Project acronym ADAPT
Project Life in a cold climate: the adaptation of cereals to new environments and the establishment of agriculture in Europe
Researcher (PI) Terence Austen Brown
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Country United Kingdom
Call Details Advanced Grant (AdG), SH6, ERC-2013-ADG
Summary "This project explores the concept of agricultural spread as analogous to enforced climate change and asks how cereals adapted to new environments when agriculture was introduced into Europe. Archaeologists have long recognized that the ecological pressures placed on crops would have had an impact on the spread and subsequent development of agriculture, but previously there has been no means of directly assessing the scale and nature of this impact. Recent work that I have directed has shown how such a study could be carried out, and the purpose of this project is to exploit these breakthroughs with the goal of assessing the influence of environmental adaptation on the spread of agriculture, its adoption as the primary subsistence strategy, and the subsequent establishment of farming in different parts of Europe. This will correct the current imbalance between our understanding of the human and environmental dimensions to the domestication of Europe. I will use methods from population genomics to identify loci within the barley and wheat genomes that have undergone selection since the beginning of cereal cultivation in Europe. I will then use ecological modelling to identify those loci whose patterns of selection are associated with ecogeographical variables and hence represent adaptations to local environmental conditions. I will assign dates to the periods when adaptations occurred by sequencing ancient DNA from archaeobotanical assemblages and by computer methods that enable the temporal order of adaptations to be deduced. I will then synthesise the information on environmental adaptations with dating evidence for the spread of agriculture in Europe, which reveals pauses that might be linked to environmental adaptation, with demographic data that indicate regions where Neolithic populations declined, possibly due to inadequate crop productivity, and with an archaeobotanical database showing changes in the prevalence of individual cereals in different regions."
Summary
"This project explores the concept of agricultural spread as analogous to enforced climate change and asks how cereals adapted to new environments when agriculture was introduced into Europe. Archaeologists have long recognized that the ecological pressures placed on crops would have had an impact on the spread and subsequent development of agriculture, but previously there has been no means of directly assessing the scale and nature of this impact. Recent work that I have directed has shown how such a study could be carried out, and the purpose of this project is to exploit these breakthroughs with the goal of assessing the influence of environmental adaptation on the spread of agriculture, its adoption as the primary subsistence strategy, and the subsequent establishment of farming in different parts of Europe. This will correct the current imbalance between our understanding of the human and environmental dimensions to the domestication of Europe. I will use methods from population genomics to identify loci within the barley and wheat genomes that have undergone selection since the beginning of cereal cultivation in Europe. I will then use ecological modelling to identify those loci whose patterns of selection are associated with ecogeographical variables and hence represent adaptations to local environmental conditions. I will assign dates to the periods when adaptations occurred by sequencing ancient DNA from archaeobotanical assemblages and by computer methods that enable the temporal order of adaptations to be deduced. I will then synthesise the information on environmental adaptations with dating evidence for the spread of agriculture in Europe, which reveals pauses that might be linked to environmental adaptation, with demographic data that indicate regions where Neolithic populations declined, possibly due to inadequate crop productivity, and with an archaeobotanical database showing changes in the prevalence of individual cereals in different regions."
Max ERC Funding
2 492 964 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym BAYES-KNOWLEDGE
Project Effective Bayesian Modelling with Knowledge before Data
Researcher (PI) Norman Fenton
Host Institution (HI) QUEEN MARY UNIVERSITY OF LONDON
Country United Kingdom
Call Details Advanced Grant (AdG), PE6, ERC-2013-ADG
Summary This project aims to improve evidence-based decision-making. What makes it radical is that it plans to do this in situations (common for critical risk assessment problems) where there is little or even no data, and hence where traditional statistics cannot be used. To address this problem Bayesian analysis, which enables domain experts to supplement observed data with subjective probabilities, is normally used. As real-world problems typically involve multiple uncertain variables, Bayesian analysis is extended using a technique called Bayesian networks (BNs). But, despite many great benefits, BNs have been under-exploited, especially in areas where they offer the greatest potential for improvements (law, medicine and systems engineering). This is mainly because of widespread resistance to relying on subjective knowledge. To address this problem much current research assumes sufficient data are available to make the expert’s input minimal or even redundant; with such data it may be possible to ‘learn’ the underlying BN model. But this approach offers nothing when there is limited or no data. Even when ‘big’ data are available the resulting models may be superficially objective but fundamentally flawed as they fail to capture the underlying causal structure that only expert knowledge can provide.
