Project acronym AutoClean
Project Cell-free reconstitution of autophagy to dissect molecular mechanisms
Researcher (PI) Claudine Simone Kraft
Host Institution (HI) UNIVERSITAETSKLINIKUM FREIBURG
Call Details Consolidator Grant (CoG), LS1, ERC-2017-COG
Summary Autophagy, a lysosomal degradation pathway in which the cell digests its own components, is an essential biological pathway that promotes organismal health and longevity and helps combat cancer and neurodegenerative diseases. Accordingly, the 2016 Nobel Prize in Physiology or Medicine was awarded for research in autophagy. Although autophagy has been extensively studied from yeast to mammals, the molecular events that underlie its induction and progression remain elusive. A highly conserved protein kinase, Atg1, plays a unique and essential role in initiating autophagy, yet despite this pivotal importance it has taken over twenty years for its first downstream target to be discovered. However, whilst our identification of the autophagy related membrane protein Atg9 as the first Atg1 substrate is an important advance, the molecular mechanisms that enable the extensive remodelling of cellular membranes that occurs during autophagy is still completely undefined. A detailed knowledge of the inputs and outputs of the Atg1 kinase will enable us to provide a definitive mechanistic understanding of autophagy. We have devised a novel permeabilized cell assay that reconstitutes the pathway in vitro, allowing us to recapitulate key steps in the autophagic process and thereby determine how the individual steps that lead up to autophagy are controlled. We will use this system to dissect the functional role of Atg1 kinase in autophagosome-vacuole fusion (Objective 1), and to determine the origin of the autophagic membrane and the role of Atg1 in expanding these (Objective 2). To reveal how Atg1/ULK1 kinase is activated in mammalian cells, we will apply the unique and carefully tailored synthetic in vivo approaches that we have recently developed (Objective 3). By focusing on the activation of the Atg1 kinase and the molecular events that it executes, we will be able to explain its central role in regulating the autophagic process and define the mechanistic steps in the pathway.
Summary
Autophagy, a lysosomal degradation pathway in which the cell digests its own components, is an essential biological pathway that promotes organismal health and longevity and helps combat cancer and neurodegenerative diseases. Accordingly, the 2016 Nobel Prize in Physiology or Medicine was awarded for research in autophagy. Although autophagy has been extensively studied from yeast to mammals, the molecular events that underlie its induction and progression remain elusive. A highly conserved protein kinase, Atg1, plays a unique and essential role in initiating autophagy, yet despite this pivotal importance it has taken over twenty years for its first downstream target to be discovered. However, whilst our identification of the autophagy related membrane protein Atg9 as the first Atg1 substrate is an important advance, the molecular mechanisms that enable the extensive remodelling of cellular membranes that occurs during autophagy is still completely undefined. A detailed knowledge of the inputs and outputs of the Atg1 kinase will enable us to provide a definitive mechanistic understanding of autophagy. We have devised a novel permeabilized cell assay that reconstitutes the pathway in vitro, allowing us to recapitulate key steps in the autophagic process and thereby determine how the individual steps that lead up to autophagy are controlled. We will use this system to dissect the functional role of Atg1 kinase in autophagosome-vacuole fusion (Objective 1), and to determine the origin of the autophagic membrane and the role of Atg1 in expanding these (Objective 2). To reveal how Atg1/ULK1 kinase is activated in mammalian cells, we will apply the unique and carefully tailored synthetic in vivo approaches that we have recently developed (Objective 3). By focusing on the activation of the Atg1 kinase and the molecular events that it executes, we will be able to explain its central role in regulating the autophagic process and define the mechanistic steps in the pathway.
Max ERC Funding
1 955 666 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym BabyRhythm
Project Tuned to the Rhythm: How Prenatally and Postnatally Heard Speech Prosody Lays the Foundations for Language Learning
Researcher (PI) Judit Gervain
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), SH4, ERC-2017-COG
Summary The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved.
The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language.
The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.
Summary
The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved.
The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language.
The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.
