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Project acronym ActiveWindFarms
Project Active Wind Farms: Optimization and Control of Atmospheric Energy Extraction in Gigawatt Wind Farms
Researcher (PI) Johan Meyers
Summary With the recognition that wind energy will become an important contributor to the world's energy portfolio, several wind farms with a capacity of over 1 gigawatt are in planning phase. In the past, engineering of wind farms focused on a bottom-up approach, in which atmospheric wind availability was considered to be fixed by climate and weather. However, farms of gigawatt size slow down the Atmospheric Boundary Layer (ABL) as a whole, reducing the availability of wind at turbine hub height. In Denmark's large off-shore farms, this leads to underperformance of turbines which can reach levels of 40%–50% compared to the same turbine in a lone-standing case. For large wind farms, the vertical structure and turbulence physics of the flow in the ABL become crucial ingredients in their design and operation. This introduces a new set of scientific challenges related to the design and control of large wind farms. The major ambition of the present research proposal is to employ optimal control techniques to control the interaction between large wind farms and the ABL, and optimize overall farm-power extraction. Individual turbines are used as flow actuators by dynamically pitching their blades using time scales ranging between 10 to 500 seconds. The application of such control efforts on the atmospheric boundary layer has never been attempted before, and introduces flow control on a physical scale which is currently unprecedented. The PI possesses a unique combination of expertise and tools enabling these developments: efficient parallel large-eddy simulations of wind farms, multi-scale turbine modeling, and gradient-based optimization in large optimization-parameter spaces using adjoint formulations. To ensure a maximum impact on the wind-engineering field, the project aims at optimal control, experimental wind-tunnel validation, and at including multi-disciplinary aspects, related to structural mechanics, power quality, and controller design.
With the recognition that wind energy will become an important contributor to the world's energy portfolio, several wind farms with a capacity of over 1 gigawatt are in planning phase. In the past, engineering of wind farms focused on a bottom-up approach, in which atmospheric wind availability was considered to be fixed by climate and weather. However, farms of gigawatt size slow down the Atmospheric Boundary Layer (ABL) as a whole, reducing the availability of wind at turbine hub height. In Denmark's large off-shore farms, this leads to underperformance of turbines which can reach levels of 40%–50% compared to the same turbine in a lone-standing case. For large wind farms, the vertical structure and turbulence physics of the flow in the ABL become crucial ingredients in their design and operation. This introduces a new set of scientific challenges related to the design and control of large wind farms. The major ambition of the present research proposal is to employ optimal control techniques to control the interaction between large wind farms and the ABL, and optimize overall farm-power extraction. Individual turbines are used as flow actuators by dynamically pitching their blades using time scales ranging between 10 to 500 seconds. The application of such control efforts on the atmospheric boundary layer has never been attempted before, and introduces flow control on a physical scale which is currently unprecedented. The PI possesses a unique combination of expertise and tools enabling these developments: efficient parallel large-eddy simulations of wind farms, multi-scale turbine modeling, and gradient-based optimization in large optimization-parameter spaces using adjoint formulations. To ensure a maximum impact on the wind-engineering field, the project aims at optimal control, experimental wind-tunnel validation, and at including multi-disciplinary aspects, related to structural mechanics, power quality, and controller design.
Project acronym AF and MSOGR
Project Automorphic Forms and Moduli Spaces of Galois Representations
Researcher (PI) Toby Gee
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.
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.
Project acronym AgricUrb
Project The Agricultural Origins of Urban Civilization
Researcher (PI) Amy Marie Bogaard
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.
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.
