Project acronym bECOMiNG
Project spontaneous Evolution and Clonal heterOgeneity in MoNoclonal Gammopathies: from mechanisms of progression to clinical management
Researcher (PI) Niccolo Bolli
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Call Details Consolidator Grant (CoG), LS7, ERC-2018-COG
Summary As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
Summary
As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
Max ERC Funding
1 998 781 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym BeyondA1
Project Set theory beyond the first uncountable cardinal
Researcher (PI) Assaf Shmuel Rinot
Host Institution (HI) BAR ILAN UNIVERSITY
Call Details Starting Grant (StG), PE1, ERC-2018-STG
Summary We propose to establish a research group that will unveil the combinatorial nature of the second uncountable cardinal. This includes its Ramsey-theoretic, order-theoretic, graph-theoretic and topological features. Among others, we will be directly addressing fundamental problems due to Erdos, Rado, Galvin, and Shelah.
While some of these problems are old and well-known, an unexpected series of breakthroughs from the last three years suggest that now is a promising point in time to carry out such a project. Indeed, through a short period, four previously unattainable problems concerning the second uncountable cardinal were successfully tackled: Aspero on a club-guessing problem of Shelah, Krueger on the club-isomorphism problem for Aronszajn trees, Neeman on the isomorphism problem for dense sets of reals, and the PI on the Souslin problem. Each of these results was obtained through the development of a completely new technical framework, and these frameworks could now pave the way for the solution of some major open questions.
A goal of the highest risk in this project is the discovery of a consistent (possibly, parameterized) forcing axiom that will (preferably, simultaneously) provide structure theorems for stationary sets, linearly ordered sets, trees, graphs, and partition relations, as well as the refutation of various forms of club-guessing principles, all at the level of the second uncountable cardinal. In comparison, at the level of the first uncountable cardinal, a forcing axiom due to Foreman, Magidor and Shelah achieves exactly that.
To approach our goals, the proposed project is divided into four core areas: Uncountable trees, Ramsey theory on ordinals, Club-guessing principles, and Forcing Axioms. There is a rich bilateral interaction between any pair of the four different cores, but the proposed division will allow an efficient allocation of manpower, and will increase the chances of parallel success.
Summary
We propose to establish a research group that will unveil the combinatorial nature of the second uncountable cardinal. This includes its Ramsey-theoretic, order-theoretic, graph-theoretic and topological features. Among others, we will be directly addressing fundamental problems due to Erdos, Rado, Galvin, and Shelah.
While some of these problems are old and well-known, an unexpected series of breakthroughs from the last three years suggest that now is a promising point in time to carry out such a project. Indeed, through a short period, four previously unattainable problems concerning the second uncountable cardinal were successfully tackled: Aspero on a club-guessing problem of Shelah, Krueger on the club-isomorphism problem for Aronszajn trees, Neeman on the isomorphism problem for dense sets of reals, and the PI on the Souslin problem. Each of these results was obtained through the development of a completely new technical framework, and these frameworks could now pave the way for the solution of some major open questions.
A goal of the highest risk in this project is the discovery of a consistent (possibly, parameterized) forcing axiom that will (preferably, simultaneously) provide structure theorems for stationary sets, linearly ordered sets, trees, graphs, and partition relations, as well as the refutation of various forms of club-guessing principles, all at the level of the second uncountable cardinal. In comparison, at the level of the first uncountable cardinal, a forcing axiom due to Foreman, Magidor and Shelah achieves exactly that.
To approach our goals, the proposed project is divided into four core areas: Uncountable trees, Ramsey theory on ordinals, Club-guessing principles, and Forcing Axioms. There is a rich bilateral interaction between any pair of the four different cores, but the proposed division will allow an efficient allocation of manpower, and will increase the chances of parallel success.
