Project acronym ALCOHOLLIFECOURSE
Project Alcohol Consumption across the Life-course: Determinants and Consequences
Researcher (PI) Anne Rebecca Britton
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
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.
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.
Max ERC Funding
1 032 815 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym AMYTOX
Project Amyloid fibril cytotoxicity: new insights from novel approaches
Researcher (PI) Sheena Radford
Host Institution (HI) UNIVERSITY OF LEEDS
Call Details Advanced Grant (AdG), LS1, ERC-2012-ADG_20120314
Summary Despite the discovery of amyloidosis more than a century ago, the molecular and cellular mechanisms of these devastating human disorders remain obscure. In addition to their involvement in disease, amyloid fibrils perform physiological functions, whilst others have potentials as biomaterials. To realise their use in nanotechnology and to enable the development of amyloid therapies, there is an urgent need to understand the molecular pathways of amyloid assembly and to determine how amyloid fibrils interact with cells and cellular components. The challenges lie in the transient nature and low population of aggregating species and the panoply of amyloid fibril structures. This molecular complexity renders identification of the culprits of amyloid disease impossible to achieve using traditional methods.
Here I propose a series of exciting experiments that aim to cast new light on the molecular and cellular mechanisms of amyloidosis by exploiting approaches capable of imaging individual protein molecules or single protein fibrils in vitro and in living cells. The proposal builds on new data from our laboratory that have shown that amyloid fibrils (disease-associated, functional and created from de novo designed sequences) kill cells by a mechanism that depends on fibril length and on cellular uptake. Specifically, I will (i) use single molecule fluorescence and non-covalent mass spectrometry and to determine why short fibril samples disrupt biological membranes more than their longer counterparts and electron tomography to determine, for the first time, the structural properties of cytotoxic fibril ends; (ii) develop single molecule force spectroscopy to probe the interactions between amyloid precursors, fibrils and cellular membranes; and (iii) develop cell biological assays to discover the biological mechanism(s) of amyloid-induced cell death and high resolution imaging and electron tomography to visualise amyloid fibrils in the act of killing living cells.
Summary
Despite the discovery of amyloidosis more than a century ago, the molecular and cellular mechanisms of these devastating human disorders remain obscure. In addition to their involvement in disease, amyloid fibrils perform physiological functions, whilst others have potentials as biomaterials. To realise their use in nanotechnology and to enable the development of amyloid therapies, there is an urgent need to understand the molecular pathways of amyloid assembly and to determine how amyloid fibrils interact with cells and cellular components. The challenges lie in the transient nature and low population of aggregating species and the panoply of amyloid fibril structures. This molecular complexity renders identification of the culprits of amyloid disease impossible to achieve using traditional methods.
Here I propose a series of exciting experiments that aim to cast new light on the molecular and cellular mechanisms of amyloidosis by exploiting approaches capable of imaging individual protein molecules or single protein fibrils in vitro and in living cells. The proposal builds on new data from our laboratory that have shown that amyloid fibrils (disease-associated, functional and created from de novo designed sequences) kill cells by a mechanism that depends on fibril length and on cellular uptake. Specifically, I will (i) use single molecule fluorescence and non-covalent mass spectrometry and to determine why short fibril samples disrupt biological membranes more than their longer counterparts and electron tomography to determine, for the first time, the structural properties of cytotoxic fibril ends; (ii) develop single molecule force spectroscopy to probe the interactions between amyloid precursors, fibrils and cellular membranes; and (iii) develop cell biological assays to discover the biological mechanism(s) of amyloid-induced cell death and high resolution imaging and electron tomography to visualise amyloid fibrils in the act of killing living cells.
Max ERC Funding
2 498 465 €
Duration
Start date: 2013-05-01, End date: 2019-04-30
Project acronym ANTINEUTRINONOVA
Project Probing Fundamental Physics with Antineutrinos at the NOvA Experiment
Researcher (PI) Jeffrey Hartnell
Host Institution (HI) THE UNIVERSITY OF SUSSEX
Call Details Starting Grant (StG), PE2, ERC-2012-StG_20111012
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."
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."
Max ERC Funding
1 415 848 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym APHIDHOST
Project Molecular determinants of aphid host range
Researcher (PI) Jorunn Indra Berit Bos
Host Institution (HI) THE JAMES HUTTON INSTITUTE
Call Details Starting Grant (StG), LS9, ERC-2012-StG_20111109
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.
