Project acronym 15CBOOKTRADE
Project The 15th-century Book Trade: An Evidence-based Assessment and Visualization of the Distribution, Sale, and Reception of Books in the Renaissance
Researcher (PI) Cristina Dondi
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Consolidator Grant (CoG), SH6, ERC-2013-CoG
Summary The idea that underpins this project is to use the material evidence from thousands of surviving 15th-c. books, as well as unique documentary evidence — the unpublished ledger of a Venetian bookseller in the 1480s which records the sale of 25,000 printed books with their prices — to address four fundamental questions relating to the introduction of printing in the West which have so far eluded scholarship, partly because of lack of evidence, partly because of the lack of effective tools to deal with existing evidence. The book trade differs from other trades operating in the medieval and early modern periods in that the goods traded survive in considerable numbers. Not only do they survive, but many of them bear stratified evidence of their history in the form of marks of ownership, prices, manuscript annotations, binding and decoration styles. A British Academy pilot project conceived by the PI produced a now internationally-used database which gathers together this kind of evidence for thousands of surviving 15th-c. printed books. For the first time, this makes it possible to track the circulation of books, their trade routes and later collecting, across Europe and the USA, and throughout the centuries. The objectives of this project are to examine (1) the distribution and trade-routes, national and international, of 15th-c. printed books, along with the identity of the buyers and users (private, institutional, religious, lay, female, male, and by profession) and their reading practices; (2) the books' contemporary market value; (3) the transmission and dissemination of the texts they contain, their survival and their loss (rebalancing potentially skewed scholarship); and (4) the circulation and re-use of the illustrations they contain. Finally, the project will experiment with the application of scientific visualization techniques to represent, geographically and chronologically, the movement of 15th-c. printed books and of the texts they contain.
Summary
The idea that underpins this project is to use the material evidence from thousands of surviving 15th-c. books, as well as unique documentary evidence — the unpublished ledger of a Venetian bookseller in the 1480s which records the sale of 25,000 printed books with their prices — to address four fundamental questions relating to the introduction of printing in the West which have so far eluded scholarship, partly because of lack of evidence, partly because of the lack of effective tools to deal with existing evidence. The book trade differs from other trades operating in the medieval and early modern periods in that the goods traded survive in considerable numbers. Not only do they survive, but many of them bear stratified evidence of their history in the form of marks of ownership, prices, manuscript annotations, binding and decoration styles. A British Academy pilot project conceived by the PI produced a now internationally-used database which gathers together this kind of evidence for thousands of surviving 15th-c. printed books. For the first time, this makes it possible to track the circulation of books, their trade routes and later collecting, across Europe and the USA, and throughout the centuries. The objectives of this project are to examine (1) the distribution and trade-routes, national and international, of 15th-c. printed books, along with the identity of the buyers and users (private, institutional, religious, lay, female, male, and by profession) and their reading practices; (2) the books' contemporary market value; (3) the transmission and dissemination of the texts they contain, their survival and their loss (rebalancing potentially skewed scholarship); and (4) the circulation and re-use of the illustrations they contain. Finally, the project will experiment with the application of scientific visualization techniques to represent, geographically and chronologically, the movement of 15th-c. printed books and of the texts they contain.
Max ERC Funding
1 999 172 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym 3D-REPAIR
Project Spatial organization of DNA repair within the nucleus
Researcher (PI) Evanthia Soutoglou
Host Institution (HI) THE UNIVERSITY OF SUSSEX
Country United Kingdom
Call Details Consolidator Grant (CoG), LS2, ERC-2015-CoG
Summary Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown.
Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps.
This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer
Summary
Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown.
Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps.
