Project acronym 3D-E
Project 3D Engineered Environments for Regenerative Medicine
Researcher (PI) Ruth Elizabeth Cameron
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), PE8, ERC-2012-ADG_20120216
Summary "This proposal develops a unified, underpinning technology to create novel, complex and biomimetic 3D environments for the control of tissue growth. As director of Cambridge Centre for Medical Materials, I have recently been approached by medical colleagues to help to solve important problems in the separate therapeutic areas of breast cancer, cardiac disease and blood disorders. In each case, the solution lies in complex 3D engineered environments for cell culture. These colleagues make it clear that existing 3D scaffolds fail to provide the required complex orientational and spatial anisotropy, and are limited in their ability to impart appropriate biochemical and mechanical cues.
I have a strong track record in this area. A particular success has been the use of a freeze drying technology to make collagen based porous implants for the cartilage-bone interface in the knee, which has now been commercialised. The novelty of this proposal lies in the broadening of the established scientific base of this technology to enable biomacromolecular structures with:
(A) controlled and complex pore orientation to mimic many normal multi-oriented tissue structures
(B) compositional and positional control to match varying local biochemical environments,
(C) the attachment of novel peptides designed to control cell behaviour, and
(D) mechanical control at both a local and macroscopic level to provide mechanical cues for cells.
These will be complemented by the development of
(E) robust characterisation methodologies for the structures created.
These advances will then be employed in each of the medical areas above.
This approach is highly interdisciplinary. Existing working relationships with experts in each medical field will guarantee expertise and licensed facilities in the required biological disciplines. Funds for this proposal would therefore establish a rich hub of mutually beneficial research and opportunities for cross-disciplinary sharing of expertise."
Summary
"This proposal develops a unified, underpinning technology to create novel, complex and biomimetic 3D environments for the control of tissue growth. As director of Cambridge Centre for Medical Materials, I have recently been approached by medical colleagues to help to solve important problems in the separate therapeutic areas of breast cancer, cardiac disease and blood disorders. In each case, the solution lies in complex 3D engineered environments for cell culture. These colleagues make it clear that existing 3D scaffolds fail to provide the required complex orientational and spatial anisotropy, and are limited in their ability to impart appropriate biochemical and mechanical cues.
I have a strong track record in this area. A particular success has been the use of a freeze drying technology to make collagen based porous implants for the cartilage-bone interface in the knee, which has now been commercialised. The novelty of this proposal lies in the broadening of the established scientific base of this technology to enable biomacromolecular structures with:
(A) controlled and complex pore orientation to mimic many normal multi-oriented tissue structures
(B) compositional and positional control to match varying local biochemical environments,
(C) the attachment of novel peptides designed to control cell behaviour, and
(D) mechanical control at both a local and macroscopic level to provide mechanical cues for cells.
These will be complemented by the development of
(E) robust characterisation methodologies for the structures created.
These advances will then be employed in each of the medical areas above.
This approach is highly interdisciplinary. Existing working relationships with experts in each medical field will guarantee expertise and licensed facilities in the required biological disciplines. Funds for this proposal would therefore establish a rich hub of mutually beneficial research and opportunities for cross-disciplinary sharing of expertise."
Max ERC Funding
2 486 267 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym A2F2
Project Beyond Biopolymers: Protein-Sized Aromatic Amide Functional Foldamers
Researcher (PI) Ivan Huc
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), PE5, ERC-2012-ADG_20120216
Summary Nature has evolved ultimate chemical functions based on controlling and altering conformation of its molecular machinery. Prominent examples include enzyme catalysis and information storage/duplication in nucleic acids. These achievements are based on large and complex yet remarkably defined structures obtained through folding of polymeric chains and a subtle interplay of non-covalent forces. Nature uses a limited set of building blocks – e.g. twenty amino-acids and four nucleobases – with specific abilities to impart well-defined folds. In the last decade, chemists have discovered foldamers: non-natural oligomers and polymers also prone to adopt folded structures. The emergence of foldamers has far reaching implications. A new major long term prospect is open to chemistry: the de novo synthesis of artificial objects resembling biopolymers in terms of their size, complexity, and efficiency at achieving defined functions, yet having chemical structures beyond the reach of biopolymers amenable to new properties and functions. The PI of this project has shown internationally recognized leadership in the development of a class of foldamers, aromatic oligoamides, whose features arguably make them the most suitable candidates to systematically explore what folded structures beyond biopolymers give access to. This project aims at developing methods to allow the routine fabrication of 20-40 units long aromatic oligoamide foldamers (6-15 kDa) designed to fold into artificial molecular containers having engineerable cavities and surfaces for molecular recognition of organic substrates, in particular large peptides and saccharides, polymers, and proteins. The methodology rests on modelling based design, multistep organic synthesis of heterocyclic monomers and their assembly into long sequences, structural elucidation using, among other techniques, x-ray crystallography, and the physico-chemical characterization of molecular recognition events.
