Project acronym 2DNanoSpec
Project Nanoscale Vibrational Spectroscopy of Sensitive 2D Molecular Materials
Researcher (PI) Renato ZENOBI
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE4, ERC-2016-ADG
Summary I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Summary
I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Max ERC Funding
2 311 696 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym 3D_Tryps
Project The role of three-dimensional genome architecture in antigenic variation
Researcher (PI) Tim Nicolai SIEGEL
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism.
The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression.
I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen.
The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.
Summary
Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism.
The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression.
I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen.
The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.
Max ERC Funding
1 498 175 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym AAA
Project Adaptive Actin Architectures
Researcher (PI) Laurent Blanchoin
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), LS3, ERC-2016-ADG
Summary Although we have extensive knowledge of many important processes in cell biology, including information on many of the molecules involved and the physical interactions among them, we still do not understand most of the dynamical features that are the essence of living systems. This is particularly true for the actin cytoskeleton, a major component of the internal architecture of eukaryotic cells. In living cells, actin networks constantly assemble and disassemble filaments while maintaining an apparent stable structure, suggesting a perfect balance between the two processes. Such behaviors are called “dynamic steady states”. They confer upon actin networks a high degree of plasticity allowing them to adapt in response to external changes and enable cells to adjust to their environments. Despite their fundamental importance in the regulation of cell physiology, the basic mechanisms that control the coordinated dynamics of co-existing actin networks are poorly understood. In the AAA project, first, we will characterize the parameters that allow the coupling among co-existing actin networks at steady state. In vitro reconstituted systems will be used to control the actin nucleation patterns, the closed volume of the reaction chamber and the physical interaction of the networks. We hope to unravel the mechanism allowing the global coherence of a dynamic actin cytoskeleton. Second, we will use our unique capacity to perform dynamic micropatterning, to add or remove actin nucleation sites in real time, in order to investigate the ability of dynamic networks to adapt to changes and the role of coupled network dynamics in this emergent property. In this part, in vitro experiments will be complemented by the analysis of actin network remodeling in living cells. In the end, our project will provide a comprehensive understanding of how the adaptive response of the cytoskeleton derives from the complex interplay between its biochemical, structural and mechanical properties.
Summary
Although we have extensive knowledge of many important processes in cell biology, including information on many of the molecules involved and the physical interactions among them, we still do not understand most of the dynamical features that are the essence of living systems. This is particularly true for the actin cytoskeleton, a major component of the internal architecture of eukaryotic cells. In living cells, actin networks constantly assemble and disassemble filaments while maintaining an apparent stable structure, suggesting a perfect balance between the two processes. Such behaviors are called “dynamic steady states”. They confer upon actin networks a high degree of plasticity allowing them to adapt in response to external changes and enable cells to adjust to their environments. Despite their fundamental importance in the regulation of cell physiology, the basic mechanisms that control the coordinated dynamics of co-existing actin networks are poorly understood. In the AAA project, first, we will characterize the parameters that allow the coupling among co-existing actin networks at steady state. In vitro reconstituted systems will be used to control the actin nucleation patterns, the closed volume of the reaction chamber and the physical interaction of the networks. We hope to unravel the mechanism allowing the global coherence of a dynamic actin cytoskeleton. Second, we will use our unique capacity to perform dynamic micropatterning, to add or remove actin nucleation sites in real time, in order to investigate the ability of dynamic networks to adapt to changes and the role of coupled network dynamics in this emergent property. In this part, in vitro experiments will be complemented by the analysis of actin network remodeling in living cells. In the end, our project will provide a comprehensive understanding of how the adaptive response of the cytoskeleton derives from the complex interplay between its biochemical, structural and mechanical properties.
