Project acronym CLaSS
Project Climate, Landscape, Settlement and Society: Exploring Human-Environment Interaction in the Ancient Near East
Researcher (PI) Daniel LAWRENCE
Host Institution (HI) UNIVERSITY OF DURHAM
Call Details Starting Grant (StG), SH6, ERC-2018-STG
Summary Over the last 8000 years, the Fertile Crescent of the Near East has seen the emergence of cities, states and empires. Climate fluctuations are generally considered to be a significant factor in these changes because in pre-industrial societies they directly relate to food production and security. In the short term, ‘collapse’ events brought about by extreme weather changes such as droughts have been blamed for declines in population, social complexity and political systems. More broadly, the relationships between environment, settlement and surplus drive most models for the development of urbanism and hierarchical political systems.
Studies seeking to correlate social and climatic changes in the past tend either to focus on highly localised analyses of specific sites and surveys or to take a more synthetic overview at much larger, even continental, scales. The CLaSS project will take a ground breaking hybrid approach using archaeological data science (or ‘big data’) to construct detailed, empirical datasets at unprecedented scales. Archaeological settlement data and archaeobotanical data (plant and tree remains) will be collated for the entire Fertile Crescent and combined with climate simulations derived from General Circulation Models using cutting edge techniques. The resulting datasets will represent the largest of their kind ever compiled, covering the period between 8000BP and 2000BP and an area of 600,000km2.
Collecting data at this scale will enable us to compare population densities and distribution, subsistence practices and landscape management strategies to investigate the question: What factors have allowed for the differential persistence of societies in the face of changing climatic and environmental conditions? This ambitious project will provide insights into the sustainability and resilience of societies through both abrupt and longer term climate changes, leveraging the deep time perspective only available to archaeology.
Summary
Over the last 8000 years, the Fertile Crescent of the Near East has seen the emergence of cities, states and empires. Climate fluctuations are generally considered to be a significant factor in these changes because in pre-industrial societies they directly relate to food production and security. In the short term, ‘collapse’ events brought about by extreme weather changes such as droughts have been blamed for declines in population, social complexity and political systems. More broadly, the relationships between environment, settlement and surplus drive most models for the development of urbanism and hierarchical political systems.
Studies seeking to correlate social and climatic changes in the past tend either to focus on highly localised analyses of specific sites and surveys or to take a more synthetic overview at much larger, even continental, scales. The CLaSS project will take a ground breaking hybrid approach using archaeological data science (or ‘big data’) to construct detailed, empirical datasets at unprecedented scales. Archaeological settlement data and archaeobotanical data (plant and tree remains) will be collated for the entire Fertile Crescent and combined with climate simulations derived from General Circulation Models using cutting edge techniques. The resulting datasets will represent the largest of their kind ever compiled, covering the period between 8000BP and 2000BP and an area of 600,000km2.
Collecting data at this scale will enable us to compare population densities and distribution, subsistence practices and landscape management strategies to investigate the question: What factors have allowed for the differential persistence of societies in the face of changing climatic and environmental conditions? This ambitious project will provide insights into the sustainability and resilience of societies through both abrupt and longer term climate changes, leveraging the deep time perspective only available to archaeology.
Max ERC Funding
1 498 650 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym COMMIOS
Project Communities and Connectivities: Iron Age Britons and their Continental Neighbours
Researcher (PI) Ian ARMIT
Host Institution (HI) UNIVERSITY OF LEICESTER
Call Details Advanced Grant (AdG), SH6, ERC-2018-ADG
Summary Recent breakthroughs in ancient DNA and isotope analysis are transforming our understanding of diversity, mobility and social dynamics in the human past. COMMIOS integrates these cutting-edge methods on a scale not previously attempted, within a ground-breaking interdisciplinary framework, to provide a radically new vision of Iron Age communities in Britain (800 BC – AD 100) within their wider European context.
