Project acronym Acclimatize
Project Hypothalamic mechanisms of thermal homeostasis and adaptation
Researcher (PI) Jan SIEMENS
Host Institution (HI) UNIVERSITATSKLINIKUM HEIDELBERG
Call Details Consolidator Grant (CoG), LS5, ERC-2017-COG
Summary Mammalian organisms possess the remarkable ability to maintain internal body temperature (Tcore) within a narrow range close to 37°C despite wide environmental temperature variations. The brain’s neural “thermostat” is made up by central circuits in the hypothalamic preoptic area (POA), which orchestrate peripheral thermoregulatory responses to maintain Tcore. Thermogenesis requires metabolic fuel, suggesting intricate connections between the thermoregulatory centre and hypothalamic circuits controlling energy balance. How the POA detects and integrates temperature and metabolic information to achieve thermal balance is largely unknown. A major question is whether this circuitry could be harnessed therapeutically to treat obesity.
We have recently identified the first known molecular temperature sensor in thermoregulatory neurons of the POA, transient receptor potential melastatin 2 (TRPM2), a thermo-sensitive ion channel. I aim to use TRPM2 as a molecular marker to gain access to and probe the function of thermoregulatory neurons in vivo. I propose a multidisciplinary approach, combining local, in vivo POA temperature stimulation with optogenetic circuit-mapping to uncover the molecular and cellular logic of the hypothalamic thermoregulatory centre and to assess its medical potential to counteract metabolic syndrome.
Acclimation is a beneficial adaptive process that fortifies thermal responses upon environmental temperature challenges. Thermoregulatory neuron plasticity is thought to mediate acclimation. Conversely, maladaptive thermoregulatory changes affect obesity. The cell-type-specific neuronal plasticity mechanisms underlying these changes within the POA, however, are unknown.
Using ex-vivo slice electrophysiology and in vivo imaging, I propose to characterize acclimation- and obesity-induced plasticity of thermoregulatory neurons. Ultimately, I aim to manipulate thermoregulatory neuron plasticity to test its potential counter-balancing effect on obesity.
Summary
Mammalian organisms possess the remarkable ability to maintain internal body temperature (Tcore) within a narrow range close to 37°C despite wide environmental temperature variations. The brain’s neural “thermostat” is made up by central circuits in the hypothalamic preoptic area (POA), which orchestrate peripheral thermoregulatory responses to maintain Tcore. Thermogenesis requires metabolic fuel, suggesting intricate connections between the thermoregulatory centre and hypothalamic circuits controlling energy balance. How the POA detects and integrates temperature and metabolic information to achieve thermal balance is largely unknown. A major question is whether this circuitry could be harnessed therapeutically to treat obesity.
We have recently identified the first known molecular temperature sensor in thermoregulatory neurons of the POA, transient receptor potential melastatin 2 (TRPM2), a thermo-sensitive ion channel. I aim to use TRPM2 as a molecular marker to gain access to and probe the function of thermoregulatory neurons in vivo. I propose a multidisciplinary approach, combining local, in vivo POA temperature stimulation with optogenetic circuit-mapping to uncover the molecular and cellular logic of the hypothalamic thermoregulatory centre and to assess its medical potential to counteract metabolic syndrome.
Acclimation is a beneficial adaptive process that fortifies thermal responses upon environmental temperature challenges. Thermoregulatory neuron plasticity is thought to mediate acclimation. Conversely, maladaptive thermoregulatory changes affect obesity. The cell-type-specific neuronal plasticity mechanisms underlying these changes within the POA, however, are unknown.
Using ex-vivo slice electrophysiology and in vivo imaging, I propose to characterize acclimation- and obesity-induced plasticity of thermoregulatory neurons. Ultimately, I aim to manipulate thermoregulatory neuron plasticity to test its potential counter-balancing effect on obesity.
Max ERC Funding
1 902 500 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym AMBH
Project Ancient Music Beyond Hellenisation
Researcher (PI) Stefan HAGEL
Host Institution (HI) OESTERREICHISCHE AKADEMIE DER WISSENSCHAFTEN
Call Details Advanced Grant (AdG), SH5, ERC-2017-ADG
Summary From medieval times, Arabic as well as European music was analysed in terms that were inherited from Classical Antiquity and had thus developed in a very different music culture. In spite of recent breakthroughs in the understanding of the latter, whose technicalities we access not only through texts and iconography, but also through instrument finds and surviving notated melodies, its relation to music traditions known from later periods and different places is almost uncharted territory.
The present project explores relations between Hellenic/Hellenistic music as pervaded the theatres and concert halls throughout and beyond the Roman empire, Near Eastern traditions – from the diatonic system emerging from cuneiform sources to the flourishing musical world of the caliphates – and, as far as possible, African musical life south of Egypt as well – a region that maintained close ties both with the Hellenised culture of its northern neighbours and with the Arabian Peninsula.
On the one hand, this demands collaboration between Classical Philology and Arabic Studies, extending methods recently developed within music archaeological research related to the Classical Mediterranean. Arabic writings need to be examined in close reading, using recent insights into the interplay between ancient music theory and practice, in order to segregate the influence of Greek thinking from ideas and facts that must relate to contemporaneous ‘Arabic’ music-making. In this way we hope better to define the relation of this tradition to the ‘Classical world’, potentially breaking free of Orientalising bias informing modern views. On the other hand, the study and reconstruction, virtual and material, of wind instruments of Hellenistic pedigree but found outside the confinements of the Hellenistic ‘heartlands’ may provide evidence of ‘foreign’ tonality employed in those regions – specifically the royal city of Meroë in modern Sudan and the Oxus Temple in modern Tajikistan.
Summary
From medieval times, Arabic as well as European music was analysed in terms that were inherited from Classical Antiquity and had thus developed in a very different music culture. In spite of recent breakthroughs in the understanding of the latter, whose technicalities we access not only through texts and iconography, but also through instrument finds and surviving notated melodies, its relation to music traditions known from later periods and different places is almost uncharted territory.
The present project explores relations between Hellenic/Hellenistic music as pervaded the theatres and concert halls throughout and beyond the Roman empire, Near Eastern traditions – from the diatonic system emerging from cuneiform sources to the flourishing musical world of the caliphates – and, as far as possible, African musical life south of Egypt as well – a region that maintained close ties both with the Hellenised culture of its northern neighbours and with the Arabian Peninsula.
On the one hand, this demands collaboration between Classical Philology and Arabic Studies, extending methods recently developed within music archaeological research related to the Classical Mediterranean. Arabic writings need to be examined in close reading, using recent insights into the interplay between ancient music theory and practice, in order to segregate the influence of Greek thinking from ideas and facts that must relate to contemporaneous ‘Arabic’ music-making. In this way we hope better to define the relation of this tradition to the ‘Classical world’, potentially breaking free of Orientalising bias informing modern views. On the other hand, the study and reconstruction, virtual and material, of wind instruments of Hellenistic pedigree but found outside the confinements of the Hellenistic ‘heartlands’ may provide evidence of ‘foreign’ tonality employed in those regions – specifically the royal city of Meroë in modern Sudan and the Oxus Temple in modern Tajikistan.
Max ERC Funding
775 959 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym ArsNova
Project European Ars Nova: Multilingual Poetry and Polyphonic Song in the Late Middle Ages
Researcher (PI) Maria Sofia LANNUTTI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI FIRENZE
Call Details Advanced Grant (AdG), SH5, ERC-2017-ADG
Summary Dante Alighieri at the dawn of the 1300s, as well as Eustache Deschamps almost a century later, conceived poetry as music in itself. But what happens with poetry when it is involved in the complex architecture of polyphony? The aim of this project is to study for the first time the corpus of 14th- and early 15th-century poetry set to music by Ars Nova polyphonists (more than 1200 texts). This repertoire gathers different poetic and musical traditions, as shown by the multilingual anthologies copied during the last years of the Schism. The choice of this corpus is motivated by two primary goals: a) to offer a new interpretation of its meaning and function in the cultural and historical context, one that may be then applied to the rest of coeval European lyric poetry; b) to overcome current disciplinary divisions in order to generate a new methodological balance between the project’s two main fields of interest (Comparative Literature / Musicology). Most Ars Nova polyphonists were directly associated with religious institutions. In many texts, the language of courtly love expresses the values of caritas, the theological virtue that guides wise rulers and leads them to desire the common good. Thus, the poetic figure of the lover becomes a metaphor for the political man, and love poetry can be used as a device for diplomacy, as well as for personal and institutional propaganda. From this unprecedented point of view, the project will develop three research lines in response to the following questions: 1) How is the relationship between poetry and music, and how is the dialogue between the different poetic and musical traditions viewed in relation to each context of production? 2) To what extent does Ars Nova poetry take part in the ‘soft power’ strategies exercised by the entire European political class of the time? 3) Is there a connection between the multilingualism of the manuscript tradition and the perception of the Ars Nova as a European, intercultural repertoire?
