Project acronym AcetyLys
Project Unravelling the role of lysine acetylation in the regulation of glycolysis in cancer cells through the development of synthetic biology-based tools
Researcher (PI) Eyal Arbely
Host Institution (HI) BEN-GURION UNIVERSITY OF THE NEGEV
Country Israel
Call Details Starting Grant (StG), LS9, ERC-2015-STG
Summary Synthetic biology is an emerging discipline that offers powerful tools to control and manipulate fundamental processes in living matter. We propose to develop and apply such tools to modify the genetic code of cultured mammalian cells and bacteria with the aim to study the role of lysine acetylation in the regulation of metabolism and in cancer development. Thousands of lysine acetylation sites were recently discovered on non-histone proteins, suggesting that acetylation is a widespread and evolutionarily conserved post translational modification, similar in scope to phosphorylation and ubiquitination. Specifically, it has been found that most of the enzymes of metabolic processes—including glycolysis—are acetylated, implying that acetylation is key regulator of cellular metabolism in general and in glycolysis in particular. The regulation of metabolic pathways is of particular importance to cancer research, as misregulation of metabolic pathways, especially upregulation of glycolysis, is common to most transformed cells and is now considered a new hallmark of cancer. These data raise an immediate question: what is the role of acetylation in the regulation of glycolysis and in the metabolic reprogramming of cancer cells? While current methods rely on mutational analyses, we will genetically encode the incorporation of acetylated lysine and directly measure the functional role of each acetylation site in cancerous and non-cancerous cell lines. Using this methodology, we will study the structural and functional implications of all the acetylation sites in glycolytic enzymes. We will also decipher the mechanism by which acetylation is regulated by deacetylases and answer a long standing question – how 18 deacetylases recognise their substrates among thousands of acetylated proteins? The developed methodologies can be applied to a wide range of protein families known to be acetylated, thereby making this study relevant to diverse research fields.
Summary
Synthetic biology is an emerging discipline that offers powerful tools to control and manipulate fundamental processes in living matter. We propose to develop and apply such tools to modify the genetic code of cultured mammalian cells and bacteria with the aim to study the role of lysine acetylation in the regulation of metabolism and in cancer development. Thousands of lysine acetylation sites were recently discovered on non-histone proteins, suggesting that acetylation is a widespread and evolutionarily conserved post translational modification, similar in scope to phosphorylation and ubiquitination. Specifically, it has been found that most of the enzymes of metabolic processes—including glycolysis—are acetylated, implying that acetylation is key regulator of cellular metabolism in general and in glycolysis in particular. The regulation of metabolic pathways is of particular importance to cancer research, as misregulation of metabolic pathways, especially upregulation of glycolysis, is common to most transformed cells and is now considered a new hallmark of cancer. These data raise an immediate question: what is the role of acetylation in the regulation of glycolysis and in the metabolic reprogramming of cancer cells? While current methods rely on mutational analyses, we will genetically encode the incorporation of acetylated lysine and directly measure the functional role of each acetylation site in cancerous and non-cancerous cell lines. Using this methodology, we will study the structural and functional implications of all the acetylation sites in glycolytic enzymes. We will also decipher the mechanism by which acetylation is regulated by deacetylases and answer a long standing question – how 18 deacetylases recognise their substrates among thousands of acetylated proteins? The developed methodologies can be applied to a wide range of protein families known to be acetylated, thereby making this study relevant to diverse research fields.
