Project acronym BABYRHYTHM
Project Oscillatory Rhythmic Entrainment and the Foundations of Language Acquisition
Researcher (PI) Usha Claire GOSWAMI
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), SH4, ERC-2015-AdG
Summary Half of “late talkers”, infants who are not yet speaking by 2 years of age, will go on to develop language impairments. Currently, we have no reliable means of identifying these infants. Here we combine our developmental approach to phonology (psycholinguistic grain size theory), to the neural mechanisms underlying speech encoding (temporal sampling [TS] theory) and our work on the developmental importance of the speech amplitude envelope (AE) to open a new research front in the foundations of language acquisition. Recent adult research confirms our decade-long focus on the importance of sensitivity to AE ‘rise time’ in children’s language development, showing that rise times (‘auditory edges’) re-set the endogenous cortical oscillations that encode speech. Accordingly, we now apply our in-house state-of-the-art methods for measuring oscillatory rhythmic entrainment in children along with our recent theoretical and behavioural advances concerning AE processing to infant studies. Our core aim is to use the TS theoretical perspective and analysis methods to generate robust early neural and behavioural markers of phonological and morphological development: TS for infants. We have published the first-ever studies of oscillatory entrainment to speech rhythm by children and we have developed methods for technically-challenging EEG speech envelope reconstruction. We now apply these innovative methods to infant language learning and infant-directed speech. Using our cutting-edge EEG methods, we will deliver a novel and innovative road map for charting early language acquisition from a rhythmic entrainment perspective. Our recent 5-year study of rise time sensitivity in infants confirms the feasibility of a TS approach. As our focus is on prosody, syllable stress and syllable processing, our methods will apply across European languages.
Summary
Half of “late talkers”, infants who are not yet speaking by 2 years of age, will go on to develop language impairments. Currently, we have no reliable means of identifying these infants. Here we combine our developmental approach to phonology (psycholinguistic grain size theory), to the neural mechanisms underlying speech encoding (temporal sampling [TS] theory) and our work on the developmental importance of the speech amplitude envelope (AE) to open a new research front in the foundations of language acquisition. Recent adult research confirms our decade-long focus on the importance of sensitivity to AE ‘rise time’ in children’s language development, showing that rise times (‘auditory edges’) re-set the endogenous cortical oscillations that encode speech. Accordingly, we now apply our in-house state-of-the-art methods for measuring oscillatory rhythmic entrainment in children along with our recent theoretical and behavioural advances concerning AE processing to infant studies. Our core aim is to use the TS theoretical perspective and analysis methods to generate robust early neural and behavioural markers of phonological and morphological development: TS for infants. We have published the first-ever studies of oscillatory entrainment to speech rhythm by children and we have developed methods for technically-challenging EEG speech envelope reconstruction. We now apply these innovative methods to infant language learning and infant-directed speech. Using our cutting-edge EEG methods, we will deliver a novel and innovative road map for charting early language acquisition from a rhythmic entrainment perspective. Our recent 5-year study of rise time sensitivity in infants confirms the feasibility of a TS approach. As our focus is on prosody, syllable stress and syllable processing, our methods will apply across European languages.
Max ERC Funding
2 614 275 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym BRAIN2MIND_NEUROCOMP
Project Developing and delivering neurocomputational models to bridge between brain and mind.
Researcher (PI) Matthew Lambon Ralph
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Advanced Grant (AdG), SH4, ERC-2014-ADG
Summary The promise of cognitive neuroscience is truly exciting – to link mind and brain in order to reveal the neural basis of higher cognitive functions. This is crucial, scientifically, if we are to understand the nature of mental processes and how they arise from neural machinery but also, clinically, if we are to establish the basis of neurological patients’ impairments, their clinical management and treatment. Cognitive-clinical neuroscience depends on three ingredients: (a) investigating complex mental behaviours and the underlying cognitive processes; (b) mapping neural systems and their function; and (c) methods and tools that can bridge the gap between brain and mental behaviour. Experimental psychology and behavioural neurology has delivered the first component. In vivo neuroimaging and other allied technologies allow us to probe and map neural systems, their connectivity and neurobiological responses. The principal aim of this ERC Advanced grant is to secure, for the first time, the crucial third ingredient – the methods and tools for bridging systematically between cognitive science and systems neuroscience.