Summary
Dante Alighieri at the dawn of the 1300s, as well as Eustache Deschamps almost a century later, conceived poetry as music in itself. But what happens with poetry when it is involved in the complex architecture of polyphony? The aim of this project is to study for the first time the corpus of 14th- and early 15th-century poetry set to music by Ars Nova polyphonists (more than 1200 texts). This repertoire gathers different poetic and musical traditions, as shown by the multilingual anthologies copied during the last years of the Schism. The choice of this corpus is motivated by two primary goals: a) to offer a new interpretation of its meaning and function in the cultural and historical context, one that may be then applied to the rest of coeval European lyric poetry; b) to overcome current disciplinary divisions in order to generate a new methodological balance between the project’s two main fields of interest (Comparative Literature / Musicology). Most Ars Nova polyphonists were directly associated with religious institutions. In many texts, the language of courtly love expresses the values of caritas, the theological virtue that guides wise rulers and leads them to desire the common good. Thus, the poetic figure of the lover becomes a metaphor for the political man, and love poetry can be used as a device for diplomacy, as well as for personal and institutional propaganda. From this unprecedented point of view, the project will develop three research lines in response to the following questions: 1) How is the relationship between poetry and music, and how is the dialogue between the different poetic and musical traditions viewed in relation to each context of production? 2) To what extent does Ars Nova poetry take part in the ‘soft power’ strategies exercised by the entire European political class of the time? 3) Is there a connection between the multilingualism of the manuscript tradition and the perception of the Ars Nova as a European, intercultural repertoire?
Max ERC Funding
2 193 375 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ARTTOUCH
Project Generating artificial touch: from the contribution of single tactile afferents to the encoding of complex percepts, and their implications for clinical innovation
Researcher (PI) Rochelle ACKERLEY
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), LS5, ERC-2017-COG
Summary Somatosensation encompass a wide range of processes, from feeling touch to temperature, as well as experiencing pleasure and pain. When afferent inputs are degraded or removed, such as in neuropathies or amputation, exploring the world becomes extremely difficult. Chronic pain is a major health issue that greatly diminishes quality of life and is one of the most disabling and costly conditions in Europe. The loss of a body part is common due to accidents, tumours, or peripheral diseases, and it has instantaneous effects on somatosensory functioning. Treating such disorders entails detailed knowledge about how somatosensory signals are encoded. Understanding these processes will enable the restoration of healthy function, such as providing real-time, naturalistic feedback in prostheses. To date, no prosthesis currently provides long-term sensory feedback, yet accomplishing this will lead to great quality of life improvements. The present proposal aims to uncover how basic tactile processes are encoded and represented centrally, as well as how more complex somatosensation is generated (e.g. wetness, pleasantness). Novel investigations will be conducted in humans to probe these mechanisms, including peripheral in vivo recording (microneurography) and neural stimulation, combined with advanced brain imaging and behavioural experiments. Preliminary work has shown the feasibility of the approach, where it is possible to visualise the activation of single mechanoreceptive afferents in the human brain. The multi-disciplinary approach unites detailed, high-resolution, functional investigations with actual sensations generated. The results will elucidate how basic and complex somatosensory processes are encoded, providing insights into the recovery of such signals. The knowledge gained aims to provide pain-free, efficient diagnostic capabilities for detecting and quantifying a range of somatosensory disorders, as well as identifying new potential therapeutic targets.
Summary
Somatosensation encompass a wide range of processes, from feeling touch to temperature, as well as experiencing pleasure and pain. When afferent inputs are degraded or removed, such as in neuropathies or amputation, exploring the world becomes extremely difficult. Chronic pain is a major health issue that greatly diminishes quality of life and is one of the most disabling and costly conditions in Europe. The loss of a body part is common due to accidents, tumours, or peripheral diseases, and it has instantaneous effects on somatosensory functioning. Treating such disorders entails detailed knowledge about how somatosensory signals are encoded. Understanding these processes will enable the restoration of healthy function, such as providing real-time, naturalistic feedback in prostheses. To date, no prosthesis currently provides long-term sensory feedback, yet accomplishing this will lead to great quality of life improvements. The present proposal aims to uncover how basic tactile processes are encoded and represented centrally, as well as how more complex somatosensation is generated (e.g. wetness, pleasantness). Novel investigations will be conducted in humans to probe these mechanisms, including peripheral in vivo recording (microneurography) and neural stimulation, combined with advanced brain imaging and behavioural experiments. Preliminary work has shown the feasibility of the approach, where it is possible to visualise the activation of single mechanoreceptive afferents in the human brain. The multi-disciplinary approach unites detailed, high-resolution, functional investigations with actual sensations generated. The results will elucidate how basic and complex somatosensory processes are encoded, providing insights into the recovery of such signals. The knowledge gained aims to provide pain-free, efficient diagnostic capabilities for detecting and quantifying a range of somatosensory disorders, as well as identifying new potential therapeutic targets.
Max ERC Funding
1 223 639 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym AstroNeuroCrosstalk
Project Astrocyte-Neuronal Crosstalk in Obesity and Diabetes
Researcher (PI) Cristina GARCÍA CÁCERES
Host Institution (HI) HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Call Details Starting Grant (StG), LS5, ERC-2017-STG
Summary Despite considerable efforts aimed at prevention and treatment, the prevalence of obesity and type 2 diabetes has increased at an alarming rate worldwide over recent decades. Given the urgent need to develop safe and efficient anti-obesity drugs, the scientific community has to intensify efforts to better understand the mechanisms involved in the pathogenesis of obesity. Based on human genome-wide association studies and targeted mouse mutagenesis models, it has recently emerged that the brain controls most aspects of systemic metabolism and that obesity may be a brain disease. I have recently shown that like neurons, astrocytes also respond to circulating nutrients, and they cooperate with neurons to efficiently regulate energy metabolism. So far, the study of brain circuits controlling energy balance has focused on neurons, ignoring the presence and role of astrocytes. Importantly, our studies were the first to describe that exposure to a high-fat, highsugar (HFHS) diet triggers hypothalamic astrogliosis prior to significant body weight gain, indicating a potentially important role in promoting obesity. Overall, my recent findings suggest a novel model in which astrocytes are actively involved in the central nervous system (CNS) control of metabolism, likely including active crosstalk between astrocytes and neurons. To test this hypothetical model, I propose to develop a functional understanding of astroglia-neuronal communication in the CNS control of metabolism focusing on: 1) dissecting the ability of astrocytes to release gliotransmitters to neurons, 2) assessing how astrocytes respond to neuronal activity, and 3) determining if HFHS-induced astrogliosis interrupts this crosstalk and contributes to the development of obesity and type 2 diabetes. These studies aim to uncover the molecular underpinnings of astrocyte-neuron inputs regulating metabolism in health and disease so as to
inspire and enable novel therapeutic strategies to fight diabetes and obesity.
