Project acronym BRAINPOWER
Project Brain energy supply and the consequences of its failure
Researcher (PI) David Ian Attwell
Host Institution (HI) University College London
Country United Kingdom
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary Energy, supplied in the form of oxygen and glucose in the blood, is essential for the brain s cognitive power. Failure of the energy supply to the nervous system underlies the mental and physical disability occurring in a wide range of economically important neurological disorders, such as stroke, spinal cord injury and cerebral palsy. Using a combination of two-photon imaging, electrophysiological, molecular and transgenic approaches, I will investigate the control of brain energy supply at the vascular level, and at the level of individual neurons and glial cells, and study the deleterious consequences for the neurons, glia and vasculature of a failure of brain energy supply. The work will focus on the following fundamental issues: A. Vascular control of the brain energy supply (1) How important is control of energy supply at the capillary level, by pericytes? (2) Which synapses control blood flow (and thus generate functional imaging signals) in the cortex? B. Neuronal and glial control of brain energy supply (3) How is grey matter neuronal activity powered? (4) How is the white matter supplied with energy? C. The pathological consequences of a loss of brain energy supply (5) How does a fall of energy supply cause neurotoxic glutamate release? (6) How similar are events in the grey and white matter in energy deprivation conditions? (7) How does a transient loss of energy supply affect blood flow regulation? (8) How does brain energy use change after a period without energy supply? Together this work will significantly advance our understanding of how the energy supply to neurons and glia is regulated in normal conditions, and how the loss of the energy supply causes disorders which consume more than 5% of the costs of European health services (5% of ~1000 billion euro/year).
Summary
Energy, supplied in the form of oxygen and glucose in the blood, is essential for the brain s cognitive power. Failure of the energy supply to the nervous system underlies the mental and physical disability occurring in a wide range of economically important neurological disorders, such as stroke, spinal cord injury and cerebral palsy. Using a combination of two-photon imaging, electrophysiological, molecular and transgenic approaches, I will investigate the control of brain energy supply at the vascular level, and at the level of individual neurons and glial cells, and study the deleterious consequences for the neurons, glia and vasculature of a failure of brain energy supply. The work will focus on the following fundamental issues: A. Vascular control of the brain energy supply (1) How important is control of energy supply at the capillary level, by pericytes? (2) Which synapses control blood flow (and thus generate functional imaging signals) in the cortex? B. Neuronal and glial control of brain energy supply (3) How is grey matter neuronal activity powered? (4) How is the white matter supplied with energy? C. The pathological consequences of a loss of brain energy supply (5) How does a fall of energy supply cause neurotoxic glutamate release? (6) How similar are events in the grey and white matter in energy deprivation conditions? (7) How does a transient loss of energy supply affect blood flow regulation? (8) How does brain energy use change after a period without energy supply? Together this work will significantly advance our understanding of how the energy supply to neurons and glia is regulated in normal conditions, and how the loss of the energy supply causes disorders which consume more than 5% of the costs of European health services (5% of ~1000 billion euro/year).
Max ERC Funding
2 499 947 €
Duration
Start date: 2010-04-01, End date: 2016-03-31
Project acronym CHROMOCOND
Project A molecular view of chromosome condensation
Researcher (PI) Frank Uhlmann
Host Institution (HI) CANCER RESEARCH UK LBG
Country United Kingdom
Call Details Advanced Grant (AdG), LS3, ERC-2009-AdG
Summary Eukaryotic cells inherit much of their genomic information in the form of chromosomes during cell division. Centimetre-long DNA molecules are packed into micrometer-sized chromosomes to enable this process. How DNA is organised within mitotic chromosomes is still largely unknown. A key structural protein component of mitotic chromosomes, implicated in their compaction, is the condensin complex. In this proposal, we aim to elucidate the molecular architecture of mitotic chromosomes, taking advantage of new genomic techniques and the relatively simple genome organisation of yeast model systems. We will place particular emphasis on elucidating the contribution of the condensin complex, and the cell cycle regulation of its activities, in promoting chromosome condensation. Our previous work has provided genome-wide maps of condensin binding to budding and fission yeast chromosomes. We will continue to decipher the molecular determinants for condensin binding. To investigate how condensin mediates DNA compaction, we propose to generate chromosome-wide DNA/DNA proximity maps. Our approach will be an extension of the chromosome conformation capture (3C) technique. High throughput sequencing of interaction points has provided a first glimpse of the interactions that govern chromosome condensation. The role that condensin plays in promoting these interactions will be investigated. The contribution of condensin s ATP-dependent activities, and cell cycle-dependent post-translational modifications, will be studied. This will be complemented by mathematical modelling of the condensation process. In addition to chromosome condensation, condensin is required for resolution of sister chromatids in anaphase. We will develop an assay to study the catenation status of sister chromatids and how condensin may contribute to their topological resolution.