The grant will be based on two main activities: (i) convergence of methods – instead of employing each neuroscience and cognitive method independently, they will be planned and executed simultaneously to force a convergence of results; and (ii) development of a new type of neurocomputational model - to provide a novel formalism for bridging between brain and cognition. Computational models are used in cognitive science to mimic normal and impaired behaviour. Such models also have an as-yet untapped potential to connect neuroanatomy and cognition: latent in every model is a kind of brain-mind duality – each model is based on a computational architecture which generates behaviour. We will retain the ability to simulate detailed cognitive behaviour but simultaneously make the models’ architecture reflect systems-level neuroanatomy and function.
Summary
The promise of cognitive neuroscience is truly exciting – to link mind and brain in order to reveal the neural basis of higher cognitive functions. This is crucial, scientifically, if we are to understand the nature of mental processes and how they arise from neural machinery but also, clinically, if we are to establish the basis of neurological patients’ impairments, their clinical management and treatment. Cognitive-clinical neuroscience depends on three ingredients: (a) investigating complex mental behaviours and the underlying cognitive processes; (b) mapping neural systems and their function; and (c) methods and tools that can bridge the gap between brain and mental behaviour. Experimental psychology and behavioural neurology has delivered the first component. In vivo neuroimaging and other allied technologies allow us to probe and map neural systems, their connectivity and neurobiological responses. The principal aim of this ERC Advanced grant is to secure, for the first time, the crucial third ingredient – the methods and tools for bridging systematically between cognitive science and systems neuroscience.
The grant will be based on two main activities: (i) convergence of methods – instead of employing each neuroscience and cognitive method independently, they will be planned and executed simultaneously to force a convergence of results; and (ii) development of a new type of neurocomputational model - to provide a novel formalism for bridging between brain and cognition. Computational models are used in cognitive science to mimic normal and impaired behaviour. Such models also have an as-yet untapped potential to connect neuroanatomy and cognition: latent in every model is a kind of brain-mind duality – each model is based on a computational architecture which generates behaviour. We will retain the ability to simulate detailed cognitive behaviour but simultaneously make the models’ architecture reflect systems-level neuroanatomy and function.
Max ERC Funding
2 294 781 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym BYPASSWITHOUTSURGERY
Project Reaching the effects of gastric bypass on diabetes and obesity without surgery
Researcher (PI) Jens Juul Holst
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), LS4, ERC-2015-AdG
Summary Gastric bypass surgery results in massive weight loss and diabetes remission. The effect is superior to intensive medical treatment, showing that there are mechanisms within the body that can cure diabetes and obesity. Revealing the nature of these mechanisms could lead to new, cost-efficient, similarly effective, non-invasive treatments of these conditions. The hypothesis is that hyper-secretion of a number of gut hormones mediates the effect of surgery, as indicated by a series of our recent studies, demonstrating that hypersecretion of GLP-1, a hormone discovered in my laboratory and basis for the antidiabetic medication of millions of patients, is essential for the improved insulin secretion and glucose tolerance. But what are the mechanisms behind the up to 30-fold elevations in secretion of these hormones following surgery? Constantly with a translational scope, all elements involved in these responses will be addressed in this project, from detailed analysis of food items responsible for hormone secretion, to identification of the responsible regions of the gut, and to the molecular mechanisms leading to hypersecretion. Novel approaches for studies of human gut hormone secreting cells, including specific expression analysis, are combined with our advanced and unique isolated perfused gut preparations, the only tool that can provide physiologically relevant results with a translational potential regarding regulation of hormone secretion in the gut. This will lead to further groundbreaking experimental attempts to mimic and engage the identified mechanisms, creating similar hypersecretion and obtaining similar improvements as the operations in patients with obesity and diabetes. Based on our profound knowledge of gut hormone biology accumulated through decades of intensive and successful research and our successful elucidation of the antidiabetic actions of gastric bypass surgery, we are in a unique position to reach this ambitious goal.