Our solution is to develop a method to systemize the way expert driven causal BN models can be built and used effectively either in the absence of data or as a means of determining what future data is really required. The method involves a new way of framing problems and extensions to BN theory, notation and tools. Working with relevant domain experts, along with cognitive psychologists, our methods will be developed and tested experimentally on real-world critical decision-problems in medicine, law, forensics, and transport. As the work complements current data-driven approaches, it will lead to improved BN modelling both when there is extensive data as well as none.
Summary
This project aims to improve evidence-based decision-making. What makes it radical is that it plans to do this in situations (common for critical risk assessment problems) where there is little or even no data, and hence where traditional statistics cannot be used. To address this problem Bayesian analysis, which enables domain experts to supplement observed data with subjective probabilities, is normally used. As real-world problems typically involve multiple uncertain variables, Bayesian analysis is extended using a technique called Bayesian networks (BNs). But, despite many great benefits, BNs have been under-exploited, especially in areas where they offer the greatest potential for improvements (law, medicine and systems engineering). This is mainly because of widespread resistance to relying on subjective knowledge. To address this problem much current research assumes sufficient data are available to make the expert’s input minimal or even redundant; with such data it may be possible to ‘learn’ the underlying BN model. But this approach offers nothing when there is limited or no data. Even when ‘big’ data are available the resulting models may be superficially objective but fundamentally flawed as they fail to capture the underlying causal structure that only expert knowledge can provide.
Our solution is to develop a method to systemize the way expert driven causal BN models can be built and used effectively either in the absence of data or as a means of determining what future data is really required. The method involves a new way of framing problems and extensions to BN theory, notation and tools. Working with relevant domain experts, along with cognitive psychologists, our methods will be developed and tested experimentally on real-world critical decision-problems in medicine, law, forensics, and transport. As the work complements current data-driven approaches, it will lead to improved BN modelling both when there is extensive data as well as none.
Max ERC Funding
1 572 562 €
Duration
Start date: 2014-04-01, End date: 2018-03-31
Project acronym BEEHIVE
Project Bridging the Evolution and Epidemiology of HIV in Europe
Researcher (PI) Christopher Fraser
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), LS2, ERC-2013-ADG
Summary The aim of the BEEHIVE project is to generate novel insight into HIV biology, evolution and epidemiology, leveraging next-generation high-throughput sequencing and bioinformatics to produce and analyse whole-genomes of viruses from approximately 3,000 European HIV-1 infected patients. These patients have known dates of infection spread over the last 25 years, good clinical follow up, and a wide range of clinical prognostic indicators and outcomes. The primary objective is to discover the viral genetic determinants of severity of infection and set-point viral load. This primary objective is high-risk & blue-skies: there is ample indirect evidence of polymorphisms that alter virulence, but they have never been identified, and it is not known how easy they are to discover. However, the project is also high-reward: it could lead to a substantial shift in the understanding of HIV disease.
Technologically, the BEEHIVE project will deliver new approaches for undertaking whole genome association studies on RNA viruses, including delivering an innovative high-throughput bioinformatics pipeline for handling genetically diverse viral quasi-species data (with viral diversity both within and between infected patients).