This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer
Max ERC Funding
1 999 750 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym ADaPt
Project Adaptation, Dispersals and Phenotype: understanding the roles of climate,
natural selection and energetics in shaping global hunter-gatherer adaptability
Researcher (PI) Jay Stock
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Consolidator Grant (CoG), SH6, ERC-2013-CoG
Summary Relative to other species, humans are characterised by considerable biological diversity despite genetic homogeneity. This diversity is reflected in skeletal variation, but we lack sufficient understanding of the underlying mechanisms to adequately interpret the archaeological record. The proposed research will address problems in our current understanding of the origins of human variation in the past by: 1) documenting and interpreting the pattern of global hunter-gatherer variation relative to genetic phylogenies and climatic variation; 2) testing the relationship between environmental and skeletal variation among genetically related hunter-gatherers from different environments; 3) examining the adaptability of living humans to different environments, through the study of energetic expenditure and life history trade-offs associated with locomotion; and 4) investigating the relationship between muscle and skeletal variation associated with locomotion in diverse environments. This will be achieved by linking: a) detailed study of the global pattern of hunter-gatherer variation in the Late Pleistocene and Holocene with; b) ground-breaking experimental research which tests the relationship between energetic stress, muscle function, and bone variation in living humans. The first component tests the correspondence between skeletal variation and both genetic and climatic history, to infer mechanisms driving variation. The second component integrates this skeletal variation with experimental studies of living humans to, for the first time, directly test adaptive implications of skeletal variation observed in the past. ADaPt will provide the first links between prehistoric hunter-gatherer variation and the evolutionary parameters of life history and energetics that may have shaped our success as a species. It will lead to breakthroughs necessary to interpret variation in the archaeological record, relative to human dispersals and adaptation in the past.
Summary
Relative to other species, humans are characterised by considerable biological diversity despite genetic homogeneity. This diversity is reflected in skeletal variation, but we lack sufficient understanding of the underlying mechanisms to adequately interpret the archaeological record. The proposed research will address problems in our current understanding of the origins of human variation in the past by: 1) documenting and interpreting the pattern of global hunter-gatherer variation relative to genetic phylogenies and climatic variation; 2) testing the relationship between environmental and skeletal variation among genetically related hunter-gatherers from different environments; 3) examining the adaptability of living humans to different environments, through the study of energetic expenditure and life history trade-offs associated with locomotion; and 4) investigating the relationship between muscle and skeletal variation associated with locomotion in diverse environments. This will be achieved by linking: a) detailed study of the global pattern of hunter-gatherer variation in the Late Pleistocene and Holocene with; b) ground-breaking experimental research which tests the relationship between energetic stress, muscle function, and bone variation in living humans. The first component tests the correspondence between skeletal variation and both genetic and climatic history, to infer mechanisms driving variation. The second component integrates this skeletal variation with experimental studies of living humans to, for the first time, directly test adaptive implications of skeletal variation observed in the past. ADaPt will provide the first links between prehistoric hunter-gatherer variation and the evolutionary parameters of life history and energetics that may have shaped our success as a species. It will lead to breakthroughs necessary to interpret variation in the archaeological record, relative to human dispersals and adaptation in the past.
Max ERC Funding
1 911 485 €
Duration
Start date: 2014-07-01, End date: 2019-06-30
Project acronym ALZSYN
Project Imaging synaptic contributors to dementia
Researcher (PI) Tara Spires-Jones
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Country United Kingdom
Call Details Consolidator Grant (CoG), LS5, ERC-2015-CoG
Summary Alzheimer's disease, the most common cause of dementia in older people, is a devastating condition that is becoming a public health crisis as our population ages. Despite great progress recently in Alzheimer’s disease research, we have no disease modifying drugs and a decade with a 99.6% failure rate of clinical trials attempting to treat the disease. This project aims to develop relevant therapeutic targets to restore brain function in Alzheimer’s disease by integrating human and model studies of synapses. It is widely accepted in the field that alterations in amyloid beta initiate the disease process. However the cascade leading from changes in amyloid to widespread tau pathology and neurodegeneration remain unclear. Synapse loss is the strongest pathological correlate of dementia in Alzheimer’s, and mounting evidence suggests that synapse degeneration plays a key role in causing cognitive decline. Here I propose to test the hypothesis that the amyloid cascade begins at the synapse leading to tau pathology, synapse dysfunction and loss, and ultimately neural circuit collapse causing cognitive impairment. The team will use cutting-edge multiphoton and array tomography imaging techniques to test mechanisms downstream of amyloid beta at synapses, and determine whether intervening in the cascade allows recovery of synapse structure and function. Importantly, I will combine studies in robust models of familial Alzheimer’s disease with studies in postmortem human brain to confirm relevance of our mechanistic studies to human disease. Finally, human stem cell derived neurons will be used to test mechanisms and potential therapeutics in neurons expressing the human proteome. Together, these experiments are ground-breaking since they have the potential to further our understanding of how synapses are lost in Alzheimer’s disease and to identify targets for effective therapeutic intervention, which is a critical unmet need in today’s health care system.