Max ERC Funding
1 499 375 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym ACO
Project The Proceedings of the Ecumenical Councils from Oral Utterance to Manuscript Edition as Evidence for Late Antique Persuasion and Self-Representation Techniques
Researcher (PI) Peter Alfred Riedlberger
Host Institution (HI) OTTO-FRIEDRICH-UNIVERSITAET BAMBERG
Country Germany
Call Details Starting Grant (StG), SH5, ERC-2015-STG
Summary The Acts of the Ecumenical Councils of Late Antiquity include (purportedly) verbatim minutes of the proceedings, a formal framework and copies of relevant documents which were either (allegedly) read out during the proceedings or which were later attached to the Acts proper. Despite this unusual wealth of documentary evidence, the daunting nature of the Acts demanding multidisciplinary competency, their complex structure with a matryoshka-like nesting of proceedings from different dates, and the stereotype that their contents bear only on Christological niceties have deterred generations of historians from studying them. Only in recent years have their fortunes begun to improve, but this recent research has not always been based on sound principles: the recorded proceedings of the sessions are still often accepted as verbatim minutes. Yet even a superficial reading quickly reveals widespread editorial interference. We must accept that in many cases the Acts will teach us less about the actual debates than about the editors who shaped their presentation. This does not depreciate the Acts’ evidence: on the contrary, they are first-rate material for the rhetoric of persuasion and self-representation. It is possible, in fact, to take the investigation to a deeper level and examine in what manner the oral proceedings were put into writing: several passages in the Acts comment upon the process of note-taking and the work of the shorthand writers. Thus, the main objective of the proposed research project could be described as an attempt to trace the destinies of the Acts’ texts, from the oral utterance to the manuscript texts we have today. This will include the fullest study on ancient transcript techniques to date; a structural analysis of the Acts’ texts with the aim of highlighting edited passages; and a careful comparison of the various editions of the Acts, which survive in Greek, Latin, Syriac and Coptic, in order to detect traces of editorial interference.
Summary
The Acts of the Ecumenical Councils of Late Antiquity include (purportedly) verbatim minutes of the proceedings, a formal framework and copies of relevant documents which were either (allegedly) read out during the proceedings or which were later attached to the Acts proper. Despite this unusual wealth of documentary evidence, the daunting nature of the Acts demanding multidisciplinary competency, their complex structure with a matryoshka-like nesting of proceedings from different dates, and the stereotype that their contents bear only on Christological niceties have deterred generations of historians from studying them. Only in recent years have their fortunes begun to improve, but this recent research has not always been based on sound principles: the recorded proceedings of the sessions are still often accepted as verbatim minutes. Yet even a superficial reading quickly reveals widespread editorial interference. We must accept that in many cases the Acts will teach us less about the actual debates than about the editors who shaped their presentation. This does not depreciate the Acts’ evidence: on the contrary, they are first-rate material for the rhetoric of persuasion and self-representation. It is possible, in fact, to take the investigation to a deeper level and examine in what manner the oral proceedings were put into writing: several passages in the Acts comment upon the process of note-taking and the work of the shorthand writers. Thus, the main objective of the proposed research project could be described as an attempt to trace the destinies of the Acts’ texts, from the oral utterance to the manuscript texts we have today. This will include the fullest study on ancient transcript techniques to date; a structural analysis of the Acts’ texts with the aim of highlighting edited passages; and a careful comparison of the various editions of the Acts, which survive in Greek, Latin, Syriac and Coptic, in order to detect traces of editorial interference.
Max ERC Funding
1 497 250 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym Age Asymmetry
Project Age-Selective Segregation of Organelles
Researcher (PI) Pekka Aleksi Katajisto
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Starting Grant (StG), LS3, ERC-2015-STG
Summary Our tissues are constantly renewed by stem cells. Over time, stem cells accumulate cellular damage that will compromise renewal and results in aging. As stem cells can divide asymmetrically, segregation of harmful factors to the differentiating daughter cell could be one possible mechanism for slowing damage accumulation in the stem cell. However, current evidence for such mechanisms comes mainly from analogous findings in yeast, and studies have concentrated only on few types of cellular damage.
I hypothesize that the chronological age of a subcellular component is a proxy for all the damage it has sustained. In order to secure regeneration, mammalian stem cells may therefore specifically sort old cellular material asymmetrically. To study this, I have developed a novel strategy and tools to address the age-selective segregation of any protein in stem cell division. Using this approach, I have already discovered that stem-like cells of the human mammary epithelium indeed apportion chronologically old mitochondria asymmetrically in cell division, and enrich old mitochondria to the differentiating daughter cell. We will investigate the mechanisms underlying this novel phenomenon, and its relevance for mammalian aging.
