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 C.o.C.O.
Project Circuits of con-specific observation
Researcher (PI) Marta De Aragao Pacheco Moita
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Starting Grant (StG), LS5, ERC-2013-StG
Summary A great deal is known about the neural basis of associative fear learning. However, many animal species are able to use social cues to recognize threats, a defence mechanism that may be less costly than learning from self-experience. We have previously shown that rats perceive the cessation of movement-evoked sound as a signal of danger and its resumption as a signal of safety. To study transmission of fear between rats we assessed the behavior of an observer while witnessing a demonstrator rat display fear responses. With this paradigm we will take advantage of the accumulated knowledge on learned fear to investigate the neural mechanisms by which the social environment regulates defense behaviors. We will unravel the neural circuits involved in detecting the transition from movement-evoked sound to silence. Moreover, since observer rats previously exposed to shock display observational freezing, but naive observer rats do not, we will determine the mechanism by which prior experience contribute to observational freezing. To this end, we will focus on the amygdala, crucial for fear learning and expression, and its auditory inputs, combining immunohistochemistry, pharmacology and optogenetics. Finally, as the detection of and responses to threat are often inherently social, we will study these behaviors in the context of large groups of individuals. To circumvent the serious limitations in using large populations of rats, we will resort to a different model system. The fruit fly is the ideal model system, as it is both amenable to the search for the neural mechanism of behavior, while at the same time allowing the study of the behavior of large groups of individuals. We will develop behavioral tasks, where conditioned demonstrator flies signal danger to other naïve ones. These experiments unravel how the brain uses defense behaviors as signals of danger and how it contributes to defense mechanisms at the population level.
Summary
A great deal is known about the neural basis of associative fear learning. However, many animal species are able to use social cues to recognize threats, a defence mechanism that may be less costly than learning from self-experience. We have previously shown that rats perceive the cessation of movement-evoked sound as a signal of danger and its resumption as a signal of safety. To study transmission of fear between rats we assessed the behavior of an observer while witnessing a demonstrator rat display fear responses. With this paradigm we will take advantage of the accumulated knowledge on learned fear to investigate the neural mechanisms by which the social environment regulates defense behaviors. We will unravel the neural circuits involved in detecting the transition from movement-evoked sound to silence. Moreover, since observer rats previously exposed to shock display observational freezing, but naive observer rats do not, we will determine the mechanism by which prior experience contribute to observational freezing. To this end, we will focus on the amygdala, crucial for fear learning and expression, and its auditory inputs, combining immunohistochemistry, pharmacology and optogenetics. Finally, as the detection of and responses to threat are often inherently social, we will study these behaviors in the context of large groups of individuals. To circumvent the serious limitations in using large populations of rats, we will resort to a different model system. The fruit fly is the ideal model system, as it is both amenable to the search for the neural mechanism of behavior, while at the same time allowing the study of the behavior of large groups of individuals. We will develop behavioral tasks, where conditioned demonstrator flies signal danger to other naïve ones. These experiments unravel how the brain uses defense behaviors as signals of danger and how it contributes to defense mechanisms at the population level.
Max ERC Funding
1 412 376 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
Project acronym CELLFITNESS
Project Active Mechanisms of Cell Selection: From Cell Competition to Cell Fitness
Researcher (PI) Eduardo Moreno Lampaya
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Consolidator Grant (CoG), LS3, ERC-2013-CoG
Summary The molecular mechanisms that mediate cell competition, cell fitness and cell selection is gaining interest. With innovative approaches, molecules and ground-breaking hypothesis, this field of research can help understand several biological processes such as development, cancer and tissue degeneration. The project has 3 clear and ambitious objectives: 1. We propose to identify all the key genes mediating cell competition and their molecular mechanisms. In order to reach this objective we will use data from two whole genome screens in Drosophila where we have identified 7 key genes. By the end of this CoG grant, we should have no big gaps in our knowledge of how slow dividing cells are recognised and eliminated in Drosophila. 2. In addition, we will explore how general the cell competition pathways are and how they can impact biomedical research, with a focus in cancer and tissue degeneration. The interest in cancer is based on experiments in Drosophila and mice where we and others have found that an active process of cell selection determines tumour growth. Preliminary results suggest that the pathways identified do not only play important roles in the elimination of slow dividing cells, but also during cancer initiation and progression. 3. We will further explore the role of cell competition in neuronal selection, specially during neurodegeneration, development of the retina and adult brain regeneration in Drosophila. This proposal is of an interdisciplinary nature because it takes a basic cellular mechanism (the genetic pathways that select cells within tissues) and crosses boundaries between different fields of research: development, cancer, regeneration and tissue degeneration. In this ERC CoG proposal, we are committed to continue our efforts from basic science to biomedical approaches. The phenomena of cell competition and its participating genes have the potential to discover novel biomarkers and therapeutic strategies against cancer and tissue degeneration.
