Project acronym 3D-PXM
Project 3D Piezoresponse X-ray Microscopy
Researcher (PI) Hugh SIMONS
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Starting Grant (StG), PE3, ERC-2018-STG
Summary Polar materials, such as piezoelectrics and ferroelectrics are essential to our modern life, yet they are mostly developed by trial-and-error. Their properties overwhelmingly depend on the defects within them, the majority of which are hidden in the bulk. The road to better materials is via mapping these defects, but our best tool for it – piezoresponse force microscopy (PFM) – is limited to surfaces. 3D-PXM aims to revolutionize our understanding by measuring the local structure-property correlations around individual defects buried deep in the bulk.
This is a completely new kind of microscopy enabling 3D maps of local strain and polarization (i.e. piezoresponse) with 10 nm resolution in mm-sized samples. It is novel, multi-scale and fast enough to capture defect dynamics in real time. Uniquely, it is a full-field method that uses a synthetic-aperture approach to improve both resolution and recover the image phase. This phase is then quantitatively correlated to local polarization and strain via a forward model. 3D-PXM combines advances in X-Ray optics, phase recovery and data analysis to create something transformative. In principle, it can achieve spatial resolution comparable to the best coherent X-Ray microscopy methods while being faster, used on larger samples, and without risk of radiation damage.
For the first time, this opens the door to solving how defects influence bulk properties under real-life conditions. 3D-PXM focuses on three types of defects prevalent in polar materials: grain boundaries, dislocations and polar nanoregions. Individually they address major gaps in the state-of-the-art, while together making great strides towards fully understanding defects. This understanding is expected to inform a new generation of multi-scale models that can account for a material’s full heterogeneity. These models are the first step towards abandoning our tradition of trial-and-error, and with this comes the potential for a new era of polar materials.
Summary
Polar materials, such as piezoelectrics and ferroelectrics are essential to our modern life, yet they are mostly developed by trial-and-error. Their properties overwhelmingly depend on the defects within them, the majority of which are hidden in the bulk. The road to better materials is via mapping these defects, but our best tool for it – piezoresponse force microscopy (PFM) – is limited to surfaces. 3D-PXM aims to revolutionize our understanding by measuring the local structure-property correlations around individual defects buried deep in the bulk.
This is a completely new kind of microscopy enabling 3D maps of local strain and polarization (i.e. piezoresponse) with 10 nm resolution in mm-sized samples. It is novel, multi-scale and fast enough to capture defect dynamics in real time. Uniquely, it is a full-field method that uses a synthetic-aperture approach to improve both resolution and recover the image phase. This phase is then quantitatively correlated to local polarization and strain via a forward model. 3D-PXM combines advances in X-Ray optics, phase recovery and data analysis to create something transformative. In principle, it can achieve spatial resolution comparable to the best coherent X-Ray microscopy methods while being faster, used on larger samples, and without risk of radiation damage.
For the first time, this opens the door to solving how defects influence bulk properties under real-life conditions. 3D-PXM focuses on three types of defects prevalent in polar materials: grain boundaries, dislocations and polar nanoregions. Individually they address major gaps in the state-of-the-art, while together making great strides towards fully understanding defects. This understanding is expected to inform a new generation of multi-scale models that can account for a material’s full heterogeneity. These models are the first step towards abandoning our tradition of trial-and-error, and with this comes the potential for a new era of polar materials.
Max ERC Funding
1 496 941 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ABACUS
Project Advancing Behavioral and Cognitive Understanding of Speech
Researcher (PI) Bart De Boer
Host Institution (HI) VRIJE UNIVERSITEIT BRUSSEL
Call Details Starting Grant (StG), SH4, ERC-2011-StG_20101124
Summary I intend to investigate what cognitive mechanisms give us combinatorial speech. Combinatorial speech is the ability to make new words using pre-existing speech sounds. Humans are the only apes that can do this, yet we do not know how our brains do it, nor how exactly we differ from other apes. Using new experimental techniques to study human behavior and new computational techniques to model human cognition, I will find out how we deal with combinatorial speech.
The experimental part will study individual and cultural learning. Experimental cultural learning is a new technique that simulates cultural evolution in the laboratory. Two types of cultural learning will be used: iterated learning, which simulates language transfer across generations, and social coordination, which simulates emergence of norms in a language community. Using the two types of cultural learning together with individual learning experiments will help to zero in, from three angles, on how humans deal with combinatorial speech. In addition it will make a methodological contribution by comparing the strengths and weaknesses of the three methods.
