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 DISKtoHALO
Project From the accretion disk to the cluster halo: the multi-scale physics of black hole feedback
Researcher (PI) Christopher REYNOLDS
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Advanced Grant (AdG), PE9, ERC-2018-ADG
Summary It is firmly established that supermassive black holes (SMBHs) have a profound influence on the evolution of galaxies and galaxy groups/clusters. Yet, almost 20 years after this realization, fundamental questions remain. What determines the efficiency with which an active galactic nucleus (AGN) couples to its surroundings? Why does AGN feedback appear to be ineffective in low-mass galaxies? In maintenance-mode feedback, how does the AGN regulate to closely balance cooling? How does the nature of AGN feedback change as we consider higher redshifts and push back to the epoch of the first galaxies? AGN feedback is a truly multi-scale phenomenon. Observations show that AGN have an energetic impact on galactic-, group-, and cluster-halo scales. Yet the efficiency with which an accreting SMBH releases energy, and the partitioning of that energy into radiation, winds, and relativistic jets, is dictated by complex processes in the accretion disk on AU scales, 10^10 times smaller than the halo. Furthermore, especially in massive systems where feedback proceeds via the heating of a hot circumgalactic or intracluster medium (CGM/ICM), the relevant microphysics of the hot baryons is unclear, requiring an understanding of plasma instabilities on 10^-9pc scales. We propose a set of projects that explore the multiscale physics of AGN feedback. Magnetohydrodynamic models of accretion disks will be constructed to study the AGN radiation/winds/jets and calibrate observable proxies of SMBH mass and accretion rate. We will use the machinery of plasma physics to characterize the CGM/ICM microphysics relevant to the thermalization of AGN-injected energy. Finally, we will produce new galaxy-, group- and cluster-scale models incorporating the new microphysical prescriptions and AGN models. Our new theoretical understanding of AGN feedback as a function of halo mass, environment, and cosmic time is essential for interpreting the torrent of data from current and future observatories
Summary
It is firmly established that supermassive black holes (SMBHs) have a profound influence on the evolution of galaxies and galaxy groups/clusters. Yet, almost 20 years after this realization, fundamental questions remain. What determines the efficiency with which an active galactic nucleus (AGN) couples to its surroundings? Why does AGN feedback appear to be ineffective in low-mass galaxies? In maintenance-mode feedback, how does the AGN regulate to closely balance cooling? How does the nature of AGN feedback change as we consider higher redshifts and push back to the epoch of the first galaxies? AGN feedback is a truly multi-scale phenomenon. Observations show that AGN have an energetic impact on galactic-, group-, and cluster-halo scales. Yet the efficiency with which an accreting SMBH releases energy, and the partitioning of that energy into radiation, winds, and relativistic jets, is dictated by complex processes in the accretion disk on AU scales, 10^10 times smaller than the halo. Furthermore, especially in massive systems where feedback proceeds via the heating of a hot circumgalactic or intracluster medium (CGM/ICM), the relevant microphysics of the hot baryons is unclear, requiring an understanding of plasma instabilities on 10^-9pc scales. We propose a set of projects that explore the multiscale physics of AGN feedback. Magnetohydrodynamic models of accretion disks will be constructed to study the AGN radiation/winds/jets and calibrate observable proxies of SMBH mass and accretion rate. We will use the machinery of plasma physics to characterize the CGM/ICM microphysics relevant to the thermalization of AGN-injected energy. Finally, we will produce new galaxy-, group- and cluster-scale models incorporating the new microphysical prescriptions and AGN models. Our new theoretical understanding of AGN feedback as a function of halo mass, environment, and cosmic time is essential for interpreting the torrent of data from current and future observatories
Max ERC Funding
2 489 918 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
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 Foldmetcat
Project Bioinspired Catalytic Metallofoldamers
Researcher (PI) ANTONIO M ECHAVARREN PABLOS
Host Institution (HI) FUNDACIO PRIVADA INSTITUT CATALA D'INVESTIGACIO QUIMICA
Country Spain
Call Details Advanced Grant (AdG), PE5, ERC-2018-ADG
Summary Inspired by mimicking the characteristics of terpenoid cyclase enzymes, the goal of this proposal is to design new types of catalysts containing electrophilic transition metal centers that could simultaneously fold and activate polyunsaturated substrates promoting non-inherent cyclization modes. Our goal is unprecedented, although it is rooted on fundamental organometallic chemistry, in particular, on the known activation of polyunsaturated substrates by highly electrophilic transition metals. These unconventional cyclizations cascades challenge the paradigm that the intrinsic reactivity of the substrate is the relevant factor in carbocation-initiated processes and would provide access to large carbocyclic skeletons such as those present in taxol and ophiobolin enantioselectively in a single step under catalytic conditions. Although the initial work will be carried out with gold catalysts, a major goal of this research is to develop other general-purpose efficient chiral electrophilic catalysts based on zinc. To attain our goal, we will study more simple catalysts to delineate the factors that control the folding of polyenynes and polyenes. Thus, we will prepare new series of C2-chiral catalysts in which the stereogenic elements are close to the reaction site. Related C2-chiral systems will be generated by supramolecular hydrogen-bond pairing. A similar chiral arrangement could also be achieved by an intramolecular chiral anion translocation from the metal to a distant hydrogen-bond donor site. In addition, we will explore larger systems based on structurally well-defined metallic clusters to generate highly electrophilic chiral reactive sites. The folding and activation of polyunsaturated substrates will be studied first with a series of catalytic prototypes based on digold or heterobimetallic complexes with N-heterocyclic carbenes, diphosphines, mixed ligands of these types, as well as resorcinarene-phosphonite cavitant ligands.