Summary
Eukaryotic cells inherit much of their genomic information in the form of chromosomes during cell division. Centimetre-long DNA molecules are packed into micrometer-sized chromosomes to enable this process. How DNA is organised within mitotic chromosomes is still largely unknown. A key structural protein component of mitotic chromosomes, implicated in their compaction, is the condensin complex. In this proposal, we aim to elucidate the molecular architecture of mitotic chromosomes, taking advantage of new genomic techniques and the relatively simple genome organisation of yeast model systems. We will place particular emphasis on elucidating the contribution of the condensin complex, and the cell cycle regulation of its activities, in promoting chromosome condensation. Our previous work has provided genome-wide maps of condensin binding to budding and fission yeast chromosomes. We will continue to decipher the molecular determinants for condensin binding. To investigate how condensin mediates DNA compaction, we propose to generate chromosome-wide DNA/DNA proximity maps. Our approach will be an extension of the chromosome conformation capture (3C) technique. High throughput sequencing of interaction points has provided a first glimpse of the interactions that govern chromosome condensation. The role that condensin plays in promoting these interactions will be investigated. The contribution of condensin s ATP-dependent activities, and cell cycle-dependent post-translational modifications, will be studied. This will be complemented by mathematical modelling of the condensation process. In addition to chromosome condensation, condensin is required for resolution of sister chromatids in anaphase. We will develop an assay to study the catenation status of sister chromatids and how condensin may contribute to their topological resolution.
Max ERC Funding
2 076 126 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
Project acronym CMR
Project Cosmic ray acceleration, magnetic field and radiation hydrodynamics
Researcher (PI) Anthony Raymond Bell
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), PE9, ERC-2009-AdG
Summary Diffusive shock acceleration is widely acknowledged as the most likely source of cosmic rays and high energy particles. The basic macroscopic theory of how cosmic rays gain energy during multiple shock crossings is well known, but the microphysics of the interaction between cosmic rays (CR) and the MHD background fluid remained poorly understood before the recent discovery of a new non-resonant instability by which the CR precursor could greatly amplify the ambient magnetic field. The aims of the project are: 1) to develop the first self-consistent non-linear simulation of the CR/MHD interaction; to calculate the magnitude of the saturated magnetic field and the maximum energy to which CR are accelerated. We will characterise the structure of the amplified magnetic field and compare it with x-ray observations of the time-evolving outer shock of supernova remnants (SNR). We will investigate the effect of various orientations of the shock relative to the ambient magnetic field, the effect of non-diffusive transport on the energy spectrum and CR escape from the SNR, and how these match observation. 2) to extend the simulation to relativistic shocks as found in gamma-ray bursts (GRB) and active galactic nuclei (AGN); to establish whether the non-resonant instability operates effectively at relativistic shock velocities, whether it explains the large magnetic field found in GRB, and determine the maximum CR energy achieved by relativistic shocks. 3) to investigate high density shocks in GRB, x-ray flashes (XRF) and supernovae (SN) where radiative processes, pair production and other particle/photon and particle/particle interactions are important. We shall investigate CR acceleration on SN shock breakout and very young SNR as a possible source of very high energy CR.