At the broad scale, we will conduct the first concerted programme of genome-wide ancient DNA analysis on Iron Age populations anywhere in the world (c. 1000 individuals in the UK, 250 in Europe), mapping genetic clusters to shed light on ancient populations themselves and on their relationships to modern genetic patterning. Together with isotope analysis, and underpinned by both osteoarchaeological and cultural archaeological approaches, this will also enable us to directly address critical issues of population movement and inter-regional connectivity in Iron Age Europe. We will utilise the power of these new scientific methods to examine the structure and social dynamics of Iron Age societies in Britain, including household and kin-group composition, the identification of familial relationships, gender-specific mobility, and the development of social inequalities. Previously the preserve of cultural anthropologists studying recent societies, we will draw these questions into the archaeological domain, opening up new areas of enquiry for prehistoric societies.
The scope and scale of the project represents a new departure for European archaeology, made possible by the coming-of-age of new analytical methods. Many of these have been pioneered by the project team, which comprises world-leaders in the fields of ancient DNA, isotope analysis, osteoarchaeology, chronological modelling and cultural archaeology. Although focussed on Iron Age Britain, the project will establish a new benchmark for future analyses of other regions and periods in Europe and beyond.
Summary
Recent breakthroughs in ancient DNA and isotope analysis are transforming our understanding of diversity, mobility and social dynamics in the human past. COMMIOS integrates these cutting-edge methods on a scale not previously attempted, within a ground-breaking interdisciplinary framework, to provide a radically new vision of Iron Age communities in Britain (800 BC – AD 100) within their wider European context.
At the broad scale, we will conduct the first concerted programme of genome-wide ancient DNA analysis on Iron Age populations anywhere in the world (c. 1000 individuals in the UK, 250 in Europe), mapping genetic clusters to shed light on ancient populations themselves and on their relationships to modern genetic patterning. Together with isotope analysis, and underpinned by both osteoarchaeological and cultural archaeological approaches, this will also enable us to directly address critical issues of population movement and inter-regional connectivity in Iron Age Europe. We will utilise the power of these new scientific methods to examine the structure and social dynamics of Iron Age societies in Britain, including household and kin-group composition, the identification of familial relationships, gender-specific mobility, and the development of social inequalities. Previously the preserve of cultural anthropologists studying recent societies, we will draw these questions into the archaeological domain, opening up new areas of enquiry for prehistoric societies.
The scope and scale of the project represents a new departure for European archaeology, made possible by the coming-of-age of new analytical methods. Many of these have been pioneered by the project team, which comprises world-leaders in the fields of ancient DNA, isotope analysis, osteoarchaeology, chronological modelling and cultural archaeology. Although focussed on Iron Age Britain, the project will establish a new benchmark for future analyses of other regions and periods in Europe and beyond.
Max ERC Funding
2 499 872 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym DNA-DOCK
Project Precision Docking of Very Large DNA Cargos in Mammalian Genomes
Researcher (PI) Imre Berger
Host Institution (HI) UNIVERSITY OF BRISTOL
Call Details Advanced Grant (AdG), LS9, ERC-2018-ADG
Summary Gene editing has developed at breath-taking speed. In particular CRISPR/Cas9 provides a tool-set thousands of researchers worldwide now utilize with unprecedented ease to edit genes, catalysing a broad range of biomedical and industrial applications. Gene synthesis technologies producing thousands of base pairs of synthetic DNA have become affordable. Current gene editing technology is highly effective for local, small genomic DNA edits and insertions. To unlock the full potential of this revolution, however, our capacities to disrupt or rewrite small local elements of code must be complemented by equal capacities to efficiently insert very large synthetic DNA cargos with a wide range of functions into genomic sites. Large designer cargos would carry multicomponent DNA circuitry including programmable and fine-tuneable functionalities, representing the vital interface between gene editing which is the state-of-the-art at present, and genome engineering, which is the future. This challenge remained largely unaddressed to date.
We aspire to resolve this bottleneck by creating ground-breaking, generally applicable, easy-to-use technology to enable docking of large DNA cargos with base pair precision and unparalleled efficiency into mammalian genomes. To achieve our ambitious goals, we will apply a whole array of sophisticated tools. We will unlock a small non-human virus to rational design, creating safe, flexible and easy-to-produce, large capacity DNA delivery nanodevices with unmatched transduction capability. We will exploit a range of techniques including Darwinian in vitro selection/evolution to accomplish unprecedented precision DNA integration efficiency into genomic sites. We will use parallelized DNA assembly methods to generate multifunctional circuits, to accelerate T cell engineering, resolving unmet needs. Once we accomplish our tasks, our technology has the potential to be exceptionally rewarding to the scientific, industrial and medical communities.
