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 CAREGIVING
Project The plasticity of parental caregiving: characterizing the brain mechanisms underlying normal and disrupted development of parenting
Researcher (PI) Morten Lindtner Kringelbach
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Consolidator Grant (CoG), SH4, ERC-2013-CoG
Summary The survival of species depends critically on infant survival and development. Human infants are, however, vulnerable and completely dependent on caregiving parents, not just for survival but also for their development. Darwin and Lorenz have long argued that there are specific infant facial features that elicit attention and responsiveness in adults. Until recently this has not been possible to study but neuroimaging has started to reveal some of the brain circuitry. However, it is not known how the brain changes over time in new parents as they gain experience with caregiving. Equally, little is known about the underlying brain mechanisms associated with disruption to normal parental caregiving.
I propose to study the brain changes associated with normal and disrupted development of parental caregiving in new parents who will undergo neuroimaging and psychological testing using standardised databases and test batteries of caregiving tasks. Subproject 1 will investigate the normal development of parental caregiving, beginning before pregnancy, using a longitudinal study of structural and functional brain changes in both women and men combined with their behavioural measures on caregiving tasks.
Subproject 2 will investigate the disrupted development of parental caregiving using a cross-sectional design to study the brain and behavioural effects on caregiving during potential disruptive changes to the parent or child. Specifically, my focus will be on A) parental sleep disruption and B) infant craniofacial abnormality of cleft lip and palate.
Finally, understanding the full brain mechanisms and architecture underlying parental caregiving requires a mechanistic synthesis of the findings of normal and disrupted development. Subproject 3 will use our existing advanced computational models to combine the findings from normal and disrupted development in order to identify the fundamental brain mechanisms and networks underlying the development of parenting.
Summary
The survival of species depends critically on infant survival and development. Human infants are, however, vulnerable and completely dependent on caregiving parents, not just for survival but also for their development. Darwin and Lorenz have long argued that there are specific infant facial features that elicit attention and responsiveness in adults. Until recently this has not been possible to study but neuroimaging has started to reveal some of the brain circuitry. However, it is not known how the brain changes over time in new parents as they gain experience with caregiving. Equally, little is known about the underlying brain mechanisms associated with disruption to normal parental caregiving.
I propose to study the brain changes associated with normal and disrupted development of parental caregiving in new parents who will undergo neuroimaging and psychological testing using standardised databases and test batteries of caregiving tasks. Subproject 1 will investigate the normal development of parental caregiving, beginning before pregnancy, using a longitudinal study of structural and functional brain changes in both women and men combined with their behavioural measures on caregiving tasks.
Subproject 2 will investigate the disrupted development of parental caregiving using a cross-sectional design to study the brain and behavioural effects on caregiving during potential disruptive changes to the parent or child. Specifically, my focus will be on A) parental sleep disruption and B) infant craniofacial abnormality of cleft lip and palate.
Finally, understanding the full brain mechanisms and architecture underlying parental caregiving requires a mechanistic synthesis of the findings of normal and disrupted development. Subproject 3 will use our existing advanced computational models to combine the findings from normal and disrupted development in order to identify the fundamental brain mechanisms and networks underlying the development of parenting.
