Project acronym ACOULOMODE
Project Advanced coupling of low order combustor simulations with thermoacoustic modelling and controller design
Researcher (PI) Aimee Morgans
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary "Combustion is essential to the world’s energy generation and transport needs, and will remain so for the foreseeable future. Mitigating its impact on the climate and human health, by reducing its associated emissions, is thus a priority. One significant challenge for gas-turbine combustion is combustion instability, which is currently inhibiting reductions in NOx emissions (these damage human health via a deterioration in air quality). Combustion instability is caused by a two-way coupling between unsteady combustion and acoustic waves - the large pressure oscillations that result can cause substantial mechanical damage. Currently, the lack of fast, accurate modelling tools for combustion instability, and the lack of reliable ways of suppressing it are severely hindering reductions in NOx emissions.
This proposal aims to make step improvements in both fast, accurate modelling of combustion instability, and in developing reliable active control strategies for its suppression. It will achieve this by coupling low order combustor models (these are fast, simplified models for simulating combustion instability) with advances in analytical modelling, CFD simulation, reduced order modelling and control theory tools. In particular:
* important advances in accurately incorporating the effect of entropy waves (temperature variations resulting from unsteady combustion) and non-linear flame models will be made;
* new active control strategies for achieving reliable suppression of combustion instability, including from within limit cycle oscillations, will be developed;
* an open-source low order combustor modelling tool will be developed and widely disseminated, opening access to researchers worldwide and improving communications between the fields of thermoacoustics and control theory.
Thus the proposal aims to use analytical and computational methods to contribute to achieving low NOx gas-turbine combustion, without the penalty of damaging combustion instability."
Summary
"Combustion is essential to the world’s energy generation and transport needs, and will remain so for the foreseeable future. Mitigating its impact on the climate and human health, by reducing its associated emissions, is thus a priority. One significant challenge for gas-turbine combustion is combustion instability, which is currently inhibiting reductions in NOx emissions (these damage human health via a deterioration in air quality). Combustion instability is caused by a two-way coupling between unsteady combustion and acoustic waves - the large pressure oscillations that result can cause substantial mechanical damage. Currently, the lack of fast, accurate modelling tools for combustion instability, and the lack of reliable ways of suppressing it are severely hindering reductions in NOx emissions.
This proposal aims to make step improvements in both fast, accurate modelling of combustion instability, and in developing reliable active control strategies for its suppression. It will achieve this by coupling low order combustor models (these are fast, simplified models for simulating combustion instability) with advances in analytical modelling, CFD simulation, reduced order modelling and control theory tools. In particular:
* important advances in accurately incorporating the effect of entropy waves (temperature variations resulting from unsteady combustion) and non-linear flame models will be made;
* new active control strategies for achieving reliable suppression of combustion instability, including from within limit cycle oscillations, will be developed;
* an open-source low order combustor modelling tool will be developed and widely disseminated, opening access to researchers worldwide and improving communications between the fields of thermoacoustics and control theory.
Thus the proposal aims to use analytical and computational methods to contribute to achieving low NOx gas-turbine combustion, without the penalty of damaging combustion instability."
Max ERC Funding
1 489 309 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym AF and MSOGR
Project Automorphic Forms and Moduli Spaces of Galois Representations
Researcher (PI) Toby Gee
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary I propose to establish a research group to develop completely new tools in order to solve three important problems on the relationships between automorphic forms and Galois representations, which lie at the heart of the Langlands program. The first is to prove Serre’s conjecture for real quadratic fields. I will use automorphic induction to transfer the problem to U(4) over the rational numbers, where I will use automorphy lifting theorems and results on the weight part of Serre's conjecture that I established in my earlier work to reduce the problem to proving results in small weight and level. I will prove these base cases via integral p-adic Hodge theory and discriminant bounds.