Summary
Gene editing has developed at breath-taking speed. In particular CRISPR/Cas9 provides a tool-set thousands of researchers worldwide now utilize with unprecedented ease to edit genes, catalysing a broad range of biomedical and industrial applications. Gene synthesis technologies producing thousands of base pairs of synthetic DNA have become affordable. Current gene editing technology is highly effective for local, small genomic DNA edits and insertions. To unlock the full potential of this revolution, however, our capacities to disrupt or rewrite small local elements of code must be complemented by equal capacities to efficiently insert very large synthetic DNA cargos with a wide range of functions into genomic sites. Large designer cargos would carry multicomponent DNA circuitry including programmable and fine-tuneable functionalities, representing the vital interface between gene editing which is the state-of-the-art at present, and genome engineering, which is the future. This challenge remained largely unaddressed to date.
We aspire to resolve this bottleneck by creating ground-breaking, generally applicable, easy-to-use technology to enable docking of large DNA cargos with base pair precision and unparalleled efficiency into mammalian genomes. To achieve our ambitious goals, we will apply a whole array of sophisticated tools. We will unlock a small non-human virus to rational design, creating safe, flexible and easy-to-produce, large capacity DNA delivery nanodevices with unmatched transduction capability. We will exploit a range of techniques including Darwinian in vitro selection/evolution to accomplish unprecedented precision DNA integration efficiency into genomic sites. We will use parallelized DNA assembly methods to generate multifunctional circuits, to accelerate T cell engineering, resolving unmet needs. Once we accomplish our tasks, our technology has the potential to be exceptionally rewarding to the scientific, industrial and medical communities.
Max ERC Funding
2 498 578 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym DUNES
Project Sea, Sand and People. An Environmental History of Coastal Dunes
Researcher (PI) Joana FREITAS
Host Institution (HI) Faculdade de letras da Universidade de Lisboa
Call Details Starting Grant (StG), SH6, ERC-2018-STG
Summary Dunes are now protected environments, being top priority for coastal managers, because of their important role as coastal defences. But, it was not like that in the past.
For centuries dunes were considered unproductive and dangerous. The sand blown by the wind was taken inland, invading fields, silting rivers and destroying villages. In the eighteenth century, a strategy was developed to fight against the dunes: trapping them with trees, with the double purpose of preventing the destruction of arable land and increasing their economic value converting them into forest areas. Different governments, in different countries supported the immobilization of the shifting sands. The strategy, developed in Europe, was taken to other places in the world. These works caused profound changes in vast coastal areas transforming arid landscapes of sandy dunes into green tree forests.
This project aims to explore human-environment relations in coastal areas worldwide, since the eighteenth century until today, through the study of dunes as hybrid landscapes. Based on selected case-studies and comparative approaches, the project will focus on the origins, reasons and means of dunes afforestation; the impacts of the creation of new landscapes to local communities and ecosystems; and the present situation of dunes as coastal defences and rehabilitated environments. The final purpose is to produce an innovative global history of coastal dunes, combining knowledges from both Humanities and Social Sciences and Physical and Life Sciences, which has never been done.
Supported by an interdisciplinary team, this research will result in new developments in the field of the Environmental History studies; provide relevant knowledge considering the need of efficient management solutions to adapt to the expected mean sea level rise; and stimulate environmental citizenship by disseminating the idea that the future of the world coasts depends on today’s actions.
Summary
Dunes are now protected environments, being top priority for coastal managers, because of their important role as coastal defences. But, it was not like that in the past.
For centuries dunes were considered unproductive and dangerous. The sand blown by the wind was taken inland, invading fields, silting rivers and destroying villages. In the eighteenth century, a strategy was developed to fight against the dunes: trapping them with trees, with the double purpose of preventing the destruction of arable land and increasing their economic value converting them into forest areas. Different governments, in different countries supported the immobilization of the shifting sands. The strategy, developed in Europe, was taken to other places in the world. These works caused profound changes in vast coastal areas transforming arid landscapes of sandy dunes into green tree forests.