Max ERC Funding
1 997 121 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym CCT
Project The psychology and neurobiology of cognitive control training in humans
Researcher (PI) Christopher David Iain Chambers
Host Institution (HI) CARDIFF UNIVERSITY
Call Details Consolidator Grant (CoG), SH4, ERC-2014-CoG
Summary Cognitive control regulates our thoughts and actions, helping us avoid impulsive behaviours that are inappropriate, costly or dangerous. In recent years, evidence has emerged that training in behavioural tasks that promote response inhibition or avoidance of specific stimuli can enhance cognitive control, reducing overeating and alcohol consumption. Despite the promising nature of cognitive control training (CCT), we know little about which CCT methods are most effective, how individual differences determine training outcomes, whether CCT produces benefits for real-life behaviour, and how CCT alters – and is determined by – the structure and function of the brain. My aim is to discover what works in CCT and how the effects of training relate to neurophysiology. Subproject 1 will be the largest ever trial on the effectiveness of different CCT methods for achieving weight loss, recruiting 36,000 participants worldwide to complete an internet-based training programme via the Guardian. This study will reveal, with high statistical power, which CCT methods are the most effective and which individual differences are most important for producing real-life benefits. Subproject 2 will investigate how CCT influences neurobiology, and how individual differences in neurobiology influence CCT outcomes. In Subproject 2a, I will focus on theoretically predicted changes to GABAergic systems in prefrontal and motor cortex, and I will test the effect of GABAergic brain stimulation on training outcomes. In Subproject 2b, I will use concurrent brain stimulation (TMS) and brain imaging (fMRI) to test how CCT alters top-down coupling between prefrontal cortex and remote regions that mediate reward and emotion. I will also study how CCT alters, and is altered by, white matter microstructure. This project promises to advance understanding of the causal determinants and moderators of CCT, with implications for its suitability as a clinical adjunct in addiction therapy and behaviour change.
Summary
Cognitive control regulates our thoughts and actions, helping us avoid impulsive behaviours that are inappropriate, costly or dangerous. In recent years, evidence has emerged that training in behavioural tasks that promote response inhibition or avoidance of specific stimuli can enhance cognitive control, reducing overeating and alcohol consumption. Despite the promising nature of cognitive control training (CCT), we know little about which CCT methods are most effective, how individual differences determine training outcomes, whether CCT produces benefits for real-life behaviour, and how CCT alters – and is determined by – the structure and function of the brain. My aim is to discover what works in CCT and how the effects of training relate to neurophysiology. Subproject 1 will be the largest ever trial on the effectiveness of different CCT methods for achieving weight loss, recruiting 36,000 participants worldwide to complete an internet-based training programme via the Guardian. This study will reveal, with high statistical power, which CCT methods are the most effective and which individual differences are most important for producing real-life benefits. Subproject 2 will investigate how CCT influences neurobiology, and how individual differences in neurobiology influence CCT outcomes. In Subproject 2a, I will focus on theoretically predicted changes to GABAergic systems in prefrontal and motor cortex, and I will test the effect of GABAergic brain stimulation on training outcomes. In Subproject 2b, I will use concurrent brain stimulation (TMS) and brain imaging (fMRI) to test how CCT alters top-down coupling between prefrontal cortex and remote regions that mediate reward and emotion. I will also study how CCT alters, and is altered by, white matter microstructure. This project promises to advance understanding of the causal determinants and moderators of CCT, with implications for its suitability as a clinical adjunct in addiction therapy and behaviour change.
Max ERC Funding
1 998 305 €
Duration
Start date: 2015-11-01, End date: 2020-10-31
Project acronym CilDyn
Project Molecular analysis of the Hedgehog signal transduction complex in the primary cilium
Researcher (PI) Christian Siebold
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Consolidator Grant (CoG), LS1, ERC-2014-CoG
Summary The unexpected connection between the primary cilium and cell-to-cell signalling is one of the most exciting discoveries in cell and developmental biology in the last decade. In particular, the Hedgehog (Hh) pathway relies on the primary cilium to fulfil its fundamental functions in orchestrating vertebrate development. This microtubule-based antenna, up to 5 µm long, protrudes from the plasma membrane of almost every human cell and is the essential compartment for the entire Hh signalling cascade. All its molecular components, from the most upstream transmembrane Hh receptor down to the ultimate transcription factors, are dynamically localised and enriched in the primary cilium. The aim of this proposal, which combines structural biology and live cell imaging, is to understand the function and signalling consequences of the multivalent interactions between Hh signal transducer proteins as well as their spatial and temporal regulation in the primary cilium. The key questions my laboratory will address are: What are the rules for assembly of Hh signal transduction complexes? How dynamic are these complexes in size and organisation? How are these processes linked to the transport and accumulation in the primary cilium?