Max ERC Funding
1 621 250 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym BiT
Project How the Human Brain Masters Time
Researcher (PI) Domenica Bueti
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Call Details Consolidator Grant (CoG), SH4, ERC-2015-CoG
Summary If you suddenly hear your song on the radio and spontaneously decide to burst into dance in your living room, you need to precisely time your movements if you do not want to find yourself on your bookshelf. Most of what we do or perceive depends on how accurately we represent the temporal properties of the environment however we cannot see or touch time. As such, time in the millisecond range is both a fundamental and elusive dimension of everyday experiences. Despite the obvious importance of time to information processing and to behavior in general, little is known yet about how the human brain process time. Existing approaches to the study of the neural mechanisms of time mainly focus on the identification of brain regions involved in temporal computations (‘where’ time is processed in the brain), whereas most computational models vary in their biological plausibility and do not always make clear testable predictions. BiT is a groundbreaking research program designed to challenge current models of time perception and to offer a new perspective in the study of the neural basis of time. The groundbreaking nature of BiT derives from the novelty of the questions asked (‘when’ and ‘how’ time is processed in the brain) and from addressing them using complementary but distinct research approaches (from human neuroimaging to brain stimulation techniques, from the investigation of the whole brain to the focus on specific brain regions). By testing a new biologically plausible hypothesis of temporal representation (via duration tuning and ‘chronotopy’) and by scrutinizing the functional properties and, for the first time, the temporal hierarchies of ‘putative’ time regions, BiT will offer a multifaceted knowledge of how the human brain represents time. This new knowledge will challenge our understanding of brain organization and function that typically lacks of a time angle and will impact our understanding of how the brain uses time information for perception and action
Summary
If you suddenly hear your song on the radio and spontaneously decide to burst into dance in your living room, you need to precisely time your movements if you do not want to find yourself on your bookshelf. Most of what we do or perceive depends on how accurately we represent the temporal properties of the environment however we cannot see or touch time. As such, time in the millisecond range is both a fundamental and elusive dimension of everyday experiences. Despite the obvious importance of time to information processing and to behavior in general, little is known yet about how the human brain process time. Existing approaches to the study of the neural mechanisms of time mainly focus on the identification of brain regions involved in temporal computations (‘where’ time is processed in the brain), whereas most computational models vary in their biological plausibility and do not always make clear testable predictions. BiT is a groundbreaking research program designed to challenge current models of time perception and to offer a new perspective in the study of the neural basis of time. The groundbreaking nature of BiT derives from the novelty of the questions asked (‘when’ and ‘how’ time is processed in the brain) and from addressing them using complementary but distinct research approaches (from human neuroimaging to brain stimulation techniques, from the investigation of the whole brain to the focus on specific brain regions). By testing a new biologically plausible hypothesis of temporal representation (via duration tuning and ‘chronotopy’) and by scrutinizing the functional properties and, for the first time, the temporal hierarchies of ‘putative’ time regions, BiT will offer a multifaceted knowledge of how the human brain represents time. This new knowledge will challenge our understanding of brain organization and function that typically lacks of a time angle and will impact our understanding of how the brain uses time information for perception and action
Max ERC Funding
1 670 830 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym cenRNA
Project The role of RNA in centromere biology and genome integrity
Researcher (PI) Sylvia Erhardt
Host Institution (HI) RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Call Details Consolidator Grant (CoG), LS1, ERC-2015-CoG
Summary One of the most astonishing processes in the life of a cell is the division into two daughter cells. Such a highly organized process would presumably be regulated tightly by the underlying centromeric DNA sequence; however, the sites of chromosome attachment to the microtubule spindle are regulated by epigenetic mechanisms. The best-characterized epigenetic mark for centromeres is the histone H3-variant CENP-A, which replaces H3 in some of the nucleosomes within centromeric chromatin. Centromeres are embedded in pericentromeric heterochromatin and it has become apparent in recent years that heterochromatin is transcribed into non-coding RNAs. We have recently shown that a long non-coding RNA from pericentromeric heterochromatin of the X chromosome (SATIII) in Drosophila melanogaster localizes in trans to centromeres of all other chromosomes and is an essential component for correct loading and maintenance of CENP-A and, therefore, genome stability. Additional RNAs in Drosophila and RNAs from other species have been linked to centromeric chromatin, but their function is not understood. We propose that a complex, RNA-based epigenetic mechanism regulates centromere establishment and function.