The second is to develop a geometric theory of moduli spaces of mod p and p-adic Galois representations, and to use it to establish the Breuil–Mézard conjecture in arbitrary dimension, by reinterpreting the conjecture in geometric terms. This will transform the subject by building the first connections between the p-adic Langlands program and the geometric Langlands program, providing an entirely new world of techniques for number theorists. As a consequence of the Breuil-Mézard conjecture, I will be able to deduce far stronger automorphy lifting theorems (in arbitrary dimension) than those currently available.
The third is to completely determine the reduction mod p of certain two-dimensional crystalline representations, and as an application prove a strengthened version of the Gouvêa–Mazur conjecture. I will do this by means of explicit computations with the p-adic local Langlands correspondence for GL_2(Q_p), as well as by improving existing arguments which prove multiplicity one theorems via automorphy lifting theorems. This work will show that the existence of counterexamples to the Gouvêa-Mazur conjecture is due to a purely local phenomenon, and that when this local obstruction vanishes, far stronger conjectures of Buzzard on the slopes of the U_p operator hold.
Summary
I propose to establish a research group to develop completely new tools in order to solve three important problems on the relationships between automorphic forms and Galois representations, which lie at the heart of the Langlands program. The first is to prove Serre’s conjecture for real quadratic fields. I will use automorphic induction to transfer the problem to U(4) over the rational numbers, where I will use automorphy lifting theorems and results on the weight part of Serre's conjecture that I established in my earlier work to reduce the problem to proving results in small weight and level. I will prove these base cases via integral p-adic Hodge theory and discriminant bounds.
The second is to develop a geometric theory of moduli spaces of mod p and p-adic Galois representations, and to use it to establish the Breuil–Mézard conjecture in arbitrary dimension, by reinterpreting the conjecture in geometric terms. This will transform the subject by building the first connections between the p-adic Langlands program and the geometric Langlands program, providing an entirely new world of techniques for number theorists. As a consequence of the Breuil-Mézard conjecture, I will be able to deduce far stronger automorphy lifting theorems (in arbitrary dimension) than those currently available.
The third is to completely determine the reduction mod p of certain two-dimensional crystalline representations, and as an application prove a strengthened version of the Gouvêa–Mazur conjecture. I will do this by means of explicit computations with the p-adic local Langlands correspondence for GL_2(Q_p), as well as by improving existing arguments which prove multiplicity one theorems via automorphy lifting theorems. This work will show that the existence of counterexamples to the Gouvêa-Mazur conjecture is due to a purely local phenomenon, and that when this local obstruction vanishes, far stronger conjectures of Buzzard on the slopes of the U_p operator hold.
Max ERC Funding
1 131 339 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym AgricUrb
Project The Agricultural Origins of Urban Civilization
Researcher (PI) Amy Marie Bogaard
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Starting Grant (StG), SH6, ERC-2012-StG_20111124
Summary The establishment of farming is a pivotal moment in human history, setting the stage for the emergence of class-based society and urbanization. Monolithic views of the nature and development of early agriculture, however, have prevented clear understanding of how exactly farming fuelled, shaped and sustained the emergence of complex societies. A breakthrough in archaeological approach is needed to determine the actual roles of farming in the emergence of social complexity. The methodology required must push beyond conventional interpretation of the most direct farming evidence – archaeobotanical remains of crops and associated arable weeds – to reconstruct not only what crops were grown, but also how, where and why farming was practised. Addressing these related aspects, in contexts ranging from early agricultural villages to some of the world’s earliest cities, would provide the key to unraveling the contribution of farming to the development of lasting social inequalities. The research proposed here takes a new interdisciplinary approach combining archaeobotany, plant stable isotope chemistry and functional plant ecology, building on groundwork laid in previous research by the applicant. These approaches will be applied to two relatively well researched areas, western Asia and Europe, where a series of sites that chart multiple pathways to early complex societies offer rich plant and other bioarchaeological assemblages. The proposed project will set a wholly new standard of insight into early farming and its relationship with early civilization, facilitating similar approaches in other parts of the world and the construction of comparative perspectives on the global significance of early agriculture in social development.