Summary
Alzheimer's disease, the most common cause of dementia in older people, is a devastating condition that is becoming a public health crisis as our population ages. Despite great progress recently in Alzheimer’s disease research, we have no disease modifying drugs and a decade with a 99.6% failure rate of clinical trials attempting to treat the disease. This project aims to develop relevant therapeutic targets to restore brain function in Alzheimer’s disease by integrating human and model studies of synapses. It is widely accepted in the field that alterations in amyloid beta initiate the disease process. However the cascade leading from changes in amyloid to widespread tau pathology and neurodegeneration remain unclear. Synapse loss is the strongest pathological correlate of dementia in Alzheimer’s, and mounting evidence suggests that synapse degeneration plays a key role in causing cognitive decline. Here I propose to test the hypothesis that the amyloid cascade begins at the synapse leading to tau pathology, synapse dysfunction and loss, and ultimately neural circuit collapse causing cognitive impairment. The team will use cutting-edge multiphoton and array tomography imaging techniques to test mechanisms downstream of amyloid beta at synapses, and determine whether intervening in the cascade allows recovery of synapse structure and function. Importantly, I will combine studies in robust models of familial Alzheimer’s disease with studies in postmortem human brain to confirm relevance of our mechanistic studies to human disease. Finally, human stem cell derived neurons will be used to test mechanisms and potential therapeutics in neurons expressing the human proteome. Together, these experiments are ground-breaking since they have the potential to further our understanding of how synapses are lost in Alzheimer’s disease and to identify targets for effective therapeutic intervention, which is a critical unmet need in today’s health care system.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym BoneMalar
Project Mechanisms of bone marrow sequestration during malaria infection
Researcher (PI) Matthias Marti
Host Institution (HI) UNIVERSITY OF GLASGOW
Country United Kingdom
Call Details Consolidator Grant (CoG), LS6, ERC-2015-CoG
Summary Malaria remains a major problem of public health in developing countries. It is responsible for about 600000 deaths per year, predominantly children in sub-Saharan Africa. There is an urgent need for novel therapies as resistance against current treatments is widespread. The complex parasite biology requires a multifaceted approach targeting multiple life cycle stages and virulence pathways. The pathogenesis of the most deadly of human malaria parasites, Plasmodium falciparum, is related to the capability of infected red blood cells to sequester in deep tissues. Sequestration is critical for the completion of the red blood cell cycle because the release of parasites into the blood circulation allows recognition by surveillance macrophages and clearance in the spleen. A series of studies have since led to the understanding that sequestration of asexually replicating parasites is caused by the adherence of parasite infected red blood cells to the vascular endothelium of various tissues in the body.
We have recently demonstrated that gametocytes, the only stage capable of transmission to the mosquito vector, develop in the extravascular environment of the human bone marrow. Preliminary studies in the mouse model have confirmed this finding and also suggest existence of an asexual reservoir in the bone marrow. In this innovative multidiscipinary proposal we aim to investigate the host pathogen interactions at the interface between infected red blood cell and bone marrow vasculature. Specifically we will focus on the following questions: how do parasites home to bone marrow? What are the changes in the bone marrow endothelium upon infection? How do parasites adhere with and transmigrate across the vascular endothelium in the bone marrow? The proposed studies initiate detailed characterization of a new paradigm in malaria parasite interaction with the host vasculature and provide a compelling new avenue for intervention strategies.
Summary
Malaria remains a major problem of public health in developing countries. It is responsible for about 600000 deaths per year, predominantly children in sub-Saharan Africa. There is an urgent need for novel therapies as resistance against current treatments is widespread. The complex parasite biology requires a multifaceted approach targeting multiple life cycle stages and virulence pathways. The pathogenesis of the most deadly of human malaria parasites, Plasmodium falciparum, is related to the capability of infected red blood cells to sequester in deep tissues. Sequestration is critical for the completion of the red blood cell cycle because the release of parasites into the blood circulation allows recognition by surveillance macrophages and clearance in the spleen. A series of studies have since led to the understanding that sequestration of asexually replicating parasites is caused by the adherence of parasite infected red blood cells to the vascular endothelium of various tissues in the body.