Max ERC Funding
1 362 500 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym BIT-ACT
Project Bottom-up initiatives and anti-corruption technologies: how citizens use ICTs to fight corruption
Researcher (PI) Alice Mattoni
Host Institution (HI) ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA
Call Details Starting Grant (StG), SH2, ERC-2018-STG
Summary Corruption is a global challenge that affects the lives of millions of citizens. In the past decade, Information and Communication Technologies (ICTs) have become indispensable tools in the fight to reduce corruption, especially when employed from the bottom-up by civil society organizations. While pioneering initiatives in this direction have flourished, to date we only have unsystematic and descriptive evidence regarding how they work and the associated consequences. With the objective of significantly advancing knowledge on this topic, BIT-ACT will open a new line of inquiry by investigating what I call anti-corruption technologies (ACTs) to: (1) assess how civil society organizations engage with ACTs to counter corruption, (2) appraise how ACTs enable intersections between bottom-up and top-down efforts against corruption, and (3) evaluate how ACTs blend with the transnational dimension in the struggle against corruption. Based on an interdisciplinary framework that combines corruption studies, science and technology studies and social movement studies, BIT-ACT will use the constructivist grounded theory method to analyze a combination of textual and visual data in a comparative and transnational research design including nine countries – Algeria, Bangladesh, Brazil, Estonia, India, Italy, Spain, Ukraine, Uruguay. BIT-ACT will be groundbreaking in three ways. At the theoretical level, it will expand the debate on anti-corruption providing grounded concepts and models to explain ACTs; at the empirical level, it will advance knowledge on how the usage of ACTs is changing the relationship between citizens and democratic institutions; at the methodological level, it will innovate in the use of grounded theory assessing a new standard for cross-national comparative grounded theory. Finally, BIT-ACT will produce sound and useful knowledge for the stakeholders involved in the fight against corruption worldwide by suggesting how to best employ ICTs from the bottom-up.
Summary
Corruption is a global challenge that affects the lives of millions of citizens. In the past decade, Information and Communication Technologies (ICTs) have become indispensable tools in the fight to reduce corruption, especially when employed from the bottom-up by civil society organizations. While pioneering initiatives in this direction have flourished, to date we only have unsystematic and descriptive evidence regarding how they work and the associated consequences. With the objective of significantly advancing knowledge on this topic, BIT-ACT will open a new line of inquiry by investigating what I call anti-corruption technologies (ACTs) to: (1) assess how civil society organizations engage with ACTs to counter corruption, (2) appraise how ACTs enable intersections between bottom-up and top-down efforts against corruption, and (3) evaluate how ACTs blend with the transnational dimension in the struggle against corruption. Based on an interdisciplinary framework that combines corruption studies, science and technology studies and social movement studies, BIT-ACT will use the constructivist grounded theory method to analyze a combination of textual and visual data in a comparative and transnational research design including nine countries – Algeria, Bangladesh, Brazil, Estonia, India, Italy, Spain, Ukraine, Uruguay. BIT-ACT will be groundbreaking in three ways. At the theoretical level, it will expand the debate on anti-corruption providing grounded concepts and models to explain ACTs; at the empirical level, it will advance knowledge on how the usage of ACTs is changing the relationship between citizens and democratic institutions; at the methodological level, it will innovate in the use of grounded theory assessing a new standard for cross-national comparative grounded theory. Finally, BIT-ACT will produce sound and useful knowledge for the stakeholders involved in the fight against corruption worldwide by suggesting how to best employ ICTs from the bottom-up.