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.
Max ERC Funding
1 463 840 €
Duration
Start date: 2013-02-01, End date: 2018-10-31
Project acronym ARCHOFCON
Project The Architecture of Consciousness
Researcher (PI) Timothy John Bayne
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Starting Grant (StG), SH4, ERC-2012-StG_20111124
Summary The nature of consciousness is one of the great unsolved mysteries of science. Although the global research effort dedicated to explaining how consciousness arises from neural and cognitive activity is now more than two decades old, as yet there is no widely accepted theory of consciousness. One reason for why no adequate theory of consciousness has yet been found is that there is a lack of clarity about what exactly a theory of consciousness needs to explain. What is needed is thus a model of the general features of consciousness — a model of the ‘architecture’ of consciousness — that will systematize the structural differences between conscious states, processes and creatures on the one hand and unconscious states, processes and creatures on the other. The aim of this project is to remove one of the central impediments to the progress of the science of consciousness by constructing such a model.
A great many of the data required for this task already exist, but these data concern different aspects of consciousness and are distributed across many disciplines. As a result, there have been few attempts to develop a truly comprehensive model of the architecture of consciousness. This project will overcome the limitations of previous work by drawing on research in philosophy, psychology, psychiatry, and cognitive neuroscience to develop a model of the architecture of consciousness that is structured around five of its core features: its subjectivity, its temporality, its unity, its selectivity, and its dimensionality (that is, the relationship between the levels of consciousness and the contents of consciousness). By providing a comprehensive characterization of what a theory of consciousness needs to explain, this project will provide a crucial piece of the puzzle of consciousness, enabling future generations of researchers to bridge the gap between raw data on the one hand and a full-blown theory of consciousness on the other
Summary
The nature of consciousness is one of the great unsolved mysteries of science. Although the global research effort dedicated to explaining how consciousness arises from neural and cognitive activity is now more than two decades old, as yet there is no widely accepted theory of consciousness. One reason for why no adequate theory of consciousness has yet been found is that there is a lack of clarity about what exactly a theory of consciousness needs to explain. What is needed is thus a model of the general features of consciousness — a model of the ‘architecture’ of consciousness — that will systematize the structural differences between conscious states, processes and creatures on the one hand and unconscious states, processes and creatures on the other. The aim of this project is to remove one of the central impediments to the progress of the science of consciousness by constructing such a model.
A great many of the data required for this task already exist, but these data concern different aspects of consciousness and are distributed across many disciplines. As a result, there have been few attempts to develop a truly comprehensive model of the architecture of consciousness. This project will overcome the limitations of previous work by drawing on research in philosophy, psychology, psychiatry, and cognitive neuroscience to develop a model of the architecture of consciousness that is structured around five of its core features: its subjectivity, its temporality, its unity, its selectivity, and its dimensionality (that is, the relationship between the levels of consciousness and the contents of consciousness). By providing a comprehensive characterization of what a theory of consciousness needs to explain, this project will provide a crucial piece of the puzzle of consciousness, enabling future generations of researchers to bridge the gap between raw data on the one hand and a full-blown theory of consciousness on the other
Max ERC Funding
1 477 483 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym ARTIMATTER
Project "Lego-Style Materials, Structures and Devices Assembled on Demand from Isolated Atomic Planes"
Researcher (PI) Andre Geim
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Advanced Grant (AdG), PE3, ERC-2012-ADG_20120216
Summary "Following the advent of graphene with its wide range of unique properties, several other one-atom-thick crystals have been isolated and their preliminary studies have been undertaken. They range from semiconducting monolayers of MoS2 and NbSe2, which similar to graphene exhibit the electric field effect and relatively high electronic quality, to wide-gap insulators such as boron-nitride monolayers that can serve as atomically-thin tunnel barriers.
This library of two-dimensional crystals opens a possibility to construct various 3D structures with on-demand properties, which do not exist in nature but can be assembled in Lego style by stacking individual atomic planes on top of each other in a desired sequence. This project is to explore this new avenue.
We will design, fabricate and study multilayer materials ranging from basic heterostructures that consist of a few alternating layers of graphene and boron nitride and already exhibit a rich spectrum of new phenomena, as recently demonstrated by the applicant’s group, to complex artificial materials containing many layers of different 2D crystals and mimicking, for example, layered superconductors. In a similar manner, various electronic, optoelectronic, micromechanical and other devices will be developed and investigated. The applicant’s aim is to search for new materials with unique properties, novel devices with better characteristics and new physics that is likely to emerge along the way.