Max ERC Funding
2 349 898 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym ADORA
Project Asymptotic approach to spatial and dynamical organizations
Researcher (PI) Benoit PERTHAME
Host Institution (HI) SORBONNE UNIVERSITE
Call Details Advanced Grant (AdG), PE1, ERC-2016-ADG
Summary The understanding of spatial, social and dynamical organization of large numbers of agents is presently a fundamental issue in modern science. ADORA focuses on problems motivated by biology because, more than anywhere else, access to precise and many data has opened the route to novel and complex biomathematical models. The problems we address are written in terms of nonlinear partial differential equations. The flux-limited Keller-Segel system, the integrate-and-fire Fokker-Planck equation, kinetic equations with internal state, nonlocal parabolic equations and constrained Hamilton-Jacobi equations are among examples of the equations under investigation.
The role of mathematics is not only to understand the analytical structure of these new problems, but it is also to explain the qualitative behavior of solutions and to quantify their properties. The challenge arises here because these goals should be achieved through a hierarchy of scales. Indeed, the problems under consideration share the common feature that the large scale behavior cannot be understood precisely without access to a hierarchy of finer scales, down to the individual behavior and sometimes its molecular determinants.
Major difficulties arise because the numerous scales present in these equations have to be discovered and singularities appear in the asymptotic process which yields deep compactness obstructions. Our vision is that the complexity inherent to models of biology can be enlightened by mathematical analysis and a classification of the possible asymptotic regimes.
However an enormous effort is needed to uncover the equations intimate mathematical structures, and bring them at the level of conceptual understanding they deserve being given the applications motivating these questions which range from medical science or neuroscience to cell biology.
Summary
The understanding of spatial, social and dynamical organization of large numbers of agents is presently a fundamental issue in modern science. ADORA focuses on problems motivated by biology because, more than anywhere else, access to precise and many data has opened the route to novel and complex biomathematical models. The problems we address are written in terms of nonlinear partial differential equations. The flux-limited Keller-Segel system, the integrate-and-fire Fokker-Planck equation, kinetic equations with internal state, nonlocal parabolic equations and constrained Hamilton-Jacobi equations are among examples of the equations under investigation.
The role of mathematics is not only to understand the analytical structure of these new problems, but it is also to explain the qualitative behavior of solutions and to quantify their properties. The challenge arises here because these goals should be achieved through a hierarchy of scales. Indeed, the problems under consideration share the common feature that the large scale behavior cannot be understood precisely without access to a hierarchy of finer scales, down to the individual behavior and sometimes its molecular determinants.
Major difficulties arise because the numerous scales present in these equations have to be discovered and singularities appear in the asymptotic process which yields deep compactness obstructions. Our vision is that the complexity inherent to models of biology can be enlightened by mathematical analysis and a classification of the possible asymptotic regimes.
However an enormous effort is needed to uncover the equations intimate mathematical structures, and bring them at the level of conceptual understanding they deserve being given the applications motivating these questions which range from medical science or neuroscience to cell biology.
Max ERC Funding
2 192 500 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym AlgTateGro
Project Constructing line bundles on algebraic varieties --around conjectures of Tate and Grothendieck
Researcher (PI) François CHARLES
Host Institution (HI) UNIVERSITE PARIS-SUD
Call Details Starting Grant (StG), PE1, ERC-2016-STG
Summary The goal of this project is to investigate two conjectures in arithmetic geometry pertaining to the geometry of projective varieties over finite and number fields. These two conjectures, formulated by Tate and Grothendieck in the 1960s, predict which cohomology classes are chern classes of line bundles. They both form an arithmetic counterpart of a theorem of Lefschetz, proved in the 1940s, which itself is the only known case of the Hodge conjecture. These two long-standing conjectures are one of the aspects of a more general web of questions regarding the topology of algebraic varieties which have been emphasized by Grothendieck and have since had a central role in modern arithmetic geometry. Special cases of these conjectures, appearing for instance in the work of Tate, Deligne, Faltings, Schneider-Lang, Masser-Wüstholz, have all had important consequences.