Max ERC Funding
1 489 115 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym BrainCircuit-on-chip
Project Microfluidic chambers for establishing physiological and pathological human iPSC-derived neuronal circuits
Researcher (PI) Vania BROCCOLI
Host Institution (HI) OSPEDALE SAN RAFFAELE SRL
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary In vitro cultures of brain cells generate an ease and accessible ensemble of neurons In vitro cultures of brain cells generate an ease and accessible ensemble of neurons which has been invaluable for innumerable cellular and molecular studies. However, brain tissue dissociation and neuronal plating in vitro causes a complete loss of the original connections present into the brain tissue. Therefore, in vitro neuronal cultures do not allow to model specific neuronal circuits and study their specific properties. The same limitation is valid for human stem cell-derived neuronal cell cultures. In fact, several neuronal cell types can be differentiated from human iPS cells (iPSCs), but without any organization in terms of connectivity or synaptic specificity. We have established a microfluidic platform, named BrainCircuit-on-chip, which allows to growth human iPSC-derived neurons with a stereotyped organization and to establish patterned connections between different neuronal cell types. These microchips contain a central chamber where synapses between the two neuronal cell types are generated establishing the correct functional integration between the two neuronal populations. PDMS-microfluidic chambers are transparent and enables high-power and time-lapse imaging in the different neuronal compartments for sub-cellular and molecular studies. Moreover, the design of the central chamber enables to expose the synapses to chemicals or other cells types like astrocytes or microglia to study their effects on a specific class of synapses. We will produce a convenient kit with the frozen human neurons, the microfluidic chamber and a detailed protocol for generating the patterned neuronal circuits for research studies, compound testing and toxicology research.
Summary
In vitro cultures of brain cells generate an ease and accessible ensemble of neurons In vitro cultures of brain cells generate an ease and accessible ensemble of neurons which has been invaluable for innumerable cellular and molecular studies. However, brain tissue dissociation and neuronal plating in vitro causes a complete loss of the original connections present into the brain tissue. Therefore, in vitro neuronal cultures do not allow to model specific neuronal circuits and study their specific properties. The same limitation is valid for human stem cell-derived neuronal cell cultures. In fact, several neuronal cell types can be differentiated from human iPS cells (iPSCs), but without any organization in terms of connectivity or synaptic specificity. We have established a microfluidic platform, named BrainCircuit-on-chip, which allows to growth human iPSC-derived neurons with a stereotyped organization and to establish patterned connections between different neuronal cell types. These microchips contain a central chamber where synapses between the two neuronal cell types are generated establishing the correct functional integration between the two neuronal populations. PDMS-microfluidic chambers are transparent and enables high-power and time-lapse imaging in the different neuronal compartments for sub-cellular and molecular studies. Moreover, the design of the central chamber enables to expose the synapses to chemicals or other cells types like astrocytes or microglia to study their effects on a specific class of synapses. We will produce a convenient kit with the frozen human neurons, the microfluidic chamber and a detailed protocol for generating the patterned neuronal circuits for research studies, compound testing and toxicology research.
Max ERC Funding
150 000 €
Duration
Start date: 2019-08-01, End date: 2021-01-31
Project acronym BRAINMINT
Project Brains and minds in transition: The dark side of neuroplasticity during sensitive life phases
Researcher (PI) Lars T. WESTLYE
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Starting Grant (StG), SH4, ERC-2018-STG
Summary The potential and boundaries of the human mind is determined by dynamic interactions between the environment and the individual genetic architecture. However, despite several breakthroughs, the genetic revolution has not provided a coherent account of the development of the mind and its disorders, and the missing heritability is large across human traits. One explanation of this impasse is the complexity of the gene-environment interactions. Current knowledge about the determinants of a healthy mind is largely based on studies whose modus operandi is to treat the environment as a static entity, neglecting to consider the crucial fact that environmental inputs and their genetic interactions vary dramatically between life phases.
The objective of BRAINMINT is to provide this missing link by zeroing in on two major life transitions, namely adolescence and pregnancy. These phases are characterized by temporarily increased brain plasticity, offering windows for adaptation and growth, but also host the emergence of common mental disorders. I propose that a multi-level investigation with this dark side of brain plasticity as the axis mundi will add a mechanistic understanding of this link between growth and vulnerability. I will test the main hypothesis that mechanisms that boost neuroplasticity promote adaptation to a dynamic environment, but at the cost of increased risk of psychopathology if exposed to a combination of genetic and environmental triggers. To this end I will utilize cutting-edge longitudinal brain imaging, electrophysiology, rich cognitive and clinical data, immune markers, gene expression and genetics. I will leverage on massive imaging data (n>40,000) and novel tools to increase power and generalizability and improve brain- and gene-based predictions of complex traits. Aiming to help resolving one of the modern day enigmas, BRAINMINT is a pioneering and high risk/high gain effort to find mechanisms of brain plasticity that support and harm the brain.
