortico-hippocampal interactions in consolidating memories. We will record ensemble activity from freely moving rats during an auditory-spatial association task and during post-behavioural sleep sessions. We will focus our ensemble recordings on two brain regions: 1) the dorsal CA1 region of the hippocampus, where the phenomenon of sleep replay has been most extensively examined, and 2) auditory cortex, a region of the brain critical for both auditory perception and long-term memory storage. This work will use behavioral and molecular-genetic techniques in combination with large-scale electrophysiological recordings, to help elucidate the role of cortico-hippocampal interactions in memory encoding and consolidation.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-04-01, End date: 2021-03-31
Project acronym ComplEvol
Project Evolutionary origins of complex ecological adaptations
Researcher (PI) Pascal-Antoine-John- Luc Christin
Host Institution (HI) THE UNIVERSITY OF SHEFFIELD
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary During evolution, organisms adapt to diverse environmental conditions by evolving new morphological and/or biochemical traits, some of which are of impressive complexity. This is for example the case of eyes, wings or complex biochemical pathways, which all involve multiple components. The evolution of such complex traits has always intrigued evolutionary biologists, including Charles Darwin, and is still only partially understood. How can natural selection on random mutations lead over time to novel complex ecological adaptations that allow organisms to thrive in diverse environments?
This question will be addressed here by studying a species complex that presents exceptional variation in a key ecological adaptation, namely C4 photosynthesis. This trait results from multiple anatomical and biochemical components that function together to increase plant productivity in warm and dry environments. Capitalizing on a species complex of grasses that includes C4 as well as the ancestral C3 photosynthetic types and multiple intermediate states, the ComplEvol project will combine methods from different fields to infer (i) the history of mutations that generated components for C4 photosynthesis during the dispersal into different ecological conditions, (ii) the factors controlling the spread of these mutations among populations, (iii) the effects of these mutations on the properties of the encoded C4 enzymes, (iv) the effects of different anatomical and biochemical C4 components on the performance of the plants (fundamental niche), and (v) the relationships between these components and the distribution of individuals in contrasted environments (realised niche).
The incorporation of these different dimensions of evolution and ecology will shed new lights on the processes that allow over time the emergence of major ecological novelties through the repeated action of natural selection on minor changes within populations.
Summary
During evolution, organisms adapt to diverse environmental conditions by evolving new morphological and/or biochemical traits, some of which are of impressive complexity. This is for example the case of eyes, wings or complex biochemical pathways, which all involve multiple components. The evolution of such complex traits has always intrigued evolutionary biologists, including Charles Darwin, and is still only partially understood. How can natural selection on random mutations lead over time to novel complex ecological adaptations that allow organisms to thrive in diverse environments?
This question will be addressed here by studying a species complex that presents exceptional variation in a key ecological adaptation, namely C4 photosynthesis. This trait results from multiple anatomical and biochemical components that function together to increase plant productivity in warm and dry environments. Capitalizing on a species complex of grasses that includes C4 as well as the ancestral C3 photosynthetic types and multiple intermediate states, the ComplEvol project will combine methods from different fields to infer (i) the history of mutations that generated components for C4 photosynthesis during the dispersal into different ecological conditions, (ii) the factors controlling the spread of these mutations among populations, (iii) the effects of these mutations on the properties of the encoded C4 enzymes, (iv) the effects of different anatomical and biochemical C4 components on the performance of the plants (fundamental niche), and (v) the relationships between these components and the distribution of individuals in contrasted environments (realised niche).
The incorporation of these different dimensions of evolution and ecology will shed new lights on the processes that allow over time the emergence of major ecological novelties through the repeated action of natural selection on minor changes within populations.
Max ERC Funding
1 498 275 €
Duration
Start date: 2015-06-01, End date: 2020-05-31
Project acronym Disasters
Project Market Beliefs and Optimal Policy in the Presence of Disasters
Researcher (PI) Ian William Richard Martin
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Call Details Starting Grant (StG), SH1, ERC-2014-STG
Summary My proposal consists of two strands linked by a common theme--namely a concern for the impact of disasters, in financial markets and more generally--and by a shared methodology.