Summary
Nature has evolved ultimate chemical functions based on controlling and altering conformation of its molecular machinery. Prominent examples include enzyme catalysis and information storage/duplication in nucleic acids. These achievements are based on large and complex yet remarkably defined structures obtained through folding of polymeric chains and a subtle interplay of non-covalent forces. Nature uses a limited set of building blocks – e.g. twenty amino-acids and four nucleobases – with specific abilities to impart well-defined folds. In the last decade, chemists have discovered foldamers: non-natural oligomers and polymers also prone to adopt folded structures. The emergence of foldamers has far reaching implications. A new major long term prospect is open to chemistry: the de novo synthesis of artificial objects resembling biopolymers in terms of their size, complexity, and efficiency at achieving defined functions, yet having chemical structures beyond the reach of biopolymers amenable to new properties and functions. The PI of this project has shown internationally recognized leadership in the development of a class of foldamers, aromatic oligoamides, whose features arguably make them the most suitable candidates to systematically explore what folded structures beyond biopolymers give access to. This project aims at developing methods to allow the routine fabrication of 20-40 units long aromatic oligoamide foldamers (6-15 kDa) designed to fold into artificial molecular containers having engineerable cavities and surfaces for molecular recognition of organic substrates, in particular large peptides and saccharides, polymers, and proteins. The methodology rests on modelling based design, multistep organic synthesis of heterocyclic monomers and their assembly into long sequences, structural elucidation using, among other techniques, x-ray crystallography, and the physico-chemical characterization of molecular recognition events.
Max ERC Funding
2 496 216 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym ADAPT
Project The Adoption of New Technological Arrays in the Production of Broadcast Television
Researcher (PI) John Cyril Paget Ellis
Host Institution (HI) ROYAL HOLLOWAY AND BEDFORD NEW COLLEGE
Call Details Advanced Grant (AdG), SH5, ERC-2012-ADG_20120411
Summary "Since 1960, the television industry has undergone successive waves of technological change. Both the methods of programme making and the programmes themselves have changed substantially. The current opening of TV’s vast archives to public and academic use has emphasised the need to explain old programming to new users. Why particular programmes are like they are is not obvious to the contemporary viewer: the prevailing technologies imposed limits and enabled forms that have fallen into disuse. The project will examine the processes of change which gave rise to the particular dominant configurations of technologies for sound and image capture and processing, and some idea of the national and regional variants that existed. It will emphasise the capabilities of the machines in use rather than the process of their invention. The project therefore studies how the technologies of film and tape were implemented; how both broadcasters and individual filmers coped with the conflicting demands of the different machines at their disposal; how new ‘standard ways of doing things’ gradually emerged; and how all of this enabled desired changes in the resultant programmes. The project will produce an overall written account of the principal changes in the technologies in use in broadcast TV since 1960 to the near present. It will offer a theory of technological innovation, and a major case study in the adoption of digital workflow management in production for broadcasting: the so-called ‘tapeless environment’ which is currently being implemented in major organisations. It will offer two historical case studies: a longditudinal study of the evolution of tape-based sound recording and one of the rapid change from 16mm film cutting to digital editing, a process that took less than five years. Reconstructions of the process of working with particular technological arrays will be filmed and will be made available as explanatory material for any online archive of TV material ."