Summary
The establishment of farming is a pivotal moment in human history, setting the stage for the emergence of class-based society and urbanization. Monolithic views of the nature and development of early agriculture, however, have prevented clear understanding of how exactly farming fuelled, shaped and sustained the emergence of complex societies. A breakthrough in archaeological approach is needed to determine the actual roles of farming in the emergence of social complexity. The methodology required must push beyond conventional interpretation of the most direct farming evidence – archaeobotanical remains of crops and associated arable weeds – to reconstruct not only what crops were grown, but also how, where and why farming was practised. Addressing these related aspects, in contexts ranging from early agricultural villages to some of the world’s earliest cities, would provide the key to unraveling the contribution of farming to the development of lasting social inequalities. The research proposed here takes a new interdisciplinary approach combining archaeobotany, plant stable isotope chemistry and functional plant ecology, building on groundwork laid in previous research by the applicant. These approaches will be applied to two relatively well researched areas, western Asia and Europe, where a series of sites that chart multiple pathways to early complex societies offer rich plant and other bioarchaeological assemblages. The proposed project will set a wholly new standard of insight into early farming and its relationship with early civilization, facilitating similar approaches in other parts of the world and the construction of comparative perspectives on the global significance of early agriculture in social development.
Max ERC Funding
1 199 647 €
Duration
Start date: 2013-02-01, End date: 2017-01-31
Project acronym APGRAPH
Project Asymptotic Graph Properties
Researcher (PI) Deryk Osthus
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Country United Kingdom
Call Details Starting Grant (StG), PE1, ERC-2012-StG_20111012
Summary Many parts of Graph Theory have witnessed a huge growth over the last years, partly because of their relation to Theoretical Computer Science and Statistical Physics. These connections arise because graphs can be used to model many diverse structures.
The focus of this proposal is on asymptotic results, i.e. the graphs under consideration are large. This often unveils patterns and connections which remain obscure when considering only small graphs.
It also allows for the use of powerful techniques such as probabilistic arguments, which have led to spectacular new developments. In particular, my aim is to make decisive progress on central problems in the following 4 areas:
(1) Factorizations: Factorizations of graphs can be viewed as partitions of the edges of a graph into simple regular structures. They have a rich history and arise in many different settings, such as edge-colouring problems, decomposition problems and in information theory. They also have applications to finding good tours for the famous Travelling salesman problem.
(2) Hamilton cycles: A Hamilton cycle is a cycle which contains all the vertices of the graph. One of the most fundamental problems in Graph Theory/Theoretical Computer Science is to find conditions which guarantee the existence of a Hamilton cycle in a graph.
(3) Embeddings of graphs: This is a natural (but difficult) continuation of the previous question where the aim is to embed more general structures than Hamilton cycles - there has been exciting progress here in recent years which has opened up new avenues.
(4) Resilience of graphs: In many cases, it is important to know whether a graph `strongly’ possesses some property, i.e. one cannot destroy the property by changing a few edges. The systematic study of this notion is a new and rapidly growing area.
I have developed new methods for deep and long-standing problems in these areas which will certainly lead to further applications elsewhere.
Summary
Many parts of Graph Theory have witnessed a huge growth over the last years, partly because of their relation to Theoretical Computer Science and Statistical Physics. These connections arise because graphs can be used to model many diverse structures.
The focus of this proposal is on asymptotic results, i.e. the graphs under consideration are large. This often unveils patterns and connections which remain obscure when considering only small graphs.
It also allows for the use of powerful techniques such as probabilistic arguments, which have led to spectacular new developments. In particular, my aim is to make decisive progress on central problems in the following 4 areas:
(1) Factorizations: Factorizations of graphs can be viewed as partitions of the edges of a graph into simple regular structures. They have a rich history and arise in many different settings, such as edge-colouring problems, decomposition problems and in information theory. They also have applications to finding good tours for the famous Travelling salesman problem.