Summary
The potential and boundaries of the human mind is determined by dynamic interactions between the environment and the individual genetic architecture. However, despite several breakthroughs, the genetic revolution has not provided a coherent account of the development of the mind and its disorders, and the missing heritability is large across human traits. One explanation of this impasse is the complexity of the gene-environment interactions. Current knowledge about the determinants of a healthy mind is largely based on studies whose modus operandi is to treat the environment as a static entity, neglecting to consider the crucial fact that environmental inputs and their genetic interactions vary dramatically between life phases.
The objective of BRAINMINT is to provide this missing link by zeroing in on two major life transitions, namely adolescence and pregnancy. These phases are characterized by temporarily increased brain plasticity, offering windows for adaptation and growth, but also host the emergence of common mental disorders. I propose that a multi-level investigation with this dark side of brain plasticity as the axis mundi will add a mechanistic understanding of this link between growth and vulnerability. I will test the main hypothesis that mechanisms that boost neuroplasticity promote adaptation to a dynamic environment, but at the cost of increased risk of psychopathology if exposed to a combination of genetic and environmental triggers. To this end I will utilize cutting-edge longitudinal brain imaging, electrophysiology, rich cognitive and clinical data, immune markers, gene expression and genetics. I will leverage on massive imaging data (n>40,000) and novel tools to increase power and generalizability and improve brain- and gene-based predictions of complex traits. Aiming to help resolving one of the modern day enigmas, BRAINMINT is a pioneering and high risk/high gain effort to find mechanisms of brain plasticity that support and harm the brain.
Max ERC Funding
1 446 113 €
Duration
Start date: 2019-08-01, End date: 2024-07-31
Project acronym BrightEyes
Project Multi-Parameter Live-Cell Observation of Biomolecular Processes with Single-Photon Detector Array
Researcher (PI) Giuseppe Vicidomini
Host Institution (HI) FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Call Details Consolidator Grant (CoG), PE7, ERC-2018-COG
Summary Fluorescence single-molecule (SM) detection techniques have the potential to provide insights into the complex functions, structures and interactions of individual, specifically labelled biomolecules. However, current SM techniques work properly only when the biomolecule is observed in controlled environments, e.g., immobilized on a glass surface. Observation of biomolecular processes in living (multi)cellular environments – which is fundamental for sound biological conclusion – always comes with a price, such as invasiveness, limitations in the accessible information and constraints in the spatial and temporal scales.
The overall objective of the BrightEyes project is to break the above limitations by creating a novel SM approach compatible with the state-of-the-art biomolecule-labelling protocols, able to track a biomolecule deep inside (multi)cellular environments – with temporal resolution in the microsecond scale, and with hundreds of micrometres tracking range – and simultaneously observe its structural changes, its nano- and micro-environments.
Specifically, by exploring a novel single-photon detectors array, the BrightEyes project will implement an optical system, able to continuously (i) track in real-time the biomolecule of interest from which to decode its dynamics and interactions; (ii) measure the nano-environment fluorescence spectroscopy properties, such as lifetime, photon-pair correlation and intensity, from which to extract the biochemical properties of the nano-environment, the structural properties of the biomolecule – via SM-FRET and anti-bunching – and the interactions of the biomolecule with other biomolecular species – via STED-FCS; (iii) visualize the sub-cellular structures within the micro-environment with sub-diffraction spatial resolution – via STED and image scanning microscopy.
This unique paradigm will enable unprecedented studies of biomolecular behaviours, interactions and self-organization at near-physiological conditions.
