Project acronym BlackBox
Project A collaborative platform to document performance composition: from conceptual structures in the backstage to customizable visualizations in the front-end
Researcher (PI) Carla Maria De Jesus Fernandes
Host Institution (HI) FACULDADE DE CIENCIAS SOCIAIS E HUMANAS DA UNIVERSIDADE NOVA DE LISBOA
Call Details Starting Grant (StG), SH5, ERC-2013-StG
Summary The global performing arts community is requiring innovative systems to: a) document, transmit and preserve the knowledge contained in choreographic-dramaturgic practices; b) assist artists with tools to facilitate their compositional processes, preferably on a collaborative basis. The existing digital archives of performing arts mostly function as conventional e-libraries, not allowing higher degrees of interactivity or active user intervention. They rarely contemplate accessible video annotation tools or provide relational querying functionalities based on artist-driven conceptual principles or idiosyncratic ontologies.
This proposal endeavours to fill that gap and create a new paradigm for the documentation of performance composition. It aims at the analysis of artists’ unique conceptual structures, by combining the empirical insights of contemporary creators with research theories from Multimodal Communication and Digital Media studies. The challenge is to design a model for a web-based collaborative platform enabling both a robust representation of performance composition methods and novel visualization technologies to support it. This can be done by analysing recurring body movement patterns and by fostering online contributions of users (a.o. performers and researchers) to the multimodal annotations stored in the platform. To accomplish this goal, two subjacent components must be developed: 1. the production of a video annotation-tool to allow artists in rehearsal periods to take notes over video in real-time and share them via the collaborative platform; 2. the linguistic analysis of a corpus of invited artists’ multimodal materials as source for the extraction of indicative conceptual structures, which will guide the architectural logics and interface design of the collaborative platform software.The outputs of these two components will generate critical case-studies to help understanding the human mind when engaged in cultural production processes.
Summary
The global performing arts community is requiring innovative systems to: a) document, transmit and preserve the knowledge contained in choreographic-dramaturgic practices; b) assist artists with tools to facilitate their compositional processes, preferably on a collaborative basis. The existing digital archives of performing arts mostly function as conventional e-libraries, not allowing higher degrees of interactivity or active user intervention. They rarely contemplate accessible video annotation tools or provide relational querying functionalities based on artist-driven conceptual principles or idiosyncratic ontologies.
This proposal endeavours to fill that gap and create a new paradigm for the documentation of performance composition. It aims at the analysis of artists’ unique conceptual structures, by combining the empirical insights of contemporary creators with research theories from Multimodal Communication and Digital Media studies. The challenge is to design a model for a web-based collaborative platform enabling both a robust representation of performance composition methods and novel visualization technologies to support it. This can be done by analysing recurring body movement patterns and by fostering online contributions of users (a.o. performers and researchers) to the multimodal annotations stored in the platform. To accomplish this goal, two subjacent components must be developed: 1. the production of a video annotation-tool to allow artists in rehearsal periods to take notes over video in real-time and share them via the collaborative platform; 2. the linguistic analysis of a corpus of invited artists’ multimodal materials as source for the extraction of indicative conceptual structures, which will guide the architectural logics and interface design of the collaborative platform software.The outputs of these two components will generate critical case-studies to help understanding the human mind when engaged in cultural production processes.
