Project acronym 5HT-OPTOGENETICS
Project Optogenetic Analysis of Serotonin Function in the Mammalian Brain
Researcher (PI) Zachary Mainen
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Summary
Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Max ERC Funding
2 318 636 €
Duration
Start date: 2010-07-01, End date: 2015-12-31
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 EXOEARTHS
Project EXtra-solar planets and stellar astrophysics: towards the detection of Other Earths
Researcher (PI) Nuno Miguel Cardoso Santos
Host Institution (HI) CENTRO DE INVESTIGACAO EM ASTRONOMIA E ASTROFISICA DA UNIVERSIDADE DO PORTO
Call Details Starting Grant (StG), PE9, ERC-2009-StG
Summary The detection of more than 300 extrasolar planets orbiting other solar-like stars opened the window to a new field of astrophysics. Many projects to search for Earth-like planets are currently under way, using a huge battery of telescopes and instruments. New instrumentation is also being developed towards this goal for use in both ground- and space-based based facilities. Since planets come as an output of the star formation process, the study of the stars hosting planets is of great importance. The stellar-planet connection is strengthened by the fact that most of the exoplanets were discovered using a Doppler radial-velocity technique, where the gravitational influence of the planet on the star and not the planet itself is actually measured. This project aims at doing frontier research to explore i) in unique detail the stellar limitations of the radial-velocity technique, as well as ways of reducing them, having in mind the detection of Earth-like planets and ii) to develop and apply software packages aiming at the study of the properties of the planet-host stars, having in mind the full characterization of the newfound planets, as well as understanding planet formation processes. These goals will improve our capacity to detect, study, and characterize new very low mass extra-solar planets. EXOEarths further fits into the fact that I am currently Co-PI of the project for a new high-resolution ultra-stable spectrograph for the VLT. The results of this project are crucial to fully exploit this new instrument. They will be also of extreme importance to current state-of-the-art planet-search projects aiming at the discovery of other Earths, in particular those making use of the radial-velocity method.
Summary
The detection of more than 300 extrasolar planets orbiting other solar-like stars opened the window to a new field of astrophysics. Many projects to search for Earth-like planets are currently under way, using a huge battery of telescopes and instruments. New instrumentation is also being developed towards this goal for use in both ground- and space-based based facilities. Since planets come as an output of the star formation process, the study of the stars hosting planets is of great importance. The stellar-planet connection is strengthened by the fact that most of the exoplanets were discovered using a Doppler radial-velocity technique, where the gravitational influence of the planet on the star and not the planet itself is actually measured. This project aims at doing frontier research to explore i) in unique detail the stellar limitations of the radial-velocity technique, as well as ways of reducing them, having in mind the detection of Earth-like planets and ii) to develop and apply software packages aiming at the study of the properties of the planet-host stars, having in mind the full characterization of the newfound planets, as well as understanding planet formation processes. These goals will improve our capacity to detect, study, and characterize new very low mass extra-solar planets. EXOEarths further fits into the fact that I am currently Co-PI of the project for a new high-resolution ultra-stable spectrograph for the VLT. The results of this project are crucial to fully exploit this new instrument. They will be also of extreme importance to current state-of-the-art planet-search projects aiming at the discovery of other Earths, in particular those making use of the radial-velocity method.
Max ERC Funding
928 090 €
Duration
Start date: 2009-10-01, End date: 2014-12-31
Project acronym FEALORA
Project "Feasibility, logic and randomness in computational complexity"
Researcher (PI) Pavel Pudlák
Host Institution (HI) MATEMATICKY USTAV AV CR V.V.I.
Call Details Advanced Grant (AdG), PE6, ERC-2013-ADG
Summary "We will study fundamental problems in complexity theory using means developed in logic, specifically, in the filed of proof complexity. Since these problems seem extremely difficult and little progress has been achieved in solving them, we will prove results that will explain why they are so difficult and in which direction theory should be developed.
Our aim is to develop a system of conjectures based on the concepts of feasible incompleteness and pseudorandomness. Feasible incompleteness refers to conjectures about unprovability of statements concerning low complexity computations and about lengths of proofs of finite consistency statements. Essentially, they say that incompleteness in the finite domain behaves in a similar way as in the infinite. Several conjectures of this kind have been already stated. They have strong consequences concerning separation of complexity classes, but only a few special cases have been proved. We want to develop a unified system which will also include conjectures connecting feasible incompleteness with pseudorandomness. A major part of our work will concern proving special cases and relativized versions of these conjectures in order to provide evidence for their truth. We believe that the essence of the fundamental problems in complexity theory is logical, and thus developing theory in the way described above will eventually lead to their solution."