This project aims to explore human-environment relations in coastal areas worldwide, since the eighteenth century until today, through the study of dunes as hybrid landscapes. Based on selected case-studies and comparative approaches, the project will focus on the origins, reasons and means of dunes afforestation; the impacts of the creation of new landscapes to local communities and ecosystems; and the present situation of dunes as coastal defences and rehabilitated environments. The final purpose is to produce an innovative global history of coastal dunes, combining knowledges from both Humanities and Social Sciences and Physical and Life Sciences, which has never been done.
Supported by an interdisciplinary team, this research will result in new developments in the field of the Environmental History studies; provide relevant knowledge considering the need of efficient management solutions to adapt to the expected mean sea level rise; and stimulate environmental citizenship by disseminating the idea that the future of the world coasts depends on today’s actions.
Max ERC Funding
1 062 330 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym ENCOUNTER
Project Demography, Cultural change, and the Diffusion of Rice and Millet during the Jomon-Yayoi transition in prehistoric Japan
Researcher (PI) Enrico Ryunosuke CREMA
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), SH6, ERC-2018-STG
Summary Human history is punctuated by episodes of large-scale diffusion of new ideas and people that lead to era-defining transitions in past societies. Investigating what promotes these events, how societies react to these, and what are their long-term consequences is a key to understand the fundamental drivers of cultural change. ENCOUNTER will push forward this research agenda by investigating the Jomon-Yayoi transition, a demic and cultural diffusion event that led the predominantly hunting, gathering, and fishing-based communities of the Japanese islands to adopt rice and millet farming during the 1st millennium BC. The continental migrants who triggered this transition event did not bring just a new economy, but also new technology and culture, deeply impacting the indigenous society. The transition was however not uniform, as different regions responded to the new culture in different ways. Some immediately adopted the new cultural repertoire to its full extent, others embraced only certain elements, and still others resisted for over 1,000 years, generating cultural, linguistic and genetic clines that are still tangible today. ENCOUNTER will investigate this pivotal moment in Japanese prehistory, seeking to determine why the indigenous inhabitants responded so differently to the arrival of the new culture. It will examine the dynamics of this transition by: synthesising one of the richest archaeological records available in the world; combining new and old lines of evidence across different disciplines, including organic chemistry, palynology, and material culture studies; and developing a suite of computational techniques to reconstruct patterns of demographic change and cultural diffusion. It will question the existing narrative that farming is inevitable and instead put new emphasis on the incumbent hunter-gatherer populations to understand their motivations to change subsistence strategies with respect to their environment settings and cultural affinities.
Summary
Human history is punctuated by episodes of large-scale diffusion of new ideas and people that lead to era-defining transitions in past societies. Investigating what promotes these events, how societies react to these, and what are their long-term consequences is a key to understand the fundamental drivers of cultural change. ENCOUNTER will push forward this research agenda by investigating the Jomon-Yayoi transition, a demic and cultural diffusion event that led the predominantly hunting, gathering, and fishing-based communities of the Japanese islands to adopt rice and millet farming during the 1st millennium BC. The continental migrants who triggered this transition event did not bring just a new economy, but also new technology and culture, deeply impacting the indigenous society. The transition was however not uniform, as different regions responded to the new culture in different ways. Some immediately adopted the new cultural repertoire to its full extent, others embraced only certain elements, and still others resisted for over 1,000 years, generating cultural, linguistic and genetic clines that are still tangible today. ENCOUNTER will investigate this pivotal moment in Japanese prehistory, seeking to determine why the indigenous inhabitants responded so differently to the arrival of the new culture. It will examine the dynamics of this transition by: synthesising one of the richest archaeological records available in the world; combining new and old lines of evidence across different disciplines, including organic chemistry, palynology, and material culture studies; and developing a suite of computational techniques to reconstruct patterns of demographic change and cultural diffusion. It will question the existing narrative that farming is inevitable and instead put new emphasis on the incumbent hunter-gatherer populations to understand their motivations to change subsistence strategies with respect to their environment settings and cultural affinities.
