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 AFFORDS-HIGHER
Project Skilled Intentionality for 'Higher' Embodied Cognition: Joining forces with a field of affordances in flux
Researcher (PI) Dirk Willem Rietveld
Host Institution (HI) ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Starting Grant (StG), SH4, ERC-2015-STG
Summary In many situations experts act adequately, yet without deliberation. Architects e.g, immediately sense opportunities offered by the site of a new project. One could label these manifestations of expert intuition as ‘higher-level’ cognition, but still these experts act unreflectively. The aim of my project is to develop the Skilled Intentionality Framework (SIF), a new conceptual framework for the field of embodied/enactive cognitive science (Chemero, 2009; Thompson, 2007). I argue that affordances - possibilities for action provided by our surroundings - are highly significant in cases of unreflective and reflective ‘higher’ cognition. Skilled Intentionality is skilled coordination with multiple affordances simultaneously.
The two central ideas behind this proposal are (a) that episodes of skilled ‘higher’ cognition can be understood as responsiveness to affordances for ‘higher’ cognition and (b) that our surroundings are highly resourceful and contribute to skillful action and cognition in a far more fundamental way than is generally acknowledged. I use embedded philosophical research in a particular practice of architecture to shed new light on the ways in which affordances for ‘higher’ cognition support creative imagination, anticipation, explicit planning and self-reflection.
The Skilled Intentionality Framework is groundbreaking in relating findings established at several complementary levels of analysis: philosophy/phenomenology, ecological psychology, affective science and neurodynamics.
Empirical findings thought to be exclusively valid for everyday unreflective action can now be used to explain skilled ‘higher’ cognition as well. Moreover, SIF brings both the context and the social back into cognitive science. I will show SIF’s relevance for Friston’s work on the anticipating brain, and apply it in the domain of architecture and public health. SIF will radically widen the scope of the increasingly influential field of embodied cognitive science.
Summary
In many situations experts act adequately, yet without deliberation. Architects e.g, immediately sense opportunities offered by the site of a new project. One could label these manifestations of expert intuition as ‘higher-level’ cognition, but still these experts act unreflectively. The aim of my project is to develop the Skilled Intentionality Framework (SIF), a new conceptual framework for the field of embodied/enactive cognitive science (Chemero, 2009; Thompson, 2007). I argue that affordances - possibilities for action provided by our surroundings - are highly significant in cases of unreflective and reflective ‘higher’ cognition. Skilled Intentionality is skilled coordination with multiple affordances simultaneously.
The two central ideas behind this proposal are (a) that episodes of skilled ‘higher’ cognition can be understood as responsiveness to affordances for ‘higher’ cognition and (b) that our surroundings are highly resourceful and contribute to skillful action and cognition in a far more fundamental way than is generally acknowledged. I use embedded philosophical research in a particular practice of architecture to shed new light on the ways in which affordances for ‘higher’ cognition support creative imagination, anticipation, explicit planning and self-reflection.
The Skilled Intentionality Framework is groundbreaking in relating findings established at several complementary levels of analysis: philosophy/phenomenology, ecological psychology, affective science and neurodynamics.
Empirical findings thought to be exclusively valid for everyday unreflective action can now be used to explain skilled ‘higher’ cognition as well. Moreover, SIF brings both the context and the social back into cognitive science. I will show SIF’s relevance for Friston’s work on the anticipating brain, and apply it in the domain of architecture and public health. SIF will radically widen the scope of the increasingly influential field of embodied cognitive science.
Max ERC Funding
1 499 850 €
Duration
Start date: 2016-05-01, End date: 2021-10-31
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 ApeAttachment
Project Are social skills determined by early live experiences?
Researcher (PI) Catherine Delia Crockford
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Country Germany
Call Details Starting Grant (StG), SH4, ERC-2015-STG
Summary Social bonding success in life impacts on health, survival and fitness. It is proposed that early and later social experience as well as heritable factors determine social bonding abilities in adulthood, although the relative influence of each is unclear. In humans, the resulting uncertainty likely impedes psychological and psychiatric assessment and therapy. One problem hampering progress for human studies is that social bonding success is hard to objectively quantify, particularly in adults. I propose to directly address this problem by determining the key influences on social bonding abilities in chimpanzees, our closest living relative, where social bonding success can be objectively quantified, and is defined as number of affiliative relationships maintained over time with high rates of affiliation.