We will first identify how old and young mitochondria differ, and how stem cells recognize them to facilitate the asymmetric segregation. Next, we will analyze the extent of asymmetric age-selective segregation by targeting several other subcellular compartments in a stem cell division. Finally, we will determine whether the discovered age-selective segregation is a general property of stem cell in vivo, and it's functional relevance for maintenance of stem cells and tissue regeneration. Our discoveries may open new possibilities to target aging associated functional decline by induction of asymmetric age-selective organelle segregation.
Summary
Our tissues are constantly renewed by stem cells. Over time, stem cells accumulate cellular damage that will compromise renewal and results in aging. As stem cells can divide asymmetrically, segregation of harmful factors to the differentiating daughter cell could be one possible mechanism for slowing damage accumulation in the stem cell. However, current evidence for such mechanisms comes mainly from analogous findings in yeast, and studies have concentrated only on few types of cellular damage.
I hypothesize that the chronological age of a subcellular component is a proxy for all the damage it has sustained. In order to secure regeneration, mammalian stem cells may therefore specifically sort old cellular material asymmetrically. To study this, I have developed a novel strategy and tools to address the age-selective segregation of any protein in stem cell division. Using this approach, I have already discovered that stem-like cells of the human mammary epithelium indeed apportion chronologically old mitochondria asymmetrically in cell division, and enrich old mitochondria to the differentiating daughter cell. We will investigate the mechanisms underlying this novel phenomenon, and its relevance for mammalian aging.
We will first identify how old and young mitochondria differ, and how stem cells recognize them to facilitate the asymmetric segregation. Next, we will analyze the extent of asymmetric age-selective segregation by targeting several other subcellular compartments in a stem cell division. Finally, we will determine whether the discovered age-selective segregation is a general property of stem cell in vivo, and it's functional relevance for maintenance of stem cells and tissue regeneration. Our discoveries may open new possibilities to target aging associated functional decline by induction of asymmetric age-selective organelle segregation.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym ARCA
Project Analysis and Representation of Complex Activities in Videos
Researcher (PI) Juergen Gall
Host Institution (HI) RHEINISCHE FRIEDRICH-WILHELMS-UNIVERSITAT BONN
Country Germany
Call Details Starting Grant (StG), PE6, ERC-2015-STG
Summary The goal of the project is to automatically analyse human activities observed in videos. Any solution to this problem will allow the development of novel applications. It could be used to create short videos that summarize daily activities to support patients suffering from Alzheimer's disease. It could also be used for education, e.g., by providing a video analysis for a trainee in the hospital that shows if the tasks have been correctly executed.
The analysis of complex activities in videos, however, is very challenging since activities vary in temporal duration between minutes and hours, involve interactions with several objects that change their appearance and shape, e.g., food during cooking, and are composed of many sub-activities, which can happen at the same time or in various orders.
While the majority of recent works in action recognition focuses on developing better feature encoding techniques for classifying sub-activities in short video clips of a few seconds, this project moves forward and aims to develop a higher level representation of complex activities to overcome the limitations of current approaches. This includes the handling of large time variations and the ability to recognize and locate complex activities in videos. To this end, we aim to develop a unified model that provides detailed information about the activities and sub-activities in terms of time and spatial location, as well as involved pose motion, objects and their transformations.
Another aspect of the project is to learn a representation from videos that is not tied to a specific source of videos or limited to a specific application. Instead we aim to learn a representation that is invariant to a perspective change, e.g., from a third-person perspective to an egocentric perspective, and can be applied to various modalities like videos or depth data without the need of collecting massive training data for all modalities. In other words, we aim to learn the essence of activities.