Summary
Diffusive shock acceleration is widely acknowledged as the most likely source of cosmic rays and high energy particles. The basic macroscopic theory of how cosmic rays gain energy during multiple shock crossings is well known, but the microphysics of the interaction between cosmic rays (CR) and the MHD background fluid remained poorly understood before the recent discovery of a new non-resonant instability by which the CR precursor could greatly amplify the ambient magnetic field. The aims of the project are: 1) to develop the first self-consistent non-linear simulation of the CR/MHD interaction; to calculate the magnitude of the saturated magnetic field and the maximum energy to which CR are accelerated. We will characterise the structure of the amplified magnetic field and compare it with x-ray observations of the time-evolving outer shock of supernova remnants (SNR). We will investigate the effect of various orientations of the shock relative to the ambient magnetic field, the effect of non-diffusive transport on the energy spectrum and CR escape from the SNR, and how these match observation. 2) to extend the simulation to relativistic shocks as found in gamma-ray bursts (GRB) and active galactic nuclei (AGN); to establish whether the non-resonant instability operates effectively at relativistic shock velocities, whether it explains the large magnetic field found in GRB, and determine the maximum CR energy achieved by relativistic shocks. 3) to investigate high density shocks in GRB, x-ray flashes (XRF) and supernovae (SN) where radiative processes, pair production and other particle/photon and particle/particle interactions are important. We shall investigate CR acceleration on SN shock breakout and very young SNR as a possible source of very high energy CR.
Max ERC Funding
900 024 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym CULTRWORLD
Project The evolution of cultural norms in real world settings
Researcher (PI) Ruth Helen Mace
Host Institution (HI) University College London
Country United Kingdom
Call Details Advanced Grant (AdG), SH4, ERC-2009-AdG
Summary An intense debate is raging within evolutionary anthropology as to whether the evolution of human behaviour is driven by selection pressure on the individual or on the group. Until recently there was consensus amongst evolutionary biologists and evolutionary anthropologists that natural selection caused behaviours to evolve that benefit the individual or close kin. However the idea that cultural behaviours that favour the group can evolve, even at the expense of individual well-being, is now being supported by some evolutionary anthropologists and economists. Models of cultural group selection rely on patterns of cultural transmission that maintain differences between cultural groups, because either decisions are based on what most others in the group do, or non-conformists are punished in some way. If such biased transmission occurs, then humans may be following a unique evolutionary trajectory towards extreme sociality; such models potentially explain behaviours such as altruism towards non-relatives or limiting your reproductive rate. However, relevant empirical evidence from real world populations, concerning behaviour that potentially influences reproductive success, is almost entirely lacking. The projects proposed here are designed to help fill that gap. In micro-evolutionary studies we will seek evidence for the patterns cultural transmission or social learning that enable cultural group selection to act, and ask how these processes depend on properties of the community, and thus how robust are they to the demographic and societal changes that accompany modernisation. These include studies of the spread of modern contraception through communities; and studies of punishment of selfish players in economic games. In macro-evolutionary studies, we will use phylogenetic cross-cultural comparative methods to show how different cultural traits change over the long term, and ask whether social or ecological variables are driving that cultural change.
Summary
An intense debate is raging within evolutionary anthropology as to whether the evolution of human behaviour is driven by selection pressure on the individual or on the group. Until recently there was consensus amongst evolutionary biologists and evolutionary anthropologists that natural selection caused behaviours to evolve that benefit the individual or close kin. However the idea that cultural behaviours that favour the group can evolve, even at the expense of individual well-being, is now being supported by some evolutionary anthropologists and economists. Models of cultural group selection rely on patterns of cultural transmission that maintain differences between cultural groups, because either decisions are based on what most others in the group do, or non-conformists are punished in some way. If such biased transmission occurs, then humans may be following a unique evolutionary trajectory towards extreme sociality; such models potentially explain behaviours such as altruism towards non-relatives or limiting your reproductive rate. However, relevant empirical evidence from real world populations, concerning behaviour that potentially influences reproductive success, is almost entirely lacking. The projects proposed here are designed to help fill that gap. In micro-evolutionary studies we will seek evidence for the patterns cultural transmission or social learning that enable cultural group selection to act, and ask how these processes depend on properties of the community, and thus how robust are they to the demographic and societal changes that accompany modernisation. These include studies of the spread of modern contraception through communities; and studies of punishment of selfish players in economic games. In macro-evolutionary studies, we will use phylogenetic cross-cultural comparative methods to show how different cultural traits change over the long term, and ask whether social or ecological variables are driving that cultural change.