Objectives. This project will quantify the relative impact of early and later social experience as well as heritable factors on social hormone levels, social cognition and social bonding success in 270 wild and captive chimpanzees, using both cohort and longitudinal data. This will reveal the degree of plasticity in social cognition and bonding behaviour throughout life. Finally, it will evaluate the potential for using endogenous hormone levels as non-invasive biomarkers of social bonding success, as well as identifying social contexts that act as strong natural social hormone releasers.
Outcomes. This project will expose what makes some better at social bonding than others. Specifically, it will show the extent to which later social experience can compensate for early social experience or heritable factors in terms of adult social bonding success, the latter being a key factor in determining health and happiness in life. This project also offers the potential for using hormonal biomarkers in clincial settings, as objective assessment of changes in relationships over time, and in therapy by engaging in social behaviours that act as strong social hormone releasers.
Summary
Social bonding success in life impacts on health, survival and fitness. It is proposed that early and later social experience as well as heritable factors determine social bonding abilities in adulthood, although the relative influence of each is unclear. In humans, the resulting uncertainty likely impedes psychological and psychiatric assessment and therapy. One problem hampering progress for human studies is that social bonding success is hard to objectively quantify, particularly in adults. I propose to directly address this problem by determining the key influences on social bonding abilities in chimpanzees, our closest living relative, where social bonding success can be objectively quantified, and is defined as number of affiliative relationships maintained over time with high rates of affiliation.
Objectives. This project will quantify the relative impact of early and later social experience as well as heritable factors on social hormone levels, social cognition and social bonding success in 270 wild and captive chimpanzees, using both cohort and longitudinal data. This will reveal the degree of plasticity in social cognition and bonding behaviour throughout life. Finally, it will evaluate the potential for using endogenous hormone levels as non-invasive biomarkers of social bonding success, as well as identifying social contexts that act as strong natural social hormone releasers.
Outcomes. This project will expose what makes some better at social bonding than others. Specifically, it will show the extent to which later social experience can compensate for early social experience or heritable factors in terms of adult social bonding success, the latter being a key factor in determining health and happiness in life. This project also offers the potential for using hormonal biomarkers in clincial settings, as objective assessment of changes in relationships over time, and in therapy by engaging in social behaviours that act as strong social hormone releasers.
Max ERC Funding
1 495 000 €
Duration
Start date: 2016-04-01, End date: 2021-03-31
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 BBRhythms
Project Brain and body rhythms: on the relationship between movement and percept
Researcher (PI) Barbara Haendel
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Country Germany
Call Details Starting Grant (StG), SH4, ERC-2015-STG
Summary Exciting findings from animal electrophysiological research in the last years suggest that an increased rate of body movements results in an enhanced response of neurons within the visual system despite the absence of visual changes. It is unclear why such modulation occurs in areas which process visual input. In humans, little is known about the influence of body movements on sensory brain areas mainly due to the technical challenges of measuring brain responses during pronounced muscle activity. However, psychophysical studies in humans show that also percept and perceptual demands are connected to the rate of movements. These two lines of evidence suggest a general link between rhythmic body movements and perceptual processes.
The main aim of the proposed research is to decode the relationship between body movements and percept and to identify the underlying mechanism. To this end human non-invasive recordings from electro- and magnetoencephalography (EEG, MEG) as well as invasive human and animal multi-electrode recordings collected during movement execution will be analyzed. Directly relating perceptual processes and their underlying neuronal oscillations to rhythmic body movements offers an approach circumventing some of the methodological problems.
This research could uncover a new mechanism of how our system modulates perceptual processes through body movements. The proof of such a mechanism would constitute a ground-breaking step in understanding perception during natural behavior. We need to keep in mind that in the awake state our body is constantly in motion. However, up to now, the vast majority of studies which investigate sensory brain responses are conducted under strict movement suppression. Besides facilitating exciting new insights, this research can strengthen the assumption that the knowledge we have gathered about artificial situations generalizes to our natural behavior.
Summary
Exciting findings from animal electrophysiological research in the last years suggest that an increased rate of body movements results in an enhanced response of neurons within the visual system despite the absence of visual changes. It is unclear why such modulation occurs in areas which process visual input. In humans, little is known about the influence of body movements on sensory brain areas mainly due to the technical challenges of measuring brain responses during pronounced muscle activity. However, psychophysical studies in humans show that also percept and perceptual demands are connected to the rate of movements. These two lines of evidence suggest a general link between rhythmic body movements and perceptual processes.