Summary
Inspired by mimicking the characteristics of terpenoid cyclase enzymes, the goal of this proposal is to design new types of catalysts containing electrophilic transition metal centers that could simultaneously fold and activate polyunsaturated substrates promoting non-inherent cyclization modes. Our goal is unprecedented, although it is rooted on fundamental organometallic chemistry, in particular, on the known activation of polyunsaturated substrates by highly electrophilic transition metals. These unconventional cyclizations cascades challenge the paradigm that the intrinsic reactivity of the substrate is the relevant factor in carbocation-initiated processes and would provide access to large carbocyclic skeletons such as those present in taxol and ophiobolin enantioselectively in a single step under catalytic conditions. Although the initial work will be carried out with gold catalysts, a major goal of this research is to develop other general-purpose efficient chiral electrophilic catalysts based on zinc. To attain our goal, we will study more simple catalysts to delineate the factors that control the folding of polyenynes and polyenes. Thus, we will prepare new series of C2-chiral catalysts in which the stereogenic elements are close to the reaction site. Related C2-chiral systems will be generated by supramolecular hydrogen-bond pairing. A similar chiral arrangement could also be achieved by an intramolecular chiral anion translocation from the metal to a distant hydrogen-bond donor site. In addition, we will explore larger systems based on structurally well-defined metallic clusters to generate highly electrophilic chiral reactive sites. The folding and activation of polyunsaturated substrates will be studied first with a series of catalytic prototypes based on digold or heterobimetallic complexes with N-heterocyclic carbenes, diphosphines, mixed ligands of these types, as well as resorcinarene-phosphonite cavitant ligands.
Max ERC Funding
2 500 000 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
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 GEMS
Project Genetically Evolving Models of Science
Researcher (PI) Fernand Gobet
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Country United Kingdom
Call Details Advanced Grant (AdG), SH4, ERC-2018-ADG
Summary The development of scientific models suffers from two related problems: ever-growing number of experimental results and scientists’ cognitive limitations (including cognitive biases). This multidisciplinary project (psychology, computer modelling, computer science and cognitive neuroscience) addresses these problems by developing a novel methodology for generating scientific models automatically. The methodology is general and can be applied to any science where experimental data are available.
The method treats models as computer programs and evolves a population of models using genetic programming. The extent to which the models fit the empirical data is used as a fitness function. The best models–potentially modified by cross-over and mutation–are selected for the next generation. Pilot simulations have established the validity of the methodology with simple experiments.
To demonstrate that the methodology is sound, can be used with complex datasets and can be generalised across sciences, four related strands of research are planned. First, ‘Building New Tools’ develops the methodology and creates techniques to understand and compare the evolved models. Second, ‘Explaining Human Data’ uses the methodology to explain a wide range of data on human cognition. This will be done in two steps: (a) data without learning (working memory and attention); and (b) data with learning (categorisation, implicit learning and explicit learning). Third, ‘Explaining Animal Data’ develops models to account for various aspects of animal behaviour, focusing on conditioning and categorisation. Finally, ‘Explaining Neuroscience Data’ extends the methodology to account for data combining information about cognitive and brain processes.
This project explores virgin territory and thus opens up a new field of research. It combines insights from experimental psychology, cognitive modelling, cognitive neuroscience and computer science, disciplines in which the PI has strong track record.
Summary
The development of scientific models suffers from two related problems: ever-growing number of experimental results and scientists’ cognitive limitations (including cognitive biases). This multidisciplinary project (psychology, computer modelling, computer science and cognitive neuroscience) addresses these problems by developing a novel methodology for generating scientific models automatically. The methodology is general and can be applied to any science where experimental data are available.
The method treats models as computer programs and evolves a population of models using genetic programming. The extent to which the models fit the empirical data is used as a fitness function. The best models–potentially modified by cross-over and mutation–are selected for the next generation. Pilot simulations have established the validity of the methodology with simple experiments.
To demonstrate that the methodology is sound, can be used with complex datasets and can be generalised across sciences, four related strands of research are planned. First, ‘Building New Tools’ develops the methodology and creates techniques to understand and compare the evolved models. Second, ‘Explaining Human Data’ uses the methodology to explain a wide range of data on human cognition. This will be done in two steps: (a) data without learning (working memory and attention); and (b) data with learning (categorisation, implicit learning and explicit learning). Third, ‘Explaining Animal Data’ develops models to account for various aspects of animal behaviour, focusing on conditioning and categorisation. Finally, ‘Explaining Neuroscience Data’ extends the methodology to account for data combining information about cognitive and brain processes.
This project explores virgin territory and thus opens up a new field of research. It combines insights from experimental psychology, cognitive modelling, cognitive neuroscience and computer science, disciplines in which the PI has strong track record.
Max ERC Funding
2 182 339 €
Duration
Start date: 2019-11-01, End date: 2024-10-31