Max ERC Funding
1 801 978 €
Duration
Start date: 2010-05-01, End date: 2016-04-30
Project acronym DENDRITE
Project Cellular and circuit determinants of dendritic computation
Researcher (PI) Michael Andreas Hausser
Host Institution (HI) University College London
Country United Kingdom
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary What is the fundamental unit of computation in the brain? Answering this question is crucial not only for understanding how the brain works, but also for building accurate models of brain function, which require abstraction based on identification of the essential elements for carrying out computations relevant to behaviour. We will directly test the possibility that single dendritic branches may act as individual computational units during behaviour, challenging the classical view that the neuron is the fundamental unit of computation. We will address this question using a combination of electrophysiological, anatomical, imaging, molecular, and modeling approaches to probe dendritic integration in pyramidal cells and Purkinje cells in mouse cortex and cerebellum. We will define the computational rules for integration of synaptic input in dendrites by examining the responses to different spatiotemporal patterns of excitatory and inhibitory inputs. We will use computational modeling to extract simple rules describing dendritic integration that captures the essence of the computation. Next, we will determine how these rules are engaged by patterns of sensory stimulation in vivo, by using various strategies to map the spatiotemporal patterns of synaptic inputs to dendrites. To understand how physiological patterns of activity in the circuit engage these dendritic computations, we will use anatomical approaches to map the wiring diagram of synaptic inputs to individual dendrites. Finally, we will manipulate dendritic function using molecular tools, in order to provide causal links between specific dendritic computations and sensory processing. These experiments will provide us with deeper insights into how single neurons act as computing devices, and how fundamental computations that drive behaviour are implemented on the level of single cells and neural circuits.
Summary
What is the fundamental unit of computation in the brain? Answering this question is crucial not only for understanding how the brain works, but also for building accurate models of brain function, which require abstraction based on identification of the essential elements for carrying out computations relevant to behaviour. We will directly test the possibility that single dendritic branches may act as individual computational units during behaviour, challenging the classical view that the neuron is the fundamental unit of computation. We will address this question using a combination of electrophysiological, anatomical, imaging, molecular, and modeling approaches to probe dendritic integration in pyramidal cells and Purkinje cells in mouse cortex and cerebellum. We will define the computational rules for integration of synaptic input in dendrites by examining the responses to different spatiotemporal patterns of excitatory and inhibitory inputs. We will use computational modeling to extract simple rules describing dendritic integration that captures the essence of the computation. Next, we will determine how these rules are engaged by patterns of sensory stimulation in vivo, by using various strategies to map the spatiotemporal patterns of synaptic inputs to dendrites. To understand how physiological patterns of activity in the circuit engage these dendritic computations, we will use anatomical approaches to map the wiring diagram of synaptic inputs to individual dendrites. Finally, we will manipulate dendritic function using molecular tools, in order to provide causal links between specific dendritic computations and sensory processing. These experiments will provide us with deeper insights into how single neurons act as computing devices, and how fundamental computations that drive behaviour are implemented on the level of single cells and neural circuits.
Max ERC Funding
2 416 078 €
Duration
Start date: 2010-06-01, End date: 2016-05-31
Project acronym EVO500
Project Origin of a cell differentiation mechanism and its evolution over 500 million years of life on land
Researcher (PI) Liam Dolan
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), LS3, ERC-2009-AdG
Summary The evolution of the first rooting systems approximately 470 million years ago was a critical event in the history of life on Earth because it allowed the growth of complex multicellular eukaryotic photosynthetic organisms – plants - on the surface of the land. Rooting systems are important because they facilitate the uptake of every chemical element in the plant body with the exception of carbon. The root systems of the
first land plants (liverworts) comprised a mass of unicellular tip-growing filaments (rhizoids) that grew from the plant surface into the soil. All root systems that evolved since then similarly comprise a system of tipgrowing filamentous cells located at the interface between the plant and the soil, indicating that the differentiation of filamentous root cells has been critical for root function for the past 470 million years. This proposal aims to characterize the origin and evolution of this essential cellular differentiation process. The proposed research is in three parts:
First we propose to define the mechanism that controlled the development of the first land plant root system by identifying genes that control liverwort rooting system (rhizoids) development and
characterizing their regulatory interactions.