The project also includes secondary and tertiary objectives that address critical open questions in HIV epidemiology and evolution. The secondary objective is to use viral genetic sequences allied to mathematical epidemic models to better understand the resurgent European epidemic amongst high-risk groups, especially men who have sex with men. The aim will not just be to establish who is at risk of infection, which is known from conventional epidemiological approaches, but also to characterise the risk factors for onwards transmission of the virus. Tertiary objectives involve understanding the relationship between the genetic diversity within viral samples, indicative of on-going evolution or dual infections, to clinical outcomes.
Summary
The aim of the BEEHIVE project is to generate novel insight into HIV biology, evolution and epidemiology, leveraging next-generation high-throughput sequencing and bioinformatics to produce and analyse whole-genomes of viruses from approximately 3,000 European HIV-1 infected patients. These patients have known dates of infection spread over the last 25 years, good clinical follow up, and a wide range of clinical prognostic indicators and outcomes. The primary objective is to discover the viral genetic determinants of severity of infection and set-point viral load. This primary objective is high-risk & blue-skies: there is ample indirect evidence of polymorphisms that alter virulence, but they have never been identified, and it is not known how easy they are to discover. However, the project is also high-reward: it could lead to a substantial shift in the understanding of HIV disease.
Technologically, the BEEHIVE project will deliver new approaches for undertaking whole genome association studies on RNA viruses, including delivering an innovative high-throughput bioinformatics pipeline for handling genetically diverse viral quasi-species data (with viral diversity both within and between infected patients).
The project also includes secondary and tertiary objectives that address critical open questions in HIV epidemiology and evolution. The secondary objective is to use viral genetic sequences allied to mathematical epidemic models to better understand the resurgent European epidemic amongst high-risk groups, especially men who have sex with men. The aim will not just be to establish who is at risk of infection, which is known from conventional epidemiological approaches, but also to characterise the risk factors for onwards transmission of the virus. Tertiary objectives involve understanding the relationship between the genetic diversity within viral samples, indicative of on-going evolution or dual infections, to clinical outcomes.
Max ERC Funding
2 499 739 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym BioBlood
Project Development of a Bio-Inspired Blood Factory for Personalised Healthcare
Researcher (PI) Athanasios Mantalaris
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Advanced Grant (AdG), PE8, ERC-2013-ADG
Summary Personalized medicine is a medical model that proposes the customization of healthcare, with decisions and practices being tailored to the individual patient by use of patient-specific information and/or application of patient-specific cell-based therapies. BioBlood aims to deliver personalised healthcare through a “step change” in the clinical field of haemato-oncology. BioBlood represents an engineered bio-inspired integrated experimental/modelling platform for normal and abnormal haematopoiesis that receives disease & patient input (patient primary cells & patient/disease-specific data) and will produce cellular (red blood cell product) and drug (optimal drug treatment) therapies as its output. Blood supply to meet demand is the primary challenge for Blood Banks and requires significant resources to avoid shortages and ensure safety. An alternative, practical and cost-effective solution to conventional donated blood is essential to reduce patient morbidity and mortality, stabilise and guarantee the donor supply, limit multiple donor exposures, reduce risk of infection of known or as yet unidentified pathogens, and ensure a robust and safe turn-around for blood supply management. BioBlood aims to meet this challenge by developing a novel in vitro platform for the mass production of RBCs for clinical use. More than £32b/year is spent to develop and bring new drugs to market, which takes 14 years. Most patients diagnosed with leukaemias are unable to tolerate treatment and would benefit from novel agents. There is a need to optimise current treatment schedules for cancers such as AML to limit toxicities and improve clinical trial pathways for new drugs to enable personalised healthcare. BioBlood’s in vitro & in silico platform would be a powerful tool to tailor treatments in a patient- and leukaemia-specific chemotherapy schedule by considering the level of toxicity to the specific individual and treatment efficiency for the specific leukaemia a priori.