(2) Hamilton cycles: A Hamilton cycle is a cycle which contains all the vertices of the graph. One of the most fundamental problems in Graph Theory/Theoretical Computer Science is to find conditions which guarantee the existence of a Hamilton cycle in a graph.
(3) Embeddings of graphs: This is a natural (but difficult) continuation of the previous question where the aim is to embed more general structures than Hamilton cycles - there has been exciting progress here in recent years which has opened up new avenues.
(4) Resilience of graphs: In many cases, it is important to know whether a graph `strongly’ possesses some property, i.e. one cannot destroy the property by changing a few edges. The systematic study of this notion is a new and rapidly growing area.
I have developed new methods for deep and long-standing problems in these areas which will certainly lead to further applications elsewhere.
Max ERC Funding
818 414 €
Duration
Start date: 2012-12-01, End date: 2018-11-30
Project acronym ARCHOFCON
Project The Architecture of Consciousness
Researcher (PI) Timothy John Bayne
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Country United Kingdom
Call Details Starting Grant (StG), SH4, ERC-2012-StG_20111124
Summary The nature of consciousness is one of the great unsolved mysteries of science. Although the global research effort dedicated to explaining how consciousness arises from neural and cognitive activity is now more than two decades old, as yet there is no widely accepted theory of consciousness. One reason for why no adequate theory of consciousness has yet been found is that there is a lack of clarity about what exactly a theory of consciousness needs to explain. What is needed is thus a model of the general features of consciousness — a model of the ‘architecture’ of consciousness — that will systematize the structural differences between conscious states, processes and creatures on the one hand and unconscious states, processes and creatures on the other. The aim of this project is to remove one of the central impediments to the progress of the science of consciousness by constructing such a model.
A great many of the data required for this task already exist, but these data concern different aspects of consciousness and are distributed across many disciplines. As a result, there have been few attempts to develop a truly comprehensive model of the architecture of consciousness. This project will overcome the limitations of previous work by drawing on research in philosophy, psychology, psychiatry, and cognitive neuroscience to develop a model of the architecture of consciousness that is structured around five of its core features: its subjectivity, its temporality, its unity, its selectivity, and its dimensionality (that is, the relationship between the levels of consciousness and the contents of consciousness). By providing a comprehensive characterization of what a theory of consciousness needs to explain, this project will provide a crucial piece of the puzzle of consciousness, enabling future generations of researchers to bridge the gap between raw data on the one hand and a full-blown theory of consciousness on the other
Summary
The nature of consciousness is one of the great unsolved mysteries of science. Although the global research effort dedicated to explaining how consciousness arises from neural and cognitive activity is now more than two decades old, as yet there is no widely accepted theory of consciousness. One reason for why no adequate theory of consciousness has yet been found is that there is a lack of clarity about what exactly a theory of consciousness needs to explain. What is needed is thus a model of the general features of consciousness — a model of the ‘architecture’ of consciousness — that will systematize the structural differences between conscious states, processes and creatures on the one hand and unconscious states, processes and creatures on the other. The aim of this project is to remove one of the central impediments to the progress of the science of consciousness by constructing such a model.