The computer modeling part will formalize hypotheses about how our brains deal with combinatorial speech. Two models will be built: a high-level model that will establish the basic algorithms with which combinatorial speech is learned and reproduced, and a neural model that will establish in more detail how the algorithms are implemented in the brain. In addition, the models, through increasing understanding of how humans deal with speech, will help bridge the performance gap between human and computer speech recognition.
The project will advance science in four ways: it will provide insight into how our unique ability for using combinatorial speech works, it will tell us how this is implemented in the brain, it will extend the novel methodology of experimental cultural learning and it will create new computer models for dealing with human speech.
Summary
I intend to investigate what cognitive mechanisms give us combinatorial speech. Combinatorial speech is the ability to make new words using pre-existing speech sounds. Humans are the only apes that can do this, yet we do not know how our brains do it, nor how exactly we differ from other apes. Using new experimental techniques to study human behavior and new computational techniques to model human cognition, I will find out how we deal with combinatorial speech.
The experimental part will study individual and cultural learning. Experimental cultural learning is a new technique that simulates cultural evolution in the laboratory. Two types of cultural learning will be used: iterated learning, which simulates language transfer across generations, and social coordination, which simulates emergence of norms in a language community. Using the two types of cultural learning together with individual learning experiments will help to zero in, from three angles, on how humans deal with combinatorial speech. In addition it will make a methodological contribution by comparing the strengths and weaknesses of the three methods.
The computer modeling part will formalize hypotheses about how our brains deal with combinatorial speech. Two models will be built: a high-level model that will establish the basic algorithms with which combinatorial speech is learned and reproduced, and a neural model that will establish in more detail how the algorithms are implemented in the brain. In addition, the models, through increasing understanding of how humans deal with speech, will help bridge the performance gap between human and computer speech recognition.
The project will advance science in four ways: it will provide insight into how our unique ability for using combinatorial speech works, it will tell us how this is implemented in the brain, it will extend the novel methodology of experimental cultural learning and it will create new computer models for dealing with human speech.
Max ERC Funding
1 276 620 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
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 CANCERSTEM
Project Stem cells in epithelial cancer initiation and growth
Researcher (PI) Cédric Blanpain
Host Institution (HI) UNIVERSITE LIBRE DE BRUXELLES
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary Cancer is the result of a multi-step process requiring the accumulation of mutations in several genes. For most cancers, the target cells of oncogenic mutations are unknown. Adult stem cells (SCs) might be the initial target cells as they self-renew for extended periods of time, providing increased opportunity to accumulate the mutations required for cancer formation. Certain cancers contain cells characteristics of SC with high self-renewal capacities and the ability to reform the parental tumor upon transplantation. However, whether the initial oncogenic mutations arise in normal stem cells or in more differentiated cells that re-acquire stem cell-like properties remains to be determined. The demonstration that SCs are the target cells of the initial transforming events and that cancers contain cells with SC characteristics await the development of tools allowing for the isolation and characterization of normal adult SCs. In most epithelia from which cancers naturally arise, such tools are not yet available. We have recently developed novel methods to specifically mark and isolate multipotent epidermal slow-cycling SCs, making it now possible to determine the role of SC during epithelial cancer formation. In this project, we will use mice epidermis as a model to define the role of SC in epithelial cancer initiation and growth. Specifically, we will determine whether epithelial SCs are the initial target cells of oncogenic mutations during skin cancer formation, whether oncogenic mutations lead preferentially to skin cancer when they arise in SC rather than in more committed cells and whether cancer stem cells contribute to epithelial tumor growth and relapse after therapy.