I will combine state-of-the art structural biology techniques (with an emphasis on X-ray crystallography) to study the molecular architecture of binary and higher-order Hh signal transduction complexes and live cell fluorescence microscopy (for protein localisation and direct protein interactions). These two approaches will allow me to identify and define specific protein-protein interfaces at the atomic level and test their functional consequences in the cell in real time. My goal is to consolidate a world-class morphogen signal transduction laboratory, deciphering fundamental biological insights. Importantly, my results and reagents can potentially feed into the development of novel anti-cancer therapeutics and reagents promoting stem cell therapy.
Summary
The unexpected connection between the primary cilium and cell-to-cell signalling is one of the most exciting discoveries in cell and developmental biology in the last decade. In particular, the Hedgehog (Hh) pathway relies on the primary cilium to fulfil its fundamental functions in orchestrating vertebrate development. This microtubule-based antenna, up to 5 µm long, protrudes from the plasma membrane of almost every human cell and is the essential compartment for the entire Hh signalling cascade. All its molecular components, from the most upstream transmembrane Hh receptor down to the ultimate transcription factors, are dynamically localised and enriched in the primary cilium. The aim of this proposal, which combines structural biology and live cell imaging, is to understand the function and signalling consequences of the multivalent interactions between Hh signal transducer proteins as well as their spatial and temporal regulation in the primary cilium. The key questions my laboratory will address are: What are the rules for assembly of Hh signal transduction complexes? How dynamic are these complexes in size and organisation? How are these processes linked to the transport and accumulation in the primary cilium?
I will combine state-of-the art structural biology techniques (with an emphasis on X-ray crystallography) to study the molecular architecture of binary and higher-order Hh signal transduction complexes and live cell fluorescence microscopy (for protein localisation and direct protein interactions). These two approaches will allow me to identify and define specific protein-protein interfaces at the atomic level and test their functional consequences in the cell in real time. My goal is to consolidate a world-class morphogen signal transduction laboratory, deciphering fundamental biological insights. Importantly, my results and reagents can potentially feed into the development of novel anti-cancer therapeutics and reagents promoting stem cell therapy.
Max ERC Funding
1 727 456 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
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 Code4Memory
Project Neural oscillations - a code for memory
Researcher (PI) Simon Hanslmayr
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Call Details Consolidator Grant (CoG), SH4, ERC-2014-CoG
Summary Episodic memory refers to the fascinating human ability to remember past events in a highly associative and information rich way. But how are these memories coded in human brains? Any mechanism accounting for episodic memory must accomplish at least two functions: to build novel associations, and to represent the information constituting the memory. Neural oscillations, regulating the synchrony of neural assemblies, are ideally suited to accomplish these two functions, but in opposing ways. On the one hand, neurophysiological work suggests that increased synchrony strengthens synaptic connections and thus forms the basis for associative memory. Neurocomputational work, on the other hand, suggests that decreased synchrony is necessary to flexibly express information rich patterns in a neural assembly. Therefore, a conundrum exists as to how oscillations code episodic memory. The aim of this project is to propose and test a new framework that has the potential to reconcile this conflict. The central idea is that synchronization and desynchronization cooperatively code episodic memories, with synchronized activity in the hippocampus in the theta (~4 Hz) and gamma (~ 40-60 Hz) frequency range mediating the building of associations, and neocortical desynchronization in the alpha (~10 Hz) and beta (~15 Hz) frequency range mediating the representation of mnemonic information. Importantly the two modules, with their respective synchronous/asynchronous behaviours, must interact during the formation and retrieval of episodic memories, but how and whether this is the case remains untested to date. I will test these fundamental questions using a multidisciplinary and multi-method approach, including human single cell recordings, neuroimaging, brain stimulation, and computational modelling. The results from these experiments have the potential to reveal the neural code that human episodic memory is based on, which is still one of the biggest mysteries of the human mind.