Summary
The molecular mechanisms that mediate cell competition, cell fitness and cell selection is gaining interest. With innovative approaches, molecules and ground-breaking hypothesis, this field of research can help understand several biological processes such as development, cancer and tissue degeneration. The project has 3 clear and ambitious objectives: 1. We propose to identify all the key genes mediating cell competition and their molecular mechanisms. In order to reach this objective we will use data from two whole genome screens in Drosophila where we have identified 7 key genes. By the end of this CoG grant, we should have no big gaps in our knowledge of how slow dividing cells are recognised and eliminated in Drosophila. 2. In addition, we will explore how general the cell competition pathways are and how they can impact biomedical research, with a focus in cancer and tissue degeneration. The interest in cancer is based on experiments in Drosophila and mice where we and others have found that an active process of cell selection determines tumour growth. Preliminary results suggest that the pathways identified do not only play important roles in the elimination of slow dividing cells, but also during cancer initiation and progression. 3. We will further explore the role of cell competition in neuronal selection, specially during neurodegeneration, development of the retina and adult brain regeneration in Drosophila. This proposal is of an interdisciplinary nature because it takes a basic cellular mechanism (the genetic pathways that select cells within tissues) and crosses boundaries between different fields of research: development, cancer, regeneration and tissue degeneration. In this ERC CoG proposal, we are committed to continue our efforts from basic science to biomedical approaches. The phenomena of cell competition and its participating genes have the potential to discover novel biomarkers and therapeutic strategies against cancer and tissue degeneration.
Max ERC Funding
1 968 062 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym DYNEINOME
Project Cytoplasmic Dynein: Mechanisms of Regulation and Novel Interactors
Researcher (PI) Reto Gassmann
Host Institution (HI) INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC
Call Details Starting Grant (StG), LS3, ERC-2013-StG
Summary "The megadalton cytoplasmic dynein complex, whose motor subunit is encoded by a single gene, provides the major microtubule minus end-directed motility in cells and is essential for a wide range of processes, ranging from the transport of proteins, RNA, and membrane vesicles to nuclear migration and cell division. To achieve this stunning functional diversity, cytoplasmic dynein is subject to tight regulation by co-factors that modulate localization, interaction with cargo, and motor activity. At present, our knowledge of the underlying mechanisms remains limited. An overarching goal of this proposal is to gain an understanding of how interactions with diverse adaptor proteins regulate dynein function in space and time. We choose the nematode C. elegans as our model system, because it will enable us to study the biology of dynein regulation in the broad context of a metazoan organism. The nematode’s versatile genetic tools, its biochemical tractability, and the powerful molecular replacement technologies available, this makes for a uniquely attractive experimental system to address the mechanisms employed by dynein regulators through a combination of biochemical, proteomic, and cell biological assays. Specifically, we propose to use a biochemical reconstitution approach to obtain a detailed molecular picture of how dynein is targeted to the mitotic kinetochore; we will perform a forward genetic and proteomic screen to expand the so-far limited inventory of metazoan dynein interactors, whose functional characterization will shed light on known dynein-dependent processes and lead to novel unanticipated lines of research into dynein regulation; we will dissect the function and regulation of the most important dynein co-factor, the multi-subunit dynactin complex; and finally we will strive to establish a novel C. elegans model for human neurodegenerative disease, based on pathogenic point mutations in a dynactin subunit."