Summary
Cancer is the result of a multi-step process requiring the accumulation of mutations in several genes. For most cancers, the target cells of oncogenic mutations are unknown. Adult stem cells (SCs) might be the initial target cells as they self-renew for extended periods of time, providing increased opportunity to accumulate the mutations required for cancer formation. Certain cancers contain cells characteristics of SC with high self-renewal capacities and the ability to reform the parental tumor upon transplantation. However, whether the initial oncogenic mutations arise in normal stem cells or in more differentiated cells that re-acquire stem cell-like properties remains to be determined. The demonstration that SCs are the target cells of the initial transforming events and that cancers contain cells with SC characteristics await the development of tools allowing for the isolation and characterization of normal adult SCs. In most epithelia from which cancers naturally arise, such tools are not yet available. We have recently developed novel methods to specifically mark and isolate multipotent epidermal slow-cycling SCs, making it now possible to determine the role of SC during epithelial cancer formation. In this project, we will use mice epidermis as a model to define the role of SC in epithelial cancer initiation and growth. Specifically, we will determine whether epithelial SCs are the initial target cells of oncogenic mutations during skin cancer formation, whether oncogenic mutations lead preferentially to skin cancer when they arise in SC rather than in more committed cells and whether cancer stem cells contribute to epithelial tumor growth and relapse after therapy.
Max ERC Funding
1 600 000 €
Duration
Start date: 2008-07-01, End date: 2013-12-31
Project acronym COGNAP
Project To nap or not to nap? Why napping habits interfere with cognitive fitness in ageing
Researcher (PI) Christina Hildegard SCHMIDT
Host Institution (HI) UNIVERSITE DE LIEGE
Call Details Starting Grant (StG), SH4, ERC-2017-STG
Summary All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.
Summary
All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.
Max ERC Funding
1 499 125 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym COMICS
Project Children in Comics: An Intercultural History from 1865 to Today
Researcher (PI) Maaheen AHMED
Host Institution (HI) UNIVERSITEIT GENT
Call Details Starting Grant (StG), SH5, ERC-2017-STG
Summary Owing to their visual essence and status as a popular, modern medium, comics – newspaper strips, comics magazines and graphic novels – provide valuable insight into the transformation of collective consciousness. This project advances the hypothesis that children in comics are distinctive embodiments of the complex experience of modernity, channeling and tempering modern anxieties and incarnating the freedom denied to adults. In testing this hypothesis, the project constructs the first intercultural history of children in European comics, tracing the changing conceptualizations of child protagonists in popular comics for both children and adults from the mid-19th century to the present. In doing so, it takes key points in European history as well as the history of comics into account.
Assembling a team of six multilingual researchers, the project uses an interdisciplinary methodology combining comics studies and childhood studies while also incorporating specific insights from cultural studies (history of family life, history of public life, history of the body, affect theory and scholarship on the carnivalesque). This enables the project to analyze the transposition of modern anxieties, conceptualizations of childishness, child-adult power relations, notions of liberty, visualizations of the body, family life, school and public life as well as the presence of affects such as nostalgia and happiness in comics starring children.
The project thus opens up a new field of research lying at the intersection of comics studies and childhood studies and illustrates its potential. In studying popular but often overlooked comics, the project provides crucial historical and analytical material that will shape future comics criticism and the fields associated with childhood studies. Furthermore, the project’s outreach activities will increase collective knowledge about comic strips, which form an important, increasingly visible part of cultural heritage.
Summary
Owing to their visual essence and status as a popular, modern medium, comics – newspaper strips, comics magazines and graphic novels – provide valuable insight into the transformation of collective consciousness. This project advances the hypothesis that children in comics are distinctive embodiments of the complex experience of modernity, channeling and tempering modern anxieties and incarnating the freedom denied to adults. In testing this hypothesis, the project constructs the first intercultural history of children in European comics, tracing the changing conceptualizations of child protagonists in popular comics for both children and adults from the mid-19th century to the present. In doing so, it takes key points in European history as well as the history of comics into account.
Assembling a team of six multilingual researchers, the project uses an interdisciplinary methodology combining comics studies and childhood studies while also incorporating specific insights from cultural studies (history of family life, history of public life, history of the body, affect theory and scholarship on the carnivalesque). This enables the project to analyze the transposition of modern anxieties, conceptualizations of childishness, child-adult power relations, notions of liberty, visualizations of the body, family life, school and public life as well as the presence of affects such as nostalgia and happiness in comics starring children.
The project thus opens up a new field of research lying at the intersection of comics studies and childhood studies and illustrates its potential. In studying popular but often overlooked comics, the project provides crucial historical and analytical material that will shape future comics criticism and the fields associated with childhood studies. Furthermore, the project’s outreach activities will increase collective knowledge about comic strips, which form an important, increasingly visible part of cultural heritage.