My goal is to investigate different lines of attack towards these conjectures, building on recent work on myself and Jean-Benoît Bost on related problems. The two main directions of the proposal are as follows. Over finite fields, the Tate conjecture is related to finiteness results for certain cohomological objects. I want to understand how to relate these to hidden boundedness properties of algebraic varieties that have appeared in my recent geometric proof of the Tate conjecture for K3 surfaces. The existence and relevance of a theory of Donaldson invariants for moduli spaces of twisted sheaves over finite fields seems to be a promising and novel direction. Over number fields, I want to combine the geometric insight above with algebraization techniques developed by Bost. In a joint project, we want to investigate how these can be used to first understand geometrically major results in transcendence theory and then attack the Grothendieck period conjecture for divisors via a number-theoretic and complex-analytic understanding of universal vector extensions of abelian schemes over curves.
Summary
The goal of this project is to investigate two conjectures in arithmetic geometry pertaining to the geometry of projective varieties over finite and number fields. These two conjectures, formulated by Tate and Grothendieck in the 1960s, predict which cohomology classes are chern classes of line bundles. They both form an arithmetic counterpart of a theorem of Lefschetz, proved in the 1940s, which itself is the only known case of the Hodge conjecture. These two long-standing conjectures are one of the aspects of a more general web of questions regarding the topology of algebraic varieties which have been emphasized by Grothendieck and have since had a central role in modern arithmetic geometry. Special cases of these conjectures, appearing for instance in the work of Tate, Deligne, Faltings, Schneider-Lang, Masser-Wüstholz, have all had important consequences.
My goal is to investigate different lines of attack towards these conjectures, building on recent work on myself and Jean-Benoît Bost on related problems. The two main directions of the proposal are as follows. Over finite fields, the Tate conjecture is related to finiteness results for certain cohomological objects. I want to understand how to relate these to hidden boundedness properties of algebraic varieties that have appeared in my recent geometric proof of the Tate conjecture for K3 surfaces. The existence and relevance of a theory of Donaldson invariants for moduli spaces of twisted sheaves over finite fields seems to be a promising and novel direction. Over number fields, I want to combine the geometric insight above with algebraization techniques developed by Bost. In a joint project, we want to investigate how these can be used to first understand geometrically major results in transcendence theory and then attack the Grothendieck period conjecture for divisors via a number-theoretic and complex-analytic understanding of universal vector extensions of abelian schemes over curves.
Max ERC Funding
1 222 329 €
Duration
Start date: 2016-12-01, End date: 2021-11-30
Project acronym ALLERGUT
Project Mucosal Tolerance and Allergic Predisposition: Does it all start in the gut?
Researcher (PI) Caspar OHNMACHT
Host Institution (HI) HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Currently, more than 30% of all Europeans suffer from one or more allergic disorder but treatment is still mostly symptomatic due to a lack of understanding the underlying causality. Allergies are caused by type 2 immune responses triggered by recognition of harmless antigens. Both genetic and environmental factors have been proposed to favour allergic predisposition and both factors have a huge impact on the symbiotic microbiota and the intestinal immune system. Recently we and others showed that the transcription factor ROR(γt) seems to play a key role in mucosal tolerance in the gut and also regulates intestinal type 2 immune responses.
Based on these results I postulate two major events in the gut for the development of an allergy in the lifetime of an individual: First, a failure to establish mucosal tolerance or anergy constitutes a necessity for the outbreak of allergic symptoms and allergic disease. Second, a certain ‘core’ microbiome or pathway of the intestinal microbiota predispose certain individuals for the later development of allergic disorders. Therefore, I will address the following aims:
1) Influence of ROR(γt) on mucosal tolerance induction and allergic disorders
2) Elucidate the T cell receptor repertoire of intestinal Th2 and ROR(γt)+ Tregs and assess the role of alternative NFκB pathway for induction of mucosal tolerance
3) Identification of ‘core’ microbiome signatures or metabolic pathways that favour allergic predisposition
ALLERGUT will provide ground-breaking knowledge on molecular mechanisms of the failure of mucosal tolerance in the gut and will prove if the resident ROR(γt)+ T(reg) cells can function as a mechanistic starting point for molecular intervention strategies on the background of the hygiene hypothesis. The vision of ALLERGUT is to diagnose mucosal disbalance, prevent and treat allergic disorders even before outbreak and thereby promote Public Health initiative for better living.