Summary
The goal of the project is to automatically analyse human activities observed in videos. Any solution to this problem will allow the development of novel applications. It could be used to create short videos that summarize daily activities to support patients suffering from Alzheimer's disease. It could also be used for education, e.g., by providing a video analysis for a trainee in the hospital that shows if the tasks have been correctly executed.
The analysis of complex activities in videos, however, is very challenging since activities vary in temporal duration between minutes and hours, involve interactions with several objects that change their appearance and shape, e.g., food during cooking, and are composed of many sub-activities, which can happen at the same time or in various orders.
While the majority of recent works in action recognition focuses on developing better feature encoding techniques for classifying sub-activities in short video clips of a few seconds, this project moves forward and aims to develop a higher level representation of complex activities to overcome the limitations of current approaches. This includes the handling of large time variations and the ability to recognize and locate complex activities in videos. To this end, we aim to develop a unified model that provides detailed information about the activities and sub-activities in terms of time and spatial location, as well as involved pose motion, objects and their transformations.
Another aspect of the project is to learn a representation from videos that is not tied to a specific source of videos or limited to a specific application. Instead we aim to learn a representation that is invariant to a perspective change, e.g., from a third-person perspective to an egocentric perspective, and can be applied to various modalities like videos or depth data without the need of collecting massive training data for all modalities. In other words, we aim to learn the essence of activities.
Max ERC Funding
1 499 875 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym ASYFAIR
Project Fair and Consistent Border Controls? A Critical, Multi-methodological and Interdisciplinary Study of Asylum Adjudication in Europe
Researcher (PI) Nicholas Mark Gill
Host Institution (HI) THE UNIVERSITY OF EXETER
Country United Kingdom
Call Details Starting Grant (StG), SH3, ERC-2015-STG
Summary ‘Consistency’ is regularly cited as a desirable attribute of border control, but it has received little critical social scientific attention. This inter-disciplinary project, at the inter-face between critical human geography, border studies and law, will scrutinise the consistency of European asylum adjudication in order to develop richer theoretical understanding of this lynchpin concept. It will move beyond the administrative legal concepts of substantive and procedural consistency by advancing a three-fold conceptualisation of consistency – as everyday practice, discursive deployment of facts and disciplinary technique. In order to generate productive intellectual tension it will also employ an explicitly antagonistic conceptualisation of the relationship between geography and law that views law as seeking to constrain and systematise lived space. The project will employ an innovative combination of methodologies that will produce unique and rich data sets including quantitative analysis, multi-sited legal ethnography, discourse analysis and interviews, and the findings are likely to be of interest both to academic communities like geographers, legal and border scholars and to policy makers and activists working in border control settings. In 2013 the Common European Asylum System (CEAS) was launched to standardise the procedures of asylum determination. But as yet no sustained multi-methodological assessment of the claims of consistency inherent to the CEAS has been carried out. This project offers not only the opportunity to assess progress towards harmonisation of asylum determination processes in Europe, but will also provide a new conceptual framework with which to approach the dilemmas and risks of inconsistency in an area of law fraught with political controversy and uncertainty around the world. Most fundamentally, the project promises to debunk the myths surrounding the possibility of fair and consistent border controls in Europe and elsewhere.
Summary
‘Consistency’ is regularly cited as a desirable attribute of border control, but it has received little critical social scientific attention. This inter-disciplinary project, at the inter-face between critical human geography, border studies and law, will scrutinise the consistency of European asylum adjudication in order to develop richer theoretical understanding of this lynchpin concept. It will move beyond the administrative legal concepts of substantive and procedural consistency by advancing a three-fold conceptualisation of consistency – as everyday practice, discursive deployment of facts and disciplinary technique. In order to generate productive intellectual tension it will also employ an explicitly antagonistic conceptualisation of the relationship between geography and law that views law as seeking to constrain and systematise lived space. The project will employ an innovative combination of methodologies that will produce unique and rich data sets including quantitative analysis, multi-sited legal ethnography, discourse analysis and interviews, and the findings are likely to be of interest both to academic communities like geographers, legal and border scholars and to policy makers and activists working in border control settings. In 2013 the Common European Asylum System (CEAS) was launched to standardise the procedures of asylum determination. But as yet no sustained multi-methodological assessment of the claims of consistency inherent to the CEAS has been carried out. This project offers not only the opportunity to assess progress towards harmonisation of asylum determination processes in Europe, but will also provide a new conceptual framework with which to approach the dilemmas and risks of inconsistency in an area of law fraught with political controversy and uncertainty around the world. Most fundamentally, the project promises to debunk the myths surrounding the possibility of fair and consistent border controls in Europe and elsewhere.