Max ERC Funding
1 499 095 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym FORMSofLABOUR
Project Forms of Labour: Gender, Freedom and Experience of Work in the Preindustrial Economy
Researcher (PI) Jane WHITTLE
Host Institution (HI) THE UNIVERSITY OF EXETER
Call Details Advanced Grant (AdG), SH6, ERC-2018-ADG
Summary The history of labour and its role in Europe’s preindustrial development has very largely been the history of adult men. FORMSofLABOUR seeks to put other workers in the picture, particularly women and servants, not simply by ‘adding them on’ but by showing how a full understanding of women’s work and of service offers a radical critique of existing approaches to work and to the idea of free labour. It focuses on England in the period 1300-1700 viewed in a comparative Western European perspective, and addressed these issues through three themes. (1) A revolutionary research technique which collects evidence of work tasks from court records to simulate a time-use study is used to explore the experience of work. This technique allows the work activities of women and men, young and old, employees and family members to be illuminated, with evidence of tasks, location and timing of work, creating an entirely new perspective on England’s early modern economy. (2) The theoretical underpinnings of the history of women’s work in the preindustrial economy are explored, reassessing key debates using interdisciplinary perspectives from economics and political science, as well as new archival evidence from themes 1 and 3. Gendered work patterns are viewed through the lens of freedom, rather than patriarchy, to create a step-change in our understanding of gender and work. (3) The issue of the extent to which labour was ‘free’ after the end of serfdom is interrogated through a careful examination of the range of forms of labour and the nature of labour laws, using a variety of archival evidence combined with a comparisons with serfdom and slavery, and the adoption of insights from development economics and anthropology. Together these interlocking themes create a new history of work in the economy which formed the background to grand narratives of Smith and Marx, arguing that with women and servants had been in picture, the story of economic development is transformed.
Summary
The history of labour and its role in Europe’s preindustrial development has very largely been the history of adult men. FORMSofLABOUR seeks to put other workers in the picture, particularly women and servants, not simply by ‘adding them on’ but by showing how a full understanding of women’s work and of service offers a radical critique of existing approaches to work and to the idea of free labour. It focuses on England in the period 1300-1700 viewed in a comparative Western European perspective, and addressed these issues through three themes. (1) A revolutionary research technique which collects evidence of work tasks from court records to simulate a time-use study is used to explore the experience of work. This technique allows the work activities of women and men, young and old, employees and family members to be illuminated, with evidence of tasks, location and timing of work, creating an entirely new perspective on England’s early modern economy. (2) The theoretical underpinnings of the history of women’s work in the preindustrial economy are explored, reassessing key debates using interdisciplinary perspectives from economics and political science, as well as new archival evidence from themes 1 and 3. Gendered work patterns are viewed through the lens of freedom, rather than patriarchy, to create a step-change in our understanding of gender and work. (3) The issue of the extent to which labour was ‘free’ after the end of serfdom is interrogated through a careful examination of the range of forms of labour and the nature of labour laws, using a variety of archival evidence combined with a comparisons with serfdom and slavery, and the adoption of insights from development economics and anthropology. Together these interlocking themes create a new history of work in the economy which formed the background to grand narratives of Smith and Marx, arguing that with women and servants had been in picture, the story of economic development is transformed.
Max ERC Funding
1 666 565 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym LIMBo
Project Zooming the link between diet and brain health: how phenolic metabolites modulate brain inflammation
Researcher (PI) Cláudia NUNES DOS SANTOS
Host Institution (HI) UNIVERSIDADE NOVA DE LISBOA
Call Details Starting Grant (StG), LS9, ERC-2018-STG
Summary Currently a big concern of our aging society is to efficiently delay the onset of neurodegenerative diseases which are progressively rising in incidence. The paradigm that a diet rich in the phenolics, prevalent e.g. in fruits, is beneficial to brain health has reached the public. However their mechanistic actions in brain functions remain to be seen, particularly since the nature of those acting in the brain remains overlooked. I wish to address this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration.
