Project acronym VisTrans
Project Visualising transport dynamics of transmembrane pumps
Researcher (PI) Bonaventura LUISI
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), LS1, ERC-2016-ADG
Summary The project will investigate multi-component molecular machines that drive substrates across the cell envelope of bacteria. Some of the machines pump antibiotics or toxins, and so contribute to drug resistance and virulence in pathogenic strains. Questions that will be addressed include what the molecular pumps look like, how they are assembled and regulated, how they capture and translocate substrates, and the stereochemical basis for the cooperative switching of substrate-binding states. Molecular pumps that will be studied include tripartite systems driven by ATP hydrolysis, which play a central role in the efflux of macrolide antibiotics and secretion of toxins in Gram-negative bacteria, and those that use secondary transporters energized by electrochemical gradients. We will build upon our earlier observations to prepare a series of intermediates encompassing the key steps in the transport processes, to visualize tertiary and quaternary structural changes, the pathway of substrates in the efflux pumps, and the threading of toxin polypeptides through the constricted channel in the secretion assembly. The pumps and secretion systems cycle through intermediate states, and these will be studied at high resolution by cryoEM and crystallography to understand how the conformational states switch with strong cooperativity and avoid futile cycles that dissipate energy. Our work indicates that the activity of these transporters can be modulated by small peptides and potential co-factors, and we will address how these work. The project will build on our novel approach to engineer the pump assemblies that enables structural analysis at high resolution in isolation and in situ, and will be complemented with mechanistic analyses in vitro and in vivo. The project will deliver a comprehensive, structure-based description of the mechanism of drug efflux and protein translocation by transport machines and their regulation in diverse pathogenic bacteria.
Summary
The project will investigate multi-component molecular machines that drive substrates across the cell envelope of bacteria. Some of the machines pump antibiotics or toxins, and so contribute to drug resistance and virulence in pathogenic strains. Questions that will be addressed include what the molecular pumps look like, how they are assembled and regulated, how they capture and translocate substrates, and the stereochemical basis for the cooperative switching of substrate-binding states. Molecular pumps that will be studied include tripartite systems driven by ATP hydrolysis, which play a central role in the efflux of macrolide antibiotics and secretion of toxins in Gram-negative bacteria, and those that use secondary transporters energized by electrochemical gradients. We will build upon our earlier observations to prepare a series of intermediates encompassing the key steps in the transport processes, to visualize tertiary and quaternary structural changes, the pathway of substrates in the efflux pumps, and the threading of toxin polypeptides through the constricted channel in the secretion assembly. The pumps and secretion systems cycle through intermediate states, and these will be studied at high resolution by cryoEM and crystallography to understand how the conformational states switch with strong cooperativity and avoid futile cycles that dissipate energy. Our work indicates that the activity of these transporters can be modulated by small peptides and potential co-factors, and we will address how these work. The project will build on our novel approach to engineer the pump assemblies that enables structural analysis at high resolution in isolation and in situ, and will be complemented with mechanistic analyses in vitro and in vivo. The project will deliver a comprehensive, structure-based description of the mechanism of drug efflux and protein translocation by transport machines and their regulation in diverse pathogenic bacteria.