In the first of these strands, I propose to develop ways of using observable asset price data to infer the beliefs of market participants about various quantities that are central to financial economics, including (i) the equity premium; (ii) the forward-looking autocorrelation of the market (i.e., time-series momentum); (iii) the risk premia associated with individual stocks; (iv) the correlation between stocks; and (v) measures of asymmetric risk, such as the forward-looking probability of a significant downward jump in the stock market over some prescribed time period.
This work will exploit theoretical techniques that I have developed in previous research, and that allow for the possibility of jumps and disasters in financial markets. I will therefore be able to avoid the unpalatable assumption—which is made, implicitly or explicitly, in much of the finance literature—that uncertainty is driven by conditionally Normally distributed shocks (or, in continuous time, by Brownian motions). The importance of doing so is underscored by the turmoil in financial markets over the last few years.
These techniques will also be applied in the second strand of my proposal, which focuses on issues related to catastrophes more generally, including for example climate change; highly contagious viruses on the scale of the influenza pandemic of 1918; or nuclear or bio-terrorism. This project will be joint with Professor Robert S. Pindyck of MIT. The goal is to provide a framework within which policymakers, faced with multiple different types of potential catastrophe, can determine how society’s limited resources should best be used to alleviate the associated risks.
Summary
My proposal consists of two strands linked by a common theme--namely a concern for the impact of disasters, in financial markets and more generally--and by a shared methodology.
In the first of these strands, I propose to develop ways of using observable asset price data to infer the beliefs of market participants about various quantities that are central to financial economics, including (i) the equity premium; (ii) the forward-looking autocorrelation of the market (i.e., time-series momentum); (iii) the risk premia associated with individual stocks; (iv) the correlation between stocks; and (v) measures of asymmetric risk, such as the forward-looking probability of a significant downward jump in the stock market over some prescribed time period.
This work will exploit theoretical techniques that I have developed in previous research, and that allow for the possibility of jumps and disasters in financial markets. I will therefore be able to avoid the unpalatable assumption—which is made, implicitly or explicitly, in much of the finance literature—that uncertainty is driven by conditionally Normally distributed shocks (or, in continuous time, by Brownian motions). The importance of doing so is underscored by the turmoil in financial markets over the last few years.
These techniques will also be applied in the second strand of my proposal, which focuses on issues related to catastrophes more generally, including for example climate change; highly contagious viruses on the scale of the influenza pandemic of 1918; or nuclear or bio-terrorism. This project will be joint with Professor Robert S. Pindyck of MIT. The goal is to provide a framework within which policymakers, faced with multiple different types of potential catastrophe, can determine how society’s limited resources should best be used to alleviate the associated risks.
Max ERC Funding
1 287 755 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym HBV1
Project Innate immune responses to human hepatotropic viral infections
Researcher (PI) Marcus Dorner
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), LS6, ERC-2014-STG
Summary Chronic hepatotropic infections including hepatitis B (HBV) and C (HCV) are a major public health
concern. Even though both viruses belong to completely distinct families the pathogenesis they elicit is
strikingly similar, leading to liver fibrosis and cirrhosis. Treatment for HBV and HCV consists of either
direct-acting antivirals or pegylated interferon (IFN)α. In contrast to HCV, these treatment regimen are noncurative
for HBV. Little is known to date about the host/pathogen interactions determining viral persistence.
Both viruses are sensitive to IFN, activating the JAK/STAT signalling pathway to activate interferonstimulated
gene expression (ISG), which are ultimately acting as antiviral immune effectors. Nevertheless,
neither type I or III IFN are very effective in their treatment.
Here, we suggest investigating the mechanistic details of type I and type III IFN action on HCV and
HBV in vitro and vivo with the goal of uncovering not only the differential ISG induction but furthermore
characterise viral immune evasion strategies. Building on our previous success in dissecting the host
response to HCV and creating the first immunocompetent mouse model for HCV we aim at using both,
novel microfluidic culture systems based on 3D hepatocyte cultures susceptible to both HCV and HBV as
well as human liver-chimeric mice in combination with single-cell analysis of the antiviral response against
HBV and HCV elicited by type I and III IFN. Additionally, we will utilize lentiviral high throughput
screening used previously for HCV to identify interferon effector molecules active against HBV. This project
will not only provide new insights into the innate immune response to chronic hepatotropic virus infections
but furthermore holds the potential of uncovering novel drug targets, aiding in the curative therapy for both,
HCV and HBV and offer novel insights into vaccine design.