Summary
Gastric bypass surgery results in massive weight loss and diabetes remission. The effect is superior to intensive medical treatment, showing that there are mechanisms within the body that can cure diabetes and obesity. Revealing the nature of these mechanisms could lead to new, cost-efficient, similarly effective, non-invasive treatments of these conditions. The hypothesis is that hyper-secretion of a number of gut hormones mediates the effect of surgery, as indicated by a series of our recent studies, demonstrating that hypersecretion of GLP-1, a hormone discovered in my laboratory and basis for the antidiabetic medication of millions of patients, is essential for the improved insulin secretion and glucose tolerance. But what are the mechanisms behind the up to 30-fold elevations in secretion of these hormones following surgery? Constantly with a translational scope, all elements involved in these responses will be addressed in this project, from detailed analysis of food items responsible for hormone secretion, to identification of the responsible regions of the gut, and to the molecular mechanisms leading to hypersecretion. Novel approaches for studies of human gut hormone secreting cells, including specific expression analysis, are combined with our advanced and unique isolated perfused gut preparations, the only tool that can provide physiologically relevant results with a translational potential regarding regulation of hormone secretion in the gut. This will lead to further groundbreaking experimental attempts to mimic and engage the identified mechanisms, creating similar hypersecretion and obtaining similar improvements as the operations in patients with obesity and diabetes. Based on our profound knowledge of gut hormone biology accumulated through decades of intensive and successful research and our successful elucidation of the antidiabetic actions of gastric bypass surgery, we are in a unique position to reach this ambitious goal.
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym CADRE
Project Cardiac Death and Regeneration
Researcher (PI) Michael David Schneider
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Advanced Grant (AdG), LS4, ERC-2008-AdG
Summary Cardiac muscle death, unmatched by muscle cell creation, is the hallmark of acute myocardial infarction and chronic cardiomyopathies. The notion of heart failure as a muscle-cell deficiency disease has driven interest worldwide in ways to increase heart muscle cell number, by over-riding cell cycle constraints, suppressing cell death, or, most directly, cell grafting. Using stem cell antigen-1, we previously identified telomerase-expressing cells in adult mouse myocardium, which have salutary properties for bona fide cardiac regeneration. Here, we seek to address systematically the mechanisms for long-term self-renewal in Sca-1+ adult cardiac progenitor cells and in the smaller side population fraction, which is clonogenic and expresses telomerase at even higher levels. Specifically, we propose to study the roles of telomerase and of the telomere-capping protein, TRF2. Aim 1, Determine the properties of adult cardiac progenitor cells in mice that lack the RNA component of telomerase (TERC). Aim 2, Determine the properties of adult cardiac progenitor cells in mice that lack the catalytic component (TERT). To distinguish between effects of these two gene products themselves versus those that depend on cumulative telomere dysfunction, G2- and G5-null mice will be compared. Aim 3, Determine the properties of adult cardiac muscle and adult cardiac progenitor cells that lack the telomere-capping protein TRF2. Aim 4, Test the prediction that forced expression of TERT and TRF2 can augment cardiac muscle engraftment in vivo and enhance the clonal derivation of adult cardiac progenitor cells in vitro, without adversely affecting the cells differentiation potential. Work proposed in Aims 1-3 would provide indispensable fundamental information about the function of endogenous telomerase in adult cardiac progenitor cells. Conversely, work in Aim 4 would test potential therapeutic implications of telomerase and a telomere-capping protein with this auspicious population.
