Project acronym ArtHistCEE
Project Art Historiographies in Central and Eastern EuropeAn Inquiry from the Perspective of Entangled Histories
Researcher (PI) Ada HAJDU
Host Institution (HI) FUNDATIA NOUA EUROPA
Call Details Starting Grant (StG), SH5, ERC-2018-STG
Summary Our project proposes a fragmentary account of the art histories produced in present-day Poland, Hungary, Slovakia, Romania, Bulgaria and Serbia between 1850 and 1950, from an entangled histories perspective. We will look at the relationships between the art histories produced in these countries and the art histories produced in Western Europe. But, more importantly, we will investigate how the art histories written in the countries mentioned above resonate with each other, either proposing conflicting interpretations of the past, or ignoring uncomfortable competing discourses. We will investigate the art histories written between 1850 and 1950 because we are interested in how art history contributed to nation building discourses. Therefore, we will focus on those art histories that concur to nationalising the past. Our project is articulated around three crucial concepts – periodisation, style and influence – set in the context of relevant contemporary historiographies produced in Western Europe, and analysing the entanglements with competing historiographies in each of the countries considered. We will focus on two main issues: 1. How did Central and Eastern European art historians adopt, adapt and respond to theoretical and methodological issues developed elsewhere, and 2. What are the periodisations of art produced on the territory of Central and Eastern European countries; what are the theoretical and methodological strategies for conceptualising local styles; and how was the concept of influence used in establishing hierarchical relationships. Researching the conceptualisation of a theoretical framework that would accommodate the artistic production of the past will show the difficulties in dealing with a complex reality without simplifying and essentializing it along ideological lines. The research will also show that the three concepts that we focus on are not neutral or strictly descriptive, and that their use in art history needs to be reconsidered.
Summary
Our project proposes a fragmentary account of the art histories produced in present-day Poland, Hungary, Slovakia, Romania, Bulgaria and Serbia between 1850 and 1950, from an entangled histories perspective. We will look at the relationships between the art histories produced in these countries and the art histories produced in Western Europe. But, more importantly, we will investigate how the art histories written in the countries mentioned above resonate with each other, either proposing conflicting interpretations of the past, or ignoring uncomfortable competing discourses. We will investigate the art histories written between 1850 and 1950 because we are interested in how art history contributed to nation building discourses. Therefore, we will focus on those art histories that concur to nationalising the past. Our project is articulated around three crucial concepts – periodisation, style and influence – set in the context of relevant contemporary historiographies produced in Western Europe, and analysing the entanglements with competing historiographies in each of the countries considered. We will focus on two main issues: 1. How did Central and Eastern European art historians adopt, adapt and respond to theoretical and methodological issues developed elsewhere, and 2. What are the periodisations of art produced on the territory of Central and Eastern European countries; what are the theoretical and methodological strategies for conceptualising local styles; and how was the concept of influence used in establishing hierarchical relationships. Researching the conceptualisation of a theoretical framework that would accommodate the artistic production of the past will show the difficulties in dealing with a complex reality without simplifying and essentializing it along ideological lines. The research will also show that the three concepts that we focus on are not neutral or strictly descriptive, and that their use in art history needs to be reconsidered.
Max ERC Funding
1 192 250 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym BIOUNCERTAINTY
Project Deep uncertainties in bioethics: genetic research, preventive medicine, reproductive decisions
Researcher (PI) Tomasz ZURADZKI
Host Institution (HI) UNIWERSYTET JAGIELLONSKI
Call Details Starting Grant (StG), SH5, ERC-2018-STG
Summary Uncertainty is everywhere, as the saying goes, but rarely considered in ethical reflections. This project aims to reinterpret ethical discussions on current advances in biomedicine: instead of understanding bioethical positions as extensions of classical normative views in ethics (consequentialism, deontologism, contractualism etc.), my project interprets them more accurately as involving various normative approaches to decision making under uncertainty. The following hard cases in bioethics provide the motivation for research:
1) Regulating scientific research under uncertainty about the ontological/moral status (e.g. parthenogenetic stem cells derived from human parthenotes) in the context of meta-reasoning under normative uncertainty.