Second we propose to determine if the mechanism that controlled the development of the first land
plant root system was inherited from algal ancestors.
Third we propose to characterize the mechanism that controls filamentous root hair growth in
Arabidopsis in response to environmental factors, and determine if it is conserved among land
plants.
In combination, these experiments will define the genetic mechanisms underpinning the development and evolution of one of the fundamental developmental processes in land plants.
Summary
The evolution of the first rooting systems approximately 470 million years ago was a critical event in the history of life on Earth because it allowed the growth of complex multicellular eukaryotic photosynthetic organisms – plants - on the surface of the land. Rooting systems are important because they facilitate the uptake of every chemical element in the plant body with the exception of carbon. The root systems of the
first land plants (liverworts) comprised a mass of unicellular tip-growing filaments (rhizoids) that grew from the plant surface into the soil. All root systems that evolved since then similarly comprise a system of tipgrowing filamentous cells located at the interface between the plant and the soil, indicating that the differentiation of filamentous root cells has been critical for root function for the past 470 million years. This proposal aims to characterize the origin and evolution of this essential cellular differentiation process. The proposed research is in three parts:
First we propose to define the mechanism that controlled the development of the first land plant root system by identifying genes that control liverwort rooting system (rhizoids) development and
characterizing their regulatory interactions.
Second we propose to determine if the mechanism that controlled the development of the first land
plant root system was inherited from algal ancestors.
Third we propose to characterize the mechanism that controls filamentous root hair growth in
Arabidopsis in response to environmental factors, and determine if it is conserved among land
plants.
In combination, these experiments will define the genetic mechanisms underpinning the development and evolution of one of the fundamental developmental processes in land plants.
Max ERC Funding
2 463 835 €
Duration
Start date: 2010-10-01, End date: 2015-09-30
Project acronym FUNCA
Project Functional Nanomaterials via Controlled Block Copolymer Assembly
Researcher (PI) Ian Manners
Host Institution (HI) UNIVERSITY OF BRISTOL
Country United Kingdom
Call Details Advanced Grant (AdG), PE5, ERC-2009-AdG
Summary We outline an ambitious 5 year interdisplinary research programme that introduces a fundamentally new platform to the fabrication of nanoelectronic and liquid crystal devices, current areas of intense scientific and technological interest. The new approach involves the use of block copolymer micelles and block comicelles prepared by Crystallization-Driven Living Polymerization (CDLP) processes. This novel method allows unprecedented access to well-defined micelle architectures (with size control, narrow size distribution, and access to segmented structures that possess heterojunctions). Crosslinking will also be used to optimize micelle mechanical properties where necessary. The new platform offers very promising advantages over competitive methods for realising nanomaterials these include ambient temperature synthesis and solution processing, easy control of dimensions and aspect ratio, electronic properties, and semiconductor/semiconductor or semiconductor/dielectric junction fabrication. In addition, the use of hydrophilic coronas should, in principle, allow the self-assembly processes and subsequent manipulations to be performed in water.
Summary
We outline an ambitious 5 year interdisplinary research programme that introduces a fundamentally new platform to the fabrication of nanoelectronic and liquid crystal devices, current areas of intense scientific and technological interest. The new approach involves the use of block copolymer micelles and block comicelles prepared by Crystallization-Driven Living Polymerization (CDLP) processes. This novel method allows unprecedented access to well-defined micelle architectures (with size control, narrow size distribution, and access to segmented structures that possess heterojunctions). Crosslinking will also be used to optimize micelle mechanical properties where necessary. The new platform offers very promising advantages over competitive methods for realising nanomaterials these include ambient temperature synthesis and solution processing, easy control of dimensions and aspect ratio, electronic properties, and semiconductor/semiconductor or semiconductor/dielectric junction fabrication. In addition, the use of hydrophilic coronas should, in principle, allow the self-assembly processes and subsequent manipulations to be performed in water.