Summary
Cardiac muscle death, unmatched by muscle cell creation, is the hallmark of acute myocardial infarction and chronic cardiomyopathies. The notion of heart failure as a muscle-cell deficiency disease has driven interest worldwide in ways to increase heart muscle cell number, by over-riding cell cycle constraints, suppressing cell death, or, most directly, cell grafting. Using stem cell antigen-1, we previously identified telomerase-expressing cells in adult mouse myocardium, which have salutary properties for bona fide cardiac regeneration. Here, we seek to address systematically the mechanisms for long-term self-renewal in Sca-1+ adult cardiac progenitor cells and in the smaller side population fraction, which is clonogenic and expresses telomerase at even higher levels. Specifically, we propose to study the roles of telomerase and of the telomere-capping protein, TRF2. Aim 1, Determine the properties of adult cardiac progenitor cells in mice that lack the RNA component of telomerase (TERC). Aim 2, Determine the properties of adult cardiac progenitor cells in mice that lack the catalytic component (TERT). To distinguish between effects of these two gene products themselves versus those that depend on cumulative telomere dysfunction, G2- and G5-null mice will be compared. Aim 3, Determine the properties of adult cardiac muscle and adult cardiac progenitor cells that lack the telomere-capping protein TRF2. Aim 4, Test the prediction that forced expression of TERT and TRF2 can augment cardiac muscle engraftment in vivo and enhance the clonal derivation of adult cardiac progenitor cells in vitro, without adversely affecting the cells differentiation potential. Work proposed in Aims 1-3 would provide indispensable fundamental information about the function of endogenous telomerase in adult cardiac progenitor cells. Conversely, work in Aim 4 would test potential therapeutic implications of telomerase and a telomere-capping protein with this auspicious population.
Max ERC Funding
2 497 576 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym CANBUILD
Project Building a Human Tumour Microenvironment
Researcher (PI) Frances Rosemary Balkwill
Host Institution (HI) QUEEN MARY UNIVERSITY OF LONDON
Call Details Advanced Grant (AdG), LS4, ERC-2012-ADG_20120314
Summary Even at their earliest stages, human cancers are more than just cells with malignant potential. Cells and extracellular matrix components that normally support and protect the body are coerced into a tumour microenvironment that is central to disease progression. My hypothesis is that recent advances in tissue engineering, biomechanics and stem cell biology make it possible to engineer, for the first time, a complex 3D human tumour microenvironment in which individual cell lineages of malignant, haemopoietic and mesenchymal origin will communicate, evolve and grow in vitro. The ultimate aim is to build this cancerous tissue with autologous cells: there is an urgent need for models in which we can study the interaction of human immune cells with malignant cells from the same individual in an appropriate 3D biomechanical microenvironment.
To achieve the objectives of the CANBUILD project, I have assembled a multi-disciplinary team of collaborators with international standing in tumour microenvironment research, cancer treatment, tissue engineering, mechanobiology, stem cell research and 3D computer-assisted imaging.
The goal is to recreate the microenvironment of high-grade serous ovarian cancer metastases in the omentum. This is a major clinical problem, my lab has extensive knowledge of this microenvironment and we have already established simple 3D models of these metastases.
The research plan involves:
Deconstruction of this specific tumour microenvironment
Construction of artificial scaffold, optimising growth of cell lineages, assembly of the model
Comparison to fresh tissue
Investigating the role of individual cell lineages
Testing therapies that target the tumour microenvironment
My vision is that this project will revolutionise the practice of human malignant cell research, replacing misleading systems based on cancer cell monoculture on plastic surfaces and allowing us to better test new treatments that target the human tumour microenvironment.
Summary
Even at their earliest stages, human cancers are more than just cells with malignant potential. Cells and extracellular matrix components that normally support and protect the body are coerced into a tumour microenvironment that is central to disease progression. My hypothesis is that recent advances in tissue engineering, biomechanics and stem cell biology make it possible to engineer, for the first time, a complex 3D human tumour microenvironment in which individual cell lineages of malignant, haemopoietic and mesenchymal origin will communicate, evolve and grow in vitro. The ultimate aim is to build this cancerous tissue with autologous cells: there is an urgent need for models in which we can study the interaction of human immune cells with malignant cells from the same individual in an appropriate 3D biomechanical microenvironment.
To achieve the objectives of the CANBUILD project, I have assembled a multi-disciplinary team of collaborators with international standing in tumour microenvironment research, cancer treatment, tissue engineering, mechanobiology, stem cell research and 3D computer-assisted imaging.
The goal is to recreate the microenvironment of high-grade serous ovarian cancer metastases in the omentum. This is a major clinical problem, my lab has extensive knowledge of this microenvironment and we have already established simple 3D models of these metastases.