2) The value of preventive medicine in healthcare (e.g. vaccinations) in the context of decision-making under metaphysical indeterminacy.
3) Population or reproductive decisions (e.g. preimplantation genetic diagnosis) in the context of valuing mere existence.
The main drive behind this project is the rapid progress in biomedical research combined with new kinds of uncertainties. These new and “deep” uncertainties trigger specific forms of emotions and cognitions that influence normative judgments and decisions. The main research questions that will be addressed by conceptual analysis, new psychological experiments, and case studies are the following: how do the heuristics and biases (H&B) documented by behavioral scientists influence the formation of normative judgments in bioethical contexts; how to demarcate between distorted and undistorted value judgments; to what extent is it permissible for individuals or policy makers to yield to H&B. The hypothesis is that many existing bioethical rules, regulations, practices seem to have emerged from unreliable reactions, rather than by means of deliberation on the possible justifications for alternative ways to decide about them under several layers and types of uncertainty.
Summary
Uncertainty is everywhere, as the saying goes, but rarely considered in ethical reflections. This project aims to reinterpret ethical discussions on current advances in biomedicine: instead of understanding bioethical positions as extensions of classical normative views in ethics (consequentialism, deontologism, contractualism etc.), my project interprets them more accurately as involving various normative approaches to decision making under uncertainty. The following hard cases in bioethics provide the motivation for research:
1) Regulating scientific research under uncertainty about the ontological/moral status (e.g. parthenogenetic stem cells derived from human parthenotes) in the context of meta-reasoning under normative uncertainty.
2) The value of preventive medicine in healthcare (e.g. vaccinations) in the context of decision-making under metaphysical indeterminacy.
3) Population or reproductive decisions (e.g. preimplantation genetic diagnosis) in the context of valuing mere existence.
The main drive behind this project is the rapid progress in biomedical research combined with new kinds of uncertainties. These new and “deep” uncertainties trigger specific forms of emotions and cognitions that influence normative judgments and decisions. The main research questions that will be addressed by conceptual analysis, new psychological experiments, and case studies are the following: how do the heuristics and biases (H&B) documented by behavioral scientists influence the formation of normative judgments in bioethical contexts; how to demarcate between distorted and undistorted value judgments; to what extent is it permissible for individuals or policy makers to yield to H&B. The hypothesis is that many existing bioethical rules, regulations, practices seem to have emerged from unreliable reactions, rather than by means of deliberation on the possible justifications for alternative ways to decide about them under several layers and types of uncertainty.
Max ERC Funding
1 499 625 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym CAFYR
Project Constructing Age for Young Readers
Researcher (PI) Vanessa JOOSEN
Host Institution (HI) UNIVERSITEIT ANTWERPEN
Call Details Starting Grant (StG), SH5, ERC-2018-STG
Summary Constructing Age for Young Readers (CAFYR)
CAFYR starts from the observations that Europe has recently witnessed a few pertinent crises in intergenerational tension, that age norms and ageism frequently go unchecked and that they are part of children’s socialization. It aims at developing pioneering research for understanding how age is constructed in cultural products. CAFYR focuses on fiction for young readers as a discourse that often naturalizes age norms as part of an engaging story and that is endorsed in educational contexts for contributing to children’s literacy, social and cultural development. The effect of three factors on the construction of age in children’s books is studied: the age of the author, the age of the intended reader, and the age of the real reader.
CAFYR aims to lay bare whether and how the age and aging process of children’s authors affect their construction of the life stages in their works. It will show how various crosswriters shape the stages in life differently for young and adult readers. It considers the age of young readers as varied in its own right, and investigates how age is constructed differently for children of different ages, from preschoolers to adolescents. Finally, it brings together readers of various stages in the life course in a reception study that will help understand how real readers construct age, during the reading process and in dialogue with each other. CAFYR also aims to break new theoretical and methodological ground. It offers an interdisciplinary approach that enriches children’s literature research with concepts and theories from age studies. It combines close reading strategies with distant reading and tools developed for digital text analysis. It provides a platform to people of different stages in life, contributing to their awareness about age, and facilitating and investigating dialogues about age, with the aim of ultimately fostering them more.