Max ERC Funding
1 378 200 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym BODYBUILDING
Project Building body representations: An investigation of the formation and maintenance of body representations
Researcher (PI) Matthew Ryan Longo
Host Institution (HI) BIRKBECK COLLEGE - UNIVERSITY OF LONDON
Call Details Starting Grant (StG), SH4, ERC-2013-StG
Summary "The body is ubiquitous in perceptual experience and is central to our sense of self and personal identity. Disordered body representations are central to several serious psychiatric and neurological disorders. Thus, identifying factors which contribute to the formation and maintenance of body representations is crucial for understanding how body representation goes awry in disease, and how it might be corrected by potential novel therapeutic interventions. Several types of sensory signals provide information about the body, making the body the multisensory object, par excellence. Little is known, however, about how information from somatosensation and from vision is integrated to construct the rich body representations we all experience. This project fills this gap in current understanding by determining how the brain builds body representations (BODYBUILDING). A hierarchical model of body representation is proposed, providing a novel theoretical framework for understanding the diversity of body representations and how they interact. The key motivating hypothesis is that body representation is determined by the dialectic between two major cognitive processes. First, from the bottom-up, somatosensation represents the body surface as a mosaic of discrete receptive fields, which become progressively agglomerated into larger and larger units of organisation, a process I call fusion. Second, from the top-down, vision starts out depicting the body as an undifferentiated whole, which is progressively broken into smaller parts, a process I call segmentation. Thus, body representation operates from the bottom-up as a process of fusion of primitive elements into larger complexes, as well as from the top-down as a process of segmentation of an initially undifferentiated whole into more basic parts. This project uses a combination of psychophysical, electrophysiological, and neuroimaging methods to provide fundamental insight into how we come to represent our body."
Summary
"The body is ubiquitous in perceptual experience and is central to our sense of self and personal identity. Disordered body representations are central to several serious psychiatric and neurological disorders. Thus, identifying factors which contribute to the formation and maintenance of body representations is crucial for understanding how body representation goes awry in disease, and how it might be corrected by potential novel therapeutic interventions. Several types of sensory signals provide information about the body, making the body the multisensory object, par excellence. Little is known, however, about how information from somatosensation and from vision is integrated to construct the rich body representations we all experience. This project fills this gap in current understanding by determining how the brain builds body representations (BODYBUILDING). A hierarchical model of body representation is proposed, providing a novel theoretical framework for understanding the diversity of body representations and how they interact. The key motivating hypothesis is that body representation is determined by the dialectic between two major cognitive processes. First, from the bottom-up, somatosensation represents the body surface as a mosaic of discrete receptive fields, which become progressively agglomerated into larger and larger units of organisation, a process I call fusion. Second, from the top-down, vision starts out depicting the body as an undifferentiated whole, which is progressively broken into smaller parts, a process I call segmentation. Thus, body representation operates from the bottom-up as a process of fusion of primitive elements into larger complexes, as well as from the top-down as a process of segmentation of an initially undifferentiated whole into more basic parts. This project uses a combination of psychophysical, electrophysiological, and neuroimaging methods to provide fundamental insight into how we come to represent our body."
Max ERC Funding
1 497 715 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym BRAINandMINDFULNESS
Project Impact of Mental Training of Attention and Emotion Regulation on Brain and Behavior: Implications for Neuroplasticity, Well-Being and Mindfulness Psychotherapy Research
Researcher (PI) Antoine Lutz
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Consolidator Grant (CoG), SH4, ERC-2013-CoG
Summary Mindfulness-based therapy has become an increasingly popular treatment to reduce stress, increase well-being and prevent relapse in depression. A key component of these therapies includes mindfulness practice that intends to train attention to detect and regulate afflictive cognitive and emotional patterns. Beyond its therapeutic application, the empirical study of mindfulness practice also represents a promising tool to understand practices that intentionally cultivate present-centeredness and openness to experience. Despite its clinical efficacy, little remains known about its means of action. Antithetic to this mode of experiential self-focus are states akin to depression, that are conducive of biased attention toward negativity, biased thoughts and rumination, and dysfunctional self schemas. The proposed research aims at implementing an innovative framework to scientifically investigate the experiential, cognitive, and neural processes underlining mindfulness practice building on the current neurocognitive understanding of the functional and anatomical architecture of cognitive control, and depression. To identify these mechanisms, this project aims to use paradigms from cognitive, and affective neuroscience (MEG, intracortical EEG, fMRI) to measure the training and plasticity of emotion regulation and cognitive control, and their effect on automatic, self-related affective processes. Using a cross-sectional design, this project aims to compare participants with trait differences in experiential self-focus mode. Using a longitudinal design, this project aims to explore mindfulness-practice training’s effect using a standard mindfulness-based intervention and an active control intervention. The PI has pioneered the neuroscientific investigation of mindfulness in the US and aspires to assemble a research team in France and a network of collaborators in Europe to pursue this research, which could lead to important outcomes for neuroscience, and mental health.