Summary
Despite considerable efforts aimed at prevention and treatment, the prevalence of obesity and type 2 diabetes has increased at an alarming rate worldwide over recent decades. Given the urgent need to develop safe and efficient anti-obesity drugs, the scientific community has to intensify efforts to better understand the mechanisms involved in the pathogenesis of obesity. Based on human genome-wide association studies and targeted mouse mutagenesis models, it has recently emerged that the brain controls most aspects of systemic metabolism and that obesity may be a brain disease. I have recently shown that like neurons, astrocytes also respond to circulating nutrients, and they cooperate with neurons to efficiently regulate energy metabolism. So far, the study of brain circuits controlling energy balance has focused on neurons, ignoring the presence and role of astrocytes. Importantly, our studies were the first to describe that exposure to a high-fat, highsugar (HFHS) diet triggers hypothalamic astrogliosis prior to significant body weight gain, indicating a potentially important role in promoting obesity. Overall, my recent findings suggest a novel model in which astrocytes are actively involved in the central nervous system (CNS) control of metabolism, likely including active crosstalk between astrocytes and neurons. To test this hypothetical model, I propose to develop a functional understanding of astroglia-neuronal communication in the CNS control of metabolism focusing on: 1) dissecting the ability of astrocytes to release gliotransmitters to neurons, 2) assessing how astrocytes respond to neuronal activity, and 3) determining if HFHS-induced astrogliosis interrupts this crosstalk and contributes to the development of obesity and type 2 diabetes. These studies aim to uncover the molecular underpinnings of astrocyte-neuron inputs regulating metabolism in health and disease so as to
inspire and enable novel therapeutic strategies to fight diabetes and obesity.
Max ERC Funding
1 499 938 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym ATTACK
Project Pressured to Attack: How Carrying-Capacity Stress Creates and Shapes Intergroup Conflict
Researcher (PI) Carsten DE DREU
Host Institution (HI) UNIVERSITEIT LEIDEN
Call Details Advanced Grant (AdG), SH3, ERC-2017-ADG
Summary Throughout history, what has been causing tremendous suffering is groups of people fighting each other. While behavioral science research has advanced our understanding of such intergroup conflict, it has exclusively focused on micro-level processes within and between groups at conflict. Disciplines that employ a more historical perspective like climate studies or political geography report that macro-level pressures due to changes in climate or economic scarcity can go along with social unrest and wars. How do these macro-level pressures relate to micro-level processes? Do they both occur independently, or do macro-level pressures trigger micro-level processes that cause intergroup conflict? And if so, which micro-level processes are triggered, and how?
With unavoidable signs of climate change and increasing resource scarcities, answers to these questions are urgently needed. Here I propose carrying-capacity stress (CCS) as the missing link between macro-level pressures and micro-level processes. A group experiences CCS when its resources do not suffice to maintain its functionality. CCS is a function of macro-level pressures and creates intergroup conflict because it impacts micro-level motivation to contribute to one’s group’s fighting capacity and shapes the coordination of individual contributions to out-group aggression through emergent norms, communication and leadership.
To test these propositions I develop a parametric model of CCS that is amenable to measurement and experimentation, and use techniques used in my work on conflict and cooperation: Meta-analyses and time-series analysis of macro-level historical data; experiments on intergroup conflict; and measurement of neuro-hormonal correlates of cooperation and conflict. In combination, this project provides novel multi-level conflict theory that integrates macro-level discoveries in climate research and political geography with micro-level processes uncovered in the biobehavioral sciences
Summary
Throughout history, what has been causing tremendous suffering is groups of people fighting each other. While behavioral science research has advanced our understanding of such intergroup conflict, it has exclusively focused on micro-level processes within and between groups at conflict. Disciplines that employ a more historical perspective like climate studies or political geography report that macro-level pressures due to changes in climate or economic scarcity can go along with social unrest and wars. How do these macro-level pressures relate to micro-level processes? Do they both occur independently, or do macro-level pressures trigger micro-level processes that cause intergroup conflict? And if so, which micro-level processes are triggered, and how?
With unavoidable signs of climate change and increasing resource scarcities, answers to these questions are urgently needed. Here I propose carrying-capacity stress (CCS) as the missing link between macro-level pressures and micro-level processes. A group experiences CCS when its resources do not suffice to maintain its functionality. CCS is a function of macro-level pressures and creates intergroup conflict because it impacts micro-level motivation to contribute to one’s group’s fighting capacity and shapes the coordination of individual contributions to out-group aggression through emergent norms, communication and leadership.
To test these propositions I develop a parametric model of CCS that is amenable to measurement and experimentation, and use techniques used in my work on conflict and cooperation: Meta-analyses and time-series analysis of macro-level historical data; experiments on intergroup conflict; and measurement of neuro-hormonal correlates of cooperation and conflict. In combination, this project provides novel multi-level conflict theory that integrates macro-level discoveries in climate research and political geography with micro-level processes uncovered in the biobehavioral sciences
Max ERC Funding
2 490 383 €
Duration
Start date: 2018-08-01, End date: 2023-07-31
Project acronym BETLIV
Project Returning to a Better Place: The (Re)assessment of the ‘Good Life’ in Times of Crisis
Researcher (PI) Valerio SIMONI RIBA
Host Institution (HI) FONDATION POUR L INSTITUT DE HAUTES ETUDES INTERNATIONALES ET DU DEVELOPPEMENT
Call Details Starting Grant (StG), SH5, ERC-2017-STG
Summary What makes for a valuable and good life is a question that many people in the contemporary world ask themselves, yet it is one that social science research has seldom addressed. Only recently have scholars started undertaking inductive comparative research on different notions of the ‘good life’, highlighting socio-cultural variations and calling for a better understanding of the different imaginaries, aspirations and values that guide people in their quest for better living conditions. Research is still lacking, however, on how people themselves evaluate, compare, and put into perspective different visions of good living and their socio-cultural anchorage. This project addresses such questions from an anthropological perspective, proposing an innovative study of how ideals of the good life are articulated, (re)assessed, and related to specific places and contexts as a result of the experience of crisis and migration. The case studies chosen to operationalize these lines of enquiry focus on the phenomenon of return migration, and consist in an analysis of the imaginaries and experience of return by Ecuadorian and Cuban men and women who migrated to Spain, are dissatisfied with their life there, and envisage/carry out the project of going back to their countries of origin (Ecuador and Cuba respectively). The project’s ambition is to bring together and contribute to three main scholarly areas of enquiry: 1) the study of morality, ethics and what counts as ‘good life’, 2) the study of the field of economic practice, its definition, value regimes, and ‘crises’, and 3) the study of migratory aspirations, projects, and trajectories. A multi-sited endeavour, the research is designed in three subprojects carried out in Spain (PhD student), Ecuador (Post-Doc), and Cuba (PI), in which ethnographic methods will be used to provide the first empirically grounded study of the links between notions and experiences of crisis, return migration, and the (re)assessment of good living.
Summary
What makes for a valuable and good life is a question that many people in the contemporary world ask themselves, yet it is one that social science research has seldom addressed. Only recently have scholars started undertaking inductive comparative research on different notions of the ‘good life’, highlighting socio-cultural variations and calling for a better understanding of the different imaginaries, aspirations and values that guide people in their quest for better living conditions. Research is still lacking, however, on how people themselves evaluate, compare, and put into perspective different visions of good living and their socio-cultural anchorage. This project addresses such questions from an anthropological perspective, proposing an innovative study of how ideals of the good life are articulated, (re)assessed, and related to specific places and contexts as a result of the experience of crisis and migration. The case studies chosen to operationalize these lines of enquiry focus on the phenomenon of return migration, and consist in an analysis of the imaginaries and experience of return by Ecuadorian and Cuban men and women who migrated to Spain, are dissatisfied with their life there, and envisage/carry out the project of going back to their countries of origin (Ecuador and Cuba respectively). The project’s ambition is to bring together and contribute to three main scholarly areas of enquiry: 1) the study of morality, ethics and what counts as ‘good life’, 2) the study of the field of economic practice, its definition, value regimes, and ‘crises’, and 3) the study of migratory aspirations, projects, and trajectories. A multi-sited endeavour, the research is designed in three subprojects carried out in Spain (PhD student), Ecuador (Post-Doc), and Cuba (PI), in which ethnographic methods will be used to provide the first empirically grounded study of the links between notions and experiences of crisis, return migration, and the (re)assessment of good living.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym BLOCKCHAINSOCIETY
Project The Disrupted Society: mapping the societal effects of blockchain technology diffusion
Researcher (PI) Balazs BODO
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Starting Grant (StG), SH3, ERC-2017-STG
Summary Recent advances in cryptography yielded the blockchain technology, which enables a radically new and decentralized method to maintain authoritative records, without the need of trusted intermediaries. Bitcoin, a cryptocurrency blockchain application has already demonstrated that it is possible to operate a purely cryptography-based, global, distributed, decentralized, anonymous financial network, independent from central and commercial banks, regulators and the state.