Summary
"Since 1960, the television industry has undergone successive waves of technological change. Both the methods of programme making and the programmes themselves have changed substantially. The current opening of TV’s vast archives to public and academic use has emphasised the need to explain old programming to new users. Why particular programmes are like they are is not obvious to the contemporary viewer: the prevailing technologies imposed limits and enabled forms that have fallen into disuse. The project will examine the processes of change which gave rise to the particular dominant configurations of technologies for sound and image capture and processing, and some idea of the national and regional variants that existed. It will emphasise the capabilities of the machines in use rather than the process of their invention. The project therefore studies how the technologies of film and tape were implemented; how both broadcasters and individual filmers coped with the conflicting demands of the different machines at their disposal; how new ‘standard ways of doing things’ gradually emerged; and how all of this enabled desired changes in the resultant programmes. The project will produce an overall written account of the principal changes in the technologies in use in broadcast TV since 1960 to the near present. It will offer a theory of technological innovation, and a major case study in the adoption of digital workflow management in production for broadcasting: the so-called ‘tapeless environment’ which is currently being implemented in major organisations. It will offer two historical case studies: a longditudinal study of the evolution of tape-based sound recording and one of the rapid change from 16mm film cutting to digital editing, a process that took less than five years. Reconstructions of the process of working with particular technological arrays will be filmed and will be made available as explanatory material for any online archive of TV material ."
Max ERC Funding
1 680 121 €
Duration
Start date: 2013-08-01, End date: 2018-07-31
Project acronym AdS-CFT-solvable
Project Origins of integrability in AdS/CFT correspondence
Researcher (PI) Vladimir Kazakov
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), PE2, ERC-2012-ADG_20120216
Summary Fundamental interactions in nature are well described by quantum gauge fields in 4 space-time dimensions (4d). When the strength of gauge interaction is weak the Feynman perturbation techniques are very efficient for the description of most of the experimentally observable consequences of the Standard model and for the study of high energy processes in QCD.
But in the intermediate and strong coupling regime, such as the relatively small energies in QCD, the perturbation theory fails leaving us with no reliable analytic methods (except the Monte-Carlo simulation). The project aims at working out new analytic and computational methods for strongly coupled gauge theories in 4d. We will employ for that two important discoveries: 1) the gauge-string duality (AdS/CFT correspondence) relating certain strongly coupled gauge Conformal Field
Theories to the weakly coupled string theories on Anty-deSitter space; 2) the solvability, or integrability of maximally supersymmetric (N=4) 4d super Yang-Mills (SYM) theory in multicolor limit. Integrability made possible pioneering exact numerical and analytic results in the N=4 multicolor SYM at any coupling, effectively summing up all 4d Feynman diagrams. Recently, we conjectured a system of functional equations - the AdS/CFT Y-system – for the exact spectrum of anomalous dimensions of all local operators in N=4 SYM. The conjecture has passed all available checks. My project is aimed at the understanding of origins of this, still mysterious integrability. Deriving the AdS/CFT Y-system from the first principles on both sides of gauge-string duality should provide a long-awaited proof of the AdS/CFT correspondence itself. I plan to use the Y-system to study the systematic weak and strong coupling expansions and the so called BFKL limit, as well as for calculation of multi-point correlation functions of N=4 SYM. We hope on new insights into the strong coupling dynamics of less supersymmetric gauge theories and of QCD.
Summary
Fundamental interactions in nature are well described by quantum gauge fields in 4 space-time dimensions (4d). When the strength of gauge interaction is weak the Feynman perturbation techniques are very efficient for the description of most of the experimentally observable consequences of the Standard model and for the study of high energy processes in QCD.
But in the intermediate and strong coupling regime, such as the relatively small energies in QCD, the perturbation theory fails leaving us with no reliable analytic methods (except the Monte-Carlo simulation). The project aims at working out new analytic and computational methods for strongly coupled gauge theories in 4d. We will employ for that two important discoveries: 1) the gauge-string duality (AdS/CFT correspondence) relating certain strongly coupled gauge Conformal Field
Theories to the weakly coupled string theories on Anty-deSitter space; 2) the solvability, or integrability of maximally supersymmetric (N=4) 4d super Yang-Mills (SYM) theory in multicolor limit. Integrability made possible pioneering exact numerical and analytic results in the N=4 multicolor SYM at any coupling, effectively summing up all 4d Feynman diagrams. Recently, we conjectured a system of functional equations - the AdS/CFT Y-system – for the exact spectrum of anomalous dimensions of all local operators in N=4 SYM. The conjecture has passed all available checks. My project is aimed at the understanding of origins of this, still mysterious integrability. Deriving the AdS/CFT Y-system from the first principles on both sides of gauge-string duality should provide a long-awaited proof of the AdS/CFT correspondence itself. I plan to use the Y-system to study the systematic weak and strong coupling expansions and the so called BFKL limit, as well as for calculation of multi-point correlation functions of N=4 SYM. We hope on new insights into the strong coupling dynamics of less supersymmetric gauge theories and of QCD.