Max ERC Funding
2 208 619 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym WEALTHPOL
Project The Politics of Wealth Inequality and Mobility in the Twenty-First Century
Researcher (PI) Benjamin William Anthony ANSELL
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Consolidator Grant (CoG), SH3, ERC-2016-COG
Summary Over the past decade scholars across the social sciences have grappled with the causes and consequences of economic inequality and social mobility. Income inequality has risen to levels unseen for a century. At the same time, economies in Europe and beyond have seen an even larger concentration in wealth, along with unprecedented volatility in asset markets such as housing and equities. These changes in the distribution of wealth have been of great economic and political consequence, with the debates over housing, inheritance, and capital taxation shaping contemporary political discourse. Yet, scholars of political economy remain beholden to analyses of inequality and mobility that examine only the flows of income in the labour market and ignore inequality and mobility in the stock of wealth held by citizens. WEALTHPOL is a ground-breaking interdisciplinary project with a series of three high-risk and novel work packages that transform our knowledge about wealth inequality and wealth mobility. WEALTHPOL 1 develops the first comprehensive collection of data about the distribution and inheritance of wealth in Europe and beyond. WEALTHPOL 2 provides the first political database of how governments shape the pattern of wealth through political pledges and policymaking, spanning seven decades and thirty-seven countries. Finally, WEALTHPOL 3 uses cutting-edge laboratory and survey experiments to expand our knowledge about what citizens think about wealth. WEALTHPOL draws these three strands together by connecting policy environments and the distribution of wealth to citizens’ attitudes to wealth inequality and the kinds of policies that might shape it. In doing so, WEALTHPOL revolutionises our understanding of - and our capacity to respond to - the politics of capital in the twenty-first century in Europe and beyond.
Summary
Over the past decade scholars across the social sciences have grappled with the causes and consequences of economic inequality and social mobility. Income inequality has risen to levels unseen for a century. At the same time, economies in Europe and beyond have seen an even larger concentration in wealth, along with unprecedented volatility in asset markets such as housing and equities. These changes in the distribution of wealth have been of great economic and political consequence, with the debates over housing, inheritance, and capital taxation shaping contemporary political discourse. Yet, scholars of political economy remain beholden to analyses of inequality and mobility that examine only the flows of income in the labour market and ignore inequality and mobility in the stock of wealth held by citizens. WEALTHPOL is a ground-breaking interdisciplinary project with a series of three high-risk and novel work packages that transform our knowledge about wealth inequality and wealth mobility. WEALTHPOL 1 develops the first comprehensive collection of data about the distribution and inheritance of wealth in Europe and beyond. WEALTHPOL 2 provides the first political database of how governments shape the pattern of wealth through political pledges and policymaking, spanning seven decades and thirty-seven countries. Finally, WEALTHPOL 3 uses cutting-edge laboratory and survey experiments to expand our knowledge about what citizens think about wealth. WEALTHPOL draws these three strands together by connecting policy environments and the distribution of wealth to citizens’ attitudes to wealth inequality and the kinds of policies that might shape it. In doing so, WEALTHPOL revolutionises our understanding of - and our capacity to respond to - the politics of capital in the twenty-first century in Europe and beyond.
Max ERC Funding
1 696 109 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym WIDE
Project Wide Incremental learning with Discrimination nEtworks
Researcher (PI) Rolf Harald BAAYEN
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Call Details Advanced Grant (AdG), SH4, ERC-2016-ADG
Summary Although homo sapiens has been endowed with language for over 50,000 years, the invention of alphabet-like scripts 3,000 years ago dominates Western linguistic thinking. Training in literacy starts in early childhood, and because of this, words and letter-like sound units can naturally seem to be the building blocks of language. The Chinese writing system highlights the cultural-specificity of this approach: characters are juxtaposed without intervening spaces, and their interpretation is highly context-dependent. Words are not singled out. And although more frequent characters contain parts indicating pronunciation, it is syllables that are referred to, not letter-like sound units.
The research proposed here seeks to break the hold that the alphabet-centric approach has on our understanding of language by exploring the idea that instead of being phone and word-based, languages use low-level properties of the acoustic signal to directly reduce uncertainty about the messages encoded in the speech signal. My work with wide learning networks (two-layer networks with many thousands of units, using the simplest possible error-driven learning rule) provides remarkable support for this suggestion: For reading and speech comprehension, their performance closely matches both the strengths and the weaknesses of human processing. Especially at a time when machine learning and artificial intelligence are moving beyond human capacity, it is a methodological imperative to study and work with algorithms reflecting both the advantages and disadvantages of human learning.