The research plan involves:
Deconstruction of this specific tumour microenvironment
Construction of artificial scaffold, optimising growth of cell lineages, assembly of the model
Comparison to fresh tissue
Investigating the role of individual cell lineages
Testing therapies that target the tumour microenvironment
My vision is that this project will revolutionise the practice of human malignant cell research, replacing misleading systems based on cancer cell monoculture on plastic surfaces and allowing us to better test new treatments that target the human tumour microenvironment.
Max ERC Funding
2 431 035 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym CANDICE
Project CEREBRAL ASYMMETRY: NEW DIRECTIONS IN CORRELATES AND ETIOLOGY
Researcher (PI) Dorothy Vera Margaret BISHOP
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), SH4, ERC-2015-AdG
Summary "150 years after Broca's seminal statement "Nous parlons avec l'hémisphère gauche" we still do not know how or why we have this bias. I propose that by studying cases of impaired language development and combining genetic and neuropsychological approaches we will be able to make a leap forward in our understanding of the quintessentially human characteristic of functional cerebral asymmetry. I argue that contradictory findings in the literature may be reconciled if we adopt a novel approach to cerebral asymmetry. In particular, I propose a network efficiency hypothesis which maintains that optimal development depends on organisation of key language functions within the same cerebral hemisphere.
In project A, I will combine behavioural measures with functional transcranial Doppler ultrasound (fTCD) measures of blood flow and functional magnetic resonance imaging (fMRI) to identify individual differences in patterns of dissociation between language functions in lateralisation. In project B I will test the prediction that risk for language and literacy impairment is increased if different language functions are represented in opposite hemispheres. For project C, simulations of predictions from genetic models will be tested using data on twin-cotwin similarity in language lateralisation. Project D will test a 'double hit' genetic model that predicts that neurodevelopmental abnormalities, including language deficits and inconsistent asymmetry, arise when there is more than one hit on a functional brain circuit. For this study we will use an existing sample of individuals already known to have one 'hit' on the neuroligin-neurexin circuit, viz people with an additional dose of neuroligin caused by an extra sex chromosome. Project E will focus on individuals with inconsistent patterns of language laterality and will look for rare genetic mutations and structural rearrangements associated with a departure from consistent left hemisphere language."
Summary
"150 years after Broca's seminal statement "Nous parlons avec l'hémisphère gauche" we still do not know how or why we have this bias. I propose that by studying cases of impaired language development and combining genetic and neuropsychological approaches we will be able to make a leap forward in our understanding of the quintessentially human characteristic of functional cerebral asymmetry. I argue that contradictory findings in the literature may be reconciled if we adopt a novel approach to cerebral asymmetry. In particular, I propose a network efficiency hypothesis which maintains that optimal development depends on organisation of key language functions within the same cerebral hemisphere.
In project A, I will combine behavioural measures with functional transcranial Doppler ultrasound (fTCD) measures of blood flow and functional magnetic resonance imaging (fMRI) to identify individual differences in patterns of dissociation between language functions in lateralisation. In project B I will test the prediction that risk for language and literacy impairment is increased if different language functions are represented in opposite hemispheres. For project C, simulations of predictions from genetic models will be tested using data on twin-cotwin similarity in language lateralisation. Project D will test a 'double hit' genetic model that predicts that neurodevelopmental abnormalities, including language deficits and inconsistent asymmetry, arise when there is more than one hit on a functional brain circuit. For this study we will use an existing sample of individuals already known to have one 'hit' on the neuroligin-neurexin circuit, viz people with an additional dose of neuroligin caused by an extra sex chromosome. Project E will focus on individuals with inconsistent patterns of language laterality and will look for rare genetic mutations and structural rearrangements associated with a departure from consistent left hemisphere language."
Max ERC Funding
2 497 907 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym CARDIOREDOX
Project Redox sensing and signalling in cardiovascular health and disease
Researcher (PI) Philip Eaton
Host Institution (HI) KING'S COLLEGE LONDON
Call Details Advanced Grant (AdG), LS4, ERC-2013-ADG
Summary "We want to determine how oxidants are sensed and transduced into a biological effect within the cardiovascular system. The proposed work will focus on thiol-based redox sensors, defining their role in heart and blood vessel function during health and disease. Although this laboratory has studied the molecular basis of redox signaling for more than a decade, the subject is still in its relative infancy with considerable scope for major advances. Oxidant signaling remains a ‘hot topic’ with high profile studies confirming a fundamental role for redox control of protein and cellular function continuing to emerge. The molecular basis of redox sensing is the reaction of an oxidant with target proteins. This gives rise to oxidative post-translational modifications, most commonly of cysteinyl thiols, potentially altering the activity of proteins to regulate cell or tissue function. One of the reasons there are so many unanswered questions about redox sensing and signaling is the diversity of oxidant molecules produced by cells that can interact with sensor proteins to alter their function. This application is aimed at extending our knowledge of redox sensing and signalling, allowing us to define its importance in cardiovascular health and disease."