This project has the aim of identifying novel host factors and drug targets enabling the development
of immunomodulatory antiviral drugs. This ranks the scope of the proposal between LS6 Immunity and
Infection and LS9 Applied Life Sciences and Non-Medical Biotechnology. Evaluating novel bioengineered
human liver culture systems and building on human liver-chimeric mice clearly places this proposal at the
forefront of identifying novel drug targets and assisting in the development of novel biotechnology and
preclinical projects.
Summary
Chronic hepatotropic infections including hepatitis B (HBV) and C (HCV) are a major public health
concern. Even though both viruses belong to completely distinct families the pathogenesis they elicit is
strikingly similar, leading to liver fibrosis and cirrhosis. Treatment for HBV and HCV consists of either
direct-acting antivirals or pegylated interferon (IFN)α. In contrast to HCV, these treatment regimen are noncurative
for HBV. Little is known to date about the host/pathogen interactions determining viral persistence.
Both viruses are sensitive to IFN, activating the JAK/STAT signalling pathway to activate interferonstimulated
gene expression (ISG), which are ultimately acting as antiviral immune effectors. Nevertheless,
neither type I or III IFN are very effective in their treatment.
Here, we suggest investigating the mechanistic details of type I and type III IFN action on HCV and
HBV in vitro and vivo with the goal of uncovering not only the differential ISG induction but furthermore
characterise viral immune evasion strategies. Building on our previous success in dissecting the host
response to HCV and creating the first immunocompetent mouse model for HCV we aim at using both,
novel microfluidic culture systems based on 3D hepatocyte cultures susceptible to both HCV and HBV as
well as human liver-chimeric mice in combination with single-cell analysis of the antiviral response against
HBV and HCV elicited by type I and III IFN. Additionally, we will utilize lentiviral high throughput
screening used previously for HCV to identify interferon effector molecules active against HBV. This project
will not only provide new insights into the innate immune response to chronic hepatotropic virus infections
but furthermore holds the potential of uncovering novel drug targets, aiding in the curative therapy for both,
HCV and HBV and offer novel insights into vaccine design.
This project has the aim of identifying novel host factors and drug targets enabling the development
of immunomodulatory antiviral drugs. This ranks the scope of the proposal between LS6 Immunity and
Infection and LS9 Applied Life Sciences and Non-Medical Biotechnology. Evaluating novel bioengineered
human liver culture systems and building on human liver-chimeric mice clearly places this proposal at the
forefront of identifying novel drug targets and assisting in the development of novel biotechnology and
preclinical projects.
Max ERC Funding
1 498 312 €
Duration
Start date: 2015-06-01, End date: 2020-05-31
Project acronym HomeoBalanceExcInh
Project Homeostatic balancing of excitation and inhibition in vivo
Researcher (PI) Andrew Lin
Host Institution (HI) THE UNIVERSITY OF SHEFFIELD
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary Balanced excitation and inhibition is a fundamental principle of neural circuit function, and perturbed excitation/inhibition (E/I) balance has been linked to diseases such as epilepsy, autism and schizophrenia. Maintaining E/I balance within normal bounds depends in part on homeostatic plasticity, in which neurons compensate for deviations in activity levels by adjusting their responsiveness to excitation and inhibition. Yet despite recent progress in elucidating molecular mechanisms underlying homeostatic plasticity in reduced preparations, little is known about such mechanisms in the intact brain.
I propose to address this gap using a simple and genetically tractable neural circuit that I recently characterized. In Drosophila, Kenyon cells (KCs), the neurons underlying olfactory associative memory, receive excitation from projection neurons (PNs) as well as feedback inhibition from a single identified neuron (‘APL’). The balance between these two forces maintains sparse odour coding in KCs, which enhances the odour-specificity of associative memory by reducing overlap between odour representations.
Preliminary evidence indicates that KCs adapt to prolonged disruption of E/I balance, providing a ground-breaking opportunity to use the powerful genetic tools of Drosophila to uncover the molecular mechanisms underlying homeostatic balancing of excitation and inhibition in vivo in a defined circuit that mediates a sophisticated behaviour.