The same technology is now being applied to other social domains (e.g. public registries of ownership and deeds, voting systems, the internet domain name registry). But research on the societal impact of blockchain innovation is scant, and we cannot properly assess its risks and promises. In addition, crucial knowledge is missing on how blockchain technologies can and should be regulated by law.
The BlockchainSociety project focuses on three research questions. (1) What internal factors contribute to the success of a blockchain application? (2) How does society adopt blockchain? (3) How to regulate blockchain? It breaks new ground as it (1) maps the most important blockchain projects, their governance, and assesses their disruptive potential; (2) documents and analyses the social diffusion of the technology, and builds scenarios about the potential impact of blockchain diffusion; and (3) it creates an inventory of emerging policy responses, compares and assesses policy tools in terms of efficiency and impact. The project will (1) build the conceptual and methodological bridges between information law, the study of the self-governance of technological systems via Science and Technology Studies, and the study of collective control efforts of complex socio-technological assemblages via Internet Governance studies; (2) address the most pressing blockchain-specific regulatory challenges via the analysis of emerging policies, and the development of new proposals.
Summary
Recent advances in cryptography yielded the blockchain technology, which enables a radically new and decentralized method to maintain authoritative records, without the need of trusted intermediaries. Bitcoin, a cryptocurrency blockchain application has already demonstrated that it is possible to operate a purely cryptography-based, global, distributed, decentralized, anonymous financial network, independent from central and commercial banks, regulators and the state.
The same technology is now being applied to other social domains (e.g. public registries of ownership and deeds, voting systems, the internet domain name registry). But research on the societal impact of blockchain innovation is scant, and we cannot properly assess its risks and promises. In addition, crucial knowledge is missing on how blockchain technologies can and should be regulated by law.
The BlockchainSociety project focuses on three research questions. (1) What internal factors contribute to the success of a blockchain application? (2) How does society adopt blockchain? (3) How to regulate blockchain? It breaks new ground as it (1) maps the most important blockchain projects, their governance, and assesses their disruptive potential; (2) documents and analyses the social diffusion of the technology, and builds scenarios about the potential impact of blockchain diffusion; and (3) it creates an inventory of emerging policy responses, compares and assesses policy tools in terms of efficiency and impact. The project will (1) build the conceptual and methodological bridges between information law, the study of the self-governance of technological systems via Science and Technology Studies, and the study of collective control efforts of complex socio-technological assemblages via Internet Governance studies; (2) address the most pressing blockchain-specific regulatory challenges via the analysis of emerging policies, and the development of new proposals.
Max ERC Funding
1 499 631 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym BSP
Project Belief Systems Project
Researcher (PI) Mark BRANDT
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT BRABANT
Call Details Starting Grant (StG), SH3, ERC-2017-STG
Summary Belief systems research is vital for understanding democratic politics, extremism, and political decision-making. What is the basic structure of belief systems? Clear answers to this fundamental question are not forthcoming. This is due to flaws in the conceptualization of belief systems. The state-of-the-art treats a belief system as a theoretical latent variable that causes people’s responses on attitudes and values relevant to the belief system. This approach cannot assess a belief system because it cannot assess the network of connections between the beliefs–attitudes and values–that make up the system; it collapses across them and the interrelationships are lost.
The Belief Systems Project conceptualizations belief systems as systems of interconnecting attitudes and values. I conceptualize attitudes and values as interactive nodes in a network that are analysed with network analyses. With these conceptual and empirical tools, I can understand the structure and dynamics of the belief system and will be able to avoid theoretical pitfalls common in belief system assessments. This project will move belief systems research beyond the state-of-the-art in four ways by:
1. Mapping the structure of systems of attitudes and values, something that is not possible using current methods.
2. Answering classic questions about central concepts and clustering of belief systems.
3. Modeling within-person belief systems and their variations, so that I can make accurate predictions about partisan motivated reasoning.
4. Testing how external and internal pressures (e.g., feelings of threat) change the underlying structure and dynamics of belief systems.
Using survey data from around the world, longitudinal panel studies, intensive longitudinal designs, experiments, and text analyses, I will triangulate on the structure of political belief systems over time, between countries, and within individuals.
Summary
Belief systems research is vital for understanding democratic politics, extremism, and political decision-making. What is the basic structure of belief systems? Clear answers to this fundamental question are not forthcoming. This is due to flaws in the conceptualization of belief systems. The state-of-the-art treats a belief system as a theoretical latent variable that causes people’s responses on attitudes and values relevant to the belief system. This approach cannot assess a belief system because it cannot assess the network of connections between the beliefs–attitudes and values–that make up the system; it collapses across them and the interrelationships are lost.
The Belief Systems Project conceptualizations belief systems as systems of interconnecting attitudes and values. I conceptualize attitudes and values as interactive nodes in a network that are analysed with network analyses. With these conceptual and empirical tools, I can understand the structure and dynamics of the belief system and will be able to avoid theoretical pitfalls common in belief system assessments. This project will move belief systems research beyond the state-of-the-art in four ways by:
1. Mapping the structure of systems of attitudes and values, something that is not possible using current methods.
2. Answering classic questions about central concepts and clustering of belief systems.
3. Modeling within-person belief systems and their variations, so that I can make accurate predictions about partisan motivated reasoning.
4. Testing how external and internal pressures (e.g., feelings of threat) change the underlying structure and dynamics of belief systems.
Using survey data from around the world, longitudinal panel studies, intensive longitudinal designs, experiments, and text analyses, I will triangulate on the structure of political belief systems over time, between countries, and within individuals.
Max ERC Funding
1 496 944 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym CALLIOPE
Project voCAL articuLations Of Parliamentary Identity and Empire
Researcher (PI) Josephine HOEGAERTS
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), SH5, ERC-2017-STG
Summary What did politicians sound like before they were on the radio and television? The fascination with politicians’ vocal characteristics and quirks is often connected to the rise of audio-visual media. But in the age of the printed press, political representatives also had to ‘speak well’ – without recourse to amplification.
Historians and linguists have provided sophisticated understandings of the discursive and aesthetic aspects of politicians’ language, but have largely ignored the importance of the acoustic character of their speech. CALLIOPE studies how vocal performances in parliament have influenced the course of political careers and political decision making in the 19th century. It shows how politicians’ voices helped to define the diverse identities they articulated. In viewing parliament through the lens of audibility, the project offers a new perspective on political representation by reframing how authority was embodied (through performances that were heard, rather than seen). It does so for the Second Chamber in Britain and France, and in dialogue with ‘colonial’ modes of speech in Kolkata and Algiers, which, we argue, exerted considerable influence on European vocal culture.
The project devises an innovative methodological approach to include the sound of the human voice in studies of the past that precede acoustic recording. Adapting methods developed in sound studies and combining them with the tools of political history, the project proposes a new way to analyse parliamentary reporting, while also drawing on a variety of sources that are rarely connected to the history of politics.
The main source material for the study comprise transcripts of parliamentary speech (official reports and renditions by journalists). However, the project also mobilizes educational, satirical and fictional sources to elucidate the convoluted processes that led to the cultivation, exertion, reception and evaluation of a voice ‘fit’ for nineteenth-century politics.
Summary
What did politicians sound like before they were on the radio and television? The fascination with politicians’ vocal characteristics and quirks is often connected to the rise of audio-visual media. But in the age of the printed press, political representatives also had to ‘speak well’ – without recourse to amplification.
Historians and linguists have provided sophisticated understandings of the discursive and aesthetic aspects of politicians’ language, but have largely ignored the importance of the acoustic character of their speech. CALLIOPE studies how vocal performances in parliament have influenced the course of political careers and political decision making in the 19th century. It shows how politicians’ voices helped to define the diverse identities they articulated. In viewing parliament through the lens of audibility, the project offers a new perspective on political representation by reframing how authority was embodied (through performances that were heard, rather than seen). It does so for the Second Chamber in Britain and France, and in dialogue with ‘colonial’ modes of speech in Kolkata and Algiers, which, we argue, exerted considerable influence on European vocal culture.