Summary
Episodic memory refers to the fascinating human ability to remember past events in a highly associative and information rich way. But how are these memories coded in human brains? Any mechanism accounting for episodic memory must accomplish at least two functions: to build novel associations, and to represent the information constituting the memory. Neural oscillations, regulating the synchrony of neural assemblies, are ideally suited to accomplish these two functions, but in opposing ways. On the one hand, neurophysiological work suggests that increased synchrony strengthens synaptic connections and thus forms the basis for associative memory. Neurocomputational work, on the other hand, suggests that decreased synchrony is necessary to flexibly express information rich patterns in a neural assembly. Therefore, a conundrum exists as to how oscillations code episodic memory. The aim of this project is to propose and test a new framework that has the potential to reconcile this conflict. The central idea is that synchronization and desynchronization cooperatively code episodic memories, with synchronized activity in the hippocampus in the theta (~4 Hz) and gamma (~ 40-60 Hz) frequency range mediating the building of associations, and neocortical desynchronization in the alpha (~10 Hz) and beta (~15 Hz) frequency range mediating the representation of mnemonic information. Importantly the two modules, with their respective synchronous/asynchronous behaviours, must interact during the formation and retrieval of episodic memories, but how and whether this is the case remains untested to date. I will test these fundamental questions using a multidisciplinary and multi-method approach, including human single cell recordings, neuroimaging, brain stimulation, and computational modelling. The results from these experiments have the potential to reveal the neural code that human episodic memory is based on, which is still one of the biggest mysteries of the human mind.
Max ERC Funding
1 897 751 €
Duration
Start date: 2015-10-01, End date: 2021-09-30
Project acronym COGTOM
Project Cognitive tomography of mental representations
Researcher (PI) Máté Miklós LENGYEL
Host Institution (HI) KOZEP-EUROPAI EGYETEM
Call Details Consolidator Grant (CoG), SH4, ERC-2016-COG
Summary Internal models are fundamental to our understanding of how the mind constructs percepts, makes decisions, controls movements, and interacts with others. Yet, we lack principled quantitative methods to systematically estimate internal models from observable behaviour, and current approaches for discovering their mental representations remain heuristic and piecemeal. I propose to develop a set of novel 'doubly Bayesian' data analytical methods, using state-of-the-art Bayesian statistical and machine learning techniques to infer humans' internal models formalised as prior distributions in Bayesian models of cognition. This approach, cognitive tomography, takes a series of behavioural observations, each of which in itself may have very limited information content, and accumulates a detailed reconstruction of the internal model based on these observations. I also propose a set of stringent, quantifiable criteria which will be systematically applied at each step of the proposed work to rigorously assess the success of our approach. These methodological advances will allow us to track how the structured, task-general internal models that are so fundamental to humans' superior cognitive abilities, change over time as a result of decay, interference, and learning. We will apply cognitive tomography to a variety of experimental data sets, collected by our collaborators, in paradigms ranging from perceptual learning, through visual and motor structure learning, to social and concept learning. These analyses will allow us to conclusively and quantitatively test our central hypothesis that, rather than simply changing along a single 'memory strength' dimension, internal models typically change via complex and consistent patterns of transformations along multiple dimensions simultaneously. To facilitate the widespread use of our methods, we will release and support off-the-shelf usable implementations of our algorithms together with synthetic and real test data sets.