Summary
Fluorescence single-molecule (SM) detection techniques have the potential to provide insights into the complex functions, structures and interactions of individual, specifically labelled biomolecules. However, current SM techniques work properly only when the biomolecule is observed in controlled environments, e.g., immobilized on a glass surface. Observation of biomolecular processes in living (multi)cellular environments – which is fundamental for sound biological conclusion – always comes with a price, such as invasiveness, limitations in the accessible information and constraints in the spatial and temporal scales.
The overall objective of the BrightEyes project is to break the above limitations by creating a novel SM approach compatible with the state-of-the-art biomolecule-labelling protocols, able to track a biomolecule deep inside (multi)cellular environments – with temporal resolution in the microsecond scale, and with hundreds of micrometres tracking range – and simultaneously observe its structural changes, its nano- and micro-environments.
Specifically, by exploring a novel single-photon detectors array, the BrightEyes project will implement an optical system, able to continuously (i) track in real-time the biomolecule of interest from which to decode its dynamics and interactions; (ii) measure the nano-environment fluorescence spectroscopy properties, such as lifetime, photon-pair correlation and intensity, from which to extract the biochemical properties of the nano-environment, the structural properties of the biomolecule – via SM-FRET and anti-bunching – and the interactions of the biomolecule with other biomolecular species – via STED-FCS; (iii) visualize the sub-cellular structures within the micro-environment with sub-diffraction spatial resolution – via STED and image scanning microscopy.
This unique paradigm will enable unprecedented studies of biomolecular behaviours, interactions and self-organization at near-physiological conditions.
Max ERC Funding
1 861 250 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym BROKEX
Project Brokering China’s Extraversion: An Ethnographic Analysis of Transnational Arbitration
Researcher (PI) Heidi Østbø HAUGEN
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Starting Grant (StG), SH2, ERC-2018-STG
Summary Chinese global engagements are deepening across sectors and geographic regions. The objective of BROKEX is to fill specific gaps in knowledge about how China’s extraversion advances. The project takes an original approach by examining brokers who mediate in transnational fields. It opens the “black box” of China’s global integration by moving beyond descriptions of input and output characteristics to elucidate underlying dynamics. The objective will be achieved in two phases. First, the PI and two postdoctoral researchers will carry out ethnographic case studies in the Pearl River Delta, South China, that yield complementary information on the common challenge of brokering across geographic scales: * Connecting low-cost Chinese manufacturing with African markets; * Integrating Chinese academic research with global scientific communities; * Transnational architecture production. The diverse cases offer insights into the mechanisms of brokerage across distinctive sectors. In the second step, we build on the empirical findings and literature to develop brokerage theory. Social scientific research on brokerage commonly uses the morphology of social networks as its starting point, and focuses on how actors positioned at the intersection between groups operate. BROKEX adopts an innovative approach by examining how actors strategically seek to shape network morphologies in order to bridge gaps between groups. By directing theoretical attention towards relationship formation that precedes acts of brokerage, this line of inquiry advances understandings of how and why brokered connections emerge. Ethnographic case studies combined with critical theorization will generate new knowledge about the processes beneath the “rise of China” ─ one of the most consequential socioeconomic developments of our times.
Summary
Chinese global engagements are deepening across sectors and geographic regions. The objective of BROKEX is to fill specific gaps in knowledge about how China’s extraversion advances. The project takes an original approach by examining brokers who mediate in transnational fields. It opens the “black box” of China’s global integration by moving beyond descriptions of input and output characteristics to elucidate underlying dynamics. The objective will be achieved in two phases. First, the PI and two postdoctoral researchers will carry out ethnographic case studies in the Pearl River Delta, South China, that yield complementary information on the common challenge of brokering across geographic scales: * Connecting low-cost Chinese manufacturing with African markets; * Integrating Chinese academic research with global scientific communities; * Transnational architecture production. The diverse cases offer insights into the mechanisms of brokerage across distinctive sectors. In the second step, we build on the empirical findings and literature to develop brokerage theory. Social scientific research on brokerage commonly uses the morphology of social networks as its starting point, and focuses on how actors positioned at the intersection between groups operate. BROKEX adopts an innovative approach by examining how actors strategically seek to shape network morphologies in order to bridge gaps between groups. By directing theoretical attention towards relationship formation that precedes acts of brokerage, this line of inquiry advances understandings of how and why brokered connections emerge. Ethnographic case studies combined with critical theorization will generate new knowledge about the processes beneath the “rise of China” ─ one of the most consequential socioeconomic developments of our times.