Max ERC Funding
1 252 067 €
Duration
Start date: 2016-09-01, End date: 2022-02-28
Project acronym AXIAL.EC
Project PRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
Researcher (PI) Claudio Franco
Host Institution (HI) INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Country Portugal
Call Details Starting Grant (StG), LS4, ERC-2015-STG
Summary The formation of a functional patterned vascular network is essential for development, tissue growth and organ physiology. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms and diabetic retinopathy. Although blood flow is recognised as a stimulus for vascular patterning, very little is known about the molecular mechanisms that regulate endothelial cell behaviour in response to flow and promote vascular patterning.
Recently, we uncovered that endothelial cells migrate extensively in the immature vascular network, and that endothelial cells polarise against the blood flow direction. Here, we put forward the hypothesis that vascular patterning is dependent on the polarisation and migration of endothelial cells against the flow direction, in a continuous flux of cells going from low-shear stress to high-shear stress regions. We will establish new reporter mouse lines to observe and manipulate endothelial polarity in vivo in order to investigate how polarisation and coordination of endothelial cells movements are orchestrated to generate vascular patterning. We will manipulate cell polarity using mouse models to understand the importance of cell polarisation in vascular patterning. Also, using a unique zebrafish line allowing analysis of endothelial cell polarity, we will perform a screen to identify novel regulators of vascular patterning. Finally, we will explore the hypothesis that defective flow-dependent endothelial polarisation underlies arteriovenous malformations using two genetic models.
This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders.
Summary
The formation of a functional patterned vascular network is essential for development, tissue growth and organ physiology. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms and diabetic retinopathy. Although blood flow is recognised as a stimulus for vascular patterning, very little is known about the molecular mechanisms that regulate endothelial cell behaviour in response to flow and promote vascular patterning.
Recently, we uncovered that endothelial cells migrate extensively in the immature vascular network, and that endothelial cells polarise against the blood flow direction. Here, we put forward the hypothesis that vascular patterning is dependent on the polarisation and migration of endothelial cells against the flow direction, in a continuous flux of cells going from low-shear stress to high-shear stress regions. We will establish new reporter mouse lines to observe and manipulate endothelial polarity in vivo in order to investigate how polarisation and coordination of endothelial cells movements are orchestrated to generate vascular patterning. We will manipulate cell polarity using mouse models to understand the importance of cell polarisation in vascular patterning. Also, using a unique zebrafish line allowing analysis of endothelial cell polarity, we will perform a screen to identify novel regulators of vascular patterning. Finally, we will explore the hypothesis that defective flow-dependent endothelial polarisation underlies arteriovenous malformations using two genetic models.
This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders.
Max ERC Funding
1 618 750 €
Duration
Start date: 2016-09-01, End date: 2022-02-28
Project acronym BIGCODE
Project Learning from Big Code: Probabilistic Models, Analysis and Synthesis
Researcher (PI) Martin Vechev
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Starting Grant (StG), PE6, ERC-2015-STG
Summary The goal of this proposal is to fundamentally change the way we build and reason about software. We aim to develop new kinds of statistical programming systems that provide probabilistically likely solutions to tasks that are difficult or impossible to solve with traditional approaches.