Max ERC Funding
1 658 544 €
Duration
Start date: 2010-04-01, End date: 2016-03-31
Project acronym GRAMPLUS
Project Grammar-Based Robust Natural Language Processing
Researcher (PI) Mark Jerome Steedman
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Country United Kingdom
Call Details Advanced Grant (AdG), SH4, ERC-2009-AdG
Summary From the late '50s until the early '70s, theoretical linguistics, computational linguistics, and psycholinguistics, were united by a common model based on Chomskian transformational generative grammar formalism. This consensus fell apart in the later 70s, because of disagreements about the role of semantics. Formal syntax has abandoned semantics and any interest in formal constraint. Semantically based functional and cognitive theories of grammar are agnostic about formalism. Current psycholinguistic theories mainly ignore formal linguistic theory, while in computational linguistics, the dominant models are generally low-level finite-state or context-free systems that are known to to be incomplete with respect to the full range of of human language. While the latter methods, aided by machine-learning, have made considerable progress in practical applications such as automatic speech recognition, machine translation, and parsing, they place inherent limits on performance that are already yielding near-asymptotic performance in some applications. The aim of the proposal is to restore grammatical theory to its necessary place in the theory of human language behaviour, by providing a more restricted theory of constructions than others on offer. This formalism is both efficiently parsable, and expressive enough to support semantic interpretation. The project seeks both to establish the explanatory adequacy of the theory in linguistic terms, and to generalize existing treebank-based computational models derived by supervised learning methods. It uses unsupervised and semi-supervised methods based on unlabeled data. A crucial component will be a fully articulated Natural Semantics closely related to the surface grammar, supporting entailment directly.
Summary
From the late '50s until the early '70s, theoretical linguistics, computational linguistics, and psycholinguistics, were united by a common model based on Chomskian transformational generative grammar formalism. This consensus fell apart in the later 70s, because of disagreements about the role of semantics. Formal syntax has abandoned semantics and any interest in formal constraint. Semantically based functional and cognitive theories of grammar are agnostic about formalism. Current psycholinguistic theories mainly ignore formal linguistic theory, while in computational linguistics, the dominant models are generally low-level finite-state or context-free systems that are known to to be incomplete with respect to the full range of of human language. While the latter methods, aided by machine-learning, have made considerable progress in practical applications such as automatic speech recognition, machine translation, and parsing, they place inherent limits on performance that are already yielding near-asymptotic performance in some applications. The aim of the proposal is to restore grammatical theory to its necessary place in the theory of human language behaviour, by providing a more restricted theory of constructions than others on offer. This formalism is both efficiently parsable, and expressive enough to support semantic interpretation. The project seeks both to establish the explanatory adequacy of the theory in linguistic terms, and to generalize existing treebank-based computational models derived by supervised learning methods. It uses unsupervised and semi-supervised methods based on unlabeled data. A crucial component will be a fully articulated Natural Semantics closely related to the surface grammar, supporting entailment directly.
Max ERC Funding
1 910 998 €
Duration
Start date: 2010-06-01, End date: 2015-05-31
Project acronym MOFDH
Project Molecular origin and function of dynamic heterogeneities in mouse ES cells and pre-implantation embryos
Researcher (PI) Alfonso Martinez Arias
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Advanced Grant (AdG), LS3, ERC-2009-AdG
Summary The mechanisms powering the transition from one cell state to another are the central engine of embryonic development. Genetic analysis over the last twenty years has provided us with a catalogue of genes and proteins that can be linked in linear and time dependent manners to specific states and transitions in this process. However this picture, characterized by complex charts of univocal relationships between different genes, is static and rigid and contrasts with the plasticity displayed by cells in many processes, in particular during repair and regeneration. The early mammalian embryo and the closely related ES cells provide extreme examples of this in the form of toti- and pluri-potency i.e. the maintenance of an open uncommitted state from which all cell types emerge. Understanding the molecular basis of these uncommitted states and the way they are established and regulated will not only provide a deeper insight into the operation of biological systems but will also new targets for regulation and therapies. This project revolves around the hypothesis that the plasticity displayed by cells in developmental and regulative processes is associated with dynamical cellular heterogeneities generated by transcriptional noise: phenotypic variability in genetically identical cells that arises from stochastic fluctuations during transcription and translation. Specifically I propose to provide measurements and analysis of gene expression noise in mammalian cells, its origin, regulation and use using ES cells and early mouse embryos as experimental systems.