Max ERC Funding
1 452 500 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym CUTS
Project Creative Undoing and Textual Scholarship:
A Rapprochement between Genetic Criticism and Scholarly Editing
Researcher (PI) Dirk Van Hulle
Host Institution (HI) UNIVERSITEIT ANTWERPEN
Call Details Starting Grant (StG), SH5, ERC-2012-StG_20111124
Summary "In the past few decades, the disciplines of textual scholarship and genetic criticism have insisted on their respective differences. Nonetheless, a rapprochement would be mutually beneficial. The proposed research endeavours to innovate scholarly editing with the combined forces of these two disciplines. Since genetic criticism has objected to the subservient role of manuscript research in textual criticism, the proposed research suggests a reversal of roles: instead of employing manuscript research with a view to making an edition, an electronic edition can be designed in such a way that it becomes a tool for manuscript research and genetic criticism. The research hypothesis is that such a rapprochement can be achieved by means of an approach to textual variants that values creative undoing (ways of de-composing a text as an integral part of composition and literary invention) more than has hitherto been the case in textual scholarship. This change of outlook will be tested by means of the marginalia, notes and manuscripts of an author whose work is paradigmatic for genetic criticism: Samuel Beckett. His manuscripts will serve as a case study to determine the functions of creative undoing in the process of literary invention and its theoretical and practical implications for electronic scholarly editing and the genetic analysis of modern manuscripts. Extrapolating from this case study, the results are employed to tackle a topical issue in European textual scholarship. The envisaged rapprochement between the disciplines of genetic criticism and textual scholarship is the core of this proposal’s endeavour to advance the state of the art in these disciplines by giving shape to a new orientation within scholarly editing."
Summary
"In the past few decades, the disciplines of textual scholarship and genetic criticism have insisted on their respective differences. Nonetheless, a rapprochement would be mutually beneficial. The proposed research endeavours to innovate scholarly editing with the combined forces of these two disciplines. Since genetic criticism has objected to the subservient role of manuscript research in textual criticism, the proposed research suggests a reversal of roles: instead of employing manuscript research with a view to making an edition, an electronic edition can be designed in such a way that it becomes a tool for manuscript research and genetic criticism. The research hypothesis is that such a rapprochement can be achieved by means of an approach to textual variants that values creative undoing (ways of de-composing a text as an integral part of composition and literary invention) more than has hitherto been the case in textual scholarship. This change of outlook will be tested by means of the marginalia, notes and manuscripts of an author whose work is paradigmatic for genetic criticism: Samuel Beckett. His manuscripts will serve as a case study to determine the functions of creative undoing in the process of literary invention and its theoretical and practical implications for electronic scholarly editing and the genetic analysis of modern manuscripts. Extrapolating from this case study, the results are employed to tackle a topical issue in European textual scholarship. The envisaged rapprochement between the disciplines of genetic criticism and textual scholarship is the core of this proposal’s endeavour to advance the state of the art in these disciplines by giving shape to a new orientation within scholarly editing."
Max ERC Funding
1 147 740 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym DigitalMemories
Project We are all Ayotzinapa: The role of Digital Media in the Shaping of Transnational Memories on Disappearance
Researcher (PI) Silvana Mandolessi
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), SH5, ERC-2015-STG
Summary The project seeks to study the role of digital media in the shaping of transnational memories on disappearance. It investigates a novel case that is in process of shaping: the disappearance of 43 students in Mexico in September 2014. The role of the new media in getting citizens’ attention and in marking a “turning point” was crucial to the upsurge of a counter-movement against the Mexican government and qualifies the event as significant for the transnational arena.
The groundbreaking aspect of the project consists in proposing a double approach:
a) a theoretical approach in which “disappearance” is considered as a particular crime that becomes a model for analyzing digital memory. Disappearance is a technology that produces a subject with a new ontological status: the disappeared are non-beings, because they are neither alive nor dead. This ontological status transgresses the clear boundaries separating life and death, past, present and future, materiality and immateriality, personal and collective spheres. “Digital memory”, i.e. a memory mediated by digital technology, is also determined by the transgression of the boundaries of given categories
b) a multidisciplinary approach situating Mexico´s case in a long transnational history of disappearance in the Hispanic World, including Argentina and Spain. This longer history seeks to compare disappearance as a mnemonic object developed in the global sphere –in social network sites as blogs, Facebook, Twitter and YouTube– in Mexico and the social performances and artistic representations –literature, photo exhibitions, and films– developed in Spain and Argentina.