A great many of the data required for this task already exist, but these data concern different aspects of consciousness and are distributed across many disciplines. As a result, there have been few attempts to develop a truly comprehensive model of the architecture of consciousness. This project will overcome the limitations of previous work by drawing on research in philosophy, psychology, psychiatry, and cognitive neuroscience to develop a model of the architecture of consciousness that is structured around five of its core features: its subjectivity, its temporality, its unity, its selectivity, and its dimensionality (that is, the relationship between the levels of consciousness and the contents of consciousness). By providing a comprehensive characterization of what a theory of consciousness needs to explain, this project will provide a crucial piece of the puzzle of consciousness, enabling future generations of researchers to bridge the gap between raw data on the one hand and a full-blown theory of consciousness on the other
Max ERC Funding
1 477 483 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym ARSEM
Project LANGUAGE–PHILOLOGY–CULTURE: Arab Cultural Semantics in Transition
Researcher (PI) Kirill Dmitriev
Host Institution (HI) THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS
Country United Kingdom
Call Details Starting Grant (StG), SH5, ERC-2012-StG_20111124
Summary This project aims to study:
• the semantic development of the vocabulary of the Arabic language,
• philological discourses on the semantic changes in the language in the classical Arabic philological tradition (8th-10th centuries A.D.), and
• the impact of Arabic philology in the wider historical and cultural context of the Judaeo-Arab neo-classical heritage (12th-13th centuries A.D.) and Christian-Arab intellectual history on the eve of modernity (19th century A.D.).
The project will explore the universal cultural significance and the pivotal role of language consciousness in the history of Arab culture. It will introduce a new dimension into the existing research on the Arabic language and Arabic philology, which until now have been studied without any comprehensive cultural and social contextualisation. The project will focus on the process of the transmission of Arabic poetry, which provides detailed evidence of the development of Arabic philological thought and its universal significance for the theological, philosophical, historical and linguistic discourses of Arab intellectual history. This project will document the transmission of early Arabic poetry and analyse its vocabulary in a systematic way for the first time. For this purpose it will create an Analytical Database of Arabic Poetry. This publicly accessible database will represent a ground-breaking contribution to European research on the Arabic language and the Arabic philological heritage, which so far lacks even such fundamental tools as an etymological dictionary of the Arabic language or a complete dictionary of Classical Arabic. The database will implement comprehensive analytical tools and will serve as a reference work for wider research on Arabic literature, history and culture. Thus, the project will create an integrative research platform for the history and semantics of the Arabic language—a subject indispensable for understanding the foundations of Arab culture past and present.
Summary
This project aims to study:
• the semantic development of the vocabulary of the Arabic language,
• philological discourses on the semantic changes in the language in the classical Arabic philological tradition (8th-10th centuries A.D.), and
• the impact of Arabic philology in the wider historical and cultural context of the Judaeo-Arab neo-classical heritage (12th-13th centuries A.D.) and Christian-Arab intellectual history on the eve of modernity (19th century A.D.).
The project will explore the universal cultural significance and the pivotal role of language consciousness in the history of Arab culture. It will introduce a new dimension into the existing research on the Arabic language and Arabic philology, which until now have been studied without any comprehensive cultural and social contextualisation. The project will focus on the process of the transmission of Arabic poetry, which provides detailed evidence of the development of Arabic philological thought and its universal significance for the theological, philosophical, historical and linguistic discourses of Arab intellectual history. This project will document the transmission of early Arabic poetry and analyse its vocabulary in a systematic way for the first time. For this purpose it will create an Analytical Database of Arabic Poetry. This publicly accessible database will represent a ground-breaking contribution to European research on the Arabic language and the Arabic philological heritage, which so far lacks even such fundamental tools as an etymological dictionary of the Arabic language or a complete dictionary of Classical Arabic. The database will implement comprehensive analytical tools and will serve as a reference work for wider research on Arabic literature, history and culture. Thus, the project will create an integrative research platform for the history and semantics of the Arabic language—a subject indispensable for understanding the foundations of Arab culture past and present.
Max ERC Funding
1 499 507 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym BACKTOBACK
Project Engineering Solutions for Back Pain: Simulation of Patient Variance
Researcher (PI) Ruth Wilcox
Host Institution (HI) UNIVERSITY OF LEEDS
Country United Kingdom
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary Back pain affects eight out of ten adults during their lifetime. It a huge economic burden on society, estimated to cost as much as 1-2% of gross national product in several European countries. Treatments for back pain have lower levels of success and are not as technologically mature as those for other musculoskeletal disorders such as hip and knee replacement. This application proposes to tackle one of the major barriers to the development of better surgical treatments for back pain.