Max ERC Funding
1 456 140 €
Duration
Start date: 2013-11-01, End date: 2018-10-31
Project acronym ALGAME
Project Algorithms, Games, Mechanisms, and the Price of Anarchy
Researcher (PI) Elias Koutsoupias
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), PE6, ERC-2012-ADG_20120216
Summary The objective of this proposal is to bring together a local team of young researchers who will work closely with international collaborators to advance the state of the art of Algorithmic Game Theory and open new venues of research at the interface of Computer Science, Game Theory, and Economics. The proposal consists mainly of three intertwined research strands: algorithmic mechanism design, price of anarchy, and online algorithms.
Specifically, we will attempt to resolve some outstanding open problems in algorithmic mechanism design: characterizing the incentive compatible mechanisms for important domains, such as the domain of combinatorial auctions, and resolving the approximation ratio of mechanisms for scheduling unrelated machines. More generally, we will study centralized and distributed algorithms whose inputs are controlled by selfish agents that are interested in the outcome of the computation. We will investigate new notions of mechanisms with strong truthfulness and limited susceptibility to externalities that can facilitate modular design of mechanisms of complex domains.
We will expand the current research on the price of anarchy to time-dependent games where the players can select not only how to act but also when to act. We also plan to resolve outstanding questions on the price of stability and to build a robust approach to these questions, similar to smooth analysis. For repeated games, we will investigate convergence of simple strategies (e.g., fictitious play), online fairness, and strategic considerations (e.g., metagames). More generally, our aim is to find a productive formulation of playing unknown games by drawing on the fields of online algorithms and machine learning.
Summary
The objective of this proposal is to bring together a local team of young researchers who will work closely with international collaborators to advance the state of the art of Algorithmic Game Theory and open new venues of research at the interface of Computer Science, Game Theory, and Economics. The proposal consists mainly of three intertwined research strands: algorithmic mechanism design, price of anarchy, and online algorithms.
Specifically, we will attempt to resolve some outstanding open problems in algorithmic mechanism design: characterizing the incentive compatible mechanisms for important domains, such as the domain of combinatorial auctions, and resolving the approximation ratio of mechanisms for scheduling unrelated machines. More generally, we will study centralized and distributed algorithms whose inputs are controlled by selfish agents that are interested in the outcome of the computation. We will investigate new notions of mechanisms with strong truthfulness and limited susceptibility to externalities that can facilitate modular design of mechanisms of complex domains.
We will expand the current research on the price of anarchy to time-dependent games where the players can select not only how to act but also when to act. We also plan to resolve outstanding questions on the price of stability and to build a robust approach to these questions, similar to smooth analysis. For repeated games, we will investigate convergence of simple strategies (e.g., fictitious play), online fairness, and strategic considerations (e.g., metagames). More generally, our aim is to find a productive formulation of playing unknown games by drawing on the fields of online algorithms and machine learning.
Max ERC Funding
2 461 000 €
Duration
Start date: 2013-04-01, End date: 2019-03-31
Project acronym ALLEGRO
Project Active large-scale learning for visual recognition
Researcher (PI) Cordelia Schmid
Host Institution (HI) INSTITUT NATIONAL DE RECHERCHE ENINFORMATIQUE ET AUTOMATIQUE
Call Details Advanced Grant (AdG), PE6, ERC-2012-ADG_20120216
Summary A massive and ever growing amount of digital image and video content
is available today, on sites such as
Flickr and YouTube, in audiovisual archives such as those of BBC and
INA, and in personal collections. In most cases, it comes with
additional information, such as text, audio or other metadata, that forms a
rather sparse and noisy, yet rich and diverse source of annotation,
ideally suited to emerging weakly supervised and active machine
learning technology. The ALLEGRO project will take visual recognition
to the next level by using this largely untapped source of data to
automatically learn visual models. The main research objective of
our project is the development of new algorithms and computer software
capable of autonomously exploring evolving data collections, selecting
the relevant information, and determining the visual models most
appropriate for different object, scene, and activity categories. An
emphasis will be put on learning visual models from video, a
particularly rich source of information, and on the representation of
human activities, one of today's most challenging problems in computer
vision. Although this project addresses fundamental research
issues, it is expected to result in significant advances in
high-impact applications that range from visual mining of the Web and
automated annotation and organization of family photo and video albums
to large-scale information retrieval in television archives.