Specifically, I will be analysing the potential of dietary phenolics in both prevention and treatment (i.e delay) of neuroinflammation – key process shared in neurodegenerative diseases. To break down the current indeterminate status of “cause vs effect”, my vision is to focus my research on metabolites derived from dietary phenolics that reach the brain. I will be investigating their effects in both established and unknown response pathways of microglia cells - the innate immune cells of the central nervous system, either alone or when communicating with other brain cells. Ultimately, to attain an integrated view of their effects I will establish nutrition trials in mice. LIMBo considers both pro- and anti- inflammatory processes to preliminary validate the action of any promising metabolite in prevention and/or therapeutics.
LIMBo provides valuable scientific insights for future implementation of healthy brain diets. My group is in a unique position to address LIMBo objectives due to multidisciplinary expertise in organic synthesis, metabolomics and molecular and cellular biology, together with our previous data on novel neuroactive metabolites.
LIMBo also creates far-reaching opportunities by generating knowledge that impacts our fundamental understanding on the diversity of phenolic metabolites and their specific influences in neuroinflammation and potential use as prodrugs.
Summary
Currently a big concern of our aging society is to efficiently delay the onset of neurodegenerative diseases which are progressively rising in incidence. The paradigm that a diet rich in the phenolics, prevalent e.g. in fruits, is beneficial to brain health has reached the public. However their mechanistic actions in brain functions remain to be seen, particularly since the nature of those acting in the brain remains overlooked. I wish to address this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration.
Specifically, I will be analysing the potential of dietary phenolics in both prevention and treatment (i.e delay) of neuroinflammation – key process shared in neurodegenerative diseases. To break down the current indeterminate status of “cause vs effect”, my vision is to focus my research on metabolites derived from dietary phenolics that reach the brain. I will be investigating their effects in both established and unknown response pathways of microglia cells - the innate immune cells of the central nervous system, either alone or when communicating with other brain cells. Ultimately, to attain an integrated view of their effects I will establish nutrition trials in mice. LIMBo considers both pro- and anti- inflammatory processes to preliminary validate the action of any promising metabolite in prevention and/or therapeutics.
LIMBo provides valuable scientific insights for future implementation of healthy brain diets. My group is in a unique position to address LIMBo objectives due to multidisciplinary expertise in organic synthesis, metabolomics and molecular and cellular biology, together with our previous data on novel neuroactive metabolites.
LIMBo also creates far-reaching opportunities by generating knowledge that impacts our fundamental understanding on the diversity of phenolic metabolites and their specific influences in neuroinflammation and potential use as prodrugs.
Max ERC Funding
1 496 022 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym Microrobots
Project Engineering Biohybrid MicroRobots from Magnetic Swimmers and S-layers
Researcher (PI) Bertram DAUM
Host Institution (HI) THE UNIVERSITY OF EXETER
Call Details Starting Grant (StG), LS9, ERC-2018-STG
Summary Biohybrid MicroRobots (BMRs) are conceptual microscopic robotic devices that combine synthetic and biological components and can be remote controlled to a specific destination, attach to a target and perform a bespoke biochemical operation at nanoscale precision. Within the 5-year Microrobots project, I intend to develop innovative BMRs by combining magnetic swimmers (MSs) with prokaryotic S-layers (SLs). MSs are microscopic devices that consist of two flexibly linked metallic beads with different magnetic properties and can be remote controlled through liquid media, simply by applying oscillating magnetic fields. SLs are highly stable 2-dimensional protein arrays that form resilient cell wall components in archaea and bacteria and can be genetically modified and reassembled on inorganic surfaces. I will introduce affinity tags into selected archaeal and bacterial SLs and reassemble them on the surfaces of MSs. This will coat MSs with unique affinity matrices, on which bioactive molecules can be conjugated at regular arrays, high density and defined distance. Through this strategy, I will generate BMRs that can be equipped with any bioactive functionality provided by nature, such as adhesive filaments, enzymes, antibodies, reporters, drug cargo or any other thinkable functional molecule. The BMRs that I will develop will elegantly miniaturise robotics and enable us to deliver bioactivity at nanometre precision. This will provide a revolutionary platform technology that will be applicable in a plethora of fields, such as medicine, nanotechnology, environmental engineering or scientific exploration and generate a real step change in the ways in which we build new materials, engineer our environment, fight disease and explore the universe in the 21st century.