At present, new spinal devices are commonly assessed in isolation in the laboratory under standardised conditions that do not represent the variation across the patient population. Consequently many interventions have failed during clinical trials or have proved to have poor long term success rates.
Using a combination of computational and experimental models, a new testing methodology will be developed that will enable the variation between patients to be simulated for the first time. This will enable spinal implants and therapies to be more robustly evaluated across a virtual patient population prior to clinical trial. The tools developed will be used in collaboration with clinicians and basic scientists to develop and, crucially, optimise new treatments that reduce back pain whilst preserving the unique functions of the spine.
If successful, this approach could be translated to evaluate and optimise emerging minimally invasive treatments in other joints such as the hip and knee. Research in the spine could then, for the first time, lead rather than follow that undertaken in other branches of orthopaedics.
Summary
Back pain affects eight out of ten adults during their lifetime. It a huge economic burden on society, estimated to cost as much as 1-2% of gross national product in several European countries. Treatments for back pain have lower levels of success and are not as technologically mature as those for other musculoskeletal disorders such as hip and knee replacement. This application proposes to tackle one of the major barriers to the development of better surgical treatments for back pain.
At present, new spinal devices are commonly assessed in isolation in the laboratory under standardised conditions that do not represent the variation across the patient population. Consequently many interventions have failed during clinical trials or have proved to have poor long term success rates.
Using a combination of computational and experimental models, a new testing methodology will be developed that will enable the variation between patients to be simulated for the first time. This will enable spinal implants and therapies to be more robustly evaluated across a virtual patient population prior to clinical trial. The tools developed will be used in collaboration with clinicians and basic scientists to develop and, crucially, optimise new treatments that reduce back pain whilst preserving the unique functions of the spine.
If successful, this approach could be translated to evaluate and optimise emerging minimally invasive treatments in other joints such as the hip and knee. Research in the spine could then, for the first time, lead rather than follow that undertaken in other branches of orthopaedics.
Max ERC Funding
1 498 777 €
Duration
Start date: 2012-12-01, End date: 2018-11-30
Project acronym BODILY SELF
Project Embodied Minds and Mentalised Bodies
Researcher (PI) Aikaterini (Katerina) Fotopoulou
Host Institution (HI) University College London
Country United Kingdom
Call Details Starting Grant (StG), SH4, ERC-2012-StG_20111124
Summary How does our acting, sensing and feeling body shape our mind? The mechanisms by which bodily signals are integrated and re-represented in the brain, as well as the relation between these processes and body awareness remain unknown. To this date, neuropsychological disorders of body awareness represent an indispensible window of insight into phenomenally rich states of body unawareness. Unfortunately, only few experimental studies have been conducted in these disorders. The BODILY SELF will aim to apply methods from cognitive neuroscience to experimental and neuroimaging studies in healthy volunteers, as well as in patients with neuropsychological disorders of body awareness. A first subproject will assess which combination of deficits in sensorimotor afferent and efferent signals leads to unawareness. The second subproject will attempt to use experimental, psychophysical interventions to treat unawareness and measure the corresponding, dynamic changes in the brain. The third subproject will assess how some bodily signals and their integration is influenced by social mechanisms. The planned studies surpass the existing state-of-the-art in the relevant fields in five ground-breaking ways, ultimately allowing us to (1) acquire an unprecedented ‘on-line’ experimental ‘handle’ over dynamic changes in body awareness; (2) restore awareness and improve health outcomes (3) understand the brain’s potential for reorganisation and plasticity in relation to higher-order processes such as awareness; (4) understand how our own body experience is modulated by our interactions and relations with others; (5) address in a genuinely interdisciplinary manner some of the oldest questions in psychology, philosophy and medicine; how embodiment influences the mind, how others influence the self and how mind–body processes affect healing.