Project acronym ALCOHOLLIFECOURSE
Project Alcohol Consumption across the Life-course: Determinants and Consequences
Researcher (PI) Anne Rebecca Britton
Summary The epidemiology of alcohol use and related health consequences plays a vital role by monitoring populations' alcohol consumption patterns and problems associated with drinking. Such studies seek to explain mechanisms linking consumption to harm and ultimately to reduce the health burden. Research needs to consider changes in drinking behaviour over the life-course. The current evidence base lacks the consideration of the complexity of lifetime consumption patterns, the predictors of change and subsequent health risks. Aims of the study 1. To describe age-related trajectories of drinking in different settings and to determine the extent to which individual and social contextual factors, including socioeconomic position, social networks and life events influence drinking pattern trajectories. 2. To estimate the impact of drinking trajectories on physical functioning and disease and to disentangle the exposure-outcome associations in terms of a) timing, i.e. health effect of drinking patterns in early, mid and late life; and b) duration, i.e. whether the impact of drinking accumulates over time. 3. To test the bidirectional associations between health and changes in consumption over the life-course in order to estimate the relative importance of these effects and to determine the dominant temporal direction. 4. To explore mechanisms and pathways through which drinking trajectories affect health and functioning in later life and to examine the role played by potential effect modifiers of the association between drinking and poor health. Several large, longitudinal cohort studies from European countries with repeated measures of alcohol consumption will be combined and analysed to address the aims. A new team will be formed consisting of the PI, a Research Associate and two PhD students. Dissemination will be through journals, conferences, and culminating in a one-day workshop for academics, practitioners and policy makers in the alcohol field.
The epidemiology of alcohol use and related health consequences plays a vital role by monitoring populations' alcohol consumption patterns and problems associated with drinking. Such studies seek to explain mechanisms linking consumption to harm and ultimately to reduce the health burden. Research needs to consider changes in drinking behaviour over the life-course. The current evidence base lacks the consideration of the complexity of lifetime consumption patterns, the predictors of change and subsequent health risks. Aims of the study 1. To describe age-related trajectories of drinking in different settings and to determine the extent to which individual and social contextual factors, including socioeconomic position, social networks and life events influence drinking pattern trajectories. 2. To estimate the impact of drinking trajectories on physical functioning and disease and to disentangle the exposure-outcome associations in terms of a) timing, i.e. health effect of drinking patterns in early, mid and late life; and b) duration, i.e. whether the impact of drinking accumulates over time. 3. To test the bidirectional associations between health and changes in consumption over the life-course in order to estimate the relative importance of these effects and to determine the dominant temporal direction. 4. To explore mechanisms and pathways through which drinking trajectories affect health and functioning in later life and to examine the role played by potential effect modifiers of the association between drinking and poor health. Several large, longitudinal cohort studies from European countries with repeated measures of alcohol consumption will be combined and analysed to address the aims. A new team will be formed consisting of the PI, a Research Associate and two PhD students. Dissemination will be through journals, conferences, and culminating in a one-day workshop for academics, practitioners and policy makers in the alcohol field.
Project acronym ANGLE
Project Accelerated design and discovery of novel molecular materials via global lattice energy minimisation
Researcher (PI) Graeme Matthew Day
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Summary The goal of crystal engineering is the design of functional crystalline materials in which the arrangement of basic structural building blocks imparts desired properties. The engineering of organic molecular crystals has, to date, relied largely on empirical rules governing the intermolecular association of functional groups in the solid state. However, many materials properties depend intricately on the complete crystal structure, i.e. the unit cell, space group and atomic positions, which cannot be predicted solely using such rules. Therefore, the development of computational methods for crystal structure prediction (CSP) from first principles has been a goal of computational chemistry that could significantly accelerate the design of new materials. It is only recently that the necessary advances in the modelling of intermolecular interactions and developments in algorithms for identifying all relevant crystal structures have come together to provide predictive methods that are becoming reliable and affordable on a timescale that could usefully complement an experimental research programme. The principle aim of the proposed work is to establish the use of state-of-the-art crystal structure prediction methods as a means of guiding the discovery and design of novel molecular materials. This research proposal both continues the development of the computational methods for CSP and, by developing a computational framework for screening of potential molecules, develops the application of these methods for materials design. The areas on which we will focus are organic molecular semiconductors with high charge carrier mobilities and, building on our recently published results in Nature [1], the development of porous organic molecular materials. The project will both deliver novel materials, as well as improvements in the reliability of computational methods that will find widespread applications in materials chemistry. [1] Nature 2011, 474, 367-371.