Summary
Mindfulness-based therapy has become an increasingly popular treatment to reduce stress, increase well-being and prevent relapse in depression. A key component of these therapies includes mindfulness practice that intends to train attention to detect and regulate afflictive cognitive and emotional patterns. Beyond its therapeutic application, the empirical study of mindfulness practice also represents a promising tool to understand practices that intentionally cultivate present-centeredness and openness to experience. Despite its clinical efficacy, little remains known about its means of action. Antithetic to this mode of experiential self-focus are states akin to depression, that are conducive of biased attention toward negativity, biased thoughts and rumination, and dysfunctional self schemas. The proposed research aims at implementing an innovative framework to scientifically investigate the experiential, cognitive, and neural processes underlining mindfulness practice building on the current neurocognitive understanding of the functional and anatomical architecture of cognitive control, and depression. To identify these mechanisms, this project aims to use paradigms from cognitive, and affective neuroscience (MEG, intracortical EEG, fMRI) to measure the training and plasticity of emotion regulation and cognitive control, and their effect on automatic, self-related affective processes. Using a cross-sectional design, this project aims to compare participants with trait differences in experiential self-focus mode. Using a longitudinal design, this project aims to explore mindfulness-practice training’s effect using a standard mindfulness-based intervention and an active control intervention. The PI has pioneered the neuroscientific investigation of mindfulness in the US and aspires to assemble a research team in France and a network of collaborators in Europe to pursue this research, which could lead to important outcomes for neuroscience, and mental health.
Max ERC Funding
1 868 520 €
Duration
Start date: 2014-11-01, End date: 2019-10-31
Project acronym BRAINIMAGES
Project "How do we keep apart internally generated mental images from externally induced percepts? Dissociating mental imagery, working memory and conscious perception."
Researcher (PI) Juha Tapani Silvanto
Host Institution (HI) THE UNIVERSITY OF WESTMINSTER LBG
Call Details Starting Grant (StG), SH4, ERC-2013-StG
Summary "Conscious experiences normally result from the flow of external input into our sensory systems. However, our minds are also able to create conscious percepts in the absence of any sensory stimulation; these internally generated percepts are referred to as mental images, and they have many similarities with real visual percepts; consequently, mental imagery is often referred to as “seeing in the mind’s eye”. Mental imagery is also believed to be closely related to working memory, a mechanism which can maintain “offline” representations of visual stimuli no longer in the observer’s view, as both involve internal representations of previously seen visual attributes. Indeed, visual imagery is often thought of as a conscious window into the content of memory representations. Imagery, working memory, and conscious perception are thus thought to rely on very similar mechanisms. However, in everyday life we are generally able to keep apart the constructs of our imagination from real physical events; this begs the question of how the brain distinguishes internal mental images from externally induced visual percepts. To answer this question, the proposed work aims to isolate the cortical mechanisms associated uniquely with WM and imagery independently of each other and independently of the influence of external conscious percepts. Furthermore, by the use of neuroimaging and brain stimulation, we aim to determine the cortical mechanisms which keep apart internally generated and externally induced percepts, in both health and disease. This is a question of great clinical interest, as the ability to distinguish the perceived from the imagined is impoverished in psychotic disorders. In addition to revealing the mechanisms underlying this confusion, the present project aims to alleviate it in psychotic patients by the use of brain stimulation. The project will thus significantly improve our understanding of these cognitive processes and will also have clinical implications."
Summary
"Conscious experiences normally result from the flow of external input into our sensory systems. However, our minds are also able to create conscious percepts in the absence of any sensory stimulation; these internally generated percepts are referred to as mental images, and they have many similarities with real visual percepts; consequently, mental imagery is often referred to as “seeing in the mind’s eye”. Mental imagery is also believed to be closely related to working memory, a mechanism which can maintain “offline” representations of visual stimuli no longer in the observer’s view, as both involve internal representations of previously seen visual attributes. Indeed, visual imagery is often thought of as a conscious window into the content of memory representations. Imagery, working memory, and conscious perception are thus thought to rely on very similar mechanisms. However, in everyday life we are generally able to keep apart the constructs of our imagination from real physical events; this begs the question of how the brain distinguishes internal mental images from externally induced visual percepts. To answer this question, the proposed work aims to isolate the cortical mechanisms associated uniquely with WM and imagery independently of each other and independently of the influence of external conscious percepts. Furthermore, by the use of neuroimaging and brain stimulation, we aim to determine the cortical mechanisms which keep apart internally generated and externally induced percepts, in both health and disease. This is a question of great clinical interest, as the ability to distinguish the perceived from the imagined is impoverished in psychotic disorders. In addition to revealing the mechanisms underlying this confusion, the present project aims to alleviate it in psychotic patients by the use of brain stimulation. The project will thus significantly improve our understanding of these cognitive processes and will also have clinical implications."