I am requesting funding to take this radically novel research program to the next level by further developing our account of auditory comprehension, by modeling more typologically diverse languages, by extending this approach to speech production, and by developing a discrimination-based language theory.
Summary
Although homo sapiens has been endowed with language for over 50,000 years, the invention of alphabet-like scripts 3,000 years ago dominates Western linguistic thinking. Training in literacy starts in early childhood, and because of this, words and letter-like sound units can naturally seem to be the building blocks of language. The Chinese writing system highlights the cultural-specificity of this approach: characters are juxtaposed without intervening spaces, and their interpretation is highly context-dependent. Words are not singled out. And although more frequent characters contain parts indicating pronunciation, it is syllables that are referred to, not letter-like sound units.
The research proposed here seeks to break the hold that the alphabet-centric approach has on our understanding of language by exploring the idea that instead of being phone and word-based, languages use low-level properties of the acoustic signal to directly reduce uncertainty about the messages encoded in the speech signal. My work with wide learning networks (two-layer networks with many thousands of units, using the simplest possible error-driven learning rule) provides remarkable support for this suggestion: For reading and speech comprehension, their performance closely matches both the strengths and the weaknesses of human processing. Especially at a time when machine learning and artificial intelligence are moving beyond human capacity, it is a methodological imperative to study and work with algorithms reflecting both the advantages and disadvantages of human learning.
I am requesting funding to take this radically novel research program to the next level by further developing our account of auditory comprehension, by modeling more typologically diverse languages, by extending this approach to speech production, and by developing a discrimination-based language theory.
Max ERC Funding
2 496 875 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym WIN2CON
Project Brain-State Dependent Perception: Finding the Windows to Consciousness
Researcher (PI) Nathan Weisz
Host Institution (HI) PARIS-LODRON-UNIVERSITAT SALZBURG
Call Details Starting Grant (StG), SH4, ERC-2011-StG_20101124
Summary "The neurophysiological mechanisms of conscious perception are a major unsolved scientific riddle. Since linking brain activity and qualia is currently difficult, the common strategy in neuroscience is first to identify the ""Neural Correlates of Consciousness"" (NCC). A major insight is that consciously versus not consciously perceived stimuli differ not so much on an early sensory level, but mainly in that only consciously perceived stimuli involve a network of frontoparietal regions recurrently connected to sensory cortex. Yet, the studies adhere to the mainstream approach in cognitive neuroscience that relevant brain activity starts with stimulus onset, degrading ongoing fluctuations as irrelevant noise. The present proposal follows an alternative strategy by regarding the history of neuronal activity preceding the stimulus as in integral part of the NCC, i.e. as a window for consciousness. Central to this novel framework, is the extent to which relevant sensory regions are functionally connected to the frontoparietal system prior to stimulus arrival, constituting brain-states that open or close the ""window"" for specific contents. Different strategies will be pursued using advanced time-sensitive electrophysiological methods: 1) Offline experiments will be conducted focussing on the functional connectivity state prior to stimulus onset. 2) A novel online approach will be pursued in which relevant features / signals derived from 1) will be used to control perception experiments in realtime. 3) Cortical stimulation (via TMS) will be applied to selectively modulate ongoing states of functional coupling and to test their effects on conscious perception. While 1) would establish the prestimulus functional network state as important part of the NCC, 2) and 3) would go beyond the correlative level, testing for their causal implication. Overall, including the prestimulus state into the NCC constitutes a paradigm shift in the neuroscience of consciousness."