This proposal is designed to the precise function of SATIII RNA by identifying the associated protein complexes as well as structural and post-transcriptional features of SATIII. We will evaluate the mechanisms by which SATIII functions as a heritable mark of centromeres through generations, during the developing germ line, and species separation. In parallel, we will systematically identify and characterize centromere-associated RNAs (cenRNAs) in Drosophila and human cells. We will elucidate their function in centromere biology and chromosome segregation, essentially as we have done and propose to do for SATIII. These experiments are designed to provide a detailed understanding of the essential, RNA-based epigenetic regulation of centromeres.
Summary
One of the most astonishing processes in the life of a cell is the division into two daughter cells. Such a highly organized process would presumably be regulated tightly by the underlying centromeric DNA sequence; however, the sites of chromosome attachment to the microtubule spindle are regulated by epigenetic mechanisms. The best-characterized epigenetic mark for centromeres is the histone H3-variant CENP-A, which replaces H3 in some of the nucleosomes within centromeric chromatin. Centromeres are embedded in pericentromeric heterochromatin and it has become apparent in recent years that heterochromatin is transcribed into non-coding RNAs. We have recently shown that a long non-coding RNA from pericentromeric heterochromatin of the X chromosome (SATIII) in Drosophila melanogaster localizes in trans to centromeres of all other chromosomes and is an essential component for correct loading and maintenance of CENP-A and, therefore, genome stability. Additional RNAs in Drosophila and RNAs from other species have been linked to centromeric chromatin, but their function is not understood. We propose that a complex, RNA-based epigenetic mechanism regulates centromere establishment and function.
This proposal is designed to the precise function of SATIII RNA by identifying the associated protein complexes as well as structural and post-transcriptional features of SATIII. We will evaluate the mechanisms by which SATIII functions as a heritable mark of centromeres through generations, during the developing germ line, and species separation. In parallel, we will systematically identify and characterize centromere-associated RNAs (cenRNAs) in Drosophila and human cells. We will elucidate their function in centromere biology and chromosome segregation, essentially as we have done and propose to do for SATIII. These experiments are designed to provide a detailed understanding of the essential, RNA-based epigenetic regulation of centromeres.
Max ERC Funding
1 896 250 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym CIRCOMMUNICATION
Project Deciphering molecular pathways of circadian clock communication
Researcher (PI) gad ASHER
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Consolidator Grant (CoG), LS1, ERC-2017-COG
Summary The overarching objective of this interdisciplinary project is to elucidate mechanisms through which billions of individual clocks in the body communicate with each other and tick in harmony. The mammalian circadian timing system consists of a master clock in the brain and subsidiary oscillators in almost every cell of the body. Since these clocks anticipate environmental changes and function together to orchestrate daily physiology and behavior their temporal synchronization is critical.
Our recent finding that oxygen serves as a resetting cue for circadian clocks points towards the unprecedented involvement of blood gases as time signals. We will apply cutting edge continuous physiological measurements in freely moving animals, alongside biochemical/molecular biology approaches and advanced cell culture setup to determine the molecular role of oxygen, carbon dioxide and pH in circadian clock communication and function.
The intricate nature of the mammalian circadian system demands the presence of communication mechanisms between clocks throughout the body at multiple levels. While previous studies primarily addressed the role of the master clock in resetting peripheral clocks, our knowledge regarding the communication among clocks between and within peripheral organs is rudimentary. We will reconstruct the mammalian circadian system from the bottom up, sequentially restoring clocks in peripheral tissues of a non-rhythmic animal to (i) obtain a system-view of the peripheral circadian communication network; and (ii) study novel tissue-derived circadian communication mechanisms.
This integrative proposal addresses fundamental aspects of circadian biology. It is expected to unravel the circadian communication network and shed light on how billions of clocks in the body function in unison. Its impact extends beyond circadian rhythms and bears great potential for research on communication between cells/tissues in various fields of biology.
Summary
The overarching objective of this interdisciplinary project is to elucidate mechanisms through which billions of individual clocks in the body communicate with each other and tick in harmony. The mammalian circadian timing system consists of a master clock in the brain and subsidiary oscillators in almost every cell of the body. Since these clocks anticipate environmental changes and function together to orchestrate daily physiology and behavior their temporal synchronization is critical.
Our recent finding that oxygen serves as a resetting cue for circadian clocks points towards the unprecedented involvement of blood gases as time signals. We will apply cutting edge continuous physiological measurements in freely moving animals, alongside biochemical/molecular biology approaches and advanced cell culture setup to determine the molecular role of oxygen, carbon dioxide and pH in circadian clock communication and function.