Summary
"The megadalton cytoplasmic dynein complex, whose motor subunit is encoded by a single gene, provides the major microtubule minus end-directed motility in cells and is essential for a wide range of processes, ranging from the transport of proteins, RNA, and membrane vesicles to nuclear migration and cell division. To achieve this stunning functional diversity, cytoplasmic dynein is subject to tight regulation by co-factors that modulate localization, interaction with cargo, and motor activity. At present, our knowledge of the underlying mechanisms remains limited. An overarching goal of this proposal is to gain an understanding of how interactions with diverse adaptor proteins regulate dynein function in space and time. We choose the nematode C. elegans as our model system, because it will enable us to study the biology of dynein regulation in the broad context of a metazoan organism. The nematode’s versatile genetic tools, its biochemical tractability, and the powerful molecular replacement technologies available, this makes for a uniquely attractive experimental system to address the mechanisms employed by dynein regulators through a combination of biochemical, proteomic, and cell biological assays. Specifically, we propose to use a biochemical reconstitution approach to obtain a detailed molecular picture of how dynein is targeted to the mitotic kinetochore; we will perform a forward genetic and proteomic screen to expand the so-far limited inventory of metazoan dynein interactors, whose functional characterization will shed light on known dynein-dependent processes and lead to novel unanticipated lines of research into dynein regulation; we will dissect the function and regulation of the most important dynein co-factor, the multi-subunit dynactin complex; and finally we will strive to establish a novel C. elegans model for human neurodegenerative disease, based on pathogenic point mutations in a dynactin subunit."
Max ERC Funding
1 367 466 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym EpiMechanism
Project Mechanisms of Chromatin-based Epigenetic Inheritance
Researcher (PI) Lars Jansen
Host Institution (HI) FUNDACAO CALOUSTE GULBENKIAN
Call Details Consolidator Grant (CoG), LS3, ERC-2013-CoG
Summary Epigenetic mechanisms heritably maintain gene expression states and chromosome organization across cell division. These include chromatin-based factors that are propagated independent of local DNA sequence elements, and are critical for normal development and prevent reprogramming, e.g. during induction of pluripotency. We focus on the role of nucleosomes, the histone-DNA complexes that make up chromatin. While prominently implicated in epigenetic memory, how histones and their local modifications can actually be inherited is largely unknown. We take aim at three fundamental aspects that we argue are central to this problem: stability of the epigenetic mark, self-templated duplication, and cell cycle coupling.
We developed a unique pulse-labeling strategy to determine whether silent and active chromatin can be inherited and how this relates to transcription, both in cancer cells and in vitro differentiating stem cells. By coupling this strategy to an imaging-based RNAi screen we aim to identify components controlling nucleosome assembly and heritability. We achieve this by focusing on the human centromere, the chromosome locus essential for chromosome segregation which serves as an ideal model for epigenetic memory. This locus is specified by nucleosomes carrying the histone H3 variant, CENP-A that we have previously shown to be highly stable in cycling cells and to be replicated in a strict cell cycle coupled manner. We build on our previous successes to uncover the molecular mechanism and cellular consequences of the coupling between CENP-A propagation and the cell cycle which we postulate, ensures proper centromere size and mitotic fidelity. Furthermore, by genome engineering we developed a strategy to delete an endogenous centromere to determine how centromeres can form de novo and how CENP-A chromatin, once formed, can template its own duplication. With this multi-facetted approach we aim to uncover general mechanistic principles of chromatin-based memory.
Summary
Epigenetic mechanisms heritably maintain gene expression states and chromosome organization across cell division. These include chromatin-based factors that are propagated independent of local DNA sequence elements, and are critical for normal development and prevent reprogramming, e.g. during induction of pluripotency. We focus on the role of nucleosomes, the histone-DNA complexes that make up chromatin. While prominently implicated in epigenetic memory, how histones and their local modifications can actually be inherited is largely unknown. We take aim at three fundamental aspects that we argue are central to this problem: stability of the epigenetic mark, self-templated duplication, and cell cycle coupling.
We developed a unique pulse-labeling strategy to determine whether silent and active chromatin can be inherited and how this relates to transcription, both in cancer cells and in vitro differentiating stem cells. By coupling this strategy to an imaging-based RNAi screen we aim to identify components controlling nucleosome assembly and heritability. We achieve this by focusing on the human centromere, the chromosome locus essential for chromosome segregation which serves as an ideal model for epigenetic memory. This locus is specified by nucleosomes carrying the histone H3 variant, CENP-A that we have previously shown to be highly stable in cycling cells and to be replicated in a strict cell cycle coupled manner. We build on our previous successes to uncover the molecular mechanism and cellular consequences of the coupling between CENP-A propagation and the cell cycle which we postulate, ensures proper centromere size and mitotic fidelity. Furthermore, by genome engineering we developed a strategy to delete an endogenous centromere to determine how centromeres can form de novo and how CENP-A chromatin, once formed, can template its own duplication. With this multi-facetted approach we aim to uncover general mechanistic principles of chromatin-based memory.