The goal of crystal engineering is the design of functional crystalline materials in which the arrangement of basic structural building blocks imparts desired properties. The engineering of organic molecular crystals has, to date, relied largely on empirical rules governing the intermolecular association of functional groups in the solid state. However, many materials properties depend intricately on the complete crystal structure, i.e. the unit cell, space group and atomic positions, which cannot be predicted solely using such rules. Therefore, the development of computational methods for crystal structure prediction (CSP) from first principles has been a goal of computational chemistry that could significantly accelerate the design of new materials. It is only recently that the necessary advances in the modelling of intermolecular interactions and developments in algorithms for identifying all relevant crystal structures have come together to provide predictive methods that are becoming reliable and affordable on a timescale that could usefully complement an experimental research programme. The principle aim of the proposed work is to establish the use of state-of-the-art crystal structure prediction methods as a means of guiding the discovery and design of novel molecular materials. This research proposal both continues the development of the computational methods for CSP and, by developing a computational framework for screening of potential molecules, develops the application of these methods for materials design. The areas on which we will focus are organic molecular semiconductors with high charge carrier mobilities and, building on our recently published results in Nature [1], the development of porous organic molecular materials. The project will both deliver novel materials, as well as improvements in the reliability of computational methods that will find widespread applications in materials chemistry. [1] Nature 2011, 474, 367-371.
Project acronym ANTINEUTRINONOVA
Project Probing Fundamental Physics with Antineutrinos at the NOvA Experiment
Researcher (PI) Jeffrey Hartnell
Summary "This proposal addresses major questions in particle physics that are at the forefront of experimental and theoretical physics research today. The results offered would have far-reaching implications in other fields such as cosmology and could help answer some of the big questions such as why the universe contains so much more matter than antimatter. The research objectives of this proposal are to (i) make world-leading tests of CPT symmetry and (ii) discover the neutrino mass hierarchy and search for indications of leptonic CP violation. The NOvA long-baseline neutrino oscillation experiment will use a novel ""totally active scintillator design"" for the detector technology and will be exposed to the world's highest power neutrino beam. Building on the first direct observation of muon antineutrino disappearance (that was made by a group founded and led by the PI at the MINOS experiment), tests of CPT symmetry will be performed by looking for differences in the mass squared splittings and mixing angles between neutrinos and antineutrinos. The potential to discover the mass hierarchy is unique to NOvA on the timescale of this proposal due to the long 810 km baseline and the well measured beam of neutrinos and antineutrinos. This proposal addresses several key challenges in a long-baseline neutrino oscillation experiment with the following tasks: (i) development of a new approach to event energy reconstruction that is expected to have widespread applicability for future neutrino experiments; (ii) undertaking a comprehensive calibration project, exploiting a novel technique developed by the PI, that will be essential to achieving the physics goals; (iii) development of a sophisticated statistical analyses. The results promised in this proposal surpass the sensitivity to antineutrino oscillation parameters of current 1st generation experiments by at least an order of magnitude, offering wide scope for profound discoveries with implications across disciplines."
"This proposal addresses major questions in particle physics that are at the forefront of experimental and theoretical physics research today. The results offered would have far-reaching implications in other fields such as cosmology and could help answer some of the big questions such as why the universe contains so much more matter than antimatter. The research objectives of this proposal are to (i) make world-leading tests of CPT symmetry and (ii) discover the neutrino mass hierarchy and search for indications of leptonic CP violation. The NOvA long-baseline neutrino oscillation experiment will use a novel ""totally active scintillator design"" for the detector technology and will be exposed to the world's highest power neutrino beam. Building on the first direct observation of muon antineutrino disappearance (that was made by a group founded and led by the PI at the MINOS experiment), tests of CPT symmetry will be performed by looking for differences in the mass squared splittings and mixing angles between neutrinos and antineutrinos. The potential to discover the mass hierarchy is unique to NOvA on the timescale of this proposal due to the long 810 km baseline and the well measured beam of neutrinos and antineutrinos. This proposal addresses several key challenges in a long-baseline neutrino oscillation experiment with the following tasks: (i) development of a new approach to event energy reconstruction that is expected to have widespread applicability for future neutrino experiments; (ii) undertaking a comprehensive calibration project, exploiting a novel technique developed by the PI, that will be essential to achieving the physics goals; (iii) development of a sophisticated statistical analyses. The results promised in this proposal surpass the sensitivity to antineutrino oscillation parameters of current 1st generation experiments by at least an order of magnitude, offering wide scope for profound discoveries with implications across disciplines."