Summary
Constructing Age for Young Readers (CAFYR)
CAFYR starts from the observations that Europe has recently witnessed a few pertinent crises in intergenerational tension, that age norms and ageism frequently go unchecked and that they are part of children’s socialization. It aims at developing pioneering research for understanding how age is constructed in cultural products. CAFYR focuses on fiction for young readers as a discourse that often naturalizes age norms as part of an engaging story and that is endorsed in educational contexts for contributing to children’s literacy, social and cultural development. The effect of three factors on the construction of age in children’s books is studied: the age of the author, the age of the intended reader, and the age of the real reader.
CAFYR aims to lay bare whether and how the age and aging process of children’s authors affect their construction of the life stages in their works. It will show how various crosswriters shape the stages in life differently for young and adult readers. It considers the age of young readers as varied in its own right, and investigates how age is constructed differently for children of different ages, from preschoolers to adolescents. Finally, it brings together readers of various stages in the life course in a reception study that will help understand how real readers construct age, during the reading process and in dialogue with each other. CAFYR also aims to break new theoretical and methodological ground. It offers an interdisciplinary approach that enriches children’s literature research with concepts and theories from age studies. It combines close reading strategies with distant reading and tools developed for digital text analysis. It provides a platform to people of different stages in life, contributing to their awareness about age, and facilitating and investigating dialogues about age, with the aim of ultimately fostering them more.
Max ERC Funding
1 400 885 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym DDRMac
Project DNA Damage Response-instructed Macrophage Differentiation in Granulomatous Diseases
Researcher (PI) Antigoni TRIANTAFYLLOPOULOU
Host Institution (HI) CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Call Details Starting Grant (StG), LS6, ERC-2018-STG
Summary Macrophage differentiation programs are critical for the outcome of immunity against infection, chronic inflammatory diseases and cancer. How diverse inflammatory signals are translated to macrophage programs in the large range of human pathologies is largely unexplored. In the last years we focused on macrophage differentiation in granulomatous diseases. These affect millions worldwide, including young adults and children and tend to run a chronic course, with a high socioeconomic burden. Their common hallmark is the formation of granulomas, macrophage-driven structures of organized inflammation that replace healthy tissue. We revealed that macrophage precursors in granulomas experience a replication block and trigger the DNA Damage Response (DDR), a fundamental cellular process activated in response to genotoxic stress. This leads to the formation of multinucleated macrophages with tissue-remodelling signatures (Herrtwich, Cell 2016). Our work unravelled an intriguing link between genotoxic stress and granuloma-specific macrophage programs. The molecular pathways regulating DDR-driven macrophage differentiation and their role in chronic inflammatory pathologies remain however a black box. We hypothesize that the DDR promotes macrophage reprogramming to inflammation-maintaining modules. Such programs operate in granulomatous diseases and in chronic arthritis. Using state-of-the art genetic models, human tissues and an array of techniques crossing the fields of immunology, cell biology and cancer biology, our goal is to unravel the macrophage-specific response to genotoxic stress as an essential regulator of chronic inflammation-induced pathologies. The anticipated results will provide the scientific community with new knowledge on the role of genotoxic stress in immune dysregulation and will carry tremendous implications for the therapeutic targeting of macrophages in the context of chronic inflammatory diseases and cancer.