Summary
The mechanisms powering the transition from one cell state to another are the central engine of embryonic development. Genetic analysis over the last twenty years has provided us with a catalogue of genes and proteins that can be linked in linear and time dependent manners to specific states and transitions in this process. However this picture, characterized by complex charts of univocal relationships between different genes, is static and rigid and contrasts with the plasticity displayed by cells in many processes, in particular during repair and regeneration. The early mammalian embryo and the closely related ES cells provide extreme examples of this in the form of toti- and pluri-potency i.e. the maintenance of an open uncommitted state from which all cell types emerge. Understanding the molecular basis of these uncommitted states and the way they are established and regulated will not only provide a deeper insight into the operation of biological systems but will also new targets for regulation and therapies. This project revolves around the hypothesis that the plasticity displayed by cells in developmental and regulative processes is associated with dynamical cellular heterogeneities generated by transcriptional noise: phenotypic variability in genetically identical cells that arises from stochastic fluctuations during transcription and translation. Specifically I propose to provide measurements and analysis of gene expression noise in mammalian cells, its origin, regulation and use using ES cells and early mouse embryos as experimental systems.
Max ERC Funding
2 299 367 €
Duration
Start date: 2010-05-01, End date: 2016-04-30
Project acronym PERCEPCON
Project From perception to conception: How the brain processes meaningful concepts
Researcher (PI) Lorraine Komisarjevsky Tyler
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Advanced Grant (AdG), SH4, ERC-2009-AdG
Summary Conceptual representations of objects and events lie at the heart of our mental lives; they enable us to interpret the world, express our thoughts and form the basis for our interactions. From a cognitive perspective, there is increasing interest in distributed accounts of conceptual representations, in which concepts are comprised of smaller elements of meaning (features), with variation in the types of features and their inter-relationships determining a concept s structure. Although interest in how the brain represents and processes concepts has flourished with the advent of modern neuroimaging technologies, cognitive and neural approaches are not well integrated. While both focus on concrete concepts or visual objects cognitive accounts focus on their meaning whereas neural accounts focus on their visual properties. The research proposed here aims to bridge this gap by addressing the central issue of how the brain processes visual objects as meaningful entities; how perception becomes conception. It does so by combining a cognitive theory of semantic representations the Conceptual Structure Account - with a neural account of hierarchical object processing in the ventral stream to generate predictions about how perceptual and conceptual processes are constructed. This combination of cognitive and neural theories, together with the use of multi-modal imaging methods, provides the essential basis for understanding how the brain transforms visual inputs into meaningful object representations. In fMRI and MEG studies, we directly test for differential effects of conceptual and perceptual variables along the ventral stream, examining specific cognitive claims for how conceptual structure guides and structures these fundamental processes of object recognition.
Summary
Conceptual representations of objects and events lie at the heart of our mental lives; they enable us to interpret the world, express our thoughts and form the basis for our interactions. From a cognitive perspective, there is increasing interest in distributed accounts of conceptual representations, in which concepts are comprised of smaller elements of meaning (features), with variation in the types of features and their inter-relationships determining a concept s structure. Although interest in how the brain represents and processes concepts has flourished with the advent of modern neuroimaging technologies, cognitive and neural approaches are not well integrated. While both focus on concrete concepts or visual objects cognitive accounts focus on their meaning whereas neural accounts focus on their visual properties. The research proposed here aims to bridge this gap by addressing the central issue of how the brain processes visual objects as meaningful entities; how perception becomes conception. It does so by combining a cognitive theory of semantic representations the Conceptual Structure Account - with a neural account of hierarchical object processing in the ventral stream to generate predictions about how perceptual and conceptual processes are constructed. This combination of cognitive and neural theories, together with the use of multi-modal imaging methods, provides the essential basis for understanding how the brain transforms visual inputs into meaningful object representations. In fMRI and MEG studies, we directly test for differential effects of conceptual and perceptual variables along the ventral stream, examining specific cognitive claims for how conceptual structure guides and structures these fundamental processes of object recognition.
Max ERC Funding
2 111 581 €
Duration
Start date: 2010-05-01, End date: 2015-09-30