We have recently demonstrated that gametocytes, the only stage capable of transmission to the mosquito vector, develop in the extravascular environment of the human bone marrow. Preliminary studies in the mouse model have confirmed this finding and also suggest existence of an asexual reservoir in the bone marrow. In this innovative multidiscipinary proposal we aim to investigate the host pathogen interactions at the interface between infected red blood cell and bone marrow vasculature. Specifically we will focus on the following questions: how do parasites home to bone marrow? What are the changes in the bone marrow endothelium upon infection? How do parasites adhere with and transmigrate across the vascular endothelium in the bone marrow? The proposed studies initiate detailed characterization of a new paradigm in malaria parasite interaction with the host vasculature and provide a compelling new avenue for intervention strategies.
Max ERC Funding
2 298 557 €
Duration
Start date: 2016-06-01, End date: 2021-11-30
Project acronym ComparingCopperbelt
Project Comparing the Copperbelt: Political Culture and Knowledge Production in Central Africa
Researcher (PI) Miles Larmer
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Consolidator Grant (CoG), SH6, ERC-2015-CoG
Summary This project provides the first comparative historical analysis – local, national and transnational - of the Central African copperbelt. This globally strategic mineral region is central to the history of two nation-states (Zambia and Democratic Republic of Congo (DRC)), as well as wider debates about the role of mineral wealth in development. The project has three interrelated and comparative objectives. First, it will examine the copperbelt as a single region divided by a (post-)colonial border, across which flowed minerals, peoples, and ideas about the relationship between them. Political economy created the circumstances in which distinct political cultures of mining communities developed, but this also involved a process of imagination, drawing on ‘modern’ notions such as national development, but also morally framed ideas about the societies and land from which minerals are extracted. The project will explain the relationship between minerals and African polities, economies, societies and ideas. Second, it will analyse how ‘top-down’ knowledge production processes of Anglo-American and Belgian academies shaped understanding of these societies. Explaining how social scientists imagined and constructed copperbelt society will enable a new understanding of the relationship between mining societies and academic knowledge production. Third, it will explore the interaction between these intellectual constructions and the copperbelt’s political culture, exploring the interchange between academic and popular perceptions. This project will investigate the hypothesis that the resultant understanding of this region is the result of a long unequal interaction of definition and determination between western observers and African participants that has only a partial relationship to the reality of mineral extraction, filtered as it has been through successive sedimentations of imagining and representation laid down over nearly a century of urban life in central Africa.
Summary
This project provides the first comparative historical analysis – local, national and transnational - of the Central African copperbelt. This globally strategic mineral region is central to the history of two nation-states (Zambia and Democratic Republic of Congo (DRC)), as well as wider debates about the role of mineral wealth in development. The project has three interrelated and comparative objectives. First, it will examine the copperbelt as a single region divided by a (post-)colonial border, across which flowed minerals, peoples, and ideas about the relationship between them. Political economy created the circumstances in which distinct political cultures of mining communities developed, but this also involved a process of imagination, drawing on ‘modern’ notions such as national development, but also morally framed ideas about the societies and land from which minerals are extracted. The project will explain the relationship between minerals and African polities, economies, societies and ideas. Second, it will analyse how ‘top-down’ knowledge production processes of Anglo-American and Belgian academies shaped understanding of these societies. Explaining how social scientists imagined and constructed copperbelt society will enable a new understanding of the relationship between mining societies and academic knowledge production. Third, it will explore the interaction between these intellectual constructions and the copperbelt’s political culture, exploring the interchange between academic and popular perceptions. This project will investigate the hypothesis that the resultant understanding of this region is the result of a long unequal interaction of definition and determination between western observers and African participants that has only a partial relationship to the reality of mineral extraction, filtered as it has been through successive sedimentations of imagining and representation laid down over nearly a century of urban life in central Africa.