Summary
Biohybrid MicroRobots (BMRs) are conceptual microscopic robotic devices that combine synthetic and biological components and can be remote controlled to a specific destination, attach to a target and perform a bespoke biochemical operation at nanoscale precision. Within the 5-year Microrobots project, I intend to develop innovative BMRs by combining magnetic swimmers (MSs) with prokaryotic S-layers (SLs). MSs are microscopic devices that consist of two flexibly linked metallic beads with different magnetic properties and can be remote controlled through liquid media, simply by applying oscillating magnetic fields. SLs are highly stable 2-dimensional protein arrays that form resilient cell wall components in archaea and bacteria and can be genetically modified and reassembled on inorganic surfaces. I will introduce affinity tags into selected archaeal and bacterial SLs and reassemble them on the surfaces of MSs. This will coat MSs with unique affinity matrices, on which bioactive molecules can be conjugated at regular arrays, high density and defined distance. Through this strategy, I will generate BMRs that can be equipped with any bioactive functionality provided by nature, such as adhesive filaments, enzymes, antibodies, reporters, drug cargo or any other thinkable functional molecule. The BMRs that I will develop will elegantly miniaturise robotics and enable us to deliver bioactivity at nanometre precision. This will provide a revolutionary platform technology that will be applicable in a plethora of fields, such as medicine, nanotechnology, environmental engineering or scientific exploration and generate a real step change in the ways in which we build new materials, engineer our environment, fight disease and explore the universe in the 21st century.
Max ERC Funding
1 766 481 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym NewHuman
Project Pathways to humanity: Adaptive niche diversity at the origins of the human lineage
Researcher (PI) Matthew Skinner
Host Institution (HI) UNIVERSITY OF KENT
Call Details Consolidator Grant (CoG), SH6, ERC-2018-COG
Summary For almost 100 years, the evolution of humans has been summarized as a transition from small-brained bipeds with an ape-like body plan (referred to as australopiths), to large-brained striding bipeds with a human-like body plan (members of the genus Homo). This characterisation dominates popular perception of human evolution in the public sphere. However, three newly discovered fossil human (hominin) species (H. naledi, H. floresiensis and Australopithecus sediba) do not fit this simple transitional model in either morphology or time (the former two surviving contemporaneously with modern humans), and have re-ignited debate about the origin of the Homo lineage, including perceptions of the earliest putative Homo species, H. habilis. These new fossils raise fundamental questions about the ecological niches occupied by hominins and the inferred transitions between niches throughout human evolution. With NewHuman, I will pioneer a novel, interdisciplinary and holistic approach using cutting-edge analyses of internal structures of fossil hominin teeth and bones to reconstruct the adaptive niche of these enigmatic species and test whether there is an unrecognized adaptive branch on the human family tree. Specifically, NewHuman will employ ground-breaking imaging techniques and analytical tools to reveal never-before-examined tooth and bone structures in these hominins. In doing so, it will 1) characterize the behaviour of these enigmatic species and place them more firmly into their ecological environment; and 2) elucidate the adaptive strategy that was likely the transition from australopith-like hominin species to later Homo, but which also represents a highly successful lifeway that persisted for over 2 million years alongside the evolving human lineage. By achieving these ambitious aims, NewHuman will have a significant impact on hypotheses about human evolution, and could result in a paradigm shift that overturns current views on human evolutionary history.
Summary
For almost 100 years, the evolution of humans has been summarized as a transition from small-brained bipeds with an ape-like body plan (referred to as australopiths), to large-brained striding bipeds with a human-like body plan (members of the genus Homo). This characterisation dominates popular perception of human evolution in the public sphere. However, three newly discovered fossil human (hominin) species (H. naledi, H. floresiensis and Australopithecus sediba) do not fit this simple transitional model in either morphology or time (the former two surviving contemporaneously with modern humans), and have re-ignited debate about the origin of the Homo lineage, including perceptions of the earliest putative Homo species, H. habilis. These new fossils raise fundamental questions about the ecological niches occupied by hominins and the inferred transitions between niches throughout human evolution. With NewHuman, I will pioneer a novel, interdisciplinary and holistic approach using cutting-edge analyses of internal structures of fossil hominin teeth and bones to reconstruct the adaptive niche of these enigmatic species and test whether there is an unrecognized adaptive branch on the human family tree. Specifically, NewHuman will employ ground-breaking imaging techniques and analytical tools to reveal never-before-examined tooth and bone structures in these hominins. In doing so, it will 1) characterize the behaviour of these enigmatic species and place them more firmly into their ecological environment; and 2) elucidate the adaptive strategy that was likely the transition from australopith-like hominin species to later Homo, but which also represents a highly successful lifeway that persisted for over 2 million years alongside the evolving human lineage. By achieving these ambitious aims, NewHuman will have a significant impact on hypotheses about human evolution, and could result in a paradigm shift that overturns current views on human evolutionary history.