Summary
"We will study fundamental problems in complexity theory using means developed in logic, specifically, in the filed of proof complexity. Since these problems seem extremely difficult and little progress has been achieved in solving them, we will prove results that will explain why they are so difficult and in which direction theory should be developed.
Our aim is to develop a system of conjectures based on the concepts of feasible incompleteness and pseudorandomness. Feasible incompleteness refers to conjectures about unprovability of statements concerning low complexity computations and about lengths of proofs of finite consistency statements. Essentially, they say that incompleteness in the finite domain behaves in a similar way as in the infinite. Several conjectures of this kind have been already stated. They have strong consequences concerning separation of complexity classes, but only a few special cases have been proved. We want to develop a unified system which will also include conjectures connecting feasible incompleteness with pseudorandomness. A major part of our work will concern proving special cases and relativized versions of these conjectures in order to provide evidence for their truth. We believe that the essence of the fundamental problems in complexity theory is logical, and thus developing theory in the way described above will eventually lead to their solution."
Max ERC Funding
1 259 596 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym IgYPurTech
Project IgY Technology: A Purification Platform using Ionic-Liquid-Based Aqueous Biphasic Systems
Researcher (PI) Mara Guadalupe Freire Martins
Host Institution (HI) UNIVERSIDADE DE AVEIRO
Call Details Starting Grant (StG), PE8, ERC-2013-StG
Summary With the emergence of antibiotic-resistant pathogens the development of antigen-specific antibodies for use in passive immunotherapy is, nowadays, a major concern in human society. Despite the most focused mammal antibodies, antibodies obtained from egg yolk of immunized hens, immunoglobulin Y (IgY), are an alternative option that can be obtained in higher titres by non-stressful and non-invasive methods. This large amount of available antibodies opens the door for a new kind of cheaper biopharmaceuticals. However, the production cost of high-quality IgY for large-scale applications remains higher than other drug therapies due to the lack of an efficient purification method. The search of new purification platforms is thus a vital demand to which liquid-liquid extraction using aqueous biphasic systems (ABS) could be the answer. Besides the conventional polymer-based systems, highly viscous and with a limited polarity/affinity range, a recent type of ABS composed of ionic liquids (ILs) may be employed. ILs are usually classified as “green solvents” due to their negligible vapour pressure. Yet, the major advantage of IL-based ABS relies on the possibility of tailoring their phases’ polarities aiming at extracting a target biomolecule. A proper manipulation of the system constituents and respective composition allows the pre-concentration, complete extraction, or purification of the most diverse biomolecules.
This research project addresses the development of a new technique for the extraction and purification of IgY from egg yolk using IL-based ABS. The proposed plan contemplates the optimization of purification systems at the laboratory scale and their use in countercurrent chromatography to achieve a simple, cost-effective and scalable process. The success of this project and its scalability to an industrial level certainly will allow the production of cheaper antibodies with a long-term impact in human healthcare.
Summary
With the emergence of antibiotic-resistant pathogens the development of antigen-specific antibodies for use in passive immunotherapy is, nowadays, a major concern in human society. Despite the most focused mammal antibodies, antibodies obtained from egg yolk of immunized hens, immunoglobulin Y (IgY), are an alternative option that can be obtained in higher titres by non-stressful and non-invasive methods. This large amount of available antibodies opens the door for a new kind of cheaper biopharmaceuticals. However, the production cost of high-quality IgY for large-scale applications remains higher than other drug therapies due to the lack of an efficient purification method. The search of new purification platforms is thus a vital demand to which liquid-liquid extraction using aqueous biphasic systems (ABS) could be the answer. Besides the conventional polymer-based systems, highly viscous and with a limited polarity/affinity range, a recent type of ABS composed of ionic liquids (ILs) may be employed. ILs are usually classified as “green solvents” due to their negligible vapour pressure. Yet, the major advantage of IL-based ABS relies on the possibility of tailoring their phases’ polarities aiming at extracting a target biomolecule. A proper manipulation of the system constituents and respective composition allows the pre-concentration, complete extraction, or purification of the most diverse biomolecules.
This research project addresses the development of a new technique for the extraction and purification of IgY from egg yolk using IL-based ABS. The proposed plan contemplates the optimization of purification systems at the laboratory scale and their use in countercurrent chromatography to achieve a simple, cost-effective and scalable process. The success of this project and its scalability to an industrial level certainly will allow the production of cheaper antibodies with a long-term impact in human healthcare.
Max ERC Funding
1 386 020 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
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