Summary
Personalized medicine is a medical model that proposes the customization of healthcare, with decisions and practices being tailored to the individual patient by use of patient-specific information and/or application of patient-specific cell-based therapies. BioBlood aims to deliver personalised healthcare through a “step change” in the clinical field of haemato-oncology. BioBlood represents an engineered bio-inspired integrated experimental/modelling platform for normal and abnormal haematopoiesis that receives disease & patient input (patient primary cells & patient/disease-specific data) and will produce cellular (red blood cell product) and drug (optimal drug treatment) therapies as its output. Blood supply to meet demand is the primary challenge for Blood Banks and requires significant resources to avoid shortages and ensure safety. An alternative, practical and cost-effective solution to conventional donated blood is essential to reduce patient morbidity and mortality, stabilise and guarantee the donor supply, limit multiple donor exposures, reduce risk of infection of known or as yet unidentified pathogens, and ensure a robust and safe turn-around for blood supply management. BioBlood aims to meet this challenge by developing a novel in vitro platform for the mass production of RBCs for clinical use. More than £32b/year is spent to develop and bring new drugs to market, which takes 14 years. Most patients diagnosed with leukaemias are unable to tolerate treatment and would benefit from novel agents. There is a need to optimise current treatment schedules for cancers such as AML to limit toxicities and improve clinical trial pathways for new drugs to enable personalised healthcare. BioBlood’s in vitro & in silico platform would be a powerful tool to tailor treatments in a patient- and leukaemia-specific chemotherapy schedule by considering the level of toxicity to the specific individual and treatment efficiency for the specific leukaemia a priori.
Max ERC Funding
2 498 903 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym BM
Project Becoming Muslim: Conversion to Islam and Islamisation in Eastern Ethiopia
Researcher (PI) Timothy Insoll
Host Institution (HI) THE UNIVERSITY OF EXETER
Country United Kingdom
Call Details Advanced Grant (AdG), SH6, ERC-2015-AdG
Summary "
Why do people convert to Islam? The contemporary relevance of this question is immediately apparent.""Becoming Muslim"" will transform our knowledge about Islamisation processes and contexts through archaeological research in Harar, Eastern Ethiopia, and examine this in comparison to other regions in sub-Saharan Africa via publication and a major conference. Assessing genuine belief is difficult, but the impact of trade, Saints, Sufis and Holy men, proselytisation, benefits gained from Arabic literacy and administration systems, enhanced power, prestige, warfare, and belonging to the larger Muslim community have all been suggested. Equally significant is the context of conversion. Why were certain sub-Saharan African cities key points for conversion to Islam, e.g. Gao and Timbuktu in the Western Sahel, and Harar in Ethiopia? Archaeological engagement with Islamisation processes and contexts of conversion in Africa is variable, and in parts of the continent research is static. This exciting 4-year project explores, for the first time, Islamic conversion and Islamisation through focusing on Harar, the most important living Islamic centre in the Horn of Africa, and its surrounding region.
Islamic archaeology has been neglected in Ethiopia, and is wholly non-existent in Harar. Excavation at 5 key sites: 2 shrines, 2 abandoned settlements, 1 urban site, will permit evaluation of urban Islam, the veneration of saints, pilgrimage and shrine based practices, rural Islam, architecture and jihad, changes in lifeways, and early and comparative evidence for Islam and long-distance trade, through analysis of, e.g. architecture, epigraphy, burial orientation, imported artifacts, and faunal and botanical remains. Although it is fully acknowledged that conversion to Islam and Islamisation processes are not universal, my project is groundbreaking in developing and applying a transferable methodology for the archaeological explanation of ""Becoming Muslim"" in sub-Saharan Africa."
Summary
"
Why do people convert to Islam? The contemporary relevance of this question is immediately apparent.""Becoming Muslim"" will transform our knowledge about Islamisation processes and contexts through archaeological research in Harar, Eastern Ethiopia, and examine this in comparison to other regions in sub-Saharan Africa via publication and a major conference. Assessing genuine belief is difficult, but the impact of trade, Saints, Sufis and Holy men, proselytisation, benefits gained from Arabic literacy and administration systems, enhanced power, prestige, warfare, and belonging to the larger Muslim community have all been suggested. Equally significant is the context of conversion. Why were certain sub-Saharan African cities key points for conversion to Islam, e.g. Gao and Timbuktu in the Western Sahel, and Harar in Ethiopia? Archaeological engagement with Islamisation processes and contexts of conversion in Africa is variable, and in parts of the continent research is static. This exciting 4-year project explores, for the first time, Islamic conversion and Islamisation through focusing on Harar, the most important living Islamic centre in the Horn of Africa, and its surrounding region.