The project devises an innovative methodological approach to include the sound of the human voice in studies of the past that precede acoustic recording. Adapting methods developed in sound studies and combining them with the tools of political history, the project proposes a new way to analyse parliamentary reporting, while also drawing on a variety of sources that are rarely connected to the history of politics.
The main source material for the study comprise transcripts of parliamentary speech (official reports and renditions by journalists). However, the project also mobilizes educational, satirical and fictional sources to elucidate the convoluted processes that led to the cultivation, exertion, reception and evaluation of a voice ‘fit’ for nineteenth-century politics.
Max ERC Funding
1 499 905 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym CAPABLE
Project Enhancing Capabilities? Rethinking Work-life Policies and their Impact from a New Perspective
Researcher (PI) Mara YERKES
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Consolidator Grant (CoG), SH3, ERC-2017-COG
Summary We have witnessed significant work-life policy advancements designed to help men and women more equally combine employment with other spheres of life in recent decades, yet gender inequality persists. Improving gender equality in work-life balance is therefore high on policy agendas throughout Europe. Decades of research in this area have produced key insights but work-family theories fail to sufficiently explain the tenacity of this inequality. Earlier applications of a capabilities approach to work-life balance offer promising inroads, yet the importance of community remains absent. The CAPABLE project will generate fundamentally new knowledge on how work-life balance policies impact an individual’s capability to achieve this balance in Europe by incorporating the understudied dimension of community.
Capabilities reflect what individuals are effectively able to achieve. CAPABLE asks: To what extent do work-life balance policies enhance men and women’s capabilities to achieve work-life balance? To answer this question, we will develop and apply complex models derived from Sen’s capability approach to analyse: 1. the availability, accessibility and design of work-family policies; 2. what these policies mean for men and women’s capabilities to achieve work-life balance based on their embeddedness in individual, community and social contexts; 3. whether work-life policies enhance individual wellbeing; and 4. what policy tools are needed for developing sustainable work-life balance policies that enhance gender equal work-life capabilities. CAPABLE will progress scientific and policy frontiers using innovative, mixed-methods approaches at multiple policy levels. The conceptual clarity and empirical advancements provided will significantly expand our understanding of work-life policies in relation to individual capabilities. Furthermore, it will produce key insights into how sustainable work-life policies addressing gender inequality in work-life can be developed.
Summary
We have witnessed significant work-life policy advancements designed to help men and women more equally combine employment with other spheres of life in recent decades, yet gender inequality persists. Improving gender equality in work-life balance is therefore high on policy agendas throughout Europe. Decades of research in this area have produced key insights but work-family theories fail to sufficiently explain the tenacity of this inequality. Earlier applications of a capabilities approach to work-life balance offer promising inroads, yet the importance of community remains absent. The CAPABLE project will generate fundamentally new knowledge on how work-life balance policies impact an individual’s capability to achieve this balance in Europe by incorporating the understudied dimension of community.
Capabilities reflect what individuals are effectively able to achieve. CAPABLE asks: To what extent do work-life balance policies enhance men and women’s capabilities to achieve work-life balance? To answer this question, we will develop and apply complex models derived from Sen’s capability approach to analyse: 1. the availability, accessibility and design of work-family policies; 2. what these policies mean for men and women’s capabilities to achieve work-life balance based on their embeddedness in individual, community and social contexts; 3. whether work-life policies enhance individual wellbeing; and 4. what policy tools are needed for developing sustainable work-life balance policies that enhance gender equal work-life capabilities. CAPABLE will progress scientific and policy frontiers using innovative, mixed-methods approaches at multiple policy levels. The conceptual clarity and empirical advancements provided will significantly expand our understanding of work-life policies in relation to individual capabilities. Furthermore, it will produce key insights into how sustainable work-life policies addressing gender inequality in work-life can be developed.
Max ERC Funding
1 999 748 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
Project acronym CAPE
Project Ghosts from the past: Consequences of Adolescent Peer Experiences across social contexts and generations
Researcher (PI) Tina KRETSCHMER
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Call Details Starting Grant (StG), SH3, ERC-2017-STG
Summary Positive peer experiences are crucial for young people’s health and wellbeing. Accordingly, multiple studies (including my own) have described long-term negative psychological and behavioral consequences when adolescents’ peer relationships are dysfunctional. Paradoxically, knowledge on adult social consequences of adolescent peer experiences –relationships with others a decade later - is much less extensive. Informed by social learning and attachment theory, I tackle this gap and investigate whether and how peer experiences are transmitted to other social contexts, and intergenerationally, i.e., passed on to the next generation. My aim is to shed light on how the “ghosts from peer past” affect young adults’ relationships and their children. To this end, I examine longitudinal links between adolescent peer and young adult close relationships and test whether parents’ peer experiences affect offspring’s peer experiences. Psychological functioning, parenting, temperament, genetic, and epigenetic transmission mechanisms are examined separately and in interplay, which 1) goes far beyond the current state-of-the-art in social development research, and 2) significantly broadens my biosocially oriented work on genetic effects in the peer context. My plans utilize data from the TRAILS (Tracking Adolescents’ Individual Lives’ Survey) cohort that has been followed from age 11 to 26. To study intergenerational transmission, the TRAILS NEXT sample of participants with children is substantially extended. This project uniquely studies adult social consequences of peer experiences and, at the same time, follows children’s first steps into the peer world. The intergenerational approach and provision for environmental, genetic, and epigenetic mediation put this project at the forefront of developmental research and equip it with the potential to generate the knowledge needed to chase away the ghosts from the peer past.
Summary
Positive peer experiences are crucial for young people’s health and wellbeing. Accordingly, multiple studies (including my own) have described long-term negative psychological and behavioral consequences when adolescents’ peer relationships are dysfunctional. Paradoxically, knowledge on adult social consequences of adolescent peer experiences –relationships with others a decade later - is much less extensive. Informed by social learning and attachment theory, I tackle this gap and investigate whether and how peer experiences are transmitted to other social contexts, and intergenerationally, i.e., passed on to the next generation. My aim is to shed light on how the “ghosts from peer past” affect young adults’ relationships and their children. To this end, I examine longitudinal links between adolescent peer and young adult close relationships and test whether parents’ peer experiences affect offspring’s peer experiences. Psychological functioning, parenting, temperament, genetic, and epigenetic transmission mechanisms are examined separately and in interplay, which 1) goes far beyond the current state-of-the-art in social development research, and 2) significantly broadens my biosocially oriented work on genetic effects in the peer context. My plans utilize data from the TRAILS (Tracking Adolescents’ Individual Lives’ Survey) cohort that has been followed from age 11 to 26. To study intergenerational transmission, the TRAILS NEXT sample of participants with children is substantially extended. This project uniquely studies adult social consequences of peer experiences and, at the same time, follows children’s first steps into the peer world. The intergenerational approach and provision for environmental, genetic, and epigenetic mediation put this project at the forefront of developmental research and equip it with the potential to generate the knowledge needed to chase away the ghosts from the peer past.
Max ERC Funding
1 464 846 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym CATENA
Project Commentary Manuscripts in the History and Transmission of the Greek New Testament
Researcher (PI) HUGH ALEXANDER GERVASE HOUGHTON
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Call Details Consolidator Grant (CoG), SH5, ERC-2017-COG
Summary Manuscripts which contain commentary alongside the biblical text are some of the most significant and complicated witnesses to the Greek New Testament. First compiled around the fifth century, the commentaries consist of chains of extracts from earlier writers (catenae). These manuscripts became the main way in which users encountered both the text and the interpretation of the New Testament; revised editions produced in the eleventh and twelfth centuries continued to hold the field until the invention of printing.
Recent advances have shown that commentary manuscripts play a much more important role than previously thought in the history of the New Testament. The number of known copies has increased by 20% following a preliminary survey last year which identified 100 additional manuscripts. A recent comprehensive textual analysis of the Catholic Epistles indicated that all witnesses from the third generation onwards (some 72% of the total) could stem from the biblical text of three commentary manuscripts occupying a key place in the textual tradition. Investigation of the catena on Mark has shown that the selection of extracts could offer a new approach to understanding the theology of the compilers and the transmission of the commentaries.