Summary
How does our acting, sensing and feeling body shape our mind? The mechanisms by which bodily signals are integrated and re-represented in the brain, as well as the relation between these processes and body awareness remain unknown. To this date, neuropsychological disorders of body awareness represent an indispensible window of insight into phenomenally rich states of body unawareness. Unfortunately, only few experimental studies have been conducted in these disorders. The BODILY SELF will aim to apply methods from cognitive neuroscience to experimental and neuroimaging studies in healthy volunteers, as well as in patients with neuropsychological disorders of body awareness. A first subproject will assess which combination of deficits in sensorimotor afferent and efferent signals leads to unawareness. The second subproject will attempt to use experimental, psychophysical interventions to treat unawareness and measure the corresponding, dynamic changes in the brain. The third subproject will assess how some bodily signals and their integration is influenced by social mechanisms. The planned studies surpass the existing state-of-the-art in the relevant fields in five ground-breaking ways, ultimately allowing us to (1) acquire an unprecedented ‘on-line’ experimental ‘handle’ over dynamic changes in body awareness; (2) restore awareness and improve health outcomes (3) understand the brain’s potential for reorganisation and plasticity in relation to higher-order processes such as awareness; (4) understand how our own body experience is modulated by our interactions and relations with others; (5) address in a genuinely interdisciplinary manner some of the oldest questions in psychology, philosophy and medicine; how embodiment influences the mind, how others influence the self and how mind–body processes affect healing.
Max ERC Funding
1 453 284 €
Duration
Start date: 2013-04-01, End date: 2018-09-30
Project acronym BP-CarDiO
Project Investigating the therapeutic potential of manipulating the IGF-IGFBP1 axis in the prevention and treatment of cardiovascular disease, diabetes and obesity
Researcher (PI) Stephen Bentley Wheatcroft
Host Institution (HI) UNIVERSITY OF LEEDS
Country United Kingdom
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary More than 30 million people are living with diabetes in the EU, with a prevalence expected to grow to over 10% of the adult population by the year 2030. Type 2 diabetes is a major cause of cardiovascular disease related death and disability, substantially increasing the risk of myocardial infarction, stroke and peripheral arterial disease. Recent landmark trials, showing that intensive glucose control does not improve cardiovascular outcomes and may increase mortality in some circumstances, provide a compelling rationale for intense research aimed at developing novel therapeutic strategies. Type 2 diabetes is underpinned by resistance to the effects of insulin, which I have shown in endothelial cells causes reduced bioavailability of the anti-atherosclerotic molecule nitric oxide and leads to accelerated atherosclerosis. The cellular effects of insulin are mirrored by insulin-like growth factor factor-1, the bioavailability of which at its receptor is in turn is regulated by a family of high affinity binding proteins (IGFBP). Epidemiological studies demonstrate and inverse association between one of these binding proteins, IGFBP1, and diabetes-related cardiovascular risk. I have recently demonstrated that IGFBP1 when expressed in mice can ameliorate insulin resistance, obesity and atherosclerosis. In endothelial cells, I showed that IGFBP1 upregulates the production of nitric oxide indepenedently of IGF. These findings suggest that IGFBP1 may be a ‘protective’ endogenous protein and that increasing circulating levels may be a therapeutic strategy to prevent development of diabetes and cardiovascular disease. In this proposal I will address this hypothesis by employing state of the art studies in cells and novel gene modified mice to unravel the molecular basis of the protective effects of IGFBP1 and to investigate the possibility of exploiting the IGF-IGFBP axis to prevent cardiovascular disease in the setting of diabetes and obesity.