Max ERC Funding
1 599 661 €
Duration
Start date: 2016-07-01, End date: 2021-09-30
Project acronym COTCA
Project Cultures of Occupation in Twentieth-century Asia
Researcher (PI) Jeremy Edmund Taylor
Host Institution (HI) THE UNIVERSITY OF NOTTINGHAM
Country United Kingdom
Call Details Consolidator Grant (CoG), SH6, ERC-2015-CoG
Summary How has foreign occupation shaped culture? What has been the lasting cultural legacy of foreign occupation in those societies where it represented the usual state of affairs for much of the modern era? These are key questions which, in light of ongoing cases of occupation around the world, remain crucial in the 21st century. Cultures of Occupation in Twentieth-century Asia (COTCA) will answer these questions by analysing how occupation―be it under colonial, wartime or Cold War powers―gave rise to unique visual, auditory and spatial regimes in East and Southeast Asia. The core objective of this important project is to produce a paradigm shift in the study of occupation, and to challenge the 'collaboration'/'resistance' dichotomy which has defined the field thus far. It will adopt a transnational, intertextual and comparative approach to the study of cultural expression produced under occupation from the 1930s to the 1970s. It will also break new methodological ground by drawing on and contributing to recent developments in visual, auditory and spatial history as a means of highlighting intersections and cultural convergences across different types of occupation. By doing so, COTCA will, for the first time, determine what occupation looked, sounded and felt like in twentieth-century Asia. The COTCA team will consist of the PI, 2 postdoctoral researchers and 3 PhD students, and will run along 3 streams: (i) Representations of occupation; (ii) sounds of occupation; and (iii) spaces of occupation. Case studies based on hitherto rarely examined examples will be undertaken in each stream. These include: A visual history of Japanese-occupied China; soundscapes of the US naval bases in the Philippines; and, spaces of occupation in late-colonial Malaya. COTCA will also build a Digital Archive which will enable researchers to trace the development of narratives, tropes and motifs common to 'occupation' cultural expression in Asia across national and temporal borders.
Summary
How has foreign occupation shaped culture? What has been the lasting cultural legacy of foreign occupation in those societies where it represented the usual state of affairs for much of the modern era? These are key questions which, in light of ongoing cases of occupation around the world, remain crucial in the 21st century. Cultures of Occupation in Twentieth-century Asia (COTCA) will answer these questions by analysing how occupation―be it under colonial, wartime or Cold War powers―gave rise to unique visual, auditory and spatial regimes in East and Southeast Asia. The core objective of this important project is to produce a paradigm shift in the study of occupation, and to challenge the 'collaboration'/'resistance' dichotomy which has defined the field thus far. It will adopt a transnational, intertextual and comparative approach to the study of cultural expression produced under occupation from the 1930s to the 1970s. It will also break new methodological ground by drawing on and contributing to recent developments in visual, auditory and spatial history as a means of highlighting intersections and cultural convergences across different types of occupation. By doing so, COTCA will, for the first time, determine what occupation looked, sounded and felt like in twentieth-century Asia. The COTCA team will consist of the PI, 2 postdoctoral researchers and 3 PhD students, and will run along 3 streams: (i) Representations of occupation; (ii) sounds of occupation; and (iii) spaces of occupation. Case studies based on hitherto rarely examined examples will be undertaken in each stream. These include: A visual history of Japanese-occupied China; soundscapes of the US naval bases in the Philippines; and, spaces of occupation in late-colonial Malaya. COTCA will also build a Digital Archive which will enable researchers to trace the development of narratives, tropes and motifs common to 'occupation' cultural expression in Asia across national and temporal borders.
Max ERC Funding
1 885 268 €
Duration
Start date: 2016-07-01, End date: 2022-06-30
Project acronym EVALVE
Project Biomechanics and signaling in models of congenital heart valve defects
Researcher (PI) Julien Jean-Louis Marie Vermot
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Consolidator Grant (CoG), LS4, ERC-2015-CoG
Summary Mechanical forces are fundamental to cardiovascular development and physiology. The interactions between mechanical forces and endothelial cells are mediated by mechanotransduction feedback loops. My lab is interested in understanding how hemodynamic forces modulate cardiovascular function and morphogenesis. Overall, our recent work is unraveling the biological links between mechanical forces, mechanotransduction and endothelial cell responses. The heart beats 2.6 billion times in a human lifetime and heart valves are amongst the most mechanically challenged structures of the body. The cardiac valves are made of endocardial cells (EdCs) and extracellular matrix components. Most valve diseases have their origins in embryogenesis, either as signs of abnormal developmental processes or the aberrant re-expression of fetal gene programs normally quiescent in adulthood.
This project is directed towards the elucidation of the biomechanical mechanism of mechanotransduction at the subcellular and molecular level and in addressing how EdCs integrate this information to form and maintain a functional cardiac valve. We will identify the mechanosensors at work in EdCs and their roles during cardiac valve development and repair. To do so, we will implement unique optical methodologies the lab has pioneered to characterize endocardial mechanotransduction: 1) Optical tweezing combined with mechanical stress reporters to test the mechanosensitivity of EdCs; 2) High resolution live microscopy and mathematical modeling to quantify mechanical forces; 3) 3D cell lineage studies to understand how cells respond and organize during pathological valve development. We will also use high-throughput mRNA- and ChIP-sequencing to characterize the transcriptional network activated by forces.