These statistical programming systems will be based on probabilistic models of massive codebases (also known as ``Big Code'') built via a combination of advanced programming languages and powerful machine learning and natural language processing techniques. To solve a particular challenge, a statistical programming system will query a probabilistic model, compute the most likely predictions, and present those to the developer.
Based on probabilistic models of ``Big Code'', we propose to investigate new statistical techniques in the context of three fundamental research directions: i) statistical program synthesis where we develop techniques that automatically synthesize and predict new programs, ii) statistical prediction of program properties where we develop new techniques that can predict important facts (e.g., types) about programs, and iii) statistical translation of programs where we investigate new techniques for statistical translation of programs (e.g., from one programming language to another, or to a natural language).
We believe the research direction outlined in this interdisciplinary proposal opens a new and exciting area of computer science. This area will combine sophisticated statistical learning and advanced programming language techniques for building the next-generation statistical programming systems.
We expect the results of this proposal to have an immediate impact upon millions of developers worldwide, triggering a paradigm shift in the way tomorrow's software is built, as well as a long-lasting impact on scientific fields such as machine learning, natural language processing, programming languages and software engineering.
Summary
The goal of this proposal is to fundamentally change the way we build and reason about software. We aim to develop new kinds of statistical programming systems that provide probabilistically likely solutions to tasks that are difficult or impossible to solve with traditional approaches.
These statistical programming systems will be based on probabilistic models of massive codebases (also known as ``Big Code'') built via a combination of advanced programming languages and powerful machine learning and natural language processing techniques. To solve a particular challenge, a statistical programming system will query a probabilistic model, compute the most likely predictions, and present those to the developer.
Based on probabilistic models of ``Big Code'', we propose to investigate new statistical techniques in the context of three fundamental research directions: i) statistical program synthesis where we develop techniques that automatically synthesize and predict new programs, ii) statistical prediction of program properties where we develop new techniques that can predict important facts (e.g., types) about programs, and iii) statistical translation of programs where we investigate new techniques for statistical translation of programs (e.g., from one programming language to another, or to a natural language).
We believe the research direction outlined in this interdisciplinary proposal opens a new and exciting area of computer science. This area will combine sophisticated statistical learning and advanced programming language techniques for building the next-generation statistical programming systems.
We expect the results of this proposal to have an immediate impact upon millions of developers worldwide, triggering a paradigm shift in the way tomorrow's software is built, as well as a long-lasting impact on scientific fields such as machine learning, natural language processing, programming languages and software engineering.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-04-01, End date: 2021-03-31
Project acronym BINDING FIBRES
Project Soluble dietary fibre: unraveling how weak bonds have a strong impact on function
Researcher (PI) Laura Nystroem
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Starting Grant (StG), LS9, ERC-2015-STG
Summary Dietary fibres are recognized for their health promoting properties; nevertheless, many of the physicochemical mechanisms behind these effects remain poorly understood. While it is understood that dietary fibres can associate with small molecules influencing, both positively or negatively their absorption, the molecular mechanism, by which these associations take place, have yet to be elucidated We propose a study of the binding in soluble dietary fibres at a molecular level to establish binding constants for various fibres and nutritionally relevant ligands. The interactions between fibres and target compounds may be quite weak, but still have a major impact on the bioavailability. To gain insight to the binding mechanisms at a level of detail that has not earlier been achieved, we will apply novel combinations of analytical techniques (MS, NMR, EPR) and both natural as well as synthetic probes to elucidate the associations in these complexes from macromolecular to atomic level. Glucans, xyloglucans and galactomannans will serve as model soluble fibres, representative of real food systems, allowing us to determine their binding constants with nutritionally relevant micronutrients, such as monosaccharides, bile acids, and metals. Furthermore, we will examine supramolecular interactions between fibre strands to evaluate possible contribution of several fibre strands to the micronutrient associations. At the atomic level, we will use complementary spectroscopies to identify the functional groups and atoms involved in the bonds between fibres and the ligands. The proposal describes a unique approach to quantify binding of small molecules by dietary fibres, which can be translated to polysaccharide interactions with ligands in a broad range of biological systems and disciplines. The findings from this study may further allow us to predictably utilize fibres in functional foods, which can have far-reaching consequences in human nutrition, and thereby also public health.