The CATENA Project will use digital tools to undertake a fuller examination of Greek New Testament commentary manuscripts than has ever before been possible. This will include an exhaustive survey to establish a complete list of witnesses; a database of extracts to examine their principles of organisation and relationships; and electronic transcriptions to determine their role in the transmission of the biblical text. The results will have a direct impact on editions of the Greek New Testament, providing a new understanding of its text and reception and leading to broader insights into history and culture.
Summary
Manuscripts which contain commentary alongside the biblical text are some of the most significant and complicated witnesses to the Greek New Testament. First compiled around the fifth century, the commentaries consist of chains of extracts from earlier writers (catenae). These manuscripts became the main way in which users encountered both the text and the interpretation of the New Testament; revised editions produced in the eleventh and twelfth centuries continued to hold the field until the invention of printing.
Recent advances have shown that commentary manuscripts play a much more important role than previously thought in the history of the New Testament. The number of known copies has increased by 20% following a preliminary survey last year which identified 100 additional manuscripts. A recent comprehensive textual analysis of the Catholic Epistles indicated that all witnesses from the third generation onwards (some 72% of the total) could stem from the biblical text of three commentary manuscripts occupying a key place in the textual tradition. Investigation of the catena on Mark has shown that the selection of extracts could offer a new approach to understanding the theology of the compilers and the transmission of the commentaries.
The CATENA Project will use digital tools to undertake a fuller examination of Greek New Testament commentary manuscripts than has ever before been possible. This will include an exhaustive survey to establish a complete list of witnesses; a database of extracts to examine their principles of organisation and relationships; and electronic transcriptions to determine their role in the transmission of the biblical text. The results will have a direct impact on editions of the Greek New Testament, providing a new understanding of its text and reception and leading to broader insights into history and culture.
Max ERC Funding
1 756 928 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym CERDEV
Project Transcriptional controls over cerebellar neuron differentiation and circuit assembly
Researcher (PI) Ludovic TELLEY
Host Institution (HI) UNIVERSITE DE LAUSANNE
Call Details Starting Grant (StG), LS5, ERC-2017-STG
Summary The cerebellum is a critical regulator of motor function, which acts to integrate ongoing body states, sensory inputs and desired outcomes to adjust motor output. This motor control is achieved by a relatively small number of neuron types receiving two main sources of inputs and forming a single output pathway, the axons of Purkinje cells. Although the cerebellum is one of the first structures of the brain to differentiate, it undergoes a prolonged differentiation period such that mature cellular and circuit configuration is achieved only late after birth. Despite the functional importance of this structure, the molecular mechanisms that control type-specific cerebellar neurons generation, differentiation, and circuit assembly are poorly understood and are the topic of the present study.
In my research program, I propose to investigate the transcriptional programs that control the generation of distinct subtypes of cerebellar neurons from progenitors, including Purkinje cells, granule cells and molecular layer interneurons (Work Package 1); the diversity of Purkinje cells across cerebellar regions (Work Package 2) and the postnatal differentiation and circuit integration of granule cells and molecular layer interneurons (Work Package 3). The general bases of the approach I propose consist in: i) specifically label cerebellar neuron progenitors and their progeny at sequential developmental time points pre- and post-natally using birthdate-based tagging, ii) FAC-sort these distinct cell types, iii) isolate these cells and identify their transcriptional signatures with single-cell resolution, iv) functionally interrogate top candidate genes and associated transcriptional programs using in vivo gain- and loss-of-function approaches. Together, these experiments aim at deciphering the cell-intrinsic processes controlling cerebellar circuit formation, towards a better understanding of the molecular mechanisms underlying cerebellar function and dysfunction.
Summary
The cerebellum is a critical regulator of motor function, which acts to integrate ongoing body states, sensory inputs and desired outcomes to adjust motor output. This motor control is achieved by a relatively small number of neuron types receiving two main sources of inputs and forming a single output pathway, the axons of Purkinje cells. Although the cerebellum is one of the first structures of the brain to differentiate, it undergoes a prolonged differentiation period such that mature cellular and circuit configuration is achieved only late after birth. Despite the functional importance of this structure, the molecular mechanisms that control type-specific cerebellar neurons generation, differentiation, and circuit assembly are poorly understood and are the topic of the present study.
In my research program, I propose to investigate the transcriptional programs that control the generation of distinct subtypes of cerebellar neurons from progenitors, including Purkinje cells, granule cells and molecular layer interneurons (Work Package 1); the diversity of Purkinje cells across cerebellar regions (Work Package 2) and the postnatal differentiation and circuit integration of granule cells and molecular layer interneurons (Work Package 3). The general bases of the approach I propose consist in: i) specifically label cerebellar neuron progenitors and their progeny at sequential developmental time points pre- and post-natally using birthdate-based tagging, ii) FAC-sort these distinct cell types, iii) isolate these cells and identify their transcriptional signatures with single-cell resolution, iv) functionally interrogate top candidate genes and associated transcriptional programs using in vivo gain- and loss-of-function approaches. Together, these experiments aim at deciphering the cell-intrinsic processes controlling cerebellar circuit formation, towards a better understanding of the molecular mechanisms underlying cerebellar function and dysfunction.
Max ERC Funding
1 499 885 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym CerebralHominoids
Project Evolutionary biology of human and great ape brain development in cerebral organoids
Researcher (PI) Madeline LANCASTER
Host Institution (HI) UNITED KINGDOM RESEARCH AND INNOVATION
Call Details Starting Grant (StG), LS5, ERC-2017-STG
Summary Humans are endowed with a number of advanced cognitive abilities not seen in other species. So what allows the human brain to stand out from the rest in these capabilities? In general, the brains of primates, including humans, have more neurons per unit volume than other mammals. But humans are also in the fortunate position of having the largest of the primate brains, making the number of neurons in the human cerebral cortex greatly expanded. Thus, the difference seems to be a matter of quantity, not quality. My laboratory is interested in understanding how neuron number, and thus brain size, is determined in human brain development.
The research proposed here is aimed at taking an evolutionary approach to this question and comparing brain development in an in vitro 3D model system, cerebral organoids. This method, which relies on self-organization from differentiating pluripotent stem cells, recapitulates remarkably well the endogenous developmental program of the human brain. Having previously established the brain organoid approach, and more recently improved upon it with the application of bioengineering, my laboratory is in a unique position to carry out functional studies of human brain development. I propose to use this approach to compare developing human brain tissue to that of other hominid species and tease apart unique features of human neural stem cells and progenitors that allow them to generate more neurons and therefore a greater cerebral cortical size. Furthermore, we will perform transcriptomic and functional screening to identify factors underlying this expansion, followed by careful genetic substitution to test the contributions of putative evolutionary changes. In this way, we will functionally test putative human evolutionary changes in a manner not previously possible.
Summary
Humans are endowed with a number of advanced cognitive abilities not seen in other species. So what allows the human brain to stand out from the rest in these capabilities? In general, the brains of primates, including humans, have more neurons per unit volume than other mammals. But humans are also in the fortunate position of having the largest of the primate brains, making the number of neurons in the human cerebral cortex greatly expanded. Thus, the difference seems to be a matter of quantity, not quality. My laboratory is interested in understanding how neuron number, and thus brain size, is determined in human brain development.
The research proposed here is aimed at taking an evolutionary approach to this question and comparing brain development in an in vitro 3D model system, cerebral organoids. This method, which relies on self-organization from differentiating pluripotent stem cells, recapitulates remarkably well the endogenous developmental program of the human brain. Having previously established the brain organoid approach, and more recently improved upon it with the application of bioengineering, my laboratory is in a unique position to carry out functional studies of human brain development. I propose to use this approach to compare developing human brain tissue to that of other hominid species and tease apart unique features of human neural stem cells and progenitors that allow them to generate more neurons and therefore a greater cerebral cortical size. Furthermore, we will perform transcriptomic and functional screening to identify factors underlying this expansion, followed by careful genetic substitution to test the contributions of putative evolutionary changes. In this way, we will functionally test putative human evolutionary changes in a manner not previously possible.