Summary
A massive and ever growing amount of digital image and video content
is available today, on sites such as
Flickr and YouTube, in audiovisual archives such as those of BBC and
INA, and in personal collections. In most cases, it comes with
additional information, such as text, audio or other metadata, that forms a
rather sparse and noisy, yet rich and diverse source of annotation,
ideally suited to emerging weakly supervised and active machine
learning technology. The ALLEGRO project will take visual recognition
to the next level by using this largely untapped source of data to
automatically learn visual models. The main research objective of
our project is the development of new algorithms and computer software
capable of autonomously exploring evolving data collections, selecting
the relevant information, and determining the visual models most
appropriate for different object, scene, and activity categories. An
emphasis will be put on learning visual models from video, a
particularly rich source of information, and on the representation of
human activities, one of today's most challenging problems in computer
vision. Although this project addresses fundamental research
issues, it is expected to result in significant advances in
high-impact applications that range from visual mining of the Web and
automated annotation and organization of family photo and video albums
to large-scale information retrieval in television archives.
Max ERC Funding
2 493 322 €
Duration
Start date: 2013-04-01, End date: 2019-03-31
Project acronym AMYLOID
Project Identification and modulation of pathogenic Amyloid beta-peptide species
Researcher (PI) Christian Haass
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS5, ERC-2012-ADG_20120314
Summary The frequency of Alzheimer's disease (AD) will dramatically increase in the ageing western society during the next decades. Currently, about 18 million people suffer worldwide from AD. Since no cure is available, this devastating disorder represents one of the most challenging socio-economical problems of our future. As onset and progression of AD is triggered by the amyloid cascade, I will put particular attention on amyloid ß-peptide (Aß). The reason for this approach is, that even though 20 years ago the Aß generating processing pathway was identified (Haass et al., Nature 1992a & b), the identity of the Aß species, which initiate the deadly cascade is still unknown. I will first tackle this challenge by investigating if a novel and so far completely overlooked proteolytic processing pathway is involved in the generation of Aß species capable to initiate spreading of pathology and neurotoxicity. I will then search for modulating proteins, which could affect generation of pathological Aß species. This includes a genome-wide screen for modifiers of gamma-secretase, one of the proteases involved in Aß generation as well as a targeted search for RNA binding proteins capable to posttranscriptionally regulate beta- and alpha-secretase. In a disease-crossing approach, RNA binding proteins, which were recently found not only to be deposited in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis but also in many AD cases, will be investigated for their potential to modulate Aß aggregation and AD pathology. Modifiers and novel antibodies specifically recognizing neurotoxic Aß assemblies will be validated for their potential not only to prevent amyloid plaque formation, but also spreading of pathology as well as neurotoxicity. In vivo validations include studies in innovative zebrafish models, which allow life imaging of neuronal cell death, as well as the establishment of microPET amyloid imaging for longitudinal studies in individual animals.
Summary
The frequency of Alzheimer's disease (AD) will dramatically increase in the ageing western society during the next decades. Currently, about 18 million people suffer worldwide from AD. Since no cure is available, this devastating disorder represents one of the most challenging socio-economical problems of our future. As onset and progression of AD is triggered by the amyloid cascade, I will put particular attention on amyloid ß-peptide (Aß). The reason for this approach is, that even though 20 years ago the Aß generating processing pathway was identified (Haass et al., Nature 1992a & b), the identity of the Aß species, which initiate the deadly cascade is still unknown. I will first tackle this challenge by investigating if a novel and so far completely overlooked proteolytic processing pathway is involved in the generation of Aß species capable to initiate spreading of pathology and neurotoxicity. I will then search for modulating proteins, which could affect generation of pathological Aß species. This includes a genome-wide screen for modifiers of gamma-secretase, one of the proteases involved in Aß generation as well as a targeted search for RNA binding proteins capable to posttranscriptionally regulate beta- and alpha-secretase. In a disease-crossing approach, RNA binding proteins, which were recently found not only to be deposited in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis but also in many AD cases, will be investigated for their potential to modulate Aß aggregation and AD pathology. Modifiers and novel antibodies specifically recognizing neurotoxic Aß assemblies will be validated for their potential not only to prevent amyloid plaque formation, but also spreading of pathology as well as neurotoxicity. In vivo validations include studies in innovative zebrafish models, which allow life imaging of neuronal cell death, as well as the establishment of microPET amyloid imaging for longitudinal studies in individual animals.