The Mexican case represents a paradigm for the redefinition of the relationship between media and memory. The main output of the project will consist in constructing a theoretical model for analyzing digital mnemonic objects in the rise of networked social movements with a transnational scope.
Summary
The project seeks to study the role of digital media in the shaping of transnational memories on disappearance. It investigates a novel case that is in process of shaping: the disappearance of 43 students in Mexico in September 2014. The role of the new media in getting citizens’ attention and in marking a “turning point” was crucial to the upsurge of a counter-movement against the Mexican government and qualifies the event as significant for the transnational arena.
The groundbreaking aspect of the project consists in proposing a double approach:
a) a theoretical approach in which “disappearance” is considered as a particular crime that becomes a model for analyzing digital memory. Disappearance is a technology that produces a subject with a new ontological status: the disappeared are non-beings, because they are neither alive nor dead. This ontological status transgresses the clear boundaries separating life and death, past, present and future, materiality and immateriality, personal and collective spheres. “Digital memory”, i.e. a memory mediated by digital technology, is also determined by the transgression of the boundaries of given categories
b) a multidisciplinary approach situating Mexico´s case in a long transnational history of disappearance in the Hispanic World, including Argentina and Spain. This longer history seeks to compare disappearance as a mnemonic object developed in the global sphere –in social network sites as blogs, Facebook, Twitter and YouTube– in Mexico and the social performances and artistic representations –literature, photo exhibitions, and films– developed in Spain and Argentina.
The Mexican case represents a paradigm for the redefinition of the relationship between media and memory. The main output of the project will consist in constructing a theoretical model for analyzing digital mnemonic objects in the rise of networked social movements with a transnational scope.
Max ERC Funding
1 444 125 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym ENVIROIMMUNE
Project Environmental modulators of the immune cell balance in health and disease
Researcher (PI) Markus Kleinewietfeld
Host Institution (HI) VIB
Call Details Starting Grant (StG), LS6, ERC-2014-STG
Summary The incidence of autoimmune diseases in developed societies is increasing at high rates, but the underlying cause for this phenomenon has not been elucidated yet. Since the genetic architect remains considerably stable, this increase is likely associated with changes in the environment. Autoimmunity is linked to an imbalance of pro-inflammatory Th17 cells and anti-inflammatory Foxp3+ regulatory T cells (Treg). However, little is known regarding environmental factors that influence the Th17/Treg balance. We recently discovered that a sodium-rich diet severely exacerbates experimental autoimmune encephalomyelitis (EAE) through an increased induction of pathogenic Th17 cells. Surprisingly, our preliminary data indicate that high-salt conditions also significantly impair Treg function, resembling a phenotype observed in several human autoimmune diseases. In addition, we have evidence that a high-salt diet affects the gut microbiota, implicating possible indirect effects on immune cells in vivo. Based on these findings we hypothesize that excess dietary salt represents an environmental risk factor for autoimmune diseases by modulating the Th17/Treg balance by several direct and indirect mechanisms. To address this hypothesis we will 1) examine the underlying mechanisms of high-salt induced Treg dysfunction and effects on the Treg/Th17 balance by molecular and functional analysis in vitro and compare it to known risk variants of human autoimmune diseases, and 2) define direct and indirect effects of excess dietary salt on the Th17/Treg balance and autoimmunity in vivo and explore potential novel pathways for targeted interventions. Thus, the proposed study will uncover the impact of a newly discovered environmental modulator of the immune cell balance and will ultimately pave the way for new approaches in therapy and prevention of autoimmune diseases.
Summary
The incidence of autoimmune diseases in developed societies is increasing at high rates, but the underlying cause for this phenomenon has not been elucidated yet. Since the genetic architect remains considerably stable, this increase is likely associated with changes in the environment. Autoimmunity is linked to an imbalance of pro-inflammatory Th17 cells and anti-inflammatory Foxp3+ regulatory T cells (Treg). However, little is known regarding environmental factors that influence the Th17/Treg balance. We recently discovered that a sodium-rich diet severely exacerbates experimental autoimmune encephalomyelitis (EAE) through an increased induction of pathogenic Th17 cells. Surprisingly, our preliminary data indicate that high-salt conditions also significantly impair Treg function, resembling a phenotype observed in several human autoimmune diseases. In addition, we have evidence that a high-salt diet affects the gut microbiota, implicating possible indirect effects on immune cells in vivo. Based on these findings we hypothesize that excess dietary salt represents an environmental risk factor for autoimmune diseases by modulating the Th17/Treg balance by several direct and indirect mechanisms. To address this hypothesis we will 1) examine the underlying mechanisms of high-salt induced Treg dysfunction and effects on the Treg/Th17 balance by molecular and functional analysis in vitro and compare it to known risk variants of human autoimmune diseases, and 2) define direct and indirect effects of excess dietary salt on the Th17/Treg balance and autoimmunity in vivo and explore potential novel pathways for targeted interventions. Thus, the proposed study will uncover the impact of a newly discovered environmental modulator of the immune cell balance and will ultimately pave the way for new approaches in therapy and prevention of autoimmune diseases.