The intricate nature of the mammalian circadian system demands the presence of communication mechanisms between clocks throughout the body at multiple levels. While previous studies primarily addressed the role of the master clock in resetting peripheral clocks, our knowledge regarding the communication among clocks between and within peripheral organs is rudimentary. We will reconstruct the mammalian circadian system from the bottom up, sequentially restoring clocks in peripheral tissues of a non-rhythmic animal to (i) obtain a system-view of the peripheral circadian communication network; and (ii) study novel tissue-derived circadian communication mechanisms.
This integrative proposal addresses fundamental aspects of circadian biology. It is expected to unravel the circadian communication network and shed light on how billions of clocks in the body function in unison. Its impact extends beyond circadian rhythms and bears great potential for research on communication between cells/tissues in various fields of biology.
Max ERC Funding
1 999 945 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym CLASS
Project Cross-Linguistic Acquisition of Sentence Structure: Integrating Experimental and Computational Approaches
Researcher (PI) Benjamin Ambridge
Host Institution (HI) THE UNIVERSITY OF LIVERPOOL
Call Details Consolidator Grant (CoG), SH4, ERC-2015-CoG
Summary How children acquire their native language remains one of the key unsolved problems in Cognitive Science. This project will answer a question that lies at the heart of this problem: How do children acquire the abstract generalizations that allow them to produce novel sentences, while avoiding the ungrammatical utterances that result from across-the-board application of these generalizations (e.g., *The clown laughed the man)? Previous single-process theories (the entrenchment, preemption and verb semantics hypotheses) fail to explain all of the current English data, and do not begin to address the issue of how learners of other languages solve this learnability problem. The aim of the present project is to solve this problem by developing and testing a new unified cross-linguistic account of the development of sentence structure. In addition to the overarching theoretical question set out above, the research will address four key questions: (1) What do learners bring to the task in terms of cognitive-semantic universals?; (2) How do children form linguistic generalizations in the first place?; (3) Why are languages the way they are; would other types of systems be difficult or impossible to learn?; (4) What is the nature of development?. These questions will be addressed by means of four Work Packages (WPs). WP1 uses grammaticality judgment and elicited production paradigms developed by the PI to investigate the acquisition of basic transitive and intransitive sentence structure (e.g., The man broke the window/The window broke) across six typologically different languages: English, K’iche’ Mayan, Japanese, Hindi, Hebrew and Turkish (at ages 3-4, 5-6, 9-10 and 18+ years). WP2 uses the same paradigms to investigate idiosyncratic language-specific generalizations within three of these languages. WP3 uses Artificial Grammar Learning to focus on the issue of language evolution. WP4 uses computational modeling to investigate and simulate development.
Summary
How children acquire their native language remains one of the key unsolved problems in Cognitive Science. This project will answer a question that lies at the heart of this problem: How do children acquire the abstract generalizations that allow them to produce novel sentences, while avoiding the ungrammatical utterances that result from across-the-board application of these generalizations (e.g., *The clown laughed the man)? Previous single-process theories (the entrenchment, preemption and verb semantics hypotheses) fail to explain all of the current English data, and do not begin to address the issue of how learners of other languages solve this learnability problem. The aim of the present project is to solve this problem by developing and testing a new unified cross-linguistic account of the development of sentence structure. In addition to the overarching theoretical question set out above, the research will address four key questions: (1) What do learners bring to the task in terms of cognitive-semantic universals?; (2) How do children form linguistic generalizations in the first place?; (3) Why are languages the way they are; would other types of systems be difficult or impossible to learn?; (4) What is the nature of development?. These questions will be addressed by means of four Work Packages (WPs). WP1 uses grammaticality judgment and elicited production paradigms developed by the PI to investigate the acquisition of basic transitive and intransitive sentence structure (e.g., The man broke the window/The window broke) across six typologically different languages: English, K’iche’ Mayan, Japanese, Hindi, Hebrew and Turkish (at ages 3-4, 5-6, 9-10 and 18+ years). WP2 uses the same paradigms to investigate idiosyncratic language-specific generalizations within three of these languages. WP3 uses Artificial Grammar Learning to focus on the issue of language evolution. WP4 uses computational modeling to investigate and simulate development.