Max ERC Funding
1 280 680 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym BRAINMINT
Project Brains and minds in transition: The dark side of neuroplasticity during sensitive life phases
Researcher (PI) Lars T. WESTLYE
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Starting Grant (StG), SH4, ERC-2018-STG
Summary The potential and boundaries of the human mind is determined by dynamic interactions between the environment and the individual genetic architecture. However, despite several breakthroughs, the genetic revolution has not provided a coherent account of the development of the mind and its disorders, and the missing heritability is large across human traits. One explanation of this impasse is the complexity of the gene-environment interactions. Current knowledge about the determinants of a healthy mind is largely based on studies whose modus operandi is to treat the environment as a static entity, neglecting to consider the crucial fact that environmental inputs and their genetic interactions vary dramatically between life phases.
The objective of BRAINMINT is to provide this missing link by zeroing in on two major life transitions, namely adolescence and pregnancy. These phases are characterized by temporarily increased brain plasticity, offering windows for adaptation and growth, but also host the emergence of common mental disorders. I propose that a multi-level investigation with this dark side of brain plasticity as the axis mundi will add a mechanistic understanding of this link between growth and vulnerability. I will test the main hypothesis that mechanisms that boost neuroplasticity promote adaptation to a dynamic environment, but at the cost of increased risk of psychopathology if exposed to a combination of genetic and environmental triggers. To this end I will utilize cutting-edge longitudinal brain imaging, electrophysiology, rich cognitive and clinical data, immune markers, gene expression and genetics. I will leverage on massive imaging data (n>40,000) and novel tools to increase power and generalizability and improve brain- and gene-based predictions of complex traits. Aiming to help resolving one of the modern day enigmas, BRAINMINT is a pioneering and high risk/high gain effort to find mechanisms of brain plasticity that support and harm the brain.
Summary
The potential and boundaries of the human mind is determined by dynamic interactions between the environment and the individual genetic architecture. However, despite several breakthroughs, the genetic revolution has not provided a coherent account of the development of the mind and its disorders, and the missing heritability is large across human traits. One explanation of this impasse is the complexity of the gene-environment interactions. Current knowledge about the determinants of a healthy mind is largely based on studies whose modus operandi is to treat the environment as a static entity, neglecting to consider the crucial fact that environmental inputs and their genetic interactions vary dramatically between life phases.
The objective of BRAINMINT is to provide this missing link by zeroing in on two major life transitions, namely adolescence and pregnancy. These phases are characterized by temporarily increased brain plasticity, offering windows for adaptation and growth, but also host the emergence of common mental disorders. I propose that a multi-level investigation with this dark side of brain plasticity as the axis mundi will add a mechanistic understanding of this link between growth and vulnerability. I will test the main hypothesis that mechanisms that boost neuroplasticity promote adaptation to a dynamic environment, but at the cost of increased risk of psychopathology if exposed to a combination of genetic and environmental triggers. To this end I will utilize cutting-edge longitudinal brain imaging, electrophysiology, rich cognitive and clinical data, immune markers, gene expression and genetics. I will leverage on massive imaging data (n>40,000) and novel tools to increase power and generalizability and improve brain- and gene-based predictions of complex traits. Aiming to help resolving one of the modern day enigmas, BRAINMINT is a pioneering and high risk/high gain effort to find mechanisms of brain plasticity that support and harm the brain.