Max ERC Funding
1 998 644 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym ProMiDis
Project A unified drug discovery platform for protein misfolding diseases
Researcher (PI) Georgios SKRETAS
Host Institution (HI) ETHNIKO IDRYMA EREVNON
Call Details Consolidator Grant (CoG), LS9, ERC-2018-COG
Summary It is now widely recognized that a variety of major diseases, such as Alzheimer’s disease, Huntington’s disease, systemic amyloidosis, cystic fibrosis, type 2 diabetes etc., are characterized by a common molecular origin: the misfolding of specific proteins. These disorders have been termed protein misfolding diseases (PMDs) and the vast majority of them remain incurable. Here, I propose the development of a unified approach for the discovery of potential therapeutics against PMDs. I will generate engineered bacterial cells that function as a broadly applicable discovery platform for compounds that rescue the misfolding of PMD-associated proteins (MisPs). These compounds will be selected from libraries of drug-like molecules biosynthesized in engineered bacteria using a technology that allows the facile production of billions of different test molecules. These libraries will then be screened in the same bacterial cells that produce them and the rare molecules that rescue MisP misfolding effectively will be selected using an ultrahigh-throughput genetic screen. The effect of the selected compounds on MisP folding will then be evaluated by biochemical and biophysical methods, while their ability to inhibit MisP-induced pathogenicity will be tested in appropriate mammalian cell assays and in established animal models of the associated PMD. The molecules that rescue the misfolding of the target MisPs and antagonize their associated pathogenicity both in vitro and in vivo, will become drug candidates against the corresponding diseases. This procedure will be applied for different MisPs to identify potential therapeutics for four major PMDs: Huntington’s disease, cardiotoxic light chain amyloidosis, dialysis-related amyloidosis and retinitis pigmentosa. Successful realization of ProMiDis will provide invaluable therapeutic leads against major diseases and a unified framework for anti-PMD drug discovery.
Summary
It is now widely recognized that a variety of major diseases, such as Alzheimer’s disease, Huntington’s disease, systemic amyloidosis, cystic fibrosis, type 2 diabetes etc., are characterized by a common molecular origin: the misfolding of specific proteins. These disorders have been termed protein misfolding diseases (PMDs) and the vast majority of them remain incurable. Here, I propose the development of a unified approach for the discovery of potential therapeutics against PMDs. I will generate engineered bacterial cells that function as a broadly applicable discovery platform for compounds that rescue the misfolding of PMD-associated proteins (MisPs). These compounds will be selected from libraries of drug-like molecules biosynthesized in engineered bacteria using a technology that allows the facile production of billions of different test molecules. These libraries will then be screened in the same bacterial cells that produce them and the rare molecules that rescue MisP misfolding effectively will be selected using an ultrahigh-throughput genetic screen. The effect of the selected compounds on MisP folding will then be evaluated by biochemical and biophysical methods, while their ability to inhibit MisP-induced pathogenicity will be tested in appropriate mammalian cell assays and in established animal models of the associated PMD. The molecules that rescue the misfolding of the target MisPs and antagonize their associated pathogenicity both in vitro and in vivo, will become drug candidates against the corresponding diseases. This procedure will be applied for different MisPs to identify potential therapeutics for four major PMDs: Huntington’s disease, cardiotoxic light chain amyloidosis, dialysis-related amyloidosis and retinitis pigmentosa. Successful realization of ProMiDis will provide invaluable therapeutic leads against major diseases and a unified framework for anti-PMD drug discovery.
Max ERC Funding
1 972 000 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