Summary
Macrophage differentiation programs are critical for the outcome of immunity against infection, chronic inflammatory diseases and cancer. How diverse inflammatory signals are translated to macrophage programs in the large range of human pathologies is largely unexplored. In the last years we focused on macrophage differentiation in granulomatous diseases. These affect millions worldwide, including young adults and children and tend to run a chronic course, with a high socioeconomic burden. Their common hallmark is the formation of granulomas, macrophage-driven structures of organized inflammation that replace healthy tissue. We revealed that macrophage precursors in granulomas experience a replication block and trigger the DNA Damage Response (DDR), a fundamental cellular process activated in response to genotoxic stress. This leads to the formation of multinucleated macrophages with tissue-remodelling signatures (Herrtwich, Cell 2016). Our work unravelled an intriguing link between genotoxic stress and granuloma-specific macrophage programs. The molecular pathways regulating DDR-driven macrophage differentiation and their role in chronic inflammatory pathologies remain however a black box. We hypothesize that the DDR promotes macrophage reprogramming to inflammation-maintaining modules. Such programs operate in granulomatous diseases and in chronic arthritis. Using state-of-the art genetic models, human tissues and an array of techniques crossing the fields of immunology, cell biology and cancer biology, our goal is to unravel the macrophage-specific response to genotoxic stress as an essential regulator of chronic inflammation-induced pathologies. The anticipated results will provide the scientific community with new knowledge on the role of genotoxic stress in immune dysregulation and will carry tremendous implications for the therapeutic targeting of macrophages in the context of chronic inflammatory diseases and cancer.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym DissectingSociety
Project Nineteenth-Century Sociographic Journalism and the Formation of Ethnographic and Sociological Knowledge
Researcher (PI) Christiane SCHWAB
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), SH5, ERC-2018-STG
Summary This project enacts cutting-edge perspectives on the multigenre history of sociological and anthropological reasoning. It represents the first comprehensive study to investigate pieces of nineteenth-century sociographic journalism as formative frames/catalysts of social knowledge and science. These social sketches (often referred to as panoramic literature) provide rich ethnographic micro-analysis and often relate to debates held by statisticians, moralists, folklorists, and ethnologists. However, in the discipline-oriented histories of the social sciences and humanities, journalism has been ignored as a form of knowledge and as a founding genre of modern (disciplinary, academic) social science. By exploring the epistemic significance of sociographic journalism, the project promises to institute a cross-genre, transdisciplinary, and transnational historiography of the evolution of social knowledge and to revise mono-disciplinary and Eurocentric tales of the past and present.
The project has five kinds of outcome: a series of essays, a conference, a public exhibition, a volume, and two monographs. The corpus comprises social sketches and examples of related knowledge frames (travel accounts, philanthropic reports, caricatures etc.) from Western Europe, the German-speaking countries, and (post-)colonial Latin America. The project develops an innovative mix of anthropological/historiographical approaches to examine (1) the representational techniques of sociographic journalism (e.g., methods of constructing social types, the influence of scientific paradigms); (2) how it connects with epistemic developments (e.g., towards materialist and historicizing conceptions of society); (3) its embeddedness in socio-spatial settings and its relations to academic, artistic, and governmental projects; and (4) how the journalistic sketches are to be situated against processes of urbanization, cultural transfer, nation-building, and the institutionalization of academic disciplines.
Summary
This project enacts cutting-edge perspectives on the multigenre history of sociological and anthropological reasoning. It represents the first comprehensive study to investigate pieces of nineteenth-century sociographic journalism as formative frames/catalysts of social knowledge and science. These social sketches (often referred to as panoramic literature) provide rich ethnographic micro-analysis and often relate to debates held by statisticians, moralists, folklorists, and ethnologists. However, in the discipline-oriented histories of the social sciences and humanities, journalism has been ignored as a form of knowledge and as a founding genre of modern (disciplinary, academic) social science. By exploring the epistemic significance of sociographic journalism, the project promises to institute a cross-genre, transdisciplinary, and transnational historiography of the evolution of social knowledge and to revise mono-disciplinary and Eurocentric tales of the past and present.
The project has five kinds of outcome: a series of essays, a conference, a public exhibition, a volume, and two monographs. The corpus comprises social sketches and examples of related knowledge frames (travel accounts, philanthropic reports, caricatures etc.) from Western Europe, the German-speaking countries, and (post-)colonial Latin America. The project develops an innovative mix of anthropological/historiographical approaches to examine (1) the representational techniques of sociographic journalism (e.g., methods of constructing social types, the influence of scientific paradigms); (2) how it connects with epistemic developments (e.g., towards materialist and historicizing conceptions of society); (3) its embeddedness in socio-spatial settings and its relations to academic, artistic, and governmental projects; and (4) how the journalistic sketches are to be situated against processes of urbanization, cultural transfer, nation-building, and the institutionalization of academic disciplines.