Max ERC Funding
1 446 113 €
Duration
Start date: 2019-08-01, End date: 2024-07-31
Project acronym BRAINSYNC
Project Brain-environment synchrony and the auditory perception problem
Researcher (PI) Molly HENRY
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Starting Grant (StG), SH4, ERC-2018-STG
Summary Synchronization of brain rhythms to the rhythms of sounds is a foundational mechanism for auditory perception. However, we know very little about why brain–environment synchrony might fail, leading to auditory perception problems like impaired speech comprehension that negatively impact quality of life. The proposed research program fills this knowledge gap in three stages: 1) Predicting auditory perception, and individual differences thereof, from the fit between neural dynamics and environment; 2) Perturbing the relationship between brain and environment to experimentally test the limits of and protective factors for brain–environment synchronization; 3) Translating gained knowledge to understand age-related dysfunctions in brain–environment synchrony and auditory perception. Stage 1 uses behavioural and neural properties of neural oscillators – brain regions and networks that generate rhythmic neural activity – to predict individual differences in brain–environment synchronization. Stage 2 assesses when and why auditory perception fails, and how auditory perception might be insulated by good brain–environment fit and neural flexibility, by challenging the brain’s ability to adapt to auditory rhythms. Stage 2 has strong potential to provide insight into compensatory listening strategies that may be adopted when neural entrainment is effortful or impossible. Stage 3 places special emphasis on listening difficulties that develop with age, and tests the hypotheses that 1) speech comprehension difficulties stem from reduced neural entrainment in older age, and 2) reduced entrainment for older adults results from age-related changes to neural flexibility. Noninvasive brain stimulation will be used to temporarily remedy these deficits by improving brain–environment synchrony. The research program will account for much currently unexplained individual variance in auditory perception, and will inspire novel interventions to support auditory perception in advancing age.
Summary
Synchronization of brain rhythms to the rhythms of sounds is a foundational mechanism for auditory perception. However, we know very little about why brain–environment synchrony might fail, leading to auditory perception problems like impaired speech comprehension that negatively impact quality of life. The proposed research program fills this knowledge gap in three stages: 1) Predicting auditory perception, and individual differences thereof, from the fit between neural dynamics and environment; 2) Perturbing the relationship between brain and environment to experimentally test the limits of and protective factors for brain–environment synchronization; 3) Translating gained knowledge to understand age-related dysfunctions in brain–environment synchrony and auditory perception. Stage 1 uses behavioural and neural properties of neural oscillators – brain regions and networks that generate rhythmic neural activity – to predict individual differences in brain–environment synchronization. Stage 2 assesses when and why auditory perception fails, and how auditory perception might be insulated by good brain–environment fit and neural flexibility, by challenging the brain’s ability to adapt to auditory rhythms. Stage 2 has strong potential to provide insight into compensatory listening strategies that may be adopted when neural entrainment is effortful or impossible. Stage 3 places special emphasis on listening difficulties that develop with age, and tests the hypotheses that 1) speech comprehension difficulties stem from reduced neural entrainment in older age, and 2) reduced entrainment for older adults results from age-related changes to neural flexibility. Noninvasive brain stimulation will be used to temporarily remedy these deficits by improving brain–environment synchrony. The research program will account for much currently unexplained individual variance in auditory perception, and will inspire novel interventions to support auditory perception in advancing age.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym Breakborder
Project Breaking borders, Functional genetic screens of structural regulatory DNA elements
Researcher (PI) Reuven AGAMI
Host Institution (HI) STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Call Details Advanced Grant (AdG), LS4, ERC-2018-ADG
Summary The human genome carries genetic information in two distinct forms: Transcribed genes and regulatory DNA elements (rDEs). rDEs control the magnitude and pattern of gene expression, and are indispensable for organismal development and cellular homeostasis. Nevertheless, while large-scale functional genetic screens greatly advanced our knowledge in studying mammalian genes, such tools to study rDEs were lacking, impeding scientific progress. Interestingly, recent advance in genome editing technologies has not only expanded the available screening toolbox to examine genes, but also opened up novel opportunities in studying rDEs. We distinguish two types of rDEs: Transcriptional rDEs that recruit transcription factors to enhancers, and structural rDEs that maintain chromatin 3D structure to insulate transcriptional activities, a feature postulated to be essential for gene expression regulation by enhancers. Recently, we developed a CRISPR strategy to target enhancers. We showed its scalability and effectivity in identifying potential oncogenic and tumour-suppressive enhancers. Here, we will exploit this line of research and develop novel strategies to target structural rDEs (e.g. insulators). By setting up functional genetic screens, we will identify key players in cell proliferation, differentiation, and survival, which are related to cancer development, metastasis induction, and acquired therapy resistance. We will validate key insulators and decipher underlying mechanisms of action that control phenotypes. In a parallel approach, we will analyse whole genome sequencing datasets of cancer to identify and characterize genetic aberrations occurring in the identified regions. Altogether, the outlined research plan forms a natural extension of our successful functional approaches to study gene regulation. Our results will setup the foundation to better understand principles of chromatin architecture in gene expression regulation in development and cancer.