Project acronym APGRAPH
Project Asymptotic Graph Properties
Researcher (PI) Deryk Osthus
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
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.
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.
Project acronym APHIDHOST
Project Molecular determinants of aphid host range
Researcher (PI) Jorunn Indra Berit Bos
Host Institution (HI) THE JAMES HUTTON INSTITUTE
Summary Many aphid species are restricted to one or few host plants, while some aphids, many of which are of agricultural importance, can infest a wide range of plant species. An important observation is that aphids spend a considerable time on nonhost species, where they probe the leaf tissue and secrete saliva, but for unknown reasons are unable to ingest phloem sap. This suggest that aphids, like plant pathogens, interact with nonhost plants at the molecular level, but potentially are not successful in suppressing plant defenses and/or releasing nutrients. To date, however, the plant cellular changes and the involvement of immune response, such as ETI and PTI, in aphid-host and -nonhost interactions remain elusive. The aim of the proposed project is to gain insight into the level of cellular host reprogramming that takes place during aphid-host interactions, the cellular processes involved in aphid nonhost resistance, and the role of aphid effectors in determining host range. We will compare interactions of two economically important aphid species, Myzus persicae (green peach aphid) and Rhopalosiphum padi (bird cherry oat aphid), with host and nonhost plants. We will investigate local changes in plant cellular processes during aphid-host and -nonhost interactions using microscopy and biochemistry approaches. We will apply a comparative transcriptomics approach and functional assays to identify aphid effectors as potential determinants of host range. Herein we will specifically looks for aphids-species specific effectors and those that are expressed in specific host interactions. To gain insight into molecular mechanisms of effector activities we will identify host targets and investigate the contribution of effector-target interactions to host range. The expected outcomes of the project will, in the long term, contribute to the development of novel strategies to control infestations by aphids and potentially other pests and pathogens, thereby improving food security.
Many aphid species are restricted to one or few host plants, while some aphids, many of which are of agricultural importance, can infest a wide range of plant species. An important observation is that aphids spend a considerable time on nonhost species, where they probe the leaf tissue and secrete saliva, but for unknown reasons are unable to ingest phloem sap. This suggest that aphids, like plant pathogens, interact with nonhost plants at the molecular level, but potentially are not successful in suppressing plant defenses and/or releasing nutrients. To date, however, the plant cellular changes and the involvement of immune response, such as ETI and PTI, in aphid-host and -nonhost interactions remain elusive. The aim of the proposed project is to gain insight into the level of cellular host reprogramming that takes place during aphid-host interactions, the cellular processes involved in aphid nonhost resistance, and the role of aphid effectors in determining host range. We will compare interactions of two economically important aphid species, Myzus persicae (green peach aphid) and Rhopalosiphum padi (bird cherry oat aphid), with host and nonhost plants. We will investigate local changes in plant cellular processes during aphid-host and -nonhost interactions using microscopy and biochemistry approaches. We will apply a comparative transcriptomics approach and functional assays to identify aphid effectors as potential determinants of host range. Herein we will specifically looks for aphids-species specific effectors and those that are expressed in specific host interactions. To gain insight into molecular mechanisms of effector activities we will identify host targets and investigate the contribution of effector-target interactions to host range. The expected outcomes of the project will, in the long term, contribute to the development of novel strategies to control infestations by aphids and potentially other pests and pathogens, thereby improving food security.
Project acronym ARCHOFCON
Project The Architecture of Consciousness
Researcher (PI) Timothy John Bayne
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
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
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
Project acronym ARSEM
Project LANGUAGE–PHILOLOGY–CULTURE: Arab Cultural Semantics in Transition
Researcher (PI) Kirill Dmitriev
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.
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.
Project acronym BACKTOBACK
Project Engineering Solutions for Back Pain: Simulation of Patient Variance
Researcher (PI) Ruth Wilcox
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.
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.