Summary
Currently, more than 30% of all Europeans suffer from one or more allergic disorder but treatment is still mostly symptomatic due to a lack of understanding the underlying causality. Allergies are caused by type 2 immune responses triggered by recognition of harmless antigens. Both genetic and environmental factors have been proposed to favour allergic predisposition and both factors have a huge impact on the symbiotic microbiota and the intestinal immune system. Recently we and others showed that the transcription factor ROR(γt) seems to play a key role in mucosal tolerance in the gut and also regulates intestinal type 2 immune responses.
Based on these results I postulate two major events in the gut for the development of an allergy in the lifetime of an individual: First, a failure to establish mucosal tolerance or anergy constitutes a necessity for the outbreak of allergic symptoms and allergic disease. Second, a certain ‘core’ microbiome or pathway of the intestinal microbiota predispose certain individuals for the later development of allergic disorders. Therefore, I will address the following aims:
1) Influence of ROR(γt) on mucosal tolerance induction and allergic disorders
2) Elucidate the T cell receptor repertoire of intestinal Th2 and ROR(γt)+ Tregs and assess the role of alternative NFκB pathway for induction of mucosal tolerance
3) Identification of ‘core’ microbiome signatures or metabolic pathways that favour allergic predisposition
ALLERGUT will provide ground-breaking knowledge on molecular mechanisms of the failure of mucosal tolerance in the gut and will prove if the resident ROR(γt)+ T(reg) cells can function as a mechanistic starting point for molecular intervention strategies on the background of the hygiene hypothesis. The vision of ALLERGUT is to diagnose mucosal disbalance, prevent and treat allergic disorders even before outbreak and thereby promote Public Health initiative for better living.
Max ERC Funding
1 498 175 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym AQUARAMAN
Project Pipet Based Scanning Probe Microscopy Tip-Enhanced Raman Spectroscopy: A Novel Approach for TERS in Liquids
Researcher (PI) Aleix Garcia Guell
Host Institution (HI) ECOLE POLYTECHNIQUE
Call Details Starting Grant (StG), PE4, ERC-2016-STG
Summary Tip-enhanced Raman spectroscopy (TERS) is often described as the most powerful tool for optical characterization of surfaces and their proximities. It combines the intrinsic spatial resolution of scanning probe techniques (AFM or STM) with the chemical information content of vibrational Raman spectroscopy. Capable to reveal surface heterogeneity at the nanoscale, TERS is currently playing a fundamental role in the understanding of interfacial physicochemical processes in key areas of science and technology such as chemistry, biology and material science.
Unfortunately, the undeniable potential of TERS as a label-free tool for nanoscale chemical and structural characterization is, nowadays, limited to air and vacuum environments, with it failing to operate in a reliable and systematic manner in liquid. The reasons are more technical than fundamental, as what is hindering the application of TERS in water is, among other issues, the low stability of the probes and their consistency. Fields of science and technology where the presence of water/electrolyte is unavoidable, such as biology and electrochemistry, remain unexplored with this powerful technique.
We propose a revolutionary approach for TERS in liquids founded on the employment of pipet-based scanning probe microscopy techniques (pb-SPM) as an alternative to AFM and STM. The use of recent but well established pb-SPM brings the opportunity to develop unprecedented pipet-based TERS probes (beyond the classic and limited metallized solid probes from AFM and STM), together with the implementation of ingenious and innovative measures to enhance tip stability, sensitivity and reliability, unattainable with the current techniques.