Islamic archaeology has been neglected in Ethiopia, and is wholly non-existent in Harar. Excavation at 5 key sites: 2 shrines, 2 abandoned settlements, 1 urban site, will permit evaluation of urban Islam, the veneration of saints, pilgrimage and shrine based practices, rural Islam, architecture and jihad, changes in lifeways, and early and comparative evidence for Islam and long-distance trade, through analysis of, e.g. architecture, epigraphy, burial orientation, imported artifacts, and faunal and botanical remains. Although it is fully acknowledged that conversion to Islam and Islamisation processes are not universal, my project is groundbreaking in developing and applying a transferable methodology for the archaeological explanation of ""Becoming Muslim"" in sub-Saharan Africa."
Max ERC Funding
1 031 105 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym CARDIOREDOX
Project Redox sensing and signalling in cardiovascular health and disease
Researcher (PI) Philip Eaton
Host Institution (HI) KING'S COLLEGE LONDON
Country United Kingdom
Call Details Advanced Grant (AdG), LS4, ERC-2013-ADG
Summary "We want to determine how oxidants are sensed and transduced into a biological effect within the cardiovascular system. The proposed work will focus on thiol-based redox sensors, defining their role in heart and blood vessel function during health and disease. Although this laboratory has studied the molecular basis of redox signaling for more than a decade, the subject is still in its relative infancy with considerable scope for major advances. Oxidant signaling remains a ‘hot topic’ with high profile studies confirming a fundamental role for redox control of protein and cellular function continuing to emerge. The molecular basis of redox sensing is the reaction of an oxidant with target proteins. This gives rise to oxidative post-translational modifications, most commonly of cysteinyl thiols, potentially altering the activity of proteins to regulate cell or tissue function. One of the reasons there are so many unanswered questions about redox sensing and signaling is the diversity of oxidant molecules produced by cells that can interact with sensor proteins to alter their function. This application is aimed at extending our knowledge of redox sensing and signalling, allowing us to define its importance in cardiovascular health and disease."
Summary
"We want to determine how oxidants are sensed and transduced into a biological effect within the cardiovascular system. The proposed work will focus on thiol-based redox sensors, defining their role in heart and blood vessel function during health and disease. Although this laboratory has studied the molecular basis of redox signaling for more than a decade, the subject is still in its relative infancy with considerable scope for major advances. Oxidant signaling remains a ‘hot topic’ with high profile studies confirming a fundamental role for redox control of protein and cellular function continuing to emerge. The molecular basis of redox sensing is the reaction of an oxidant with target proteins. This gives rise to oxidative post-translational modifications, most commonly of cysteinyl thiols, potentially altering the activity of proteins to regulate cell or tissue function. One of the reasons there are so many unanswered questions about redox sensing and signaling is the diversity of oxidant molecules produced by cells that can interact with sensor proteins to alter their function. This application is aimed at extending our knowledge of redox sensing and signalling, allowing us to define its importance in cardiovascular health and disease."