Max ERC Funding
1 477 125 €
Duration
Start date: 2020-05-01, End date: 2025-04-30
Project acronym ENTRI
Project Enteric-nervous-system-mediated regulation of intestinal inflammation
Researcher (PI) Christoph Klose
Host Institution (HI) CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Call Details Starting Grant (StG), LS6, ERC-2018-STG
Summary Environmental and internal stimuli are constantly sensed by the body’s two large sensory units, the nervous system and the immune system. Integration of these sensory signals and translation into effector responses are essential for maintaining body homeostasis. While some of the intrinsic pathways of the immune or nervous system have been investigated, how the two sensory interfaces coordinate their responses remains elusive. We have recently investigated neuro-immune interaction at the mucosa of the intestine, which is densely innervated by the enteric nervous system (ENS). Our research has exposed a previously unrecognized pathway used by enteric neurons to shape type 2 immunity at mucosal barriers. Cholinergic enteric neurons produce the neuropeptide Neuromedin U (NMU) to elicit potent activation of type 2 innate lymphoid cells (ILC2s) via Neuromedin U receptor 1, selectively expressed by ILC2s. Interestingly, NMU stimulated protective immunity against the parasite Nippostrongylus brasiliensis but also triggered allergic lung inflammation. Therefore, the NMU-NMUR1 axis provides an excellent opportunity to study how neurons and immune cells interact to regulate immune responses and maintain body homeostasis. We propose to generate and use elegant genetic tools, which will allow us to systematically investigate the consequences of neuro-immune crosstalk at mucosal surfaces in various disease models. These tools will enable us to selectively measure and interfere with neuronal and ILC2 gene expression and function, thereby leading to an unprecedented understanding of how the components of neuro-immune crosstalk contribute to parasite immunity or allergic disease development. Furthermore, we will progress into translational aspects of NMU-regulated immune activation for human immunology. Therefore, our research has the potential to develop basic concepts of mucosal immune regulation and such discoveries could also be harnessed for therapeutic intervention.
Summary
Environmental and internal stimuli are constantly sensed by the body’s two large sensory units, the nervous system and the immune system. Integration of these sensory signals and translation into effector responses are essential for maintaining body homeostasis. While some of the intrinsic pathways of the immune or nervous system have been investigated, how the two sensory interfaces coordinate their responses remains elusive. We have recently investigated neuro-immune interaction at the mucosa of the intestine, which is densely innervated by the enteric nervous system (ENS). Our research has exposed a previously unrecognized pathway used by enteric neurons to shape type 2 immunity at mucosal barriers. Cholinergic enteric neurons produce the neuropeptide Neuromedin U (NMU) to elicit potent activation of type 2 innate lymphoid cells (ILC2s) via Neuromedin U receptor 1, selectively expressed by ILC2s. Interestingly, NMU stimulated protective immunity against the parasite Nippostrongylus brasiliensis but also triggered allergic lung inflammation. Therefore, the NMU-NMUR1 axis provides an excellent opportunity to study how neurons and immune cells interact to regulate immune responses and maintain body homeostasis. We propose to generate and use elegant genetic tools, which will allow us to systematically investigate the consequences of neuro-immune crosstalk at mucosal surfaces in various disease models. These tools will enable us to selectively measure and interfere with neuronal and ILC2 gene expression and function, thereby leading to an unprecedented understanding of how the components of neuro-immune crosstalk contribute to parasite immunity or allergic disease development. Furthermore, we will progress into translational aspects of NMU-regulated immune activation for human immunology. Therefore, our research has the potential to develop basic concepts of mucosal immune regulation and such discoveries could also be harnessed for therapeutic intervention.
Max ERC Funding
1 499 638 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym EpiTune
Project Epigenetic fine-tuning of T cells for improved adoptive cell therapy
Researcher (PI) Julia Polansky-Biskup
Host Institution (HI) CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Call Details Starting Grant (StG), LS6, ERC-2018-STG
Summary "Adoptive T cell therapy is a promising approach in various clinical settings, from target-specific immune reconstitution fighting cancer and chronic infections to combating undesired immune reactivity during auto-immunity and after organ transplantation.
However, its clinical application is currently hampered by: 1) the acquisition of senescence during the required in vitro expansion phase of T cells which limits their survival and fitness after infusion into the patient, and 2) the functional plasticity of T cells, which is sensitive to the inflammatory environment they encounter after transfusion and which might result in a functional switch from the desired effect (e.g. immunosuppressive) to the opposite one (pro-inflammatory).