We will be in possession of a unique nano-spectroscopy platform capable of experiments in liquids, to follow dynamic processes in-situ, addressing fundamental questions and bringing insight into interfacial phenomena spanning from materials science, physics, chemistry and biology.
Summary
Tip-enhanced Raman spectroscopy (TERS) is often described as the most powerful tool for optical characterization of surfaces and their proximities. It combines the intrinsic spatial resolution of scanning probe techniques (AFM or STM) with the chemical information content of vibrational Raman spectroscopy. Capable to reveal surface heterogeneity at the nanoscale, TERS is currently playing a fundamental role in the understanding of interfacial physicochemical processes in key areas of science and technology such as chemistry, biology and material science.
Unfortunately, the undeniable potential of TERS as a label-free tool for nanoscale chemical and structural characterization is, nowadays, limited to air and vacuum environments, with it failing to operate in a reliable and systematic manner in liquid. The reasons are more technical than fundamental, as what is hindering the application of TERS in water is, among other issues, the low stability of the probes and their consistency. Fields of science and technology where the presence of water/electrolyte is unavoidable, such as biology and electrochemistry, remain unexplored with this powerful technique.
We propose a revolutionary approach for TERS in liquids founded on the employment of pipet-based scanning probe microscopy techniques (pb-SPM) as an alternative to AFM and STM. The use of recent but well established pb-SPM brings the opportunity to develop unprecedented pipet-based TERS probes (beyond the classic and limited metallized solid probes from AFM and STM), together with the implementation of ingenious and innovative measures to enhance tip stability, sensitivity and reliability, unattainable with the current techniques.
We will be in possession of a unique nano-spectroscopy platform capable of experiments in liquids, to follow dynamic processes in-situ, addressing fundamental questions and bringing insight into interfacial phenomena spanning from materials science, physics, chemistry and biology.
Max ERC Funding
1 528 442 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym ARTEFACT
Project The Global as Artefact: Understanding the Patterns of Global Political History Through an Anthropology of Knowledge -- The Case of Agriculture in Four Global Systems from the Neolithic to the Present
Researcher (PI) INANNA HAMATI-ATAYA
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), SH2, ERC-2016-COG
Summary Knowledge is an anthropological constant that is indissociable from the birth and interactions of human societies, but is at best a secondary concern for scholars of international relations and globalization. Contemporary global studies are thus unable to account for the co-constitution of knowledge and politics at a macro-scale, and remain especially blind to the historical patterns of epistemic development that operate at the level of the species as a whole and have shaped its global political history in specific, path-dependent ways up to now.
ARTEFACT is the first project to pursue a knowledge-centered investigation of global politics. It is uniquely grounded in an anthropological approach that treats globalization and human knowledges beyond their modern manifestations, from the longue-durée perspective of our species’ social history. 'The global as artefact' is more than a metaphor. It reflects the premise that human collectives 'make' the political world not merely through ideas, language, or norms, but primordially through the material infrastructures, solutions, objects, practices, and skills they develop in response to evolving structural challenges.
ARTEFACT takes agriculture as an exemplary and especially timely case-study to illuminate the entangled global histories of knowledge and politics, analyzing and comparing four increasingly inclusive 'global political systems' of the Ancient, Medieval, Modern, and Contemporary eras and their associated agrarian socio-epistemic revolutions.
ARTEFACT ultimately aims to 1) develop an original theory of the global, 2) launch Global Knowledge Studies as a new cross-disciplinary domain of systematic empirical and theoretical study, and 3) push the respective boundaries of the anthropology of knowledge, global history, and international theory beyond the state-of-the-art and toward a holistic understanding that can illuminate how past trends of socio-epistemic evolution might shape future paths of global life.
Summary
Knowledge is an anthropological constant that is indissociable from the birth and interactions of human societies, but is at best a secondary concern for scholars of international relations and globalization. Contemporary global studies are thus unable to account for the co-constitution of knowledge and politics at a macro-scale, and remain especially blind to the historical patterns of epistemic development that operate at the level of the species as a whole and have shaped its global political history in specific, path-dependent ways up to now.