The proposed research offers many exciting opportunities and can lead to the development of a large unexplored field with impact exceeding even that of graphene research. This presents a unique, once-in-decade, opportunity to make a very significant breakthrough in condensed matter physics and materials science."
Summary
"Following the advent of graphene with its wide range of unique properties, several other one-atom-thick crystals have been isolated and their preliminary studies have been undertaken. They range from semiconducting monolayers of MoS2 and NbSe2, which similar to graphene exhibit the electric field effect and relatively high electronic quality, to wide-gap insulators such as boron-nitride monolayers that can serve as atomically-thin tunnel barriers.
This library of two-dimensional crystals opens a possibility to construct various 3D structures with on-demand properties, which do not exist in nature but can be assembled in Lego style by stacking individual atomic planes on top of each other in a desired sequence. This project is to explore this new avenue.
We will design, fabricate and study multilayer materials ranging from basic heterostructures that consist of a few alternating layers of graphene and boron nitride and already exhibit a rich spectrum of new phenomena, as recently demonstrated by the applicant’s group, to complex artificial materials containing many layers of different 2D crystals and mimicking, for example, layered superconductors. In a similar manner, various electronic, optoelectronic, micromechanical and other devices will be developed and investigated. The applicant’s aim is to search for new materials with unique properties, novel devices with better characteristics and new physics that is likely to emerge along the way.
The proposed research offers many exciting opportunities and can lead to the development of a large unexplored field with impact exceeding even that of graphene research. This presents a unique, once-in-decade, opportunity to make a very significant breakthrough in condensed matter physics and materials science."
Max ERC Funding
2 200 000 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym AXONSURVIVAL
Project Axon survival: the role of protein synthesis
Researcher (PI) Christine Elizabeth Holt
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), LS5, ERC-2012-ADG_20120314
Summary Neurons make long-distance connections with synaptic targets via axons. These axons survive throughout the lifetime of an organism, often many years in mammals, yet how axons are maintained is not fully understood. Recently, we provided in vivo evidence that local mRNA translation in mature axons is required for their maintenance. This new finding, along with in vitro work from other groups, indicates that promoting axonal protein synthesis is a key mechanism by which trophic factors act to prevent axon degeneration. Here we propose a program of research to investigate the importance of ribosomal proteins (RPs) in axon maintenance and degeneration. The rationale for this is fourfold. First, recent genome-wide studies of axonal transcriptomes have revealed that protein synthesis (including RP mRNAs) is the highest functional category in several neuronal types. Second, some RPs have evolved extra-ribosomal functions that include signalling, such as 67LR which acts both as a cell surface receptor for laminin and as a RP. Third, mutations in different RPs in vertebrates cause unexpectedly specific defects, such as the loss of optic axons. Fourth, preliminary results show that RP mRNAs are translated in optic axons in response to trophic factors. Collectively these findings lead us to propose that locally synthesized RPs play a role in axon maintenance through either ribosomal or extra-ribosomal function. To pursue this proposal, we will perform unbiased screens and functional assays using an array of experimental approaches and animal models. By gaining an understanding of how local RP synthesis contributes to axon survival, our studies have the potential to provide novel insights into how components conventionally associated with a housekeeping role (translation) are linked to axon degeneration. Our findings could provide new directions for developing therapeutic tools for neurodegenerative disorders and may have an impact on more diverse areas of biology and disease.
Summary
Neurons make long-distance connections with synaptic targets via axons. These axons survive throughout the lifetime of an organism, often many years in mammals, yet how axons are maintained is not fully understood. Recently, we provided in vivo evidence that local mRNA translation in mature axons is required for their maintenance. This new finding, along with in vitro work from other groups, indicates that promoting axonal protein synthesis is a key mechanism by which trophic factors act to prevent axon degeneration. Here we propose a program of research to investigate the importance of ribosomal proteins (RPs) in axon maintenance and degeneration. The rationale for this is fourfold. First, recent genome-wide studies of axonal transcriptomes have revealed that protein synthesis (including RP mRNAs) is the highest functional category in several neuronal types. Second, some RPs have evolved extra-ribosomal functions that include signalling, such as 67LR which acts both as a cell surface receptor for laminin and as a RP. Third, mutations in different RPs in vertebrates cause unexpectedly specific defects, such as the loss of optic axons. Fourth, preliminary results show that RP mRNAs are translated in optic axons in response to trophic factors. Collectively these findings lead us to propose that locally synthesized RPs play a role in axon maintenance through either ribosomal or extra-ribosomal function. To pursue this proposal, we will perform unbiased screens and functional assays using an array of experimental approaches and animal models. By gaining an understanding of how local RP synthesis contributes to axon survival, our studies have the potential to provide novel insights into how components conventionally associated with a housekeeping role (translation) are linked to axon degeneration. Our findings could provide new directions for developing therapeutic tools for neurodegenerative disorders and may have an impact on more diverse areas of biology and disease.