Summary
"We want to determine how oxidants are sensed and transduced into a biological effect within the cardiovascular system. The proposed work will focus on thiol-based redox sensors, defining their role in heart and blood vessel function during health and disease. Although this laboratory has studied the molecular basis of redox signaling for more than a decade, the subject is still in its relative infancy with considerable scope for major advances. Oxidant signaling remains a ‘hot topic’ with high profile studies confirming a fundamental role for redox control of protein and cellular function continuing to emerge. The molecular basis of redox sensing is the reaction of an oxidant with target proteins. This gives rise to oxidative post-translational modifications, most commonly of cysteinyl thiols, potentially altering the activity of proteins to regulate cell or tissue function. One of the reasons there are so many unanswered questions about redox sensing and signaling is the diversity of oxidant molecules produced by cells that can interact with sensor proteins to alter their function. This application is aimed at extending our knowledge of redox sensing and signalling, allowing us to define its importance in cardiovascular health and disease."
Max ERC Funding
2 255 659 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
Project acronym CAUSCOG
Project Tool Use As A Tool For Understanding Causal Cognition In Humans And Corvids
Researcher (PI) Nicola Susan Clayton
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), SH4, ERC-2013-ADG
Summary "Our ability to understand causality is at the very core of modern civilization. We see potential antecedents of this understanding in some non-human animals, notably apes and corvids. To date, behaviour thought to be indicative of causal understanding, particularly tool-use, has been mainly described as a phenomenon rather than studied as a mechanism and thus suffers from the lack of an experimentally-tested theoretical framework and deconstructive analysis. This significantly constrains our progress in answering key questions such as: (1) how do humans understand the physical world and solve problems? (2) what other ways of understanding causality and problem solving has evolution produced? (3) what selective pressures lead to the evolution of causal cognition? Each of these questions constitutes an area where there exists enormous potential to advance cognitive science. The overarching aim is to create a coherent, experimentally-tested, theoretical framework of the cognitive mechanisms underlying causal knowledge in corvids and humans, both young and adult. The advantage of our approach is that we will study two types of mind that have very different neural machineries and investigate the similarities and differences in their cognitive processes. We will create a sufficient level of abstraction to develop a deep theory of cognition, something that would not be possible by studying only a single species and its close evolutionary relatives. One of the most exciting aspects is that we will begin to map the ‘universal mind’ (i.e. the cognitive mechanisms that are repeatedly created by convergent evolution) to provide a quantum leap in our understanding of cognition. Finally, by discovering evolved biases in children’s learning and reasoning mechanisms we will pave the way for new teaching methods that boost learning in the classroom by appealing to the way children naturally understand the world."
Summary
"Our ability to understand causality is at the very core of modern civilization. We see potential antecedents of this understanding in some non-human animals, notably apes and corvids. To date, behaviour thought to be indicative of causal understanding, particularly tool-use, has been mainly described as a phenomenon rather than studied as a mechanism and thus suffers from the lack of an experimentally-tested theoretical framework and deconstructive analysis. This significantly constrains our progress in answering key questions such as: (1) how do humans understand the physical world and solve problems? (2) what other ways of understanding causality and problem solving has evolution produced? (3) what selective pressures lead to the evolution of causal cognition? Each of these questions constitutes an area where there exists enormous potential to advance cognitive science. The overarching aim is to create a coherent, experimentally-tested, theoretical framework of the cognitive mechanisms underlying causal knowledge in corvids and humans, both young and adult. The advantage of our approach is that we will study two types of mind that have very different neural machineries and investigate the similarities and differences in their cognitive processes. We will create a sufficient level of abstraction to develop a deep theory of cognition, something that would not be possible by studying only a single species and its close evolutionary relatives. One of the most exciting aspects is that we will begin to map the ‘universal mind’ (i.e. the cognitive mechanisms that are repeatedly created by convergent evolution) to provide a quantum leap in our understanding of cognition. Finally, by discovering evolved biases in children’s learning and reasoning mechanisms we will pave the way for new teaching methods that boost learning in the classroom by appealing to the way children naturally understand the world."