When completed this proposal will shed light on a critical, but little explored, aspect of congenital valve defects and will be useful for identifying new targets for therapeutic interventions.
Summary
Mechanical forces are fundamental to cardiovascular development and physiology. The interactions between mechanical forces and endothelial cells are mediated by mechanotransduction feedback loops. My lab is interested in understanding how hemodynamic forces modulate cardiovascular function and morphogenesis. Overall, our recent work is unraveling the biological links between mechanical forces, mechanotransduction and endothelial cell responses. The heart beats 2.6 billion times in a human lifetime and heart valves are amongst the most mechanically challenged structures of the body. The cardiac valves are made of endocardial cells (EdCs) and extracellular matrix components. Most valve diseases have their origins in embryogenesis, either as signs of abnormal developmental processes or the aberrant re-expression of fetal gene programs normally quiescent in adulthood.
This project is directed towards the elucidation of the biomechanical mechanism of mechanotransduction at the subcellular and molecular level and in addressing how EdCs integrate this information to form and maintain a functional cardiac valve. We will identify the mechanosensors at work in EdCs and their roles during cardiac valve development and repair. To do so, we will implement unique optical methodologies the lab has pioneered to characterize endocardial mechanotransduction: 1) Optical tweezing combined with mechanical stress reporters to test the mechanosensitivity of EdCs; 2) High resolution live microscopy and mathematical modeling to quantify mechanical forces; 3) 3D cell lineage studies to understand how cells respond and organize during pathological valve development. We will also use high-throughput mRNA- and ChIP-sequencing to characterize the transcriptional network activated by forces.
When completed this proposal will shed light on a critical, but little explored, aspect of congenital valve defects and will be useful for identifying new targets for therapeutic interventions.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-12-01, End date: 2023-05-31
Project acronym GLYCOSURF
Project Surface-Based Molecular Imprinting for Glycoprotein Recognition
Researcher (PI) Paula Maria Da Silva Mendes
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Country United Kingdom
Call Details Consolidator Grant (CoG), PE8, ERC-2013-CoG
Summary "There is now overwhelming evidence that glycosylation changes during the development and progression of various malignancies. Altered glycosylation has been implicated in cancer, immune deficiencies, neurodegenerative diseases, hereditary disorders and cardiovascular diseases. Currently, antibodies are playing a central role in enabling the detection of glycoprotein biomarkers using a variety of immunodiagnostic tests. Nonetheless, antibodies do have their own set of drawbacks that limit the commercialization of antibody sensing technology. They suffer from poor stability, need special handling and require a complicated, costly production procedure. More importantly, they lack specificity because they bind only to a small site on the biomarker and are not able to discriminate, for instance, among different glycosylated proteins. The current antibody diagnostic technology has well recognized limitations regarding their accuracy and timeliness of diagnose of disease. This project will focus on research into the means of developing a generic, robust, reliable and cost-effective alternative to monoclonal antibody technology. The project aims to exploit concepts and tools from nanochemistry, supramolecular chemistry and molecular imprinting to provide highly innovative synthetic recognition platforms with high sensitivity and specificity for glycoproteins. Such novel type of platforms will make a profound and significant impact in the broad fields of biosensors and protein separation devices with applications in many areas such as biomedical diagnostics, pharmaceutical industry, defense and environmental monitoring. The proposed technology may open an untraveled path in the successful diagnosis, prognosis and monitoring of therapeutic treatment for major diseases such as cancer, immune deficiencies, neurodegenerative diseases, hereditary disorders and cardiovascular diseases."