I want to tackle these obstacles from a new molecular angle, utilizing the profound impact of epigenetic mechanisms on the senescence process as well as on the functional imprinting of T lymphocytes. Epigenetic players such as DNA methylation essentially contribute to T cell differentiation and harbor the unique prospect to imprint a stable developmental and functional state in the genomic structure of a cell, as we could recently show in our basic immune-epigenetic studies. Therefore, I here propose to equip T lymphocytes with the required properties for their successful and safe therapeutic application, including their functional fine-tuning according to the clinical need by directed modifications of the epigenome
('Epi-tuning').
To reach these goals I want: 1) to reveal strategies for the directed manipulation of the epigenetically-driven mechanism of cellular senescence and 2) to apply state-of-the-art CRISPR/Cas9-mediated epigenetic editing approaches for the imprinting of a desired functional state of therapeutic T cell products. These innovative epigenetic ""one-shot"" manipulations during the in vitro expansion phase should advance T cell therapy towards improved efficiency, stability as well as safety."
Summary
"Adoptive T cell therapy is a promising approach in various clinical settings, from target-specific immune reconstitution fighting cancer and chronic infections to combating undesired immune reactivity during auto-immunity and after organ transplantation.
However, its clinical application is currently hampered by: 1) the acquisition of senescence during the required in vitro expansion phase of T cells which limits their survival and fitness after infusion into the patient, and 2) the functional plasticity of T cells, which is sensitive to the inflammatory environment they encounter after transfusion and which might result in a functional switch from the desired effect (e.g. immunosuppressive) to the opposite one (pro-inflammatory).
I want to tackle these obstacles from a new molecular angle, utilizing the profound impact of epigenetic mechanisms on the senescence process as well as on the functional imprinting of T lymphocytes. Epigenetic players such as DNA methylation essentially contribute to T cell differentiation and harbor the unique prospect to imprint a stable developmental and functional state in the genomic structure of a cell, as we could recently show in our basic immune-epigenetic studies. Therefore, I here propose to equip T lymphocytes with the required properties for their successful and safe therapeutic application, including their functional fine-tuning according to the clinical need by directed modifications of the epigenome
('Epi-tuning').
To reach these goals I want: 1) to reveal strategies for the directed manipulation of the epigenetically-driven mechanism of cellular senescence and 2) to apply state-of-the-art CRISPR/Cas9-mediated epigenetic editing approaches for the imprinting of a desired functional state of therapeutic T cell products. These innovative epigenetic ""one-shot"" manipulations during the in vitro expansion phase should advance T cell therapy towards improved efficiency, stability as well as safety."
Max ERC Funding
1 489 725 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym FunDiT
Project Functional Diversity of T cells
Researcher (PI) Ondrej STEPANEK
Host Institution (HI) USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE
Call Details Starting Grant (StG), LS6, ERC-2018-STG
Summary T cells have a central role in most adaptive immune responses, including immunity to infection, cancer, and autoimmunity. Increasing evidence shows that even resting steady-state T cells form many different subsets with unique functions. Variable level of self-reactivity and previous antigenic exposure are most likely two major determinants of the T-cell diversity. However, the number, identity, and biological function of steady-state T-cell subsets are still very incompletely understood. Receptors to ligands from TNF and B7 families exhibit variable expression among T-cell subsets and are important regulators of T-cell fate decisions. We hypothesize that pathways triggered by these receptors substantially contribute to the functional diversity of T cells.The FunDiT project uses a set of novel tools to systematically identify steady-state CD8+ T cell subsets and characterize their biological roles. The project has three complementary objectives.
(1) Identification of CD8+ T cell subsets. We will identify subsets based on single cell gene expression profiling. We will determine the role of self and foreign antigens in the formation of these subsets and match corresponding subsets between mice and humans.
(2) Role of particular subsets in the immune response. We will compare antigenic responses of particular subsets using our novel model allowing inducible expression of a defined TCR. The activity of T-cell subsets in three disease models (infection, cancer, autoimmunity) will be characterized.