Summary
The human genome carries genetic information in two distinct forms: Transcribed genes and regulatory DNA elements (rDEs). rDEs control the magnitude and pattern of gene expression, and are indispensable for organismal development and cellular homeostasis. Nevertheless, while large-scale functional genetic screens greatly advanced our knowledge in studying mammalian genes, such tools to study rDEs were lacking, impeding scientific progress. Interestingly, recent advance in genome editing technologies has not only expanded the available screening toolbox to examine genes, but also opened up novel opportunities in studying rDEs. We distinguish two types of rDEs: Transcriptional rDEs that recruit transcription factors to enhancers, and structural rDEs that maintain chromatin 3D structure to insulate transcriptional activities, a feature postulated to be essential for gene expression regulation by enhancers. Recently, we developed a CRISPR strategy to target enhancers. We showed its scalability and effectivity in identifying potential oncogenic and tumour-suppressive enhancers. Here, we will exploit this line of research and develop novel strategies to target structural rDEs (e.g. insulators). By setting up functional genetic screens, we will identify key players in cell proliferation, differentiation, and survival, which are related to cancer development, metastasis induction, and acquired therapy resistance. We will validate key insulators and decipher underlying mechanisms of action that control phenotypes. In a parallel approach, we will analyse whole genome sequencing datasets of cancer to identify and characterize genetic aberrations occurring in the identified regions. Altogether, the outlined research plan forms a natural extension of our successful functional approaches to study gene regulation. Our results will setup the foundation to better understand principles of chromatin architecture in gene expression regulation in development and cancer.
Max ERC Funding
2 497 000 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym BreakingBarriers
Project Targeting endothelial barriers to combat disease
Researcher (PI) Anne Eichmann
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Advanced Grant (AdG), LS4, ERC-2018-ADG
Summary Tissue homeostasis requires coordinated barrier function in blood and lymphatic vessels. Opening of junctions between endothelial cells (ECs) lining blood vessels leads to tissue fluid accumulation that is drained by lymphatic vessels. A pathological increase in blood vessel permeability or lack or malfunction of lymphatic vessels leads to edema and associated defects in macromolecule and immune cell clearance. Unbalanced barrier function between blood and lymphatic vessels contributes to neurodegeneration, chronic inflammation, and cardiovascular disease. In this proposal, we seek to gain mechanistic understanding into coordination of barrier function between blood and lymphatic vessels, how this process is altered in disease models and how it can be manipulated for therapeutic purposes. We will focus on two critical barriers with diametrically opposing functions, the blood-brain barrier (BBB) and the lymphatic capillary barrier (LCB). ECs of the BBB form very tight junctions that restrict paracellular access to the brain. In contrast, open junctions of the LCB ensure uptake of extravasated fluid, macromolecules and immune cells, as well as lipid in the gut. We have identified novel effectors of BBB and LCB junctions and will determine their role in adult homeostasis and in disease models. Mouse genetic gain and loss of function approaches in combination with histological, ultrastructural, functional and molecular analysis will determine mechanisms underlying formation of tissue specific EC barriers. Deliverables include in vivo validated targets that could be used for i) opening the BBB on demand for drug delivery into the brain, and ii) to lower plasma lipid uptake via interfering with the LCB, with implications for prevention of obesity, cardiovascular disease and inflammation. These pioneering studies promise to open up new opportunities for research and treatment of neurovascular and cardiovascular disease.