Project acronym BALDWINIAN_BEETLES
Project "The origin of the fittest: canalization, plasticity and selection as a consequence of provisioning during development"
Researcher (PI) Rebecca Kilner
Summary "A major outstanding challenge for evolutionary biology is to explain how novel adaptations arise. We propose to test whether developmental plasticity initiates evolutionary change in morphological, behavioural and social traits, using laboratory experiments, fieldwork and comparative analyses. Using burying beetles Nicrophorus spp as our model experimental system, we shall: 1) Test whether variation in parental provisioning during development induces correlated phenotypic change in adult body size and a suite of life history traits; whether these phenotypic changes can be genetically accommodated under experimental evolution (the Baldwin Effect); and whether changes induced by experimental evolution mimic natural variation in adult body size and life history strategy among Nicrophorus species; 2) Test whether parental provisioning has a canalizing effect on the developmental environment, potentially storing up cryptic genetic variation which might then be released as random new phenotypes, if offspring are exposed to a new developmental environment; 3) Investigate whether developmental trade-offs, induced by under-provisioning from parents, provide the first step towards the evolution of a novel interspecific mutualism. Is a second species recruited in adulthood to carry out the function of a structure that was under-nourished during development? 4) Using comparative analyses of data from the literature on insects, frogs, birds and mammals, we shall test whether the evolution of parental provisioning in a given lineage is positively correlated with the number of species in the lineage. Our proposal is original in focusing on developmental plasticity induced by variation in parental provisioning. Given the diverse and numerous species that provision their young, including several whose genomes have now been sequenced, this potentially opens up a rich new area for future work on the developmental mechanisms underlying evolutionary innovations."
"A major outstanding challenge for evolutionary biology is to explain how novel adaptations arise. We propose to test whether developmental plasticity initiates evolutionary change in morphological, behavioural and social traits, using laboratory experiments, fieldwork and comparative analyses. Using burying beetles Nicrophorus spp as our model experimental system, we shall: 1) Test whether variation in parental provisioning during development induces correlated phenotypic change in adult body size and a suite of life history traits; whether these phenotypic changes can be genetically accommodated under experimental evolution (the Baldwin Effect); and whether changes induced by experimental evolution mimic natural variation in adult body size and life history strategy among Nicrophorus species; 2) Test whether parental provisioning has a canalizing effect on the developmental environment, potentially storing up cryptic genetic variation which might then be released as random new phenotypes, if offspring are exposed to a new developmental environment; 3) Investigate whether developmental trade-offs, induced by under-provisioning from parents, provide the first step towards the evolution of a novel interspecific mutualism. Is a second species recruited in adulthood to carry out the function of a structure that was under-nourished during development? 4) Using comparative analyses of data from the literature on insects, frogs, birds and mammals, we shall test whether the evolution of parental provisioning in a given lineage is positively correlated with the number of species in the lineage. Our proposal is original in focusing on developmental plasticity induced by variation in parental provisioning. Given the diverse and numerous species that provision their young, including several whose genomes have now been sequenced, this potentially opens up a rich new area for future work on the developmental mechanisms underlying evolutionary innovations."
Project acronym BIOFINDER
Project New biomarkers for Alzheimer's & Parkinson's diseases - key tools for early diagnosis and drug development
Researcher (PI) Oskar Hansson
Summary Alzheimer's disease (AD) and Parkinson's disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity. AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets. We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays. New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging
Alzheimer's disease (AD) and Parkinson's disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity. AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets. We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays. New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging
Project acronym BIOSYNCEN
Project Dissection of centromeric chromatin and components: A biosynthetic approach
Researcher (PI) Patrick Heun
Summary The centromere is one of the most important chromosomal elements. It is required for proper chromosome segregation in mitosis and meiosis and readily recognizable as the primary constriction of mitotic chromosomes. Proper centromere function is essential to ensure genome stability; therefore understanding centromere identity is directly relevant to cancer biology and gene therapy. How centromeres are established and maintained is however still an open question in the field. In most organisms this appears to be regulated by an epigenetic mechanism. The key candidate for such an epigenetic mark is CENH3 (CENP-A in mammals, CID in Drosophila), a centromere-specific histone H3 variant that is essential for centromere function and exclusively found in the nucleosomes of centromeric chromatin. Using a biosynthetic approach of force-targeting CENH3 in Drosophila to non-centromeric DNA, we were able to induce centromere function and demonstrate that CENH3 is sufficient to determine centromere identity. Here we propose to move this experimental setup across evolutionary boundaries into human cells to develop improved human artificial chromosomes (HACs). We will make further use of this unique setup to dissect the function of targeted CENH3 both in Drosophila and human cells. Contributing centromeric components and histone modifications of centromeric chromatin will be characterized in detail by mass spectroscopy in Drosophila. Finally we are proposing to develop a technique that allows high-resolution mapping of proteins on repetitive DNA to help further characterizing known and novel centromere components. This will be achieved by combining two independently established techniques: DNA methylation and DNA fiber combing. This ambitious proposal will significantly advance our understanding of how centromeres are determined and help the development of improved HACs for therapeutic applications in the future.