Specific aims:
1. Characterize homeostatic plasticity in the PN-KC-APL circuit.
2. Identify genes up- and down-regulated in response to perturbations of E/I balance.
3. Determine role of candidate genes and cellular mechanisms in homeostatic plasticity.
Establishing the PN-KC-APL circuit as a novel model system for homeostatic plasticity will reveal for the first time the molecular mechanisms underlying homeostatic balancing of excitation and inhibition in the intact brain.
Summary
Balanced excitation and inhibition is a fundamental principle of neural circuit function, and perturbed excitation/inhibition (E/I) balance has been linked to diseases such as epilepsy, autism and schizophrenia. Maintaining E/I balance within normal bounds depends in part on homeostatic plasticity, in which neurons compensate for deviations in activity levels by adjusting their responsiveness to excitation and inhibition. Yet despite recent progress in elucidating molecular mechanisms underlying homeostatic plasticity in reduced preparations, little is known about such mechanisms in the intact brain.
I propose to address this gap using a simple and genetically tractable neural circuit that I recently characterized. In Drosophila, Kenyon cells (KCs), the neurons underlying olfactory associative memory, receive excitation from projection neurons (PNs) as well as feedback inhibition from a single identified neuron (‘APL’). The balance between these two forces maintains sparse odour coding in KCs, which enhances the odour-specificity of associative memory by reducing overlap between odour representations.
Preliminary evidence indicates that KCs adapt to prolonged disruption of E/I balance, providing a ground-breaking opportunity to use the powerful genetic tools of Drosophila to uncover the molecular mechanisms underlying homeostatic balancing of excitation and inhibition in vivo in a defined circuit that mediates a sophisticated behaviour.
Specific aims:
1. Characterize homeostatic plasticity in the PN-KC-APL circuit.
2. Identify genes up- and down-regulated in response to perturbations of E/I balance.
3. Determine role of candidate genes and cellular mechanisms in homeostatic plasticity.
Establishing the PN-KC-APL circuit as a novel model system for homeostatic plasticity will reveal for the first time the molecular mechanisms underlying homeostatic balancing of excitation and inhibition in the intact brain.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
Project acronym INFO TECHNOLOGY
Project Information Technology and Institutions Supporting Human Capital Accumulation and Exchange
Researcher (PI) Jeremiah Edward Dittmar
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Call Details Starting Grant (StG), SH1, ERC-2014-STG
Summary Information technology revolutions transform the production and exchange of ideas and drive profound institutional and cultural change. History provides unique settings to document the causal impact of changes in information technology and institutions, and the best evidence on their long-run effects.
The objective of the research is to document the impact of revolutionary transformations in information technology and institutions using evidence from the European Renaissance. Printing was the new information technology of the Renaissance and is arguably the best parallel to the internet. Print media transmitted ideas that led to significant institutional change. But no quantitative research systematically documents the impact of these innovations.
The research will innovate by constructing ground-breaking micro-data on media markets, human capital, and institutions; developing cutting edge estimators for high-dimensional data to measure ideas in the media; and using historical sources of exogenous variation to identify cause and effect.
The research has three strands. The first will document the impact of competition on idea diffusion and institutional change during the Protestant Reformation. The research will construct firm-level data on all known books in German-speaking Europe 1450-1600, use high-dimensional estimators to measure ideas in print, and identify exogenous variation in competition from archival data.
The second strand will document the origins of persistent differences in human capital accumulation by constructing new data on city laws that set up the first experiments in public education and on virtually all German university students 1400-1550, and by using local shocks to support causal inference.
The third strand will document the impact of organizations supporting knowledge diffusion that were complementary to printing by constructing data on all European scholarly societies and journals and using historical shocks to identify their impact.
Summary
Information technology revolutions transform the production and exchange of ideas and drive profound institutional and cultural change. History provides unique settings to document the causal impact of changes in information technology and institutions, and the best evidence on their long-run effects.
The objective of the research is to document the impact of revolutionary transformations in information technology and institutions using evidence from the European Renaissance. Printing was the new information technology of the Renaissance and is arguably the best parallel to the internet. Print media transmitted ideas that led to significant institutional change. But no quantitative research systematically documents the impact of these innovations.