Summary
"The neurophysiological mechanisms of conscious perception are a major unsolved scientific riddle. Since linking brain activity and qualia is currently difficult, the common strategy in neuroscience is first to identify the ""Neural Correlates of Consciousness"" (NCC). A major insight is that consciously versus not consciously perceived stimuli differ not so much on an early sensory level, but mainly in that only consciously perceived stimuli involve a network of frontoparietal regions recurrently connected to sensory cortex. Yet, the studies adhere to the mainstream approach in cognitive neuroscience that relevant brain activity starts with stimulus onset, degrading ongoing fluctuations as irrelevant noise. The present proposal follows an alternative strategy by regarding the history of neuronal activity preceding the stimulus as in integral part of the NCC, i.e. as a window for consciousness. Central to this novel framework, is the extent to which relevant sensory regions are functionally connected to the frontoparietal system prior to stimulus arrival, constituting brain-states that open or close the ""window"" for specific contents. Different strategies will be pursued using advanced time-sensitive electrophysiological methods: 1) Offline experiments will be conducted focussing on the functional connectivity state prior to stimulus onset. 2) A novel online approach will be pursued in which relevant features / signals derived from 1) will be used to control perception experiments in realtime. 3) Cortical stimulation (via TMS) will be applied to selectively modulate ongoing states of functional coupling and to test their effects on conscious perception. While 1) would establish the prestimulus functional network state as important part of the NCC, 2) and 3) would go beyond the correlative level, testing for their causal implication. Overall, including the prestimulus state into the NCC constitutes a paradigm shift in the neuroscience of consciousness."
Max ERC Funding
1 499 000 €
Duration
Start date: 2012-05-01, End date: 2017-10-31
Project acronym XSPECT
Project Expecting Ourselves: Embodied Prediction and the Construction of Conscious Experience
Researcher (PI) Andy CLARK
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Advanced Grant (AdG), SH4, ERC-2015-AdG
Summary This project (short name, XSPECT) aims to harness the emerging science of the predictive brain to deliver new insights into the nature, scope, mechanisms and (most importantly) the very possibility of conscious experience. The project thus explores and extends the vision of the brain as an inner engine continuously striving to predict the incoming sensory barrage. The key innovation is to consider this increasingly popular vision in the special context of embodied agents able to predict many of their own evolving states and responses – agents able to ‘expect themselves’. These crucial self-expectations span the interoceptive (targeting the internal sensory flows signaling our own physiological states, such as hunger, arousal, itch, and muscular and visceral sensations) and the exteroceptive (targeting the world, and our own behaviors as they might unfold over multiple scales of space and time). XSPECT explores the idea that such interacting states of complex, layered self-prediction hold the key to understanding much that is puzzling about conscious experience.
The project is divided into three simultaneously active sub-projects. The first sub-project concerns relations between prediction, motor action, and experience. The second sub-project targets the role of interoceptive prediction in the construction of experience. The third sub-project considers ways in which more reflective forms of conscious experience (involving agency, selfhood, and the introspection of own experiential states) are further enriched by a spiraling array of socially mediated higher-level self-predictions.
XSPECT will combine integrative philosophical argument, collaborative experimentation, and leading edge interdisciplinary research and discussion, leveraging two very successful but under-communicating research programs (‘embodied cognition’ and ‘the predictive brain’) to offer new perspectives on the puzzle of conscious experience.
Summary
This project (short name, XSPECT) aims to harness the emerging science of the predictive brain to deliver new insights into the nature, scope, mechanisms and (most importantly) the very possibility of conscious experience. The project thus explores and extends the vision of the brain as an inner engine continuously striving to predict the incoming sensory barrage. The key innovation is to consider this increasingly popular vision in the special context of embodied agents able to predict many of their own evolving states and responses – agents able to ‘expect themselves’. These crucial self-expectations span the interoceptive (targeting the internal sensory flows signaling our own physiological states, such as hunger, arousal, itch, and muscular and visceral sensations) and the exteroceptive (targeting the world, and our own behaviors as they might unfold over multiple scales of space and time). XSPECT explores the idea that such interacting states of complex, layered self-prediction hold the key to understanding much that is puzzling about conscious experience.