The centromere is one of the most important chromosomal elements. It is required for proper chromosome segregation in mitosis and meiosis and readily recognizable as the primary constriction of mitotic chromosomes. Proper centromere function is essential to ensure genome stability; therefore understanding centromere identity is directly relevant to cancer biology and gene therapy. How centromeres are established and maintained is however still an open question in the field. In most organisms this appears to be regulated by an epigenetic mechanism. The key candidate for such an epigenetic mark is CENH3 (CENP-A in mammals, CID in Drosophila), a centromere-specific histone H3 variant that is essential for centromere function and exclusively found in the nucleosomes of centromeric chromatin. Using a biosynthetic approach of force-targeting CENH3 in Drosophila to non-centromeric DNA, we were able to induce centromere function and demonstrate that CENH3 is sufficient to determine centromere identity. Here we propose to move this experimental setup across evolutionary boundaries into human cells to develop improved human artificial chromosomes (HACs). We will make further use of this unique setup to dissect the function of targeted CENH3 both in Drosophila and human cells. Contributing centromeric components and histone modifications of centromeric chromatin will be characterized in detail by mass spectroscopy in Drosophila. Finally we are proposing to develop a technique that allows high-resolution mapping of proteins on repetitive DNA to help further characterizing known and novel centromere components. This will be achieved by combining two independently established techniques: DNA methylation and DNA fiber combing. This ambitious proposal will significantly advance our understanding of how centromeres are determined and help the development of improved HACs for therapeutic applications in the future.
Project acronym BODILY SELF
Project Embodied Minds and Mentalised Bodies
Researcher (PI) Aikaterini (Katerina) Fotopoulou
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.
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.
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
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.
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.
Project acronym BrainGutTalk
Project Brain-gut interactions in Drosophila melanogaster
Researcher (PI) Irene Miguel-Aliaga
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.
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.
Project acronym BrainReadFBPredCode
Project Brain reading of contextual feedback and predictions
Researcher (PI) Lars Muckli
Summary We are currently witnessing a paradigm shift in our understanding of human brain function, moving towards a clearer description of cortical processing. Sensory systems are no longer considered as 'passively recording' but rather as dynamically anticipating and adapting to the rapidly changing environment. These new ideas are encompassed in the predictive coding framework, and indeed in a unifying theory of the brain (Friston, 2010). In terms of brain computation, a predictive model is created in higher cortical areas and communicated to lower sensory areas through feedback connections. Based on my pioneering research I propose experiments that are capable of 'brain-reading' cortical feedback– which would contribute invaluable data to theoretical frameworks. The proposed research project will advance our understanding of ongoing brain activity, contextual processing, and cortical feedback - contributing to what is known about general cortical functions. By providing new insights as to the information content of cortical feedback, the proposal will fill one of the most important gaps in today's knowledge about brain function. Friston's unifying theory of the brain (Friston, 2010) and contemporary models of the predictive-coding framework (Hawkins and Blakeslee, 2004;Mumford, 1992;Rao and Ballard, 1999) assign feedback processing an essential role in cortical processing. Compared to feedforward information processing, our knowledge about feedback processing is in its infancy. The proposal introduces parametric and explorative brain reading designs to investigate this feedback processing. The chief goal of my proposal will be precision measures of cortical feedback, and a more ambitious objective is to read mental images and inner thoughts.