Summary
Dietary fibres are recognized for their health promoting properties; nevertheless, many of the physicochemical mechanisms behind these effects remain poorly understood. While it is understood that dietary fibres can associate with small molecules influencing, both positively or negatively their absorption, the molecular mechanism, by which these associations take place, have yet to be elucidated We propose a study of the binding in soluble dietary fibres at a molecular level to establish binding constants for various fibres and nutritionally relevant ligands. The interactions between fibres and target compounds may be quite weak, but still have a major impact on the bioavailability. To gain insight to the binding mechanisms at a level of detail that has not earlier been achieved, we will apply novel combinations of analytical techniques (MS, NMR, EPR) and both natural as well as synthetic probes to elucidate the associations in these complexes from macromolecular to atomic level. Glucans, xyloglucans and galactomannans will serve as model soluble fibres, representative of real food systems, allowing us to determine their binding constants with nutritionally relevant micronutrients, such as monosaccharides, bile acids, and metals. Furthermore, we will examine supramolecular interactions between fibre strands to evaluate possible contribution of several fibre strands to the micronutrient associations. At the atomic level, we will use complementary spectroscopies to identify the functional groups and atoms involved in the bonds between fibres and the ligands. The proposal describes a unique approach to quantify binding of small molecules by dietary fibres, which can be translated to polysaccharide interactions with ligands in a broad range of biological systems and disciplines. The findings from this study may further allow us to predictably utilize fibres in functional foods, which can have far-reaching consequences in human nutrition, and thereby also public health.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-04-01, End date: 2022-03-31
Project acronym BroadSem
Project Induction of Broad-Coverage Semantic Parsers
Researcher (PI) Ivan Titov
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Country United Kingdom
Call Details Starting Grant (StG), PE6, ERC-2015-STG
Summary In the last one or two decades, language technology has achieved a number of important successes, for example, producing functional machine translation systems and beating humans in quiz games. The key bottleneck which prevents further progress in these and many other natural language processing (NLP) applications (e.g., text summarization, information retrieval, opinion mining, dialog and tutoring systems) is the lack of accurate methods for producing meaning representations of texts. Accurately predicting such meaning representations on an open domain with an automatic parser is a challenging and unsolved problem, primarily because of language variability and ambiguity. The reason for the unsatisfactory performance is reliance on supervised learning (learning from annotated resources), with the amounts of annotation required for accurate open-domain parsing exceeding what is practically feasible. Moreover, representations defined in these resources typically do not provide abstractions suitable for reasoning.
In this project, we will induce semantic representations from large amounts of unannotated data (i.e. text which has not been labeled by humans) while guided by information contained in human-annotated data and other forms of linguistic knowledge. This will allow us to scale our approach to many domains and across languages. We will specialize meaning representations for reasoning by modeling relations (e.g., facts) appearing across sentences in texts (document-level modeling), across different texts, and across texts and knowledge bases. Learning to predict this linked data is closely related to learning to reason, including learning the notions of semantic equivalence and entailment. We will jointly induce semantic parsers (e.g., log-linear feature-rich models) and reasoning models (latent factor models) relying on this data, thus, ensuring that the semantic representations are informative for applications requiring reasoning.
Summary
In the last one or two decades, language technology has achieved a number of important successes, for example, producing functional machine translation systems and beating humans in quiz games. The key bottleneck which prevents further progress in these and many other natural language processing (NLP) applications (e.g., text summarization, information retrieval, opinion mining, dialog and tutoring systems) is the lack of accurate methods for producing meaning representations of texts. Accurately predicting such meaning representations on an open domain with an automatic parser is a challenging and unsolved problem, primarily because of language variability and ambiguity. The reason for the unsatisfactory performance is reliance on supervised learning (learning from annotated resources), with the amounts of annotation required for accurate open-domain parsing exceeding what is practically feasible. Moreover, representations defined in these resources typically do not provide abstractions suitable for reasoning.