ARTEFACT is the first project to pursue a knowledge-centered investigation of global politics. It is uniquely grounded in an anthropological approach that treats globalization and human knowledges beyond their modern manifestations, from the longue-durée perspective of our species’ social history. 'The global as artefact' is more than a metaphor. It reflects the premise that human collectives 'make' the political world not merely through ideas, language, or norms, but primordially through the material infrastructures, solutions, objects, practices, and skills they develop in response to evolving structural challenges.
ARTEFACT takes agriculture as an exemplary and especially timely case-study to illuminate the entangled global histories of knowledge and politics, analyzing and comparing four increasingly inclusive 'global political systems' of the Ancient, Medieval, Modern, and Contemporary eras and their associated agrarian socio-epistemic revolutions.
ARTEFACT ultimately aims to 1) develop an original theory of the global, 2) launch Global Knowledge Studies as a new cross-disciplinary domain of systematic empirical and theoretical study, and 3) push the respective boundaries of the anthropology of knowledge, global history, and international theory beyond the state-of-the-art and toward a holistic understanding that can illuminate how past trends of socio-epistemic evolution might shape future paths of global life.
Max ERC Funding
1 428 165 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym Baby DCs
Project Age-dependent Regulation of Dendritic Cell Development and Function
Researcher (PI) Barbara Ursula SCHRAML
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Early life immune balance is essential for survival and establishment of healthy immunity in later life. We aim to define how age-dependent regulation of dendritic cell (DC) development contributes to this crucial immune balance. DCs are versatile controllers of immunity that in neonates are qualitatively distinct from adults. Why such age-dependent differences exist is unclear but newborn DCs are considered underdeveloped and functionally immature.
Using ontogenetic tracing of conventional DC precursors, I have found a previously unappreciated developmental heterogeneity of DCs that is particularly prominent in young mice. Preliminary data indicate that distinct waves of DC poiesis contribute to the functional differences between neonatal and adult DCs. I hypothesize that the neonatal DC compartment is not immature but rather that DC poiesis is developmentally regulated to create essential age-dependent immune balance. Further, I have identified a unique situation in early life to address a fundamental biological question, namely to what extent cellular function is pre-programmed by developmental origin (nature) versus environmental factors (nurture).
In this proposal, we will first use novel models to fate map the origin of the DC compartment with age. We will then define to what extent cellular origin determines age-dependent functions of DCs in immunity. Using innovative comparative gene expression profiling and integrative epigenomic analysis the cell intrinsic mechanisms regulating the age-dependent functions of DCs will be characterized. Because environmental factors in utero and after birth critically influence immune balance, we will finally define the impact of maternal infection and metabolic disease, as well as early microbial encounter on DC poiesis. Characterizing how developmentally regulated DC poiesis shapes the unique features of early life immunity will provide novel insights into immune development that are vital to advance vaccine strategies.
Summary
Early life immune balance is essential for survival and establishment of healthy immunity in later life. We aim to define how age-dependent regulation of dendritic cell (DC) development contributes to this crucial immune balance. DCs are versatile controllers of immunity that in neonates are qualitatively distinct from adults. Why such age-dependent differences exist is unclear but newborn DCs are considered underdeveloped and functionally immature.
Using ontogenetic tracing of conventional DC precursors, I have found a previously unappreciated developmental heterogeneity of DCs that is particularly prominent in young mice. Preliminary data indicate that distinct waves of DC poiesis contribute to the functional differences between neonatal and adult DCs. I hypothesize that the neonatal DC compartment is not immature but rather that DC poiesis is developmentally regulated to create essential age-dependent immune balance. Further, I have identified a unique situation in early life to address a fundamental biological question, namely to what extent cellular function is pre-programmed by developmental origin (nature) versus environmental factors (nurture).