Max ERC Funding
1 499 041 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym ERSTRESS
Project Role of Endoplasmic Reticulum Stress in dendritic cells and immune-mediated lung diseases
Researcher (PI) Bart Lambrecht
Host Institution (HI) UNIVERSITEIT GENT
Call Details Starting Grant (StG), LS6, ERC-2010-StG_20091118
Summary My overall aim is to understand the physiologic and medical importance of lung dendritic cells (DC) and to define the suitability of inhibitors of their function for the treatment of inflammatory lung diseases like asthma and COPD.
Lung dendritic cells (DC) play crucial roles in the regulation of lung immunity. We still do not fully understand how they get activated in response to different types of environmental triggers like allergens, cigarette smoke and pathogens. Although recognition of conserved motifs by pattern recognition receptors on DCs could be a key event, these stimuli are also accompanied by accumulation of unfolded proteins in the endoplasmic reticulum (ER). Cells respond by mounting the unfolded protein response (UPR) that acts to ameliorate protein folding, but intersects with metabolism, induction of alarm signals and cellular suicide mechanisms. I hypothesize that the presence of unfolded proteins and ER stress in DCs is a crucial endogenous danger signal that is vital to understanding their biology and their involvement in inflammatory lung diseases.
My specific aims are to :
1.define the fine tuning of ER stress pathways in various lung DC subsets in health and disease
2. define the specific role of ER stress proteins XBP1, JIK and ORMDL3 in DCs
3. test if interfering with ER stress pathways alters the course of inflammatory lung disease
To approach these aims, I have developed mouse models of lung disease that are centered around lung DCs and where ER stress pathways can be genetically deleted. Using a combination of cell biological and immunological techniques I hope to achieve definitive answers as to how ER stress pathways regulate the function of DCs. Manipulation of ER stress pathways by drugs will have a major impact on very common diseases like diabetes, cardiovascular and neurodegenerative disease. Through the current proposal, I hope to extend this exciting field to lung biology.
Summary
My overall aim is to understand the physiologic and medical importance of lung dendritic cells (DC) and to define the suitability of inhibitors of their function for the treatment of inflammatory lung diseases like asthma and COPD.
Lung dendritic cells (DC) play crucial roles in the regulation of lung immunity. We still do not fully understand how they get activated in response to different types of environmental triggers like allergens, cigarette smoke and pathogens. Although recognition of conserved motifs by pattern recognition receptors on DCs could be a key event, these stimuli are also accompanied by accumulation of unfolded proteins in the endoplasmic reticulum (ER). Cells respond by mounting the unfolded protein response (UPR) that acts to ameliorate protein folding, but intersects with metabolism, induction of alarm signals and cellular suicide mechanisms. I hypothesize that the presence of unfolded proteins and ER stress in DCs is a crucial endogenous danger signal that is vital to understanding their biology and their involvement in inflammatory lung diseases.
My specific aims are to :
1.define the fine tuning of ER stress pathways in various lung DC subsets in health and disease
2. define the specific role of ER stress proteins XBP1, JIK and ORMDL3 in DCs
3. test if interfering with ER stress pathways alters the course of inflammatory lung disease
To approach these aims, I have developed mouse models of lung disease that are centered around lung DCs and where ER stress pathways can be genetically deleted. Using a combination of cell biological and immunological techniques I hope to achieve definitive answers as to how ER stress pathways regulate the function of DCs. Manipulation of ER stress pathways by drugs will have a major impact on very common diseases like diabetes, cardiovascular and neurodegenerative disease. Through the current proposal, I hope to extend this exciting field to lung biology.
Max ERC Funding
1 499 580 €
Duration
Start date: 2010-12-01, End date: 2015-11-30