In this project, we will induce semantic representations from large amounts of unannotated data (i.e. text which has not been labeled by humans) while guided by information contained in human-annotated data and other forms of linguistic knowledge. This will allow us to scale our approach to many domains and across languages. We will specialize meaning representations for reasoning by modeling relations (e.g., facts) appearing across sentences in texts (document-level modeling), across different texts, and across texts and knowledge bases. Learning to predict this linked data is closely related to learning to reason, including learning the notions of semantic equivalence and entailment. We will jointly induce semantic parsers (e.g., log-linear feature-rich models) and reasoning models (latent factor models) relying on this data, thus, ensuring that the semantic representations are informative for applications requiring reasoning.
Max ERC Funding
1 457 185 €
Duration
Start date: 2016-05-01, End date: 2021-10-31
Project acronym BUMP
Project BETTER UNDERSTANDING the METAPHYSICS of PREGNANCY
Researcher (PI) Elisabeth Marjolijn Kingma
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Country United Kingdom
Call Details Starting Grant (StG), SH5, ERC-2015-STG
Summary Every single human is the product of a pregnancy: an approximately nine-month period during which a foetus develops within its mother’s body. Yet pregnancy has not been a traditional focus in philosophy. That is remarkable, for two reasons:
First, because pregnancy presents fascinating philosophical problems: what, during the pregnancy, is the nature of the relationship between the foetus and the maternal organism? What is the relationship between the pregnant organism and the later baby? And when does one person or organism become two?
Second, because so many topics immediately adjacent to or involved in pregnancy have taken centre stage in philosophical enquiry. Examples include questions about personhood, foetuses, personal identity and the self.
This project launches the metaphysics of pregnancy as an important and fundamental area of philosophical research.
The core aims of the project are:
(1) to develop a philosophically sophisticated account of human pregnancy and birth, and the entities involved in this, that is attentive to our best empirical understanding of human reproductive biology;
(2) to articulate the metaphysics of organisms, persons and selves in a way that acknowledges the details of how we come into existence; and
(3) to start the process of rewriting the legal, social and moral language we use to classify ourselves and our actions, so that it is compatible with and can accommodate the nature of pregnancy.
The project will investigate these questions in the context of a range of philosophical sub disciplines, including analytic metaphysics, philosophy of biology and feminist philosophy, and in close dialogue with our best empirical understanding of the life sciences – most notably physiology.
Summary
Every single human is the product of a pregnancy: an approximately nine-month period during which a foetus develops within its mother’s body. Yet pregnancy has not been a traditional focus in philosophy. That is remarkable, for two reasons:
First, because pregnancy presents fascinating philosophical problems: what, during the pregnancy, is the nature of the relationship between the foetus and the maternal organism? What is the relationship between the pregnant organism and the later baby? And when does one person or organism become two?
Second, because so many topics immediately adjacent to or involved in pregnancy have taken centre stage in philosophical enquiry. Examples include questions about personhood, foetuses, personal identity and the self.
This project launches the metaphysics of pregnancy as an important and fundamental area of philosophical research.
The core aims of the project are:
(1) to develop a philosophically sophisticated account of human pregnancy and birth, and the entities involved in this, that is attentive to our best empirical understanding of human reproductive biology;
(2) to articulate the metaphysics of organisms, persons and selves in a way that acknowledges the details of how we come into existence; and
(3) to start the process of rewriting the legal, social and moral language we use to classify ourselves and our actions, so that it is compatible with and can accommodate the nature of pregnancy.
The project will investigate these questions in the context of a range of philosophical sub disciplines, including analytic metaphysics, philosophy of biology and feminist philosophy, and in close dialogue with our best empirical understanding of the life sciences – most notably physiology.
Max ERC Funding
1 273 290 €
Duration
Start date: 2016-04-01, End date: 2021-03-31