In this proposal, we will first use novel models to fate map the origin of the DC compartment with age. We will then define to what extent cellular origin determines age-dependent functions of DCs in immunity. Using innovative comparative gene expression profiling and integrative epigenomic analysis the cell intrinsic mechanisms regulating the age-dependent functions of DCs will be characterized. Because environmental factors in utero and after birth critically influence immune balance, we will finally define the impact of maternal infection and metabolic disease, as well as early microbial encounter on DC poiesis. Characterizing how developmentally regulated DC poiesis shapes the unique features of early life immunity will provide novel insights into immune development that are vital to advance vaccine strategies.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym BabyVir
Project The role of the virome in shaping the gut ecosystem during the first year of life
Researcher (PI) Alexandra Petrovna ZHERNAKOVA
Host Institution (HI) ACADEMISCH ZIEKENHUIS GRONINGEN
Call Details Starting Grant (StG), LS8, ERC-2016-STG
Summary The role of intestinal bacteria in human health and disease has been intensively studied; however the viral composition of the microbiome, the virome, remains largely unknown. As many of the viruses are bacteriophages, they are expected to be a major factor shaping the human microbiome. The dynamics of the virome during early life, its interaction with host and environmental factors, is likely to have profound effects on human physiology. Therefore it is extremely timely to study the virome in depth and on a wide scale.
This ERC project aims at understanding how the gut virome develops during the first year of life and how that relates to the composition of the bacterial microbiome. In particular, we will determine which intrinsic and environmental factors, including genetics and the mother’s microbiome and diet, interact with the virome in shaping the early gut microbiome ecosystem. In a longitudinal study of 1,000 newborns followed at 7 time points from birth till age 12 months, I will investigate: (1) the composition and evolution of the virome and bacterial microbiome in the first year of life; (2) the role of factors coming from the mother and from the host genome on virome and bacterial microbiome development and their co-evolution; and (3) the role of environmental factors, like infectious diseases, vaccinations and diet habits, on establishing the virome and overall microbiome composition during the first year of life.
This project will provide crucial knowledge about composition and maturation of the virome during the first year of life, and its symbiotic relation with the bacterial microbiome. This longitudinal dataset will be instrumental for identification of microbiome markers of diseases and for the follow up analysis of the long-term effect of microbiota maturation later in life. Knowledge of the role of viruses in shaping the microbiota may promote future directions for manipulating the human gut microbiota in health and disease.
Summary
The role of intestinal bacteria in human health and disease has been intensively studied; however the viral composition of the microbiome, the virome, remains largely unknown. As many of the viruses are bacteriophages, they are expected to be a major factor shaping the human microbiome. The dynamics of the virome during early life, its interaction with host and environmental factors, is likely to have profound effects on human physiology. Therefore it is extremely timely to study the virome in depth and on a wide scale.
This ERC project aims at understanding how the gut virome develops during the first year of life and how that relates to the composition of the bacterial microbiome. In particular, we will determine which intrinsic and environmental factors, including genetics and the mother’s microbiome and diet, interact with the virome in shaping the early gut microbiome ecosystem. In a longitudinal study of 1,000 newborns followed at 7 time points from birth till age 12 months, I will investigate: (1) the composition and evolution of the virome and bacterial microbiome in the first year of life; (2) the role of factors coming from the mother and from the host genome on virome and bacterial microbiome development and their co-evolution; and (3) the role of environmental factors, like infectious diseases, vaccinations and diet habits, on establishing the virome and overall microbiome composition during the first year of life.
This project will provide crucial knowledge about composition and maturation of the virome during the first year of life, and its symbiotic relation with the bacterial microbiome. This longitudinal dataset will be instrumental for identification of microbiome markers of diseases and for the follow up analysis of the long-term effect of microbiota maturation later in life. Knowledge of the role of viruses in shaping the microbiota may promote future directions for manipulating the human gut microbiota in health and disease.
Max ERC Funding
1 499 881 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