Max ERC Funding
1 490 773 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym BRuSH
Project Oral bacteria as determinants for respiratory health
Researcher (PI) Randi BERTELSEN
Host Institution (HI) UNIVERSITETET I BERGEN
Call Details Starting Grant (StG), LS7, ERC-2018-STG
Summary The oral cavity is the gateway to the lower respiratory tract, and oral bacteria are likely to play a role in lung health. This may be the case for pathogens as well as commensal bacteria and the balance between species. The oral bacterial community of patients with periodontitis is dominated by gram-negative bacteria and a higher lipopolysaccharide (LPS) activity than in healthy microbiota. Furthermore, bacteria with especially potent pro-inflammatory LPS have been shown to be more common in the lungs of asthmatic than in healthy individuals. The working hypothesis of BRuSH is that microbiome communities dominated by LPS-producing bacteria which induce a particularly strong pro-inflammatory immune response in the host, will have a negative effect on respiratory health. I will test this hypothesis in two longitudinally designed population-based lung health studies. I aim to identify whether specific bacterial composition and types of LPS producing bacteria in oral and dust samples predict lung function and respiratory health over time; and if the different types of LPS-producing bacteria affect LPS in saliva saliva and dust. BRuSH will apply functional genome annotation that can assign biological significance to raw bacterial DNA sequences. With this bioinformatics tool I will cluster microbiome data into various LPS-producers: bacteria with LPS with strong inflammatory effects and others with weak- or antagonistic effects. The epidemiological studies will be supported by mice-models of asthma and cell assays of human bronchial epithelial cells, by exposing mice and bronchial cells to chemically synthesized Lipid A (the component that drive the LPS-induced immune responses) of various potency. The goal of BRuSH is to prove a causal relationship between oral microbiome and lung health, and gain knowledge that will enable us to make oral health a feasible target for intervention programs aimed at optimizing lung health and preventing respiratory disease.
Summary
The oral cavity is the gateway to the lower respiratory tract, and oral bacteria are likely to play a role in lung health. This may be the case for pathogens as well as commensal bacteria and the balance between species. The oral bacterial community of patients with periodontitis is dominated by gram-negative bacteria and a higher lipopolysaccharide (LPS) activity than in healthy microbiota. Furthermore, bacteria with especially potent pro-inflammatory LPS have been shown to be more common in the lungs of asthmatic than in healthy individuals. The working hypothesis of BRuSH is that microbiome communities dominated by LPS-producing bacteria which induce a particularly strong pro-inflammatory immune response in the host, will have a negative effect on respiratory health. I will test this hypothesis in two longitudinally designed population-based lung health studies. I aim to identify whether specific bacterial composition and types of LPS producing bacteria in oral and dust samples predict lung function and respiratory health over time; and if the different types of LPS-producing bacteria affect LPS in saliva saliva and dust. BRuSH will apply functional genome annotation that can assign biological significance to raw bacterial DNA sequences. With this bioinformatics tool I will cluster microbiome data into various LPS-producers: bacteria with LPS with strong inflammatory effects and others with weak- or antagonistic effects. The epidemiological studies will be supported by mice-models of asthma and cell assays of human bronchial epithelial cells, by exposing mice and bronchial cells to chemically synthesized Lipid A (the component that drive the LPS-induced immune responses) of various potency. The goal of BRuSH is to prove a causal relationship between oral microbiome and lung health, and gain knowledge that will enable us to make oral health a feasible target for intervention programs aimed at optimizing lung health and preventing respiratory disease.