Max ERC Funding
1 621 400 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym INTIMATE
Project "Citizenship, Care and Choice: The Micropolitics of Intimacy in Southern Europe"
Researcher (PI) Ana Cristina Alvarez Caiano Da Silva Santos
Host Institution (HI) CENTRO DE ESTUDOS SOCIAIS
Call Details Starting Grant (StG), SH2, ERC-2013-StG
Summary "Changes in personal life in recent decades illustrate significant socio-cultural transformations. However, the focus of mainstream sociological literature has been the heterosexual, monogamic and reproductive couple, with little research exploring non-conventional intimacy in Southern Europe. INTIMATE’s main aim is to contribute to legal, policy and cultural innovation through the findings of a comparative, empirically-grounded, research project designed to rethink citizenship, care and choice from the point of view of 'non-standard intimacies' (Berlant and Warner, 2000) in 3 contrasting Southern European countries: Italy, Portugal and Spain.
Guided by the fundamental sociological question of how change takes place and, concomitantly, how law and social policy adjust to and/or shape the practices and expectations of individuals concerning personal life, this research will address intimacy from the perspective of those on the margins of social, legal and policy concerns in Southern Europe – lesbians, gay men, bisexuals and transgendered people.
INTIMATE is based on 3 strands – Strand 1: the micropolitics of partnering; Strand 2: the micropolitics of parenting; and Strand 3: the micropolitics of friendship. The notion of micropolitics enables a double focus on everyday practices and expectations (biographic dimension) within the wider contextual framework of law and social policy (socio-legal dimension).
This qualitative research involves conducting 6 cross-national qualitative studies across the strands of partnering, parenting and friendship in each of the chosen countries. Topics covered are lesbian coupledom, polyamorous relationships, assisted conception and surrogacy, naming a child, transgender and care, and living with friends in adult life.
Expected results include a range of both international and national publications targeting academia and beyond, thematic conferences and participatory workshops, policy briefs, media briefs and an interactive website."
Summary
"Changes in personal life in recent decades illustrate significant socio-cultural transformations. However, the focus of mainstream sociological literature has been the heterosexual, monogamic and reproductive couple, with little research exploring non-conventional intimacy in Southern Europe. INTIMATE’s main aim is to contribute to legal, policy and cultural innovation through the findings of a comparative, empirically-grounded, research project designed to rethink citizenship, care and choice from the point of view of 'non-standard intimacies' (Berlant and Warner, 2000) in 3 contrasting Southern European countries: Italy, Portugal and Spain.
Guided by the fundamental sociological question of how change takes place and, concomitantly, how law and social policy adjust to and/or shape the practices and expectations of individuals concerning personal life, this research will address intimacy from the perspective of those on the margins of social, legal and policy concerns in Southern Europe – lesbians, gay men, bisexuals and transgendered people.
INTIMATE is based on 3 strands – Strand 1: the micropolitics of partnering; Strand 2: the micropolitics of parenting; and Strand 3: the micropolitics of friendship. The notion of micropolitics enables a double focus on everyday practices and expectations (biographic dimension) within the wider contextual framework of law and social policy (socio-legal dimension).
This qualitative research involves conducting 6 cross-national qualitative studies across the strands of partnering, parenting and friendship in each of the chosen countries. Topics covered are lesbian coupledom, polyamorous relationships, assisted conception and surrogacy, naming a child, transgender and care, and living with friends in adult life.
Expected results include a range of both international and national publications targeting academia and beyond, thematic conferences and participatory workshops, policy briefs, media briefs and an interactive website."
Max ERC Funding
1 462 537 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym NEURALCHUNK
Project Neural bases of action chunking in basal ganglia subcircuits
Researcher (PI) Rui Manuel Marques Fernandes Da Costa
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary "Chunking allows the brain to efficiently organize memories and actions. Although basal ganglia circuits have been implicated in action chunking, little is known about how individual elements are concatenated into a behavioral unit at the neuronal level. Using a differential reinforcement procedure where mice learn to chunk rapid action sequences, we uncovered neuronal activity encoding entire sequences as single actions in basal ganglia circuits. Besides activity signaling sequence initiation (start), we found neurons with sustained or inhibited activity throughout the execution of an entire sequence. These findings clearly show that basal ganglia circuits display neural activity related to the execution of whole action sequences, rather than unitary elements. Neurons with start, sustained and inhibited sequence-related activity were observed throughout the basal ganglia, namely in the main input (striatum), and output (substantia nigra reticulata) nuclei of the basal ganglia. However, the basal ganglia have different cell types/subcircuits linking input to output, the so called direct ves. indirect pathways. Furthermore, basal ganglia output projects to different target areas. Here we will 1) determine if these correlates of motor concatenation are differentially expressed in direct versus indirect basal ganglia pathways by optogenetic identification of cell types in the striatum and in vivo imaging, 2) test the necessity and sufficiency of these two pathways in action sequence initiation and performance, and 3) test if different basal ganglia output circuits express and mediate different aspects of action chunking. These experiments will dissect with unprecedented spatial and temporal precision the role of basal ganglia subcircuits in the initiation and performance of action chunks."