Max ERC Funding
1 600 000 €
Duration
Start date: 2016-09-01, End date: 2020-08-31
Project acronym CoAct
Project Communication in Action: Towards a model of Contextualized Action and Language Processing
Researcher (PI) Judith HOLLER
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Consolidator Grant (CoG), SH4, ERC-2017-COG
Summary Language is fundamental to human sociality. While the last century has given us many fundamental insights into how we use and understand it, core issues that we face when doing so within its natural environment—face-to-face conversation—remain untackled. When we speak we also send signals with our head, eyes, face, hands, torso, etc. How do we orchestrate and integrate all this information into meaningful messages? CoAct will lead to a new model with in situ language processing at its core, the Contextualized Action and Language (CoALa) processing model. The defining characteristic of in situ language is its multimodal nature. Moreover, the essence of language use is social action; that is, we use language to do things—we question, offer, decline etc. These social actions are embedded in conversational structure where one speaking turn follows another at a remarkable speed, with millisecond gaps between them. Conversation thus confronts us with a significant psycholinguistic challenge. While one could expect that the many co-speech bodily signals exacerbate this challenge, CoAct proposes that they actually play a key role in dealing with it. It tests this in three subprojects that combine methods from a variety of disciplines but focus on the social actions performed by questions and responses as a uniting theme: (1) ProdAct uses conversational corpora to investigate the multimodal architecture of social actions with the assumption that they differ in their ‘visual signatures’, (2) CompAct tests whether these bodily signatures contribute to social action comprehension, and if they do so early and rapidly, (3) IntAct investigates whether bodily signals play a facilitating role also when faced with the complex task of comprehending while planning a next social action. Thus, CoAct aims to advance current psycholinguistic theory by developing a new model of language processing based on an integrative framework uniting aspects from psychology , philosophy and sociology.
Summary
Language is fundamental to human sociality. While the last century has given us many fundamental insights into how we use and understand it, core issues that we face when doing so within its natural environment—face-to-face conversation—remain untackled. When we speak we also send signals with our head, eyes, face, hands, torso, etc. How do we orchestrate and integrate all this information into meaningful messages? CoAct will lead to a new model with in situ language processing at its core, the Contextualized Action and Language (CoALa) processing model. The defining characteristic of in situ language is its multimodal nature. Moreover, the essence of language use is social action; that is, we use language to do things—we question, offer, decline etc. These social actions are embedded in conversational structure where one speaking turn follows another at a remarkable speed, with millisecond gaps between them. Conversation thus confronts us with a significant psycholinguistic challenge. While one could expect that the many co-speech bodily signals exacerbate this challenge, CoAct proposes that they actually play a key role in dealing with it. It tests this in three subprojects that combine methods from a variety of disciplines but focus on the social actions performed by questions and responses as a uniting theme: (1) ProdAct uses conversational corpora to investigate the multimodal architecture of social actions with the assumption that they differ in their ‘visual signatures’, (2) CompAct tests whether these bodily signatures contribute to social action comprehension, and if they do so early and rapidly, (3) IntAct investigates whether bodily signals play a facilitating role also when faced with the complex task of comprehending while planning a next social action. Thus, CoAct aims to advance current psycholinguistic theory by developing a new model of language processing based on an integrative framework uniting aspects from psychology , philosophy and sociology.
Max ERC Funding
2 000 000 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym COLOURMIND
Project Colouring the Mind: the Impact of Visual Environment on Colour Perception
Researcher (PI) Anna FRANKLIN
Host Institution (HI) THE UNIVERSITY OF SUSSEX
Call Details Consolidator Grant (CoG), SH4, ERC-2017-COG
Summary Visual perception is central to how we think and behave. However, there are major unresolved issues in understanding how the human mind draws on experience to perceive the dynamic and variable world. The COLOURMIND project, led by Franklin, will tackle these crucial issues with an ambitious investigation of the impact of the visual environment on colour perception that will provide a new theoretical framework for the field. The project will ask ground-breaking questions: What aspects of colour perception are affected by the visual environment, such that people from different environments perceive colour differently?; What processes enable colour perception to calibrate to visual experience and what is their nature and scope?; Does colour perception ‘tune-in’ to the visual input experienced during infancy? COLOURMIND will adopt a diverse range of innovative methods to address these questions, and will: i.) investigate the colour perception of people immersed in natural non-industrialised environments in some of the remotest parts of the world to identify the extent to which visual environment shapes colour perception; ii.) use innovative neuroimaging methods to identify how the visual cortex changes in response to chromatic experience; iii.) pioneer the use of ‘Altered-Reality' (next generation virtual reality) to elucidate calibrative processes in colour perception; and iv.) conduct carefully controlled experiments with infants to address the role of development. The cutting-edge questions, innovative approaches and theoretical power of the COLOURMIND project will lead to breakthroughs on issues that are fundamental to understanding the complexity of the human mind (e.g., learning, plasticity and inference; perceptual development; cultural relativity), and findings will have practical application. Overall, the ambitious project will push the frontiers of multidisciplinary research on colour perception, and will resonate throughout the cognitive and social sciences.