Max ERC Funding
1 444 911 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym CLAUSTRUM
Project The Claustrum: A Circuit Hub for Attention
Researcher (PI) Amihai CITRI
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Consolidator Grant (CoG), LS5, ERC-2017-COG
Summary Our senses face a constant barrage of information. Hence, understanding how our brain enables us to attend to relevant stimuli, while ignoring distractions, is of increasing biomedical importance. Recently, I discovered that the claustrum, a multi-sensory hub and recipient of extensive neuromodulatory input, enables resilience to distraction.
In my ERC project, I will explore the mechanisms underlying claustral mediation of resilience to distraction and develop novel approaches for assessing and modulating attention in mice, with implications for humans. Transgenic mouse models that I identified as enabling selective access to claustral neurons overcome its limiting anatomy, making the claustrum accessible to functional investigation. Using this novel genetic access, I obtained preliminary results strongly suggesting that the claustrum functions to filter distractions by adjusting cortical sensory gain.
My specific aims are: 1) To delineate the mechanisms whereby the claustrum achieves sensory gain control, by applying in-vivo cell-attached, multi-unit and fiber photometry recordings from claustral and cortical neurons during attention-demanding tasks. 2) To discriminate between the functions of the claustrum in multi-sensory integration and implementation of attention strategies, by employing multi-sensory behavioral paradigms while modulating claustral function. 3) To develop validated complementary physiological and behavioral protocols for adjusting claustral mediation of attention via neuromodulation.
This study is unique in its focus and aims: it will provide a stringent neurophysiological framework for defining a key mechanism underlying cognitive concepts of attention, and establish a novel platform for studying the function of the claustrum and manipulating its activity. The project is designed to achieve breakthroughs of fundamental nature and potentially lead to diagnostic and therapeutic advances relevant to attention disorders.
Summary
Our senses face a constant barrage of information. Hence, understanding how our brain enables us to attend to relevant stimuli, while ignoring distractions, is of increasing biomedical importance. Recently, I discovered that the claustrum, a multi-sensory hub and recipient of extensive neuromodulatory input, enables resilience to distraction.
In my ERC project, I will explore the mechanisms underlying claustral mediation of resilience to distraction and develop novel approaches for assessing and modulating attention in mice, with implications for humans. Transgenic mouse models that I identified as enabling selective access to claustral neurons overcome its limiting anatomy, making the claustrum accessible to functional investigation. Using this novel genetic access, I obtained preliminary results strongly suggesting that the claustrum functions to filter distractions by adjusting cortical sensory gain.
My specific aims are: 1) To delineate the mechanisms whereby the claustrum achieves sensory gain control, by applying in-vivo cell-attached, multi-unit and fiber photometry recordings from claustral and cortical neurons during attention-demanding tasks. 2) To discriminate between the functions of the claustrum in multi-sensory integration and implementation of attention strategies, by employing multi-sensory behavioral paradigms while modulating claustral function. 3) To develop validated complementary physiological and behavioral protocols for adjusting claustral mediation of attention via neuromodulation.
This study is unique in its focus and aims: it will provide a stringent neurophysiological framework for defining a key mechanism underlying cognitive concepts of attention, and establish a novel platform for studying the function of the claustrum and manipulating its activity. The project is designed to achieve breakthroughs of fundamental nature and potentially lead to diagnostic and therapeutic advances relevant to attention disorders.
Max ERC Funding
1 995 000 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym CMTaaRS
Project Defective protein translation as a pathogenic mechanism of peripheral neuropathy
Researcher (PI) Erik Jan Marthe STORKEBAUM
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Consolidator Grant (CoG), LS5, ERC-2017-COG
Summary Familial forms of neurodegenerative diseases are caused by mutations in a single gene. It is unknown whether distinct mutations in the same gene or in functionally related genes cause disease through similar or disparate mechanisms. Furthermore, the precise molecular mechanisms underlying virtually all neurodegenerative disorders are poorly understood, and effective treatments are typically lacking.
This is also the case for Charcot-Marie-Tooth (CMT) peripheral neuropathy caused by mutations in five distinct tRNA synthetase (aaRS) genes. We previously generated Drosophila CMT-aaRS models and used a novel method for cell-type-specific labeling of newly synthesized proteins in vivo to show that impaired protein translation may represent a common pathogenic mechanism.
In this proposal, I aim to determine whether translation is also inhibited in CMT-aaRS mouse models, and whether all mutations cause disease through gain-of-toxic-function, or alternatively, whether some mutations act through a dominant-negative mechanism. In addition, I will evaluate whether all CMT-aaRS mutant proteins inhibit translation, and I will test the hypothesis, raised by our unpublished preliminary data shown here, that a defect in the transfer of the (aminoacylated) tRNA from the mutant synthetase to elongation factor eEF1A is the molecular mechanism underlying CMT-aaRS. Finally, I will validate the identified molecular mechanism in CMT-aaRS mouse models, as the most disease-relevant mammalian model.
I expect to elucidate whether all CMT-aaRS mutations cause disease through a common molecular mechanism that involves inhibition of translation. This is of key importance from a therapeutic perspective, as a common pathogenic mechanism allows for a unified therapeutic approach. Furthermore, this proposal has the potential to unravel the detailed molecular mechanism underlying CMT-aaRS, what would constitute a breakthrough and a requirement for rational drug design for this incurable disease.
Summary
Familial forms of neurodegenerative diseases are caused by mutations in a single gene. It is unknown whether distinct mutations in the same gene or in functionally related genes cause disease through similar or disparate mechanisms. Furthermore, the precise molecular mechanisms underlying virtually all neurodegenerative disorders are poorly understood, and effective treatments are typically lacking.
This is also the case for Charcot-Marie-Tooth (CMT) peripheral neuropathy caused by mutations in five distinct tRNA synthetase (aaRS) genes. We previously generated Drosophila CMT-aaRS models and used a novel method for cell-type-specific labeling of newly synthesized proteins in vivo to show that impaired protein translation may represent a common pathogenic mechanism.
In this proposal, I aim to determine whether translation is also inhibited in CMT-aaRS mouse models, and whether all mutations cause disease through gain-of-toxic-function, or alternatively, whether some mutations act through a dominant-negative mechanism. In addition, I will evaluate whether all CMT-aaRS mutant proteins inhibit translation, and I will test the hypothesis, raised by our unpublished preliminary data shown here, that a defect in the transfer of the (aminoacylated) tRNA from the mutant synthetase to elongation factor eEF1A is the molecular mechanism underlying CMT-aaRS. Finally, I will validate the identified molecular mechanism in CMT-aaRS mouse models, as the most disease-relevant mammalian model.
I expect to elucidate whether all CMT-aaRS mutations cause disease through a common molecular mechanism that involves inhibition of translation. This is of key importance from a therapeutic perspective, as a common pathogenic mechanism allows for a unified therapeutic approach. Furthermore, this proposal has the potential to unravel the detailed molecular mechanism underlying CMT-aaRS, what would constitute a breakthrough and a requirement for rational drug design for this incurable disease.
Max ERC Funding
2 000 000 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym COFBMIX
Project Cortical feedback in figure background segregation of odors.
Researcher (PI) Dan ROKNI
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), LS5, ERC-2017-STG
Summary A key question in neuroscience is how information is processed by sensory systems to guide behavior. Most of our knowledge about sensory processing is based on presentation of simple isolated stimuli and recording corresponding neural activity in relevant brain areas. Yet sensory stimuli in real life are never isolated and typically not simple. How the brain processes complex stimuli, simultaneously arising from multiple objects is unknown. Our daily experience (as well as well-controlled experiments) shows that only parts of a complex sensory scene can be perceived - we cannot listen to more than one speaker in a party. Importantly, one can easily choose what is important and should be processed and what can be ignored as background. These observations lead to the prevalent hypothesis that feedback projections from ‘higher’ brain areas to more peripheral sensory areas are involved in processing of complex stimuli. However experimental analysis of signals conveyed by feedback projections in behaving animals is scarce. The nature of these signals and how they relate to behavior is unknown.