Summary
"Chunking allows the brain to efficiently organize memories and actions. Although basal ganglia circuits have been implicated in action chunking, little is known about how individual elements are concatenated into a behavioral unit at the neuronal level. Using a differential reinforcement procedure where mice learn to chunk rapid action sequences, we uncovered neuronal activity encoding entire sequences as single actions in basal ganglia circuits. Besides activity signaling sequence initiation (start), we found neurons with sustained or inhibited activity throughout the execution of an entire sequence. These findings clearly show that basal ganglia circuits display neural activity related to the execution of whole action sequences, rather than unitary elements. Neurons with start, sustained and inhibited sequence-related activity were observed throughout the basal ganglia, namely in the main input (striatum), and output (substantia nigra reticulata) nuclei of the basal ganglia. However, the basal ganglia have different cell types/subcircuits linking input to output, the so called direct ves. indirect pathways. Furthermore, basal ganglia output projects to different target areas. Here we will 1) determine if these correlates of motor concatenation are differentially expressed in direct versus indirect basal ganglia pathways by optogenetic identification of cell types in the striatum and in vivo imaging, 2) test the necessity and sufficiency of these two pathways in action sequence initiation and performance, and 3) test if different basal ganglia output circuits express and mediate different aspects of action chunking. These experiments will dissect with unprecedented spatial and temporal precision the role of basal ganglia subcircuits in the initiation and performance of action chunks."
Max ERC Funding
1 998 600 €
Duration
Start date: 2014-11-01, End date: 2019-10-31
Project acronym PHONICS
Project Positioning the nucleus for cell migration and muscle fiber function
Researcher (PI) Edgar Rodrigues Almeida Gomes
Host Institution (HI) INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Call Details Consolidator Grant (CoG), LS4, ERC-2013-CoG
Summary The cell nucleus is positioned at specific places within the cytoplasm and this position is important for different cellular, developmental and physiological processes. Nuclear positioning depends on connections between nuclear envelope proteins and the cytoskeleton. In migrating cells, we found that the nucleus is positioned away from the front of the cell and this event is important for cell migration. We performed an RNAi screen for nuclear positioning and found new nuclear envelope proteins involved in nuclear positioning. In fully developed myofibers, nuclei are specifically positioned at the periphery of the myofiber, while during development and regeneration, as well as in multiple muscle pathologies, the nucleus is centrally positioned. We found new mechanisms drive nuclear movement during myofiber formation. We also showed that nuclear position is important for muscle function. However why nuclear positioning is important for myofiber activity remains an open question.
We now propose to use unique systems to monitor cell migration and myofiber formation in combination with biochemistry, cell biology, high- and super-resolution microscopy approaches to:
1) Identify novel molecular mechanisms that mediate nuclear positioning during cell migration and myofiber formation.
3) Determine a role for nuclear positioning in myofiber function as well as the significance of altered nuclear positioning in different forms of muscle pathology.
The proposed work will establish new mechanisms for nuclear positioning. Importantly, by identifying mechanisms and understanding the role of nuclear positioning in myofiber function, we will lay the foundations for future studies to ameliorate or treat muscle disorders as well as other conditions where nucleus positioning may prove to play a role such as cancer.
Summary
The cell nucleus is positioned at specific places within the cytoplasm and this position is important for different cellular, developmental and physiological processes. Nuclear positioning depends on connections between nuclear envelope proteins and the cytoskeleton. In migrating cells, we found that the nucleus is positioned away from the front of the cell and this event is important for cell migration. We performed an RNAi screen for nuclear positioning and found new nuclear envelope proteins involved in nuclear positioning. In fully developed myofibers, nuclei are specifically positioned at the periphery of the myofiber, while during development and regeneration, as well as in multiple muscle pathologies, the nucleus is centrally positioned. We found new mechanisms drive nuclear movement during myofiber formation. We also showed that nuclear position is important for muscle function. However why nuclear positioning is important for myofiber activity remains an open question.