Max ERC Funding
2 255 659 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
Project acronym CLONCELLBREAST
Project CLONAL AND CELLULAR HETEROGENEITY OF BREAST CANCER AND ITS DYNAMIC EVOLUTION WITH TREATMENT
Researcher (PI) Carlos Manuel SIMAO DA SILVA CALDAS
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Advanced Grant (AdG), LS4, ERC-2015-AdG
Summary CLONAL AND CELLULAR HETEROGENEITY OF BREAST CANCER AND ITS DYNAMIC EVOLUTION WITH TREATMENT
Breast cancer remains one of the leading causes of cancer death in women. One of the greatest challenges is that breast cancer is a heterogeneous group of 10 diseases defined by genomic profiling. In addition, each tumor is composed of clones and clonal evolution underpins the successive acquisition of the hallmarks of cancer, including metastasis and resistance to therapy. Furthermore tumors display biologically and clinically relevant cellular heterogeneity: immune system, vasculature, and stroma. This cellular heterogeneity both shapes and is shaped by the malignant compartment and modulates response to therapy.
This proposal will use longitudinal studies to unravel the clonal and cellular heterogeneity of breast cancer and its dynamic evolution with treatment. The overall goal is to provide a systems level view of evolving clonal and cellular architectures in space and time along the clinical continuum of breast cancers in the clinic, leading to the discovery of new biological and clinical paradigms which will transform our understanding of the disease.
The overall approach is to capture the evolution of clonal and cellular heterogeneity of breast cancers in space and time using unique clinical cohorts where samples (biopsies and blood/plasma) are available spanning the whole disease continuum: early breast cancer surgically treated with curative intent, neo-adjuvant therapy, and matched relapse/metastasis. The 4 aims of the proposal are:
1. Characterization of the clonal and cellular heterogeneity of primary tumours from the 10 genomic driver-based breast cancer subtypes (ICs)
2. Comparative characterization of the clonal and cellular heterogeneity of matched pairs of primary and metastatic cancers
3. Characterization of the clonal and epigenetic evolution across therapy courses
4. Characterization of the immune response across therapy courses
Summary
CLONAL AND CELLULAR HETEROGENEITY OF BREAST CANCER AND ITS DYNAMIC EVOLUTION WITH TREATMENT
Breast cancer remains one of the leading causes of cancer death in women. One of the greatest challenges is that breast cancer is a heterogeneous group of 10 diseases defined by genomic profiling. In addition, each tumor is composed of clones and clonal evolution underpins the successive acquisition of the hallmarks of cancer, including metastasis and resistance to therapy. Furthermore tumors display biologically and clinically relevant cellular heterogeneity: immune system, vasculature, and stroma. This cellular heterogeneity both shapes and is shaped by the malignant compartment and modulates response to therapy.
This proposal will use longitudinal studies to unravel the clonal and cellular heterogeneity of breast cancer and its dynamic evolution with treatment. The overall goal is to provide a systems level view of evolving clonal and cellular architectures in space and time along the clinical continuum of breast cancers in the clinic, leading to the discovery of new biological and clinical paradigms which will transform our understanding of the disease.
The overall approach is to capture the evolution of clonal and cellular heterogeneity of breast cancers in space and time using unique clinical cohorts where samples (biopsies and blood/plasma) are available spanning the whole disease continuum: early breast cancer surgically treated with curative intent, neo-adjuvant therapy, and matched relapse/metastasis. The 4 aims of the proposal are:
1. Characterization of the clonal and cellular heterogeneity of primary tumours from the 10 genomic driver-based breast cancer subtypes (ICs)
2. Comparative characterization of the clonal and cellular heterogeneity of matched pairs of primary and metastatic cancers
3. Characterization of the clonal and epigenetic evolution across therapy courses
4. Characterization of the immune response across therapy courses
Max ERC Funding
2 497 660 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym CORREL-CT
Project Correlative tomography
Researcher (PI) Philip Withers
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Country United Kingdom
Call Details Advanced Grant (AdG), PE8, ERC-2015-AdG
Summary Proposal summary (half page)
The vision is firstly, to develop correlative tomography to radically increase the nature and level of information (morphological, structural and chemical) that can be obtained for a 3D volume of interest (VoI) deep within a material or component by coupling non-destructive (3D+time) X-ray tomography with destructive (3D) electron tomography and, secondly to exploit this new approach to shed light on damage accumulation processes arising under demanding conditions. Successful completion of this project will provide new 3D & 4D insights across many areas and yield key experimental data for multiscale models.