Summary
"There is now overwhelming evidence that glycosylation changes during the development and progression of various malignancies. Altered glycosylation has been implicated in cancer, immune deficiencies, neurodegenerative diseases, hereditary disorders and cardiovascular diseases. Currently, antibodies are playing a central role in enabling the detection of glycoprotein biomarkers using a variety of immunodiagnostic tests. Nonetheless, antibodies do have their own set of drawbacks that limit the commercialization of antibody sensing technology. They suffer from poor stability, need special handling and require a complicated, costly production procedure. More importantly, they lack specificity because they bind only to a small site on the biomarker and are not able to discriminate, for instance, among different glycosylated proteins. The current antibody diagnostic technology has well recognized limitations regarding their accuracy and timeliness of diagnose of disease. This project will focus on research into the means of developing a generic, robust, reliable and cost-effective alternative to monoclonal antibody technology. The project aims to exploit concepts and tools from nanochemistry, supramolecular chemistry and molecular imprinting to provide highly innovative synthetic recognition platforms with high sensitivity and specificity for glycoproteins. Such novel type of platforms will make a profound and significant impact in the broad fields of biosensors and protein separation devices with applications in many areas such as biomedical diagnostics, pharmaceutical industry, defense and environmental monitoring. The proposed technology may open an untraveled path in the successful diagnosis, prognosis and monitoring of therapeutic treatment for major diseases such as cancer, immune deficiencies, neurodegenerative diseases, hereditary disorders and cardiovascular diseases."
Max ERC Funding
1 894 046 €
Duration
Start date: 2014-12-01, End date: 2019-11-30
Project acronym HAZE
Project Reducing the Burden of Smouldering Megafires: an Earth-Scale Challenge
Researcher (PI) Guillermo Jose Rein
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Consolidator Grant (CoG), PE8, ERC-2015-CoG
Summary Smouldering megafires are the largest and longest-burning fires on Earth. They destroy essential peatland ecosystems, and are responsible for 15% of annual global greenhouse gas emissions. This is the same amount attributed to the whole of the European Union, and yet it is not accounted for in global carbon budgets. Peat fires also induce surges of respiratory emergencies in the population and disrupt shipping and aviation routes for long periods, weeks even months. The ambition of HAZE is to advance the science and create the technology that will reduce the burden of smouldering fires. Despite their importance, we do not understand how smouldering fires ignite, spread or extinguish, which impedes the development of any successful mitigation strategy. Megafires are routinely fought across the globe with techniques that were developed for flaming fires, and are thus ineffective for smouldering. Moreover, the burning of deep peat affects older soil carbon that has not been part of the active carbon cycle for centuries to millennia, and thus creates a positive feedback to the climate system. HAZE wants to turn the challenges faced by smouldering research into opportunities and has the following three novel aims:
1) To conduct controlled laboratory experiments and discover how peat fires ignite, spread and extinguish.
2) To develop multidimensional computational models for the field scale (~1 km) and simulate the real phenomena.
3) To create pathways for novel mitigation technologies in accurate prevention, quick detection systems, and simulation-driven suppression strategies.
With my proposal, Europe has the chance to lead the way and pioneer technologies against this Earth-scale and important but unconventional source of emissions. I am confident that with the support of ERC, I can deliver the science and excellence needed to tackle this global challenge, and in doing so, I will advance the knowledge frontier, foster innovation and develop new young talent for Europe
Summary
Smouldering megafires are the largest and longest-burning fires on Earth. They destroy essential peatland ecosystems, and are responsible for 15% of annual global greenhouse gas emissions. This is the same amount attributed to the whole of the European Union, and yet it is not accounted for in global carbon budgets. Peat fires also induce surges of respiratory emergencies in the population and disrupt shipping and aviation routes for long periods, weeks even months. The ambition of HAZE is to advance the science and create the technology that will reduce the burden of smouldering fires. Despite their importance, we do not understand how smouldering fires ignite, spread or extinguish, which impedes the development of any successful mitigation strategy. Megafires are routinely fought across the globe with techniques that were developed for flaming fires, and are thus ineffective for smouldering. Moreover, the burning of deep peat affects older soil carbon that has not been part of the active carbon cycle for centuries to millennia, and thus creates a positive feedback to the climate system. HAZE wants to turn the challenges faced by smouldering research into opportunities and has the following three novel aims:
1) To conduct controlled laboratory experiments and discover how peat fires ignite, spread and extinguish.
2) To develop multidimensional computational models for the field scale (~1 km) and simulate the real phenomena.
3) To create pathways for novel mitigation technologies in accurate prevention, quick detection systems, and simulation-driven suppression strategies.
With my proposal, Europe has the chance to lead the way and pioneer technologies against this Earth-scale and important but unconventional source of emissions. I am confident that with the support of ERC, I can deliver the science and excellence needed to tackle this global challenge, and in doing so, I will advance the knowledge frontier, foster innovation and develop new young talent for Europe
Max ERC Funding
1 958 900 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