(3) Characterization of key costimulatory/inhibitory pathways. We will use our novel mass spectrometry-based approach to identify receptors and signaling molecules involved in the signaling by ligands from TNF and B7 families in T cells.
The results will provide understanding of the adaptive immunity in particular disease context and resolve long-standing questions concerning the roles of T-cell diversity in protective immunity and tolerance to healthy tissues and tumors.
Summary
T cells have a central role in most adaptive immune responses, including immunity to infection, cancer, and autoimmunity. Increasing evidence shows that even resting steady-state T cells form many different subsets with unique functions. Variable level of self-reactivity and previous antigenic exposure are most likely two major determinants of the T-cell diversity. However, the number, identity, and biological function of steady-state T-cell subsets are still very incompletely understood. Receptors to ligands from TNF and B7 families exhibit variable expression among T-cell subsets and are important regulators of T-cell fate decisions. We hypothesize that pathways triggered by these receptors substantially contribute to the functional diversity of T cells.The FunDiT project uses a set of novel tools to systematically identify steady-state CD8+ T cell subsets and characterize their biological roles. The project has three complementary objectives.
(1) Identification of CD8+ T cell subsets. We will identify subsets based on single cell gene expression profiling. We will determine the role of self and foreign antigens in the formation of these subsets and match corresponding subsets between mice and humans.
(2) Role of particular subsets in the immune response. We will compare antigenic responses of particular subsets using our novel model allowing inducible expression of a defined TCR. The activity of T-cell subsets in three disease models (infection, cancer, autoimmunity) will be characterized.
(3) Characterization of key costimulatory/inhibitory pathways. We will use our novel mass spectrometry-based approach to identify receptors and signaling molecules involved in the signaling by ligands from TNF and B7 families in T cells.
The results will provide understanding of the adaptive immunity in particular disease context and resolve long-standing questions concerning the roles of T-cell diversity in protective immunity and tolerance to healthy tissues and tumors.
Max ERC Funding
1 725 000 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym HANDLING
Project Writers handling pictures: a material intermediality (1880-today)
Researcher (PI) anne REVERSEAU
Host Institution (HI) UNIVERSITE CATHOLIQUE DE LOUVAIN
Call Details Starting Grant (StG), SH5, ERC-2018-STG
Summary Not only does the writer’s hand hold the pen, it manipulates pictures as well. Writers touch, hoard, cut, copy, pin and paste various kinds of pictures and these actions integrate literature in visual culture in many ways that have never been tackled as a whole before.
Some writers spent their life surrounded by pictures taken from magazines, creating an inspirational environment; yet others nurtured their imagination with touristic leaflets and visual advertisements; others created fictional characters based on collected portraits. What do writers do with pictures? How does literature stage the pictures handled? From very concrete and banal uses of pictures will emerge a new vision of literature as intermediality in action.
This investigation applies the tool set of visual anthropology and visual studies to writers for a deeper understanding of visual ecosystems. Covering a large period, from the beginning of mass reproduction in the 1880s and the digital practices of today, HANDLING focuses on the French and French-speaking field and stands as a laboratory to refashion a broader model for relationships between image and text. Its main challenge is to get to the root of contemporary iconographic practices.
HANDLING is unconventional because literary studies usually focus on the text: contrary to the norm, it sets the image at the very centre of the literary act. This approach might yield promising results for the visibility of literature in the future, especially in exhibitions. Making these practices visible will make literature itself more visible.
As an internationally recognized specialist of text-image relationships with an in-depth knowledge of French/Belgian literature and photography, I will build a team and lead this 5-year ambitious project. Grounded in interdisciplinarity, it will show the significant and unexpected role of literature in material visual culture.
Summary
Not only does the writer’s hand hold the pen, it manipulates pictures as well. Writers touch, hoard, cut, copy, pin and paste various kinds of pictures and these actions integrate literature in visual culture in many ways that have never been tackled as a whole before.
Some writers spent their life surrounded by pictures taken from magazines, creating an inspirational environment; yet others nurtured their imagination with touristic leaflets and visual advertisements; others created fictional characters based on collected portraits. What do writers do with pictures? How does literature stage the pictures handled? From very concrete and banal uses of pictures will emerge a new vision of literature as intermediality in action.