Objective 1: To build the capability of correlative tomography
- To connect platforms across scales and modalities in order to track a VoI that may be located deep below the surface and to combine multiple techniques within a single platform.
- To add new facets to correlative tomography including
+ 3D chemical imaging
+ 3D crystal grain mapping
+ the local stress distribution
+ mechanical performance mapping at the VoI scale
Objective 2: To apply it to gain new insights into damage accumulation
Correlative tomography will provide a much richer multi-faceted hierarchical picture of materials behaviour from life science to food science from geology to cultural heritage. This project will focus specifically on identifying the nucleation, propagation and aggregation of damage processes in engineering materials.
- We will identify and track the mechanisms that control the progressive degradation of conventional bulk engineering materials operating under demanding conditions.
- We will examine the hierarchical strategies nature uses to control failure in natural materials through heterogeneous chemistry, morphology and properties. Alongside this we will examine the behaviour of man-made nano-structured analogues and whether we can exploit some of these strategies.
Summary
Proposal summary (half page)
The vision is firstly, to develop correlative tomography to radically increase the nature and level of information (morphological, structural and chemical) that can be obtained for a 3D volume of interest (VoI) deep within a material or component by coupling non-destructive (3D+time) X-ray tomography with destructive (3D) electron tomography and, secondly to exploit this new approach to shed light on damage accumulation processes arising under demanding conditions. Successful completion of this project will provide new 3D & 4D insights across many areas and yield key experimental data for multiscale models.
Objective 1: To build the capability of correlative tomography
- To connect platforms across scales and modalities in order to track a VoI that may be located deep below the surface and to combine multiple techniques within a single platform.
- To add new facets to correlative tomography including
+ 3D chemical imaging
+ 3D crystal grain mapping
+ the local stress distribution
+ mechanical performance mapping at the VoI scale
Objective 2: To apply it to gain new insights into damage accumulation
Correlative tomography will provide a much richer multi-faceted hierarchical picture of materials behaviour from life science to food science from geology to cultural heritage. This project will focus specifically on identifying the nucleation, propagation and aggregation of damage processes in engineering materials.
- We will identify and track the mechanisms that control the progressive degradation of conventional bulk engineering materials operating under demanding conditions.
- We will examine the hierarchical strategies nature uses to control failure in natural materials through heterogeneous chemistry, morphology and properties. Alongside this we will examine the behaviour of man-made nano-structured analogues and whether we can exploit some of these strategies.
Max ERC Funding
2 926 425 €
Duration
Start date: 2016-11-01, End date: 2022-07-31
Project acronym COS
Project "The Cult of Saints: a christendom-wide study of its origins, spread and development"
Researcher (PI) Bryan Ward-Perkins
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), SH6, ERC-2013-ADG
Summary "An investigation of the origins and development of a central feature of late-antique, medieval and modern culture: the belief that dead saints can act as mediators between a distant God and humankind, and that they are active on earth in many different ways (such as healing the sick, punishing the irreverent, or even controlling the weather).
The project will investigate the emergence of this belief by systematically collecting all the available evidence - across several academic disciplines and six linguistic cultures (Latin, Greek, Syriac, Coptic, Armenian and Georgian), from the first stirrings of the phenomenon in the third century until around the year 700, by which time the cult of saints was fully developed and firmly rooted throughout the Christian world, from Ireland to Iran.
The work will be done by a team of researchers (under expert supervision for four of the eastern languages), closely co-ordinated by the PI. The project will operate concurrently at two levels. The individual researchers will produce free-standing regional studies on aspects of the cult of saints that are essential to the wider project, but at present under-researched. While doing this, they will collect the full range of evidence from their regions within a single searchable database. This will provide the basis for a christendom-wide monograph on the emergence of the cult of saints authored by the PI, and also the context essential to give breadth and depth to the regional studies.