Max ERC Funding
2 426 573 €
Duration
Start date: 2013-03-01, End date: 2018-09-30
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
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
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."
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."
Max ERC Funding
1 499 914 €
Duration
Start date: 2012-11-01, End date: 2017-10-31
Project acronym BIOSYNCEN
Project Dissection of centromeric chromatin and components: A biosynthetic approach
Researcher (PI) Patrick Heun
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Starting Grant (StG), LS2, ERC-2012-StG_20111109
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.
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.
Max ERC Funding
1 755 960 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym BODILY SELF
Project Embodied Minds and Mentalised Bodies
Researcher (PI) Aikaterini (Katerina) Fotopoulou
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Starting Grant (StG), SH4, ERC-2012-StG_20111124
Summary How does our acting, sensing and feeling body shape our mind? The mechanisms by which bodily signals are integrated and re-represented in the brain, as well as the relation between these processes and body awareness remain unknown. To this date, neuropsychological disorders of body awareness represent an indispensible window of insight into phenomenally rich states of body unawareness. Unfortunately, only few experimental studies have been conducted in these disorders. The BODILY SELF will aim to apply methods from cognitive neuroscience to experimental and neuroimaging studies in healthy volunteers, as well as in patients with neuropsychological disorders of body awareness. A first subproject will assess which combination of deficits in sensorimotor afferent and efferent signals leads to unawareness. The second subproject will attempt to use experimental, psychophysical interventions to treat unawareness and measure the corresponding, dynamic changes in the brain. The third subproject will assess how some bodily signals and their integration is influenced by social mechanisms. The planned studies surpass the existing state-of-the-art in the relevant fields in five ground-breaking ways, ultimately allowing us to (1) acquire an unprecedented ‘on-line’ experimental ‘handle’ over dynamic changes in body awareness; (2) restore awareness and improve health outcomes (3) understand the brain’s potential for reorganisation and plasticity in relation to higher-order processes such as awareness; (4) understand how our own body experience is modulated by our interactions and relations with others; (5) address in a genuinely interdisciplinary manner some of the oldest questions in psychology, philosophy and medicine; how embodiment influences the mind, how others influence the self and how mind–body processes affect healing.
Summary
How does our acting, sensing and feeling body shape our mind? The mechanisms by which bodily signals are integrated and re-represented in the brain, as well as the relation between these processes and body awareness remain unknown. To this date, neuropsychological disorders of body awareness represent an indispensible window of insight into phenomenally rich states of body unawareness. Unfortunately, only few experimental studies have been conducted in these disorders. The BODILY SELF will aim to apply methods from cognitive neuroscience to experimental and neuroimaging studies in healthy volunteers, as well as in patients with neuropsychological disorders of body awareness. A first subproject will assess which combination of deficits in sensorimotor afferent and efferent signals leads to unawareness. The second subproject will attempt to use experimental, psychophysical interventions to treat unawareness and measure the corresponding, dynamic changes in the brain. The third subproject will assess how some bodily signals and their integration is influenced by social mechanisms. The planned studies surpass the existing state-of-the-art in the relevant fields in five ground-breaking ways, ultimately allowing us to (1) acquire an unprecedented ‘on-line’ experimental ‘handle’ over dynamic changes in body awareness; (2) restore awareness and improve health outcomes (3) understand the brain’s potential for reorganisation and plasticity in relation to higher-order processes such as awareness; (4) understand how our own body experience is modulated by our interactions and relations with others; (5) address in a genuinely interdisciplinary manner some of the oldest questions in psychology, philosophy and medicine; how embodiment influences the mind, how others influence the self and how mind–body processes affect healing.
Max ERC Funding
1 453 284 €
Duration
Start date: 2013-04-01, End date: 2018-09-30