The main aim of the proposed research is to decode the relationship between body movements and percept and to identify the underlying mechanism. To this end human non-invasive recordings from electro- and magnetoencephalography (EEG, MEG) as well as invasive human and animal multi-electrode recordings collected during movement execution will be analyzed. Directly relating perceptual processes and their underlying neuronal oscillations to rhythmic body movements offers an approach circumventing some of the methodological problems.
This research could uncover a new mechanism of how our system modulates perceptual processes through body movements. The proof of such a mechanism would constitute a ground-breaking step in understanding perception during natural behavior. We need to keep in mind that in the awake state our body is constantly in motion. However, up to now, the vast majority of studies which investigate sensory brain responses are conducted under strict movement suppression. Besides facilitating exciting new insights, this research can strengthen the assumption that the knowledge we have gathered about artificial situations generalizes to our natural behavior.
Max ERC Funding
1 422 907 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
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 BRISC
Project Bounded Rationality in Sensorimotor Coordination
Researcher (PI) Daniel Alexander Braun
Host Institution (HI) UNIVERSITAET ULM
Country Germany
Call Details Starting Grant (StG), SH4, ERC-2015-STG
Summary Despite their many successes and great computational power and speed, why are machines still so blatantly outperformed by humans in uncertain environments that require flexible sensorimotor behavior like playing football or navigating a disaster zone? Answering this question requires understanding the mathematical principles of biological sensorimotor control and learning. Over the recent years Bayes-optimal actor models have widely become the gold standard in the mathematical understanding of sensorimotor processing in well-controlled laboratory tasks. However, these models quickly become intractable for real-world problems because they ignore the computational effort required to search for the Bayes-optimum. What is therefore needed is a framework of sensorimotor processing that takes the limited information-processing capacity of bounded rational actors into account and that explains their robust real-world performance. It is the aim of BRISC to establish such a framework by drawing out theoretical predictions and gathering experimental evidence in human motor control, in particular to understand (i) how single bounded rational actors deviate from Bayes-optimal behavior in motor tasks, (ii) how multiple bounded rational actors organize themselves to solve motor tasks that no individual can solve by themselves and (iii) how this drives the emergence of hierarchical control structures that simultaneously process multiple degrees of abstraction at different time scales. Understanding how abstract concepts are formed autonomously from the sensorimotor stream based on resource allocation principles will establish an essential missing link between high-level symbolic and low-level perceptual processing. These advances will provide a decisive step towards a framework for robust and flexible sensorimotor processing, which is not only essential for understanding the fundamental principles of intelligent behavior, but it is also of potentially great technological value.
Summary
Despite their many successes and great computational power and speed, why are machines still so blatantly outperformed by humans in uncertain environments that require flexible sensorimotor behavior like playing football or navigating a disaster zone? Answering this question requires understanding the mathematical principles of biological sensorimotor control and learning. Over the recent years Bayes-optimal actor models have widely become the gold standard in the mathematical understanding of sensorimotor processing in well-controlled laboratory tasks. However, these models quickly become intractable for real-world problems because they ignore the computational effort required to search for the Bayes-optimum. What is therefore needed is a framework of sensorimotor processing that takes the limited information-processing capacity of bounded rational actors into account and that explains their robust real-world performance. It is the aim of BRISC to establish such a framework by drawing out theoretical predictions and gathering experimental evidence in human motor control, in particular to understand (i) how single bounded rational actors deviate from Bayes-optimal behavior in motor tasks, (ii) how multiple bounded rational actors organize themselves to solve motor tasks that no individual can solve by themselves and (iii) how this drives the emergence of hierarchical control structures that simultaneously process multiple degrees of abstraction at different time scales. Understanding how abstract concepts are formed autonomously from the sensorimotor stream based on resource allocation principles will establish an essential missing link between high-level symbolic and low-level perceptual processing. These advances will provide a decisive step towards a framework for robust and flexible sensorimotor processing, which is not only essential for understanding the fundamental principles of intelligent behavior, but it is also of potentially great technological value.
Max ERC Funding
1 434 250 €
Duration
Start date: 2016-10-01, End date: 2022-09-30