The research will innovate by constructing ground-breaking micro-data on media markets, human capital, and institutions; developing cutting edge estimators for high-dimensional data to measure ideas in the media; and using historical sources of exogenous variation to identify cause and effect.
The research has three strands. The first will document the impact of competition on idea diffusion and institutional change during the Protestant Reformation. The research will construct firm-level data on all known books in German-speaking Europe 1450-1600, use high-dimensional estimators to measure ideas in print, and identify exogenous variation in competition from archival data.
The second strand will document the origins of persistent differences in human capital accumulation by constructing new data on city laws that set up the first experiments in public education and on virtually all German university students 1400-1550, and by using local shocks to support causal inference.
The third strand will document the impact of organizations supporting knowledge diffusion that were complementary to printing by constructing data on all European scholarly societies and journals and using historical shocks to identify their impact.
Max ERC Funding
1 275 044 €
Duration
Start date: 2015-05-01, End date: 2020-10-31
Project acronym LTI
Project Long-Term Investment
Researcher (PI) Alexander Edmans
Host Institution (HI) LONDON BUSINESS SCHOOL
Call Details Starting Grant (StG), SH1, ERC-2014-STG
Summary The typical 20th-century firm was capital-intensive and competed on cost efficiency. The 21st-century firm is different. Competitive success increasingly depends on product quality, which in turn hinges on intangible assets such as brand strength, innovation, and corporate culture. Unlike tangible investment such as buying a factory, the fruits of intangible investment may take several years to appear. A manager pressured to maximise short-term earnings may fail to invest, jeopardising the long-term future of his firm. This project will study the determinants and consequences of long-term investment through three linked components.
Financial Markets. The traditional view is that financial markets dissuade investment by forcing firms to cater to short-term shareholders. I will study two channels through which markets promote investment. First, traders gather information about a firm’s past investments and incorporate it into stock prices by trading - rewarding the manager for good investment. Second, traders can gather information about a firm’s future investment opportunities - informing the manager about his future investment decisions. I aim to analyse what determines the efficiency of both channels.
Incentives. Most research on incentives focuses on either the level of pay, or the sensitivity of pay to performance, but it is the horizon of incentives that is key to promoting investment. I will theoretically analyse the optimal incentive horizon, and empirically demonstrate how it affects long-term decisions. Moving beyond managers, I will study how to incentivise teachers to focus on their pupils’ long-run development rather than “teaching-to-the-test.”
Effects of Investment. A key to inducing long-run investment is to demonstrate its benefits, but this is difficult due to data availability. I aim to gather data on a firm’s corporate social responsibility – its investment in its stakeholders – and link it to firm value.
Summary
The typical 20th-century firm was capital-intensive and competed on cost efficiency. The 21st-century firm is different. Competitive success increasingly depends on product quality, which in turn hinges on intangible assets such as brand strength, innovation, and corporate culture. Unlike tangible investment such as buying a factory, the fruits of intangible investment may take several years to appear. A manager pressured to maximise short-term earnings may fail to invest, jeopardising the long-term future of his firm. This project will study the determinants and consequences of long-term investment through three linked components.
Financial Markets. The traditional view is that financial markets dissuade investment by forcing firms to cater to short-term shareholders. I will study two channels through which markets promote investment. First, traders gather information about a firm’s past investments and incorporate it into stock prices by trading - rewarding the manager for good investment. Second, traders can gather information about a firm’s future investment opportunities - informing the manager about his future investment decisions. I aim to analyse what determines the efficiency of both channels.
Incentives. Most research on incentives focuses on either the level of pay, or the sensitivity of pay to performance, but it is the horizon of incentives that is key to promoting investment. I will theoretically analyse the optimal incentive horizon, and empirically demonstrate how it affects long-term decisions. Moving beyond managers, I will study how to incentivise teachers to focus on their pupils’ long-run development rather than “teaching-to-the-test.”
Effects of Investment. A key to inducing long-run investment is to demonstrate its benefits, but this is difficult due to data availability. I aim to gather data on a firm’s corporate social responsibility – its investment in its stakeholders – and link it to firm value.
Max ERC Funding
899 105 €
Duration
Start date: 2015-04-01, End date: 2018-03-31