Summary
Internal models are fundamental to our understanding of how the mind constructs percepts, makes decisions, controls movements, and interacts with others. Yet, we lack principled quantitative methods to systematically estimate internal models from observable behaviour, and current approaches for discovering their mental representations remain heuristic and piecemeal. I propose to develop a set of novel 'doubly Bayesian' data analytical methods, using state-of-the-art Bayesian statistical and machine learning techniques to infer humans' internal models formalised as prior distributions in Bayesian models of cognition. This approach, cognitive tomography, takes a series of behavioural observations, each of which in itself may have very limited information content, and accumulates a detailed reconstruction of the internal model based on these observations. I also propose a set of stringent, quantifiable criteria which will be systematically applied at each step of the proposed work to rigorously assess the success of our approach. These methodological advances will allow us to track how the structured, task-general internal models that are so fundamental to humans' superior cognitive abilities, change over time as a result of decay, interference, and learning. We will apply cognitive tomography to a variety of experimental data sets, collected by our collaborators, in paradigms ranging from perceptual learning, through visual and motor structure learning, to social and concept learning. These analyses will allow us to conclusively and quantitatively test our central hypothesis that, rather than simply changing along a single 'memory strength' dimension, internal models typically change via complex and consistent patterns of transformations along multiple dimensions simultaneously. To facilitate the widespread use of our methods, we will release and support off-the-shelf usable implementations of our algorithms together with synthetic and real test data sets.
Max ERC Funding
1 179 462 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
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 CRYOREP
Project Chromosome Replication Visualised by Cryo-EM
Researcher (PI) Alessandro COSTA
Host Institution (HI) THE FRANCIS CRICK INSTITUTE LIMITED
Call Details Consolidator Grant (CoG), LS1, ERC-2018-COG
Summary In eukaryotic cells, DNA replication is tightly regulated to ensure that the genome is duplicated only once per cell cycle. Errors in the control mechanisms that regulate chromosome ploidy cause genomic instability, which is linked to the development of cellular abnormalities, genetic disease and the onset of cancer. Recent reconstitution experiments performed with purified proteins revealed that initiation of eukaryotic genome duplication requires three distinct steps. First, DNA replication start sites are identified and targeted for the loading of an inactive MCM helicase motor, which encircles the double helix. Second, MCM activators are recruited, causing duplex-DNA untwisting. Third, upon interaction with a firing factor, the MCM ring opens to eject one DNA strand, leading to unwinding of the replication fork and duplication by dedicated replicative polymerases. These three events are not understood at a molecular level. Structural investigations so far aimed at imaging artificially isolated replication steps and used simplified templates, such as linear duplex DNA to study helicase loading or pre-formed forks to understand unwinding. However, the natural substrate of the eukaryotic replication machinery is not DNA but rather chromatin, formed of nucleosome arrays that compact the genome. Chromatin plays important regulatory roles in all steps of DNA replication, by dictating origin start-site selection and stimulating replication fork progression. Only by studying chromatin replication, we argue, will we understand the molecular basis of genome propagation. To this end, we have developed new protocols to perform visual biochemistry experiments under the cryo-electron microscope, to image chromatin duplication at high resolution, frozen as it is being catalysed. Using these strategies we want to generate a molecular movie of the entire replication reaction. Our achievements will change the way we think about genome stability in eukaryotic cells.