Max ERC Funding
2 497 020 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym AMYTOX
Project Amyloid fibril cytotoxicity: new insights from novel approaches
Researcher (PI) Sheena Radford
Host Institution (HI) UNIVERSITY OF LEEDS
Call Details Advanced Grant (AdG), LS1, ERC-2012-ADG_20120314
Summary Despite the discovery of amyloidosis more than a century ago, the molecular and cellular mechanisms of these devastating human disorders remain obscure. In addition to their involvement in disease, amyloid fibrils perform physiological functions, whilst others have potentials as biomaterials. To realise their use in nanotechnology and to enable the development of amyloid therapies, there is an urgent need to understand the molecular pathways of amyloid assembly and to determine how amyloid fibrils interact with cells and cellular components. The challenges lie in the transient nature and low population of aggregating species and the panoply of amyloid fibril structures. This molecular complexity renders identification of the culprits of amyloid disease impossible to achieve using traditional methods.
Here I propose a series of exciting experiments that aim to cast new light on the molecular and cellular mechanisms of amyloidosis by exploiting approaches capable of imaging individual protein molecules or single protein fibrils in vitro and in living cells. The proposal builds on new data from our laboratory that have shown that amyloid fibrils (disease-associated, functional and created from de novo designed sequences) kill cells by a mechanism that depends on fibril length and on cellular uptake. Specifically, I will (i) use single molecule fluorescence and non-covalent mass spectrometry and to determine why short fibril samples disrupt biological membranes more than their longer counterparts and electron tomography to determine, for the first time, the structural properties of cytotoxic fibril ends; (ii) develop single molecule force spectroscopy to probe the interactions between amyloid precursors, fibrils and cellular membranes; and (iii) develop cell biological assays to discover the biological mechanism(s) of amyloid-induced cell death and high resolution imaging and electron tomography to visualise amyloid fibrils in the act of killing living cells.
Summary
Despite the discovery of amyloidosis more than a century ago, the molecular and cellular mechanisms of these devastating human disorders remain obscure. In addition to their involvement in disease, amyloid fibrils perform physiological functions, whilst others have potentials as biomaterials. To realise their use in nanotechnology and to enable the development of amyloid therapies, there is an urgent need to understand the molecular pathways of amyloid assembly and to determine how amyloid fibrils interact with cells and cellular components. The challenges lie in the transient nature and low population of aggregating species and the panoply of amyloid fibril structures. This molecular complexity renders identification of the culprits of amyloid disease impossible to achieve using traditional methods.
Here I propose a series of exciting experiments that aim to cast new light on the molecular and cellular mechanisms of amyloidosis by exploiting approaches capable of imaging individual protein molecules or single protein fibrils in vitro and in living cells. The proposal builds on new data from our laboratory that have shown that amyloid fibrils (disease-associated, functional and created from de novo designed sequences) kill cells by a mechanism that depends on fibril length and on cellular uptake. Specifically, I will (i) use single molecule fluorescence and non-covalent mass spectrometry and to determine why short fibril samples disrupt biological membranes more than their longer counterparts and electron tomography to determine, for the first time, the structural properties of cytotoxic fibril ends; (ii) develop single molecule force spectroscopy to probe the interactions between amyloid precursors, fibrils and cellular membranes; and (iii) develop cell biological assays to discover the biological mechanism(s) of amyloid-induced cell death and high resolution imaging and electron tomography to visualise amyloid fibrils in the act of killing living cells.
Max ERC Funding
2 498 465 €
Duration
Start date: 2013-05-01, End date: 2019-04-30
Project acronym ANALYTICAL SOCIOLOGY
Project Analytical Sociology: Theoretical Developments and Empirical Research
Researcher (PI) Mats Peter Hedström
Host Institution (HI) LINKOPINGS UNIVERSITET
Call Details Advanced Grant (AdG), SH2, ERC-2012-ADG_20120411
Summary This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction.
One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link.
The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed.
Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.
Summary
This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction.
One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link.
The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed.
Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.
Max ERC Funding
1 745 098 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym ANGEOM
Project Geometric analysis in the