Summary
More than 30 million people are living with diabetes in the EU, with a prevalence expected to grow to over 10% of the adult population by the year 2030. Type 2 diabetes is a major cause of cardiovascular disease related death and disability, substantially increasing the risk of myocardial infarction, stroke and peripheral arterial disease. Recent landmark trials, showing that intensive glucose control does not improve cardiovascular outcomes and may increase mortality in some circumstances, provide a compelling rationale for intense research aimed at developing novel therapeutic strategies. Type 2 diabetes is underpinned by resistance to the effects of insulin, which I have shown in endothelial cells causes reduced bioavailability of the anti-atherosclerotic molecule nitric oxide and leads to accelerated atherosclerosis. The cellular effects of insulin are mirrored by insulin-like growth factor factor-1, the bioavailability of which at its receptor is in turn is regulated by a family of high affinity binding proteins (IGFBP). Epidemiological studies demonstrate and inverse association between one of these binding proteins, IGFBP1, and diabetes-related cardiovascular risk. I have recently demonstrated that IGFBP1 when expressed in mice can ameliorate insulin resistance, obesity and atherosclerosis. In endothelial cells, I showed that IGFBP1 upregulates the production of nitric oxide indepenedently of IGF. These findings suggest that IGFBP1 may be a ‘protective’ endogenous protein and that increasing circulating levels may be a therapeutic strategy to prevent development of diabetes and cardiovascular disease. In this proposal I will address this hypothesis by employing state of the art studies in cells and novel gene modified mice to unravel the molecular basis of the protective effects of IGFBP1 and to investigate the possibility of exploiting the IGF-IGFBP axis to prevent cardiovascular disease in the setting of diabetes and obesity.
Max ERC Funding
1 493 543 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym BrainGutTalk
Project Brain-gut interactions in Drosophila melanogaster
Researcher (PI) Irene Miguel-Aliaga
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary The gastrointestinal tract is emerging as a key regulator of appetite and metabolism, but studies aimed at identifying the signals involved are faced with daunting neuroanatomical complexity: there are as many as 500 million neurons in the human gut. Drosophila should provide a simple and genetically amenable alternative, but both its autonomic nervous system and the signalling significance of its digestive tract have remained largely unexplored. My research programme will characterize the signals and neurons mediating the interaction between the nervous and digestive systems, and will establish their significance both in the maintenance of metabolic homeostasis and in response to nutritional challenges. To achieve these goals, we will capitalize on a multi-disciplinary approach that combines the genetic manipulation of defined neuronal lineages, a cell-biological approach to the study of enterocyte metabolism, and our recently developed physiological and behavioural readouts. Our work will provide new insights into the signals and mechanisms modulating internal metabolism and food intake: processes which, when deregulated, contribute to increasingly prevalent conditions such as diabetes, metabolic syndrome and obesity. Our recent finding of conserved mechanisms of autonomic control in the fruit fly makes us confident that the signals we identify will be relevant to mammalian systems.
Summary
The gastrointestinal tract is emerging as a key regulator of appetite and metabolism, but studies aimed at identifying the signals involved are faced with daunting neuroanatomical complexity: there are as many as 500 million neurons in the human gut. Drosophila should provide a simple and genetically amenable alternative, but both its autonomic nervous system and the signalling significance of its digestive tract have remained largely unexplored. My research programme will characterize the signals and neurons mediating the interaction between the nervous and digestive systems, and will establish their significance both in the maintenance of metabolic homeostasis and in response to nutritional challenges. To achieve these goals, we will capitalize on a multi-disciplinary approach that combines the genetic manipulation of defined neuronal lineages, a cell-biological approach to the study of enterocyte metabolism, and our recently developed physiological and behavioural readouts. Our work will provide new insights into the signals and mechanisms modulating internal metabolism and food intake: processes which, when deregulated, contribute to increasingly prevalent conditions such as diabetes, metabolic syndrome and obesity. Our recent finding of conserved mechanisms of autonomic control in the fruit fly makes us confident that the signals we identify will be relevant to mammalian systems.
Max ERC Funding
1 499 740 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