Summary
In eukaryotic cells, DNA replication is tightly regulated to ensure that the genome is duplicated only once per cell cycle. Errors in the control mechanisms that regulate chromosome ploidy cause genomic instability, which is linked to the development of cellular abnormalities, genetic disease and the onset of cancer. Recent reconstitution experiments performed with purified proteins revealed that initiation of eukaryotic genome duplication requires three distinct steps. First, DNA replication start sites are identified and targeted for the loading of an inactive MCM helicase motor, which encircles the double helix. Second, MCM activators are recruited, causing duplex-DNA untwisting. Third, upon interaction with a firing factor, the MCM ring opens to eject one DNA strand, leading to unwinding of the replication fork and duplication by dedicated replicative polymerases. These three events are not understood at a molecular level. Structural investigations so far aimed at imaging artificially isolated replication steps and used simplified templates, such as linear duplex DNA to study helicase loading or pre-formed forks to understand unwinding. However, the natural substrate of the eukaryotic replication machinery is not DNA but rather chromatin, formed of nucleosome arrays that compact the genome. Chromatin plays important regulatory roles in all steps of DNA replication, by dictating origin start-site selection and stimulating replication fork progression. Only by studying chromatin replication, we argue, will we understand the molecular basis of genome propagation. To this end, we have developed new protocols to perform visual biochemistry experiments under the cryo-electron microscope, to image chromatin duplication at high resolution, frozen as it is being catalysed. Using these strategies we want to generate a molecular movie of the entire replication reaction. Our achievements will change the way we think about genome stability in eukaryotic cells.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym DNAMEREP
Project The role of essential DNA metabolism genes in vertebrate chromosome replication
Researcher (PI) Vincenzo Costanzo
Host Institution (HI) IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE
Call Details Consolidator Grant (CoG), LS1, ERC-2013-CoG
Summary "Faithful chromosomal DNA replication is essential to maintain genome stability. A number of DNA metabolism genes are involved at different levels in DNA replication. These factors are thought to facilitate the establishment of replication origins, assist the replication of chromatin regions with repetitive DNA, coordinate the repair of DNA molecules resulting from aberrant DNA replication events or protect replication forks in the presence of DNA lesions that impair their progression. Some DNA metabolism genes are present mainly in higher eukaryotes, suggesting the existence of more complex repair and replication mechanisms in organisms with complex genomes. The impact on cell survival of many DNA metabolism genes has so far precluded in depth molecular analysis. The use of cell free extracts able to recapitulate cell cycle events might help overcoming survival issues and facilitate these studies. The Xenopus laevis egg cell free extract represents an ideal system to study replication-associated functions of essential genes in vertebrate organisms. We will take advantage of this system together with innovative imaging and proteomic based experimental approaches that we are currently developing to characterize the molecular function of some essential DNA metabolism genes. In particular, we will characterize DNA metabolism genes involved in the assembly and distribution of replication origins in vertebrate cells, elucidate molecular mechanisms underlying the role of essential homologous recombination and fork protection proteins in chromosomal DNA replication, and finally identify and characterize factors required for faithful replication of specific vertebrate genomic regions.
The results of these studies will provide groundbreaking information on several aspects of vertebrate genome metabolism and will allow long-awaited understanding of the function of a number of vertebrate essential DNA metabolism genes involved in the duplication of large and complex genomes."
Summary
"Faithful chromosomal DNA replication is essential to maintain genome stability. A number of DNA metabolism genes are involved at different levels in DNA replication. These factors are thought to facilitate the establishment of replication origins, assist the replication of chromatin regions with repetitive DNA, coordinate the repair of DNA molecules resulting from aberrant DNA replication events or protect replication forks in the presence of DNA lesions that impair their progression. Some DNA metabolism genes are present mainly in higher eukaryotes, suggesting the existence of more complex repair and replication mechanisms in organisms with complex genomes. The impact on cell survival of many DNA metabolism genes has so far precluded in depth molecular analysis. The use of cell free extracts able to recapitulate cell cycle events might help overcoming survival issues and facilitate these studies. The Xenopus laevis egg cell free extract represents an ideal system to study replication-associated functions of essential genes in vertebrate organisms. We will take advantage of this system together with innovative imaging and proteomic based experimental approaches that we are currently developing to characterize the molecular function of some essential DNA metabolism genes. In particular, we will characterize DNA metabolism genes involved in the assembly and distribution of replication origins in vertebrate cells, elucidate molecular mechanisms underlying the role of essential homologous recombination and fork protection proteins in chromosomal DNA replication, and finally identify and characterize factors required for faithful replication of specific vertebrate genomic regions.
The results of these studies will provide groundbreaking information on several aspects of vertebrate genome metabolism and will allow long-awaited understanding of the function of a number of vertebrate essential DNA metabolism genes involved in the duplication of large and complex genomes."
Max ERC Funding
1 999 800 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