We are currently witnessing a paradigm shift in our understanding of human brain function, moving towards a clearer description of cortical processing. Sensory systems are no longer considered as 'passively recording' but rather as dynamically anticipating and adapting to the rapidly changing environment. These new ideas are encompassed in the predictive coding framework, and indeed in a unifying theory of the brain (Friston, 2010). In terms of brain computation, a predictive model is created in higher cortical areas and communicated to lower sensory areas through feedback connections. Based on my pioneering research I propose experiments that are capable of 'brain-reading' cortical feedback– which would contribute invaluable data to theoretical frameworks. The proposed research project will advance our understanding of ongoing brain activity, contextual processing, and cortical feedback - contributing to what is known about general cortical functions. By providing new insights as to the information content of cortical feedback, the proposal will fill one of the most important gaps in today's knowledge about brain function. Friston's unifying theory of the brain (Friston, 2010) and contemporary models of the predictive-coding framework (Hawkins and Blakeslee, 2004;Mumford, 1992;Rao and Ballard, 1999) assign feedback processing an essential role in cortical processing. Compared to feedforward information processing, our knowledge about feedback processing is in its infancy. The proposal introduces parametric and explorative brain reading designs to investigate this feedback processing. The chief goal of my proposal will be precision measures of cortical feedback, and a more ambitious objective is to read mental images and inner thoughts.
Project acronym BRAVE
Project "Bicuspid Related Aortopathy, a Vibrant Exploration"
Researcher (PI) Bart Leo Loeys
Host Institution (HI) UNIVERSITEIT ANTWERPEN
Summary "Bicuspid aortic valve, a heart valve with only two leaflets instead of three, is the most common congenital heart defect with an estimated prevalence of about 1-2%. The heart defect often remains asymptomatic but in at least 10% of the bicuspid aortic valve patients, an ascending aortic aneurysm develops as well. If not detected in a timely fashion, this can lead to an aortic aneurysm dissection with a high mortality. In view of the prevalent nature of this heart defect, this implies an important health care problem. Historically, it was always hypothesized that abnormal blood flow across the bicuspid aortic valve led to aneurysm formation. However in recent years, the importance of a genetic contribution has been suggested based on the high heritability and it is currently believed that the same genetic factors predispose to the developmental valve defect and the aortic aneurysm formation. The inheritance pattern is most consistent with an autosomal dominant disorder with variable penetrance and expressivity. Until now, the latter have significantly hampered the causal gene identification but the era of next generation sequencing is now offering unprecedented opportunities for a major breakthrough in this area. Through detailed signalling pathway analysis, miRNA profiling and next generation sequencing, this project will contribute significantly to resolving the genetic causes of bicuspid related aortopathy, provide critical knowledge on the pathogenesis of aortic aneurysmal disease and deliver a mouse model for future therapeutical trials."
"Bicuspid aortic valve, a heart valve with only two leaflets instead of three, is the most common congenital heart defect with an estimated prevalence of about 1-2%. The heart defect often remains asymptomatic but in at least 10% of the bicuspid aortic valve patients, an ascending aortic aneurysm develops as well. If not detected in a timely fashion, this can lead to an aortic aneurysm dissection with a high mortality. In view of the prevalent nature of this heart defect, this implies an important health care problem. Historically, it was always hypothesized that abnormal blood flow across the bicuspid aortic valve led to aneurysm formation. However in recent years, the importance of a genetic contribution has been suggested based on the high heritability and it is currently believed that the same genetic factors predispose to the developmental valve defect and the aortic aneurysm formation. The inheritance pattern is most consistent with an autosomal dominant disorder with variable penetrance and expressivity. Until now, the latter have significantly hampered the causal gene identification but the era of next generation sequencing is now offering unprecedented opportunities for a major breakthrough in this area. Through detailed signalling pathway analysis, miRNA profiling and next generation sequencing, this project will contribute significantly to resolving the genetic causes of bicuspid related aortopathy, provide critical knowledge on the pathogenesis of aortic aneurysmal disease and deliver a mouse model for future therapeutical trials."


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