Max ERC Funding
1 499 938 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym CALENDARS
Project Co-production of seasonal representations for adaptive institutions
Researcher (PI) Scott Ronald BREMER
Host Institution (HI) UNIVERSITETET I BERGEN
Call Details Starting Grant (StG), SH2, ERC-2018-STG
Summary Climate change may be undermining the stock of seasonal representations that society draws on to understand and live according to the weather. The CALENDARS project studies how modern society represents seasons, and how these representations shape institutions and help people live with seasonal change. The project opens an important emerging field in climate adaptation research by examining the representations of ‘normal’ seasons underlying key institutions, assesses their quality for successful adaptation to rapid climate change, and analyses facilitators and barriers to adopting representations more flexibly to new climates. It contributes a novel perspective on how to transform our institutions – from schools to farmer cooperatives – from the foundational culture and representations up, to better fit the changing seasonal cycles we are experiencing.
CALENDARS empirically explores the relationship between different institutions’ ideas of seasons and their successful adaptation through an in-depth comparative study of a set of institutions in two local communities, in Norway and New Zealand. It is steered by an overall objective to: ‘Advance knowledge and understanding of how seasonal representations shape and are shaped by institutions, and critically appraise the quality of these representations for contributing to successful adaptation to seasonal change’.
Conceptually, CALENDARS looks at representations as continuously ‘co-produced’ at the boundary of nature and society, and society and institutions. It tests a novel reconceptualisation of co-production as a prism; with each of the project’s three phases looking at the complex processes by which representations emerge through different ‘lenses’ of co-production. Methodologically, the project tests the feasibility of a novel basket of bespoke methods spanning narrative interviews, calendar boundary objects and collaborative sustainability science.
Summary
Climate change may be undermining the stock of seasonal representations that society draws on to understand and live according to the weather. The CALENDARS project studies how modern society represents seasons, and how these representations shape institutions and help people live with seasonal change. The project opens an important emerging field in climate adaptation research by examining the representations of ‘normal’ seasons underlying key institutions, assesses their quality for successful adaptation to rapid climate change, and analyses facilitators and barriers to adopting representations more flexibly to new climates. It contributes a novel perspective on how to transform our institutions – from schools to farmer cooperatives – from the foundational culture and representations up, to better fit the changing seasonal cycles we are experiencing.
CALENDARS empirically explores the relationship between different institutions’ ideas of seasons and their successful adaptation through an in-depth comparative study of a set of institutions in two local communities, in Norway and New Zealand. It is steered by an overall objective to: ‘Advance knowledge and understanding of how seasonal representations shape and are shaped by institutions, and critically appraise the quality of these representations for contributing to successful adaptation to seasonal change’.
Conceptually, CALENDARS looks at representations as continuously ‘co-produced’ at the boundary of nature and society, and society and institutions. It tests a novel reconceptualisation of co-production as a prism; with each of the project’s three phases looking at the complex processes by which representations emerge through different ‘lenses’ of co-production. Methodologically, the project tests the feasibility of a novel basket of bespoke methods spanning narrative interviews, calendar boundary objects and collaborative sustainability science.
Max ERC Funding
1 489 426 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym CHIPTRANSFORM
Project On-chip optical communication with transformation optics
Researcher (PI) Ulf LEONHARDT
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary Transformation optics grew out of ideas for invisibility cloaking and exploits connections between electromagnetism in media and in geometries. This Proof of Concept project uses transformation optics for improving on-chip optical communication in silicon photonics. The goal is reaching a performance that matches industry standards such that the idea becomes sufficiently convincing to be commercialized.
Summary
Transformation optics grew out of ideas for invisibility cloaking and exploits connections between electromagnetism in media and in geometries. This Proof of Concept project uses transformation optics for improving on-chip optical communication in silicon photonics. The goal is reaching a performance that matches industry standards such that the idea becomes sufficiently convincing to be commercialized.
Max ERC Funding
150 000 €
Duration
Start date: 2018-06-01, End date: 2019-11-30