Max ERC Funding
2 164 833 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym CCFIB
Project Cardiac Control of Fear in Brain
Researcher (PI) Hugo Dyfrig Critchley
Host Institution (HI) THE UNIVERSITY OF SUSSEX
Call Details Advanced Grant (AdG), SH4, ERC-2012-ADG_20120411
Summary "Imagine what might be possible if you can turn fear on and off. In exploring the contribution of bodily arousal to emotions, we uncovered a specific mechanism whereby the brain’s processing of threatening / fear stimuli is ‘gated’ by the occurrence of heartbeats: Fear stimuli presented when the heart has just made a beat are processed more effectively than at other times, modulating their emotional impact. We term this effect the Cardiac Control of Fear in Brain (CCFIB). Specifically, I wish to refine, develop and exploit CCFIB as; 1) a clinical screening tool for drugs and patients; 2) as the basis of an intervention to accelerate unlearning of fear, e.g. for treatment of anxiety disorders; 3) as a means to optimise and enrich human-machine interactions, in anticipation of the rapid development of virtual or augmented reality (VR/AR) as a therapeutic tool, and to open possibilities for improving machine operation. This ground-breaking project will have impact in many areas, notably in the clinical management of anxiety disorders, which affect 69.1 million European Union citizens at an annual cost of €74.4 billion, and in the educational, recreational and occupational realms of human-machine interaction. The proposal 1) will refine knowledge about the neurochemistry and stimulus-specificity of CCFIB for implementation as a clinical screening tool, using pharmacological and neuroimaging methods. 2) Test in clinical anxiety patients the power of CCFIB to predict symptom profile and response to psychological and pharmacological treatment. 3) Optimize CCFIB to augment psychological and behavioural treatments and validate this in phobic individuals. 4) Instantiate CCFIB in VR/AR settings to enhance engagement with virtual environments, develop VR/AR as a ‘training platform’ in clinical and recreational contexts and to demonstrate how reactions to rapid threats fluctuate with cardiac cycle, motivating corresponding changes in sensitivity of user interfaces (e.g. brakes)."
Summary
"Imagine what might be possible if you can turn fear on and off. In exploring the contribution of bodily arousal to emotions, we uncovered a specific mechanism whereby the brain’s processing of threatening / fear stimuli is ‘gated’ by the occurrence of heartbeats: Fear stimuli presented when the heart has just made a beat are processed more effectively than at other times, modulating their emotional impact. We term this effect the Cardiac Control of Fear in Brain (CCFIB). Specifically, I wish to refine, develop and exploit CCFIB as; 1) a clinical screening tool for drugs and patients; 2) as the basis of an intervention to accelerate unlearning of fear, e.g. for treatment of anxiety disorders; 3) as a means to optimise and enrich human-machine interactions, in anticipation of the rapid development of virtual or augmented reality (VR/AR) as a therapeutic tool, and to open possibilities for improving machine operation. This ground-breaking project will have impact in many areas, notably in the clinical management of anxiety disorders, which affect 69.1 million European Union citizens at an annual cost of €74.4 billion, and in the educational, recreational and occupational realms of human-machine interaction. The proposal 1) will refine knowledge about the neurochemistry and stimulus-specificity of CCFIB for implementation as a clinical screening tool, using pharmacological and neuroimaging methods. 2) Test in clinical anxiety patients the power of CCFIB to predict symptom profile and response to psychological and pharmacological treatment. 3) Optimize CCFIB to augment psychological and behavioural treatments and validate this in phobic individuals. 4) Instantiate CCFIB in VR/AR settings to enhance engagement with virtual environments, develop VR/AR as a ‘training platform’ in clinical and recreational contexts and to demonstrate how reactions to rapid threats fluctuate with cardiac cycle, motivating corresponding changes in sensitivity of user interfaces (e.g. brakes)."