Summary
Visual perception is central to how we think and behave. However, there are major unresolved issues in understanding how the human mind draws on experience to perceive the dynamic and variable world. The COLOURMIND project, led by Franklin, will tackle these crucial issues with an ambitious investigation of the impact of the visual environment on colour perception that will provide a new theoretical framework for the field. The project will ask ground-breaking questions: What aspects of colour perception are affected by the visual environment, such that people from different environments perceive colour differently?; What processes enable colour perception to calibrate to visual experience and what is their nature and scope?; Does colour perception ‘tune-in’ to the visual input experienced during infancy? COLOURMIND will adopt a diverse range of innovative methods to address these questions, and will: i.) investigate the colour perception of people immersed in natural non-industrialised environments in some of the remotest parts of the world to identify the extent to which visual environment shapes colour perception; ii.) use innovative neuroimaging methods to identify how the visual cortex changes in response to chromatic experience; iii.) pioneer the use of ‘Altered-Reality' (next generation virtual reality) to elucidate calibrative processes in colour perception; and iv.) conduct carefully controlled experiments with infants to address the role of development. The cutting-edge questions, innovative approaches and theoretical power of the COLOURMIND project will lead to breakthroughs on issues that are fundamental to understanding the complexity of the human mind (e.g., learning, plasticity and inference; perceptual development; cultural relativity), and findings will have practical application. Overall, the ambitious project will push the frontiers of multidisciplinary research on colour perception, and will resonate throughout the cognitive and social sciences.
Max ERC Funding
1 999 975 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym CondStruct
Project Structural basis for the coordination of chromosome architecture by condensin complexes
Researcher (PI) Christian Helmut Haering
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Call Details Consolidator Grant (CoG), LS1, ERC-2015-CoG
Summary Chromosomes undergo dramatic changes in their three-dimensional organisation during all aspects of genome function, ranging from the regulation of gene expression during cellular differentiation to chromosome duplication and partitioning over the course of a cell division cycle. The multi-subunit condensin protein complex plays major roles for these changes in DNA topology. Despite its fundamental importance, the mechanisms of condensin’s action are not understood.
Here, I propose a comprehensive research program that aims to reveal the elusive mechanisms behind the functions of the condensin complex. We intend to unravel how the condensin complex engages DNA, how this interaction activates large-scale ATPase-dependent conformational rearrangements within the complex, and how condensin eventually encircles chromatin fibres within its ring-shaped architecture. Insights from these mechanistic studies will be invaluable for understanding how networks of condensin-mediated linkages can shape linear DNA helices into higher-order chromosome structures. To achieve this ambitious and timely goal, we will combine an integrative structural biology approach with biochemical and cell biological methods. By applying complementary technologies, including X-ray protein crystallography, electron microscopy, cross-linking mass spectrometry, single molecule fluorescence microscopy and reconstitution experiments, we anticipate to build the first model of the entire condensin complex at near-atomic resolution and explain how dynamic conformational changes confer function.
The insights gained from this research program will provide an in-depth mechanistic comprehension of the core molecular machinery that determines the architecture of our genomes and will have major implications for understanding how genomic integrity is affected in various disease conditions.
Summary
Chromosomes undergo dramatic changes in their three-dimensional organisation during all aspects of genome function, ranging from the regulation of gene expression during cellular differentiation to chromosome duplication and partitioning over the course of a cell division cycle. The multi-subunit condensin protein complex plays major roles for these changes in DNA topology. Despite its fundamental importance, the mechanisms of condensin’s action are not understood.