The project is divided into three simultaneously active sub-projects. The first sub-project concerns relations between prediction, motor action, and experience. The second sub-project targets the role of interoceptive prediction in the construction of experience. The third sub-project considers ways in which more reflective forms of conscious experience (involving agency, selfhood, and the introspection of own experiential states) are further enriched by a spiraling array of socially mediated higher-level self-predictions.
XSPECT will combine integrative philosophical argument, collaborative experimentation, and leading edge interdisciplinary research and discussion, leveraging two very successful but under-communicating research programs (‘embodied cognition’ and ‘the predictive brain’) to offer new perspectives on the puzzle of conscious experience.
Max ERC Funding
1 391 134 €
Duration
Start date: 2017-01-01, End date: 2020-12-31
Project acronym YOUCITIZEN
Project Youth Citizenship in Divided Societies: Between Cosmpolitanism, Nation, and Civil Society
Researcher (PI) Lynn Staeheli
Host Institution (HI) UNIVERSITY OF DURHAM
Call Details Advanced Grant (AdG), SH3, ERC-2011-ADG_20110406
Summary YouCitizen is a comparative, multi-level ethnographic research project that examines the efforts of international organisations, civil society organisations, and states to foster citizenship for youth in divided societies. In their efforts, agents working in such organisations often engage in paradoxical, if not contradictory, acts to promote both cosmopolitanism within civil society and national identities, even when aspects of national identity have been a source of division. A central premise of the research is that the outcomes of these efforts are conditioned by the contexts in which programmes for youth are delivered and enacted. In these contexts – which include histories of division and marginalisation, societal and communal norms, family histories, and the spaces of daily life – youth interpret and experience citizenship. YouCitizen’s critical intervention is in extending the examination of citizenship formation to consider the ways in which youth interpret, experience, and potentially remake citizenship that is different to, and may actually challenge, the forms of citizenship that organisations and states attempt to instil.
The empirical foci of the study are the networks of organisations promoting citizenship and/or civic engagement, and youth, aged 15-24 in South Africa, Bosnia-Herzegovina and Lebanon who have been involved with those programmes. It explores the goals of those organisations, their funding sources and activities to understand both the vision of citizenship they promote and the traditions and influences from which they draw; particular attention is paid to ideals and values associated with cosmopolitanism vis-à-vis the nation and the ways in which they address social division. Interviews and participant observation with youth explore the ways in which their experiences and understanding of citizenship are influenced by those programmes, but are also entwined with daily life in their homes and communities.
Summary
YouCitizen is a comparative, multi-level ethnographic research project that examines the efforts of international organisations, civil society organisations, and states to foster citizenship for youth in divided societies. In their efforts, agents working in such organisations often engage in paradoxical, if not contradictory, acts to promote both cosmopolitanism within civil society and national identities, even when aspects of national identity have been a source of division. A central premise of the research is that the outcomes of these efforts are conditioned by the contexts in which programmes for youth are delivered and enacted. In these contexts – which include histories of division and marginalisation, societal and communal norms, family histories, and the spaces of daily life – youth interpret and experience citizenship. YouCitizen’s critical intervention is in extending the examination of citizenship formation to consider the ways in which youth interpret, experience, and potentially remake citizenship that is different to, and may actually challenge, the forms of citizenship that organisations and states attempt to instil.
The empirical foci of the study are the networks of organisations promoting citizenship and/or civic engagement, and youth, aged 15-24 in South Africa, Bosnia-Herzegovina and Lebanon who have been involved with those programmes. It explores the goals of those organisations, their funding sources and activities to understand both the vision of citizenship they promote and the traditions and influences from which they draw; particular attention is paid to ideals and values associated with cosmopolitanism vis-à-vis the nation and the ways in which they address social division. Interviews and participant observation with youth explore the ways in which their experiences and understanding of citizenship are influenced by those programmes, but are also entwined with daily life in their homes and communities.
Max ERC Funding
2 419 013 €
Duration
Start date: 2012-07-01, End date: 2017-06-30