We now propose to use unique systems to monitor cell migration and myofiber formation in combination with biochemistry, cell biology, high- and super-resolution microscopy approaches to:
1) Identify novel molecular mechanisms that mediate nuclear positioning during cell migration and myofiber formation.
3) Determine a role for nuclear positioning in myofiber function as well as the significance of altered nuclear positioning in different forms of muscle pathology.
The proposed work will establish new mechanisms for nuclear positioning. Importantly, by identifying mechanisms and understanding the role of nuclear positioning in myofiber function, we will lay the foundations for future studies to ameliorate or treat muscle disorders as well as other conditions where nucleus positioning may prove to play a role such as cancer.
Max ERC Funding
1 968 000 €
Duration
Start date: 2014-07-01, End date: 2019-06-30
Project acronym TRANSRIGHTS
Project Gender citizenship and sexual rights in Europe: transgender lives from a transnational perspective
Researcher (PI) Sofia Isabel Da Costa D'aboim Inglez
Host Institution (HI) INSTITUTO DE CIENCIAS SOCIAIS
Call Details Consolidator Grant (CoG), SH2, ERC-2013-CoG
Summary "The TRANSRIGHTS project investigates transgender lives and the institutional apparatus that frames them. Rather than focusing exclusively on self displayed identities, four lines of inquiry will be developed. Firstly, gender politics and sexual rights are analyzed as the opposition between politics of equality and of difference is unable to provide answers for the inclusion of trans-people. Secondly, by comparing the lives of trans-people in five European countries – Portugal, France, United Kingdom, the Netherlands and Sweden – we wish to attain an overview of how institutional frameworks impact on these lives. Thirdly, our approach will take into account the immigration of trans-individuals to Europe, whether in search for recognition or as a way of survival often leading to sex work. Fourthly, by comparing different countries, different groups of transgender people, different forms of attaining inclusion or dealing with exclusion, different conceptions of gender citizenship and sexual rights, we wish not only to gain a deeper understanding of societal change and its impact on the lives of transgender individuals, but also to identify the gaps between policies and rights and the categories actually mobilized for self-identification. Such a task implies examining the voices of trans-people, the effect of policies on the materiality of lives as well as conceptualizations of selfhood that do not necessarily confine to the European context. Project outputs will contribute to the fields of gender, sexuality and citizenship by providing a grounded theoretical debate, discussing the gender categories of citizenship. Trans-people are a heterogeneous group that represents one of the most challenging boundaries for framing this debate within and beyond Europe. The voices of trans-people are essential to avoid an excessive reduction of lives to institutional categories, whether from the institutional apparatus, the LGBT movements or the social sciences."
Summary
"The TRANSRIGHTS project investigates transgender lives and the institutional apparatus that frames them. Rather than focusing exclusively on self displayed identities, four lines of inquiry will be developed. Firstly, gender politics and sexual rights are analyzed as the opposition between politics of equality and of difference is unable to provide answers for the inclusion of trans-people. Secondly, by comparing the lives of trans-people in five European countries – Portugal, France, United Kingdom, the Netherlands and Sweden – we wish to attain an overview of how institutional frameworks impact on these lives. Thirdly, our approach will take into account the immigration of trans-individuals to Europe, whether in search for recognition or as a way of survival often leading to sex work. Fourthly, by comparing different countries, different groups of transgender people, different forms of attaining inclusion or dealing with exclusion, different conceptions of gender citizenship and sexual rights, we wish not only to gain a deeper understanding of societal change and its impact on the lives of transgender individuals, but also to identify the gaps between policies and rights and the categories actually mobilized for self-identification. Such a task implies examining the voices of trans-people, the effect of policies on the materiality of lives as well as conceptualizations of selfhood that do not necessarily confine to the European context. Project outputs will contribute to the fields of gender, sexuality and citizenship by providing a grounded theoretical debate, discussing the gender categories of citizenship. Trans-people are a heterogeneous group that represents one of the most challenging boundaries for framing this debate within and beyond Europe. The voices of trans-people are essential to avoid an excessive reduction of lives to institutional categories, whether from the institutional apparatus, the LGBT movements or the social sciences."
Max ERC Funding
1 262 943 €
Duration
Start date: 2014-09-01, End date: 2019-08-31