Summary
Tissue homeostasis requires coordinated barrier function in blood and lymphatic vessels. Opening of junctions between endothelial cells (ECs) lining blood vessels leads to tissue fluid accumulation that is drained by lymphatic vessels. A pathological increase in blood vessel permeability or lack or malfunction of lymphatic vessels leads to edema and associated defects in macromolecule and immune cell clearance. Unbalanced barrier function between blood and lymphatic vessels contributes to neurodegeneration, chronic inflammation, and cardiovascular disease. In this proposal, we seek to gain mechanistic understanding into coordination of barrier function between blood and lymphatic vessels, how this process is altered in disease models and how it can be manipulated for therapeutic purposes. We will focus on two critical barriers with diametrically opposing functions, the blood-brain barrier (BBB) and the lymphatic capillary barrier (LCB). ECs of the BBB form very tight junctions that restrict paracellular access to the brain. In contrast, open junctions of the LCB ensure uptake of extravasated fluid, macromolecules and immune cells, as well as lipid in the gut. We have identified novel effectors of BBB and LCB junctions and will determine their role in adult homeostasis and in disease models. Mouse genetic gain and loss of function approaches in combination with histological, ultrastructural, functional and molecular analysis will determine mechanisms underlying formation of tissue specific EC barriers. Deliverables include in vivo validated targets that could be used for i) opening the BBB on demand for drug delivery into the brain, and ii) to lower plasma lipid uptake via interfering with the LCB, with implications for prevention of obesity, cardiovascular disease and inflammation. These pioneering studies promise to open up new opportunities for research and treatment of neurovascular and cardiovascular disease.
Max ERC Funding
2 499 969 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym BRITE
Project Elucidating the molecular mechanisms underlying brite adipocyte specification and activation
Researcher (PI) Ferdinand VON MEYENN
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), LS4, ERC-2018-STG
Summary Brown adipocytes can dissipate energy in a process called adaptive thermogenesis. Whilst the classical brown adipose tissue (BAT) depots disappear during early life in humans, cold exposure can promote the appearance of brown-like adipocytes within the white adipose tissue (WAT), termed brite (brown-in-white). Increased BAT activity results in increased energy expenditure and has been correlated with leanness in humans. Hence, recruitment of brite adipocytes may constitute a promising therapeutic strategy to treat obesity and its associated metabolic diseases. Despite the beneficial metabolic properties of brown and brite adipocytes, little is known about the molecular mechanisms underlying their specification and activation in vivo. This proposal focuses on understanding the complex biology of thermogenic adipocyte biology by studying the epigenetic and transcriptional aspects of WAT britening and BAT recruitment in vivo to identify pathways of therapeutic relevance and to better define the brite precursor cells. Specific aims are to 1) investigate epigenetic and transcriptional states and heterogeneity in human and mouse adipose tissue; 2) develop a novel time-resolved method to correlate preceding chromatin states and cell fate decisions during adipose tissue remodelling; 3) identify and validate key (drugable) epigenetic and transcriptional regulators involved in brite adipocyte specification. Experimentally, I will use adipose tissue samples from human donors and mouse models, to asses at the single-cell level cellular heterogeneity, transcriptional and epigenetic states, to identify subpopulations, and to define the adaptive responses to cold or β-adrenergic stimulation. Using computational methods and in vitro and in vivo validation experiments, I will define epigenetic and transcriptional networks that control WAT britening, and develop a model of the molecular events underlying adipocyte tissue plasticity.