Here I propose a cutting edge approach to directly record feedback signals in the olfactory system of behaving mice. We will use chronically implanted electrodes to record the modulation of olfactory bulb (OB) principal neurons by task related context. Additionally, we will record from piriform cortical (PC) neurons that project back to the OB. These will be tagged with channelrhodopsin-2 and identified by light sensitivity. Finally, we will express the spectrally distinct Ca++ indicators GCaMP6 and RCaMP2 in PC neurons and in olfactory sensory neurons, respectively, and use 2-photon microscopy to analyze the spatio-temporal relationship between feedforward and feedback inputs in the OB. This comprehensive approach will provide an explanation of how feedforward and feedback inputs are integrated to process complex stimuli.
Summary
A key question in neuroscience is how information is processed by sensory systems to guide behavior. Most of our knowledge about sensory processing is based on presentation of simple isolated stimuli and recording corresponding neural activity in relevant brain areas. Yet sensory stimuli in real life are never isolated and typically not simple. How the brain processes complex stimuli, simultaneously arising from multiple objects is unknown. Our daily experience (as well as well-controlled experiments) shows that only parts of a complex sensory scene can be perceived - we cannot listen to more than one speaker in a party. Importantly, one can easily choose what is important and should be processed and what can be ignored as background. These observations lead to the prevalent hypothesis that feedback projections from ‘higher’ brain areas to more peripheral sensory areas are involved in processing of complex stimuli. However experimental analysis of signals conveyed by feedback projections in behaving animals is scarce. The nature of these signals and how they relate to behavior is unknown.
Here I propose a cutting edge approach to directly record feedback signals in the olfactory system of behaving mice. We will use chronically implanted electrodes to record the modulation of olfactory bulb (OB) principal neurons by task related context. Additionally, we will record from piriform cortical (PC) neurons that project back to the OB. These will be tagged with channelrhodopsin-2 and identified by light sensitivity. Finally, we will express the spectrally distinct Ca++ indicators GCaMP6 and RCaMP2 in PC neurons and in olfactory sensory neurons, respectively, and use 2-photon microscopy to analyze the spatio-temporal relationship between feedforward and feedback inputs in the OB. This comprehensive approach will provide an explanation of how feedforward and feedback inputs are integrated to process complex stimuli.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym COLSOC
Project The Legacy of Colonialism: Origins and Outcomes of Social Protection
Researcher (PI) Carina SCHMITT
Host Institution (HI) UNIVERSITAET BREMEN
Call Details Starting Grant (StG), SH3, ERC-2017-STG
Summary Social protection has been one of the most popular instruments for promoting human development across the globe. However, the great majority of the global population is not or only partly covered by social protection. Especially in developing countries it is often the very poorest who do not receive essential social benefits. This is highly problematic since inclusive social protection is assumed to be a key factor for national productivity, global economic growth and domestic stability. Social protection in many developing countries can be traced back to colonial times. Surprisingly, the influence of colonialism has been a blind spot for existing theories and empirical studies of comparative social policy. In this project it is argued that the colonial legacy in terms of the imperial strategy of the colonial power, the characteristics of the colonized society and the interplay between the two is crucial in explaining early and contemporary social protection. Hence, the main objective of this project is to systematically understand how colonialism has shaped the remarkable differences in social protection and its postcolonial outcomes. Given the paucity of our information and understanding of social protection in former colonies, an interactive dataset on the characteristics, origins and outcomes of social protection will be developed including comprehensive data on former British and French colonies from the beginning of the 20th century until today. The dataset will be backed by insights derived from four case studies elucidating the causal mechanisms between the colonial legacy and early and contemporary social protection. The proposed project breaks new ground by improving our understanding of why social protection in some developing countries has led to more inclusive societies while reinforcing existing inequalities in others. Such an understanding is a prerequisite in informing the contemporary struggle against poverty and social inequality.
Summary
Social protection has been one of the most popular instruments for promoting human development across the globe. However, the great majority of the global population is not or only partly covered by social protection. Especially in developing countries it is often the very poorest who do not receive essential social benefits. This is highly problematic since inclusive social protection is assumed to be a key factor for national productivity, global economic growth and domestic stability. Social protection in many developing countries can be traced back to colonial times. Surprisingly, the influence of colonialism has been a blind spot for existing theories and empirical studies of comparative social policy. In this project it is argued that the colonial legacy in terms of the imperial strategy of the colonial power, the characteristics of the colonized society and the interplay between the two is crucial in explaining early and contemporary social protection. Hence, the main objective of this project is to systematically understand how colonialism has shaped the remarkable differences in social protection and its postcolonial outcomes. Given the paucity of our information and understanding of social protection in former colonies, an interactive dataset on the characteristics, origins and outcomes of social protection will be developed including comprehensive data on former British and French colonies from the beginning of the 20th century until today. The dataset will be backed by insights derived from four case studies elucidating the causal mechanisms between the colonial legacy and early and contemporary social protection. The proposed project breaks new ground by improving our understanding of why social protection in some developing countries has led to more inclusive societies while reinforcing existing inequalities in others. Such an understanding is a prerequisite in informing the contemporary struggle against poverty and social inequality.
Max ERC Funding
1 486 250 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym CONT-END
Project Attempts to Control the End of Life in People with Dementia: Two-level Approach to Examine Controversies
Researcher (PI) Jenny VAN DER STEEN
Host Institution (HI) ACADEMISCH ZIEKENHUIS LEIDEN
Call Details Consolidator Grant (CoG), SH3, ERC-2017-COG
Summary In dementia at the end of life, cognitive and physical decline imply that control is typically lost. CONT-END will examine control in the context of three emerging interventions which contain a controversial element of striving for control in the process of dying with dementia: advance care planning of the end of life, use of new technology to monitor symptoms when unable to self-report, and euthanasia. To perform outstanding research, the proposed research examines control at the level of clinical practice, but also at the level of end-of-life research practice. The latter provides ample opportunities for researchers to control the research process. That is, research designs are often flexible and we will study if and how this impacts research in an emotionally charged area. I will take an empirical mixed-methods approach to study the two practices in parallel. The work is organised in three related Work Packages around three research questions. (1) In a 6-country study, I will examine if and when people with dementia, family caregivers and physicians (900 respondents) find the interventions, shown on video, acceptable. (2) A cluster-randomised 3-armed controlled trial in 279 patients and their family caregivers assesses effects of two types of advance care planning differing in level of control (detailed advance treatment orders versus goal setting and coping based) on outcomes ranging from favourable to less favourable, and whether effects differ in subgroups. Cases in which the technology is preferred or applied are observed. (3) Ethnographic fieldwork in two different end-of-life research practices and a Delphi study to synthesize CONT-END’s findings assess how researchers shape findings. This greatly improves the quality of CONT-END and provides the input to develop new methodology for improving research quality and integrity.
Summary
In dementia at the end of life, cognitive and physical decline imply that control is typically lost. CONT-END will examine control in the context of three emerging interventions which contain a controversial element of striving for control in the process of dying with dementia: advance care planning of the end of life, use of new technology to monitor symptoms when unable to self-report, and euthanasia. To perform outstanding research, the proposed research examines control at the level of clinical practice, but also at the level of end-of-life research practice. The latter provides ample opportunities for researchers to control the research process. That is, research designs are often flexible and we will study if and how this impacts research in an emotionally charged area. I will take an empirical mixed-methods approach to study the two practices in parallel. The work is organised in three related Work Packages around three research questions. (1) In a 6-country study, I will examine if and when people with dementia, family caregivers and physicians (900 respondents) find the interventions, shown on video, acceptable. (2) A cluster-randomised 3-armed controlled trial in 279 patients and their family caregivers assesses effects of two types of advance care planning differing in level of control (detailed advance treatment orders versus goal setting and coping based) on outcomes ranging from favourable to less favourable, and whether effects differ in subgroups. Cases in which the technology is preferred or applied are observed. (3) Ethnographic fieldwork in two different end-of-life research practices and a Delphi study to synthesize CONT-END’s findings assess how researchers shape findings. This greatly improves the quality of CONT-END and provides the input to develop new methodology for improving research quality and integrity.
Max ERC Funding
1 988 972 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