Max ERC Funding
1 912 383 €
Duration
Start date: 2013-06-01, End date: 2017-05-31
Project acronym CLONCELLBREAST
Project CLONAL AND CELLULAR HETEROGENEITY OF BREAST CANCER AND ITS DYNAMIC EVOLUTION WITH TREATMENT
Researcher (PI) Carlos Manuel SIMAO DA SILVA CALDAS
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), LS4, ERC-2015-AdG
Summary CLONAL AND CELLULAR HETEROGENEITY OF BREAST CANCER AND ITS DYNAMIC EVOLUTION WITH TREATMENT
Breast cancer remains one of the leading causes of cancer death in women. One of the greatest challenges is that breast cancer is a heterogeneous group of 10 diseases defined by genomic profiling. In addition, each tumor is composed of clones and clonal evolution underpins the successive acquisition of the hallmarks of cancer, including metastasis and resistance to therapy. Furthermore tumors display biologically and clinically relevant cellular heterogeneity: immune system, vasculature, and stroma. This cellular heterogeneity both shapes and is shaped by the malignant compartment and modulates response to therapy.
This proposal will use longitudinal studies to unravel the clonal and cellular heterogeneity of breast cancer and its dynamic evolution with treatment. The overall goal is to provide a systems level view of evolving clonal and cellular architectures in space and time along the clinical continuum of breast cancers in the clinic, leading to the discovery of new biological and clinical paradigms which will transform our understanding of the disease.
The overall approach is to capture the evolution of clonal and cellular heterogeneity of breast cancers in space and time using unique clinical cohorts where samples (biopsies and blood/plasma) are available spanning the whole disease continuum: early breast cancer surgically treated with curative intent, neo-adjuvant therapy, and matched relapse/metastasis. The 4 aims of the proposal are:
1. Characterization of the clonal and cellular heterogeneity of primary tumours from the 10 genomic driver-based breast cancer subtypes (ICs)
2. Comparative characterization of the clonal and cellular heterogeneity of matched pairs of primary and metastatic cancers
3. Characterization of the clonal and epigenetic evolution across therapy courses
4. Characterization of the immune response across therapy courses
Summary
CLONAL AND CELLULAR HETEROGENEITY OF BREAST CANCER AND ITS DYNAMIC EVOLUTION WITH TREATMENT
Breast cancer remains one of the leading causes of cancer death in women. One of the greatest challenges is that breast cancer is a heterogeneous group of 10 diseases defined by genomic profiling. In addition, each tumor is composed of clones and clonal evolution underpins the successive acquisition of the hallmarks of cancer, including metastasis and resistance to therapy. Furthermore tumors display biologically and clinically relevant cellular heterogeneity: immune system, vasculature, and stroma. This cellular heterogeneity both shapes and is shaped by the malignant compartment and modulates response to therapy.
This proposal will use longitudinal studies to unravel the clonal and cellular heterogeneity of breast cancer and its dynamic evolution with treatment. The overall goal is to provide a systems level view of evolving clonal and cellular architectures in space and time along the clinical continuum of breast cancers in the clinic, leading to the discovery of new biological and clinical paradigms which will transform our understanding of the disease.
The overall approach is to capture the evolution of clonal and cellular heterogeneity of breast cancers in space and time using unique clinical cohorts where samples (biopsies and blood/plasma) are available spanning the whole disease continuum: early breast cancer surgically treated with curative intent, neo-adjuvant therapy, and matched relapse/metastasis. The 4 aims of the proposal are:
1. Characterization of the clonal and cellular heterogeneity of primary tumours from the 10 genomic driver-based breast cancer subtypes (ICs)
2. Comparative characterization of the clonal and cellular heterogeneity of matched pairs of primary and metastatic cancers
3. Characterization of the clonal and epigenetic evolution across therapy courses
4. Characterization of the immune response across therapy courses
Max ERC Funding
2 497 660 €
Duration
Start date: 2017-01-01, End date: 2021-12-31