Summary
Brown adipocytes can dissipate energy in a process called adaptive thermogenesis. Whilst the classical brown adipose tissue (BAT) depots disappear during early life in humans, cold exposure can promote the appearance of brown-like adipocytes within the white adipose tissue (WAT), termed brite (brown-in-white). Increased BAT activity results in increased energy expenditure and has been correlated with leanness in humans. Hence, recruitment of brite adipocytes may constitute a promising therapeutic strategy to treat obesity and its associated metabolic diseases. Despite the beneficial metabolic properties of brown and brite adipocytes, little is known about the molecular mechanisms underlying their specification and activation in vivo. This proposal focuses on understanding the complex biology of thermogenic adipocyte biology by studying the epigenetic and transcriptional aspects of WAT britening and BAT recruitment in vivo to identify pathways of therapeutic relevance and to better define the brite precursor cells. Specific aims are to 1) investigate epigenetic and transcriptional states and heterogeneity in human and mouse adipose tissue; 2) develop a novel time-resolved method to correlate preceding chromatin states and cell fate decisions during adipose tissue remodelling; 3) identify and validate key (drugable) epigenetic and transcriptional regulators involved in brite adipocyte specification. Experimentally, I will use adipose tissue samples from human donors and mouse models, to asses at the single-cell level cellular heterogeneity, transcriptional and epigenetic states, to identify subpopulations, and to define the adaptive responses to cold or β-adrenergic stimulation. Using computational methods and in vitro and in vivo validation experiments, I will define epigenetic and transcriptional networks that control WAT britening, and develop a model of the molecular events underlying adipocyte tissue plasticity.
Max ERC Funding
1 552 620 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym BROKEX
Project Brokering China’s Extraversion: An Ethnographic Analysis of Transnational Arbitration
Researcher (PI) Heidi Østbø HAUGEN
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Starting Grant (StG), SH2, ERC-2018-STG
Summary Chinese global engagements are deepening across sectors and geographic regions. The objective of BROKEX is to fill specific gaps in knowledge about how China’s extraversion advances. The project takes an original approach by examining brokers who mediate in transnational fields. It opens the “black box” of China’s global integration by moving beyond descriptions of input and output characteristics to elucidate underlying dynamics. The objective will be achieved in two phases. First, the PI and two postdoctoral researchers will carry out ethnographic case studies in the Pearl River Delta, South China, that yield complementary information on the common challenge of brokering across geographic scales: * Connecting low-cost Chinese manufacturing with African markets; * Integrating Chinese academic research with global scientific communities; * Transnational architecture production. The diverse cases offer insights into the mechanisms of brokerage across distinctive sectors. In the second step, we build on the empirical findings and literature to develop brokerage theory. Social scientific research on brokerage commonly uses the morphology of social networks as its starting point, and focuses on how actors positioned at the intersection between groups operate. BROKEX adopts an innovative approach by examining how actors strategically seek to shape network morphologies in order to bridge gaps between groups. By directing theoretical attention towards relationship formation that precedes acts of brokerage, this line of inquiry advances understandings of how and why brokered connections emerge. Ethnographic case studies combined with critical theorization will generate new knowledge about the processes beneath the “rise of China” ─ one of the most consequential socioeconomic developments of our times.
Summary
Chinese global engagements are deepening across sectors and geographic regions. The objective of BROKEX is to fill specific gaps in knowledge about how China’s extraversion advances. The project takes an original approach by examining brokers who mediate in transnational fields. It opens the “black box” of China’s global integration by moving beyond descriptions of input and output characteristics to elucidate underlying dynamics. The objective will be achieved in two phases. First, the PI and two postdoctoral researchers will carry out ethnographic case studies in the Pearl River Delta, South China, that yield complementary information on the common challenge of brokering across geographic scales: * Connecting low-cost Chinese manufacturing with African markets; * Integrating Chinese academic research with global scientific communities; * Transnational architecture production. The diverse cases offer insights into the mechanisms of brokerage across distinctive sectors. In the second step, we build on the empirical findings and literature to develop brokerage theory. Social scientific research on brokerage commonly uses the morphology of social networks as its starting point, and focuses on how actors positioned at the intersection between groups operate. BROKEX adopts an innovative approach by examining how actors strategically seek to shape network morphologies in order to bridge gaps between groups. By directing theoretical attention towards relationship formation that precedes acts of brokerage, this line of inquiry advances understandings of how and why brokered connections emerge. Ethnographic case studies combined with critical theorization will generate new knowledge about the processes beneath the “rise of China” ─ one of the most consequential socioeconomic developments of our times.
Max ERC Funding
1 490 773 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