This investigation applies the tool set of visual anthropology and visual studies to writers for a deeper understanding of visual ecosystems. Covering a large period, from the beginning of mass reproduction in the 1880s and the digital practices of today, HANDLING focuses on the French and French-speaking field and stands as a laboratory to refashion a broader model for relationships between image and text. Its main challenge is to get to the root of contemporary iconographic practices.
HANDLING is unconventional because literary studies usually focus on the text: contrary to the norm, it sets the image at the very centre of the literary act. This approach might yield promising results for the visibility of literature in the future, especially in exhibitions. Making these practices visible will make literature itself more visible.
As an internationally recognized specialist of text-image relationships with an in-depth knowledge of French/Belgian literature and photography, I will build a team and lead this 5-year ambitious project. Grounded in interdisciplinarity, it will show the significant and unexpected role of literature in material visual culture.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym IM-ID
Project Defining the intrinsic transcriptional programs and the microenvironmental signals tailoring lung Interstitial Macrophage IDentity
Researcher (PI) Thomas MARICHAL
Host Institution (HI) UNIVERSITE DE LIEGE
Call Details Starting Grant (StG), LS6, ERC-2018-STG
Summary The mechanisms underlying lung homeostasis are of fundamental biological importance and have critical implications for the prevention of immune-mediated diseases such as asthma. We have demonstrated that lung Interstitial Macrophages (IM) exhibit a tolerogenic profile and are able to prevent and limit the development of aberrant immune responses against allergens, thus underscoring their role as crucial regulators of lung homeostasis. In addition, we have shown that IM could expand from monocyte precursors upon host exposure to bacterial unmethylated CpG-DNA, resulting in robust protection against allergic asthma. To date, however, IM have only been characterized as a bulk population in functional studies, and little is known about the tissue-instructive signals, specific transcription factors and differentiation programs which contribute to determining their identity (ID) and function, as proposed by the macrophage niche model. We have developed an innovative transgenic tool to selectively target IM which, in combination with high dimensional single cell technologies, will allow us to (1) define the precise ID of IM, i.e. their spatial organization, heterogeneity, molecular signature and the specific TF governing their differentiation and function; (2) investigate how IM ID is imprinted by the local niche to sustain lung homeostasis. Specifically, we aim to identify the epithelial cell-derived chemo-attractive signals controlling IM precursor recruitment and to elucidate the contribution of the lung cholinergic nervous system to IM ID and lung homeostasis. This research will increase our understanding of the basic mechanisms underlying the fine-tuning of tolerogenic IM and will thus provide robust foundations for novel IM-targeted approaches promoting health and preventing airway diseases in which IM (dys)functions have been implicated.
Summary
The mechanisms underlying lung homeostasis are of fundamental biological importance and have critical implications for the prevention of immune-mediated diseases such as asthma. We have demonstrated that lung Interstitial Macrophages (IM) exhibit a tolerogenic profile and are able to prevent and limit the development of aberrant immune responses against allergens, thus underscoring their role as crucial regulators of lung homeostasis. In addition, we have shown that IM could expand from monocyte precursors upon host exposure to bacterial unmethylated CpG-DNA, resulting in robust protection against allergic asthma. To date, however, IM have only been characterized as a bulk population in functional studies, and little is known about the tissue-instructive signals, specific transcription factors and differentiation programs which contribute to determining their identity (ID) and function, as proposed by the macrophage niche model. We have developed an innovative transgenic tool to selectively target IM which, in combination with high dimensional single cell technologies, will allow us to (1) define the precise ID of IM, i.e. their spatial organization, heterogeneity, molecular signature and the specific TF governing their differentiation and function; (2) investigate how IM ID is imprinted by the local niche to sustain lung homeostasis. Specifically, we aim to identify the epithelial cell-derived chemo-attractive signals controlling IM precursor recruitment and to elucidate the contribution of the lung cholinergic nervous system to IM ID and lung homeostasis. This research will increase our understanding of the basic mechanisms underlying the fine-tuning of tolerogenic IM and will thus provide robust foundations for novel IM-targeted approaches promoting health and preventing airway diseases in which IM (dys)functions have been implicated.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