Here, I propose a comprehensive research program that aims to reveal the elusive mechanisms behind the functions of the condensin complex. We intend to unravel how the condensin complex engages DNA, how this interaction activates large-scale ATPase-dependent conformational rearrangements within the complex, and how condensin eventually encircles chromatin fibres within its ring-shaped architecture. Insights from these mechanistic studies will be invaluable for understanding how networks of condensin-mediated linkages can shape linear DNA helices into higher-order chromosome structures. To achieve this ambitious and timely goal, we will combine an integrative structural biology approach with biochemical and cell biological methods. By applying complementary technologies, including X-ray protein crystallography, electron microscopy, cross-linking mass spectrometry, single molecule fluorescence microscopy and reconstitution experiments, we anticipate to build the first model of the entire condensin complex at near-atomic resolution and explain how dynamic conformational changes confer function.
The insights gained from this research program will provide an in-depth mechanistic comprehension of the core molecular machinery that determines the architecture of our genomes and will have major implications for understanding how genomic integrity is affected in various disease conditions.
Max ERC Funding
1 982 479 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym Ctrl-ImpAct
Project Control of impulsive action
Researcher (PI) Frederick Leon Julien VERBRUGGEN
Host Institution (HI) UNIVERSITEIT GENT
Call Details Consolidator Grant (CoG), SH4, ERC-2017-COG
Summary Adaptive behaviour is typically attributed to an executive-control system that allows people to regulate impulsive actions and to fulfil long-term goals instead. Failures to regulate impulsive actions have been associated with a variety of clinical and behavioural disorders. Therefore, establishing a good understanding of impulse-control mechanisms and how to improve them could be hugely beneficial for both individuals and society at large. Yet many fundamental questions remain unanswered. This stems from a narrow focus on reactive inhibitory control and well-practiced actions. To make significant progress, we need to develop new models that integrate different aspects of impulsive action and executive control. The proposed research program aims to answer five fundamental questions. (1) Can novel impulsive actions arise during task-preparation stages?; (2) What is the role of negative emotions in the origin and control of impulsive actions?; (3) How does learning modulate impulsive behaviour?; (4) When are impulsive actions (dys)functional?; and (5) How is variation in state impulsivity associated with trait impulsivity?
To answer these questions, we will use carefully designed behavioural paradigms, cognitive neuroscience techniques (TMS & EEG), physiological measures (e.g. facial EMG), and mathematical modelling of decision-making to specify the origin and control of impulsive actions. Our ultimate goal is to transform the impulsive action field by replacing the currently dominant ‘inhibitory control’ models of impulsive action with detailed multifaceted models that can explain impulsivity and control across time and space. Developing a new behavioural model of impulsive action will also contribute to a better understanding of the causes of individual differences in impulsivity and the many disorders associated with impulse-control deficits.
Summary
Adaptive behaviour is typically attributed to an executive-control system that allows people to regulate impulsive actions and to fulfil long-term goals instead. Failures to regulate impulsive actions have been associated with a variety of clinical and behavioural disorders. Therefore, establishing a good understanding of impulse-control mechanisms and how to improve them could be hugely beneficial for both individuals and society at large. Yet many fundamental questions remain unanswered. This stems from a narrow focus on reactive inhibitory control and well-practiced actions. To make significant progress, we need to develop new models that integrate different aspects of impulsive action and executive control. The proposed research program aims to answer five fundamental questions. (1) Can novel impulsive actions arise during task-preparation stages?; (2) What is the role of negative emotions in the origin and control of impulsive actions?; (3) How does learning modulate impulsive behaviour?; (4) When are impulsive actions (dys)functional?; and (5) How is variation in state impulsivity associated with trait impulsivity?
To answer these questions, we will use carefully designed behavioural paradigms, cognitive neuroscience techniques (TMS & EEG), physiological measures (e.g. facial EMG), and mathematical modelling of decision-making to specify the origin and control of impulsive actions. Our ultimate goal is to transform the impulsive action field by replacing the currently dominant ‘inhibitory control’ models of impulsive action with detailed multifaceted models that can explain impulsivity and control across time and space. Developing a new behavioural model of impulsive action will also contribute to a better understanding of the causes of individual differences in impulsivity and the many disorders associated with impulse-control deficits.
Max ERC Funding
1 998 438 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