For the first time it will be possible to tell the history of the emergence of the cult of saints across the full geographical and cultural range of early Christendom. Of great importance in itself, this will also link, and thereby enhance, the many pre-existing works of scholarship on aspects of the cult of saints.
The ‘Cult of Saints’ will result in a major summative monograph, a comprehensive international conference, a series of ground-breaking regional studies, and a freely-available database."
Summary
"An investigation of the origins and development of a central feature of late-antique, medieval and modern culture: the belief that dead saints can act as mediators between a distant God and humankind, and that they are active on earth in many different ways (such as healing the sick, punishing the irreverent, or even controlling the weather).
The project will investigate the emergence of this belief by systematically collecting all the available evidence - across several academic disciplines and six linguistic cultures (Latin, Greek, Syriac, Coptic, Armenian and Georgian), from the first stirrings of the phenomenon in the third century until around the year 700, by which time the cult of saints was fully developed and firmly rooted throughout the Christian world, from Ireland to Iran.
The work will be done by a team of researchers (under expert supervision for four of the eastern languages), closely co-ordinated by the PI. The project will operate concurrently at two levels. The individual researchers will produce free-standing regional studies on aspects of the cult of saints that are essential to the wider project, but at present under-researched. While doing this, they will collect the full range of evidence from their regions within a single searchable database. This will provide the basis for a christendom-wide monograph on the emergence of the cult of saints authored by the PI, and also the context essential to give breadth and depth to the regional studies.
For the first time it will be possible to tell the history of the emergence of the cult of saints across the full geographical and cultural range of early Christendom. Of great importance in itself, this will also link, and thereby enhance, the many pre-existing works of scholarship on aspects of the cult of saints.
The ‘Cult of Saints’ will result in a major summative monograph, a comprehensive international conference, a series of ground-breaking regional studies, and a freely-available database."
Max ERC Funding
2 499 240 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym DENDRITECIRCUITS
Project The origins of dendritic computation within mammalian neural circuits
Researcher (PI) Michael HAUSSER
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Country United Kingdom
Call Details Advanced Grant (AdG), LS5, ERC-2015-AdG
Summary This proposal aims to address a simple question: 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 if we are to build accurate models of brain function, which require abstraction based on identification of the essential elements for carrying out computations relevant to behaviour. In this proposal, we will build on recent work demonstrating that dendrites are highly electrically excitable to 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 electrophysiolgical, anatomical, imaging, molecular, and modeling approaches to probe dendritic integration in pyramidal cells and Purkinje cells in mouse cortex and cerebellum.
We will first define the computational rules for integration of synaptic input in single and multiple dendrites by examining the somatic and dendritic responses to different spatiotemporal patterns of excitatory and inhibitory inputs in brain slices. 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 onto single 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 perturb the dendritic computational rules by manipulating dendritic function using molecular and optogenetic tools, in order to provide causal links between specific dendritic computations and sensory processing relevant to behaviour.
These experiments will provide us with deeper insights into how single neurons act as computing devices.
Summary
This proposal aims to address a simple question: 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 if we are to build accurate models of brain function, which require abstraction based on identification of the essential elements for carrying out computations relevant to behaviour. In this proposal, we will build on recent work demonstrating that dendrites are highly electrically excitable to 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 electrophysiolgical, anatomical, imaging, molecular, and modeling approaches to probe dendritic integration in pyramidal cells and Purkinje cells in mouse cortex and cerebellum.
We will first define the computational rules for integration of synaptic input in single and multiple dendrites by examining the somatic and dendritic responses to different spatiotemporal patterns of excitatory and inhibitory inputs in brain slices. 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 onto single 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 perturb the dendritic computational rules by manipulating dendritic function using molecular and optogenetic tools, in order to provide causal links between specific dendritic computations and sensory processing relevant to behaviour.
These experiments will provide us with deeper insights into how single neurons act as computing devices.
Max ERC Funding
2 495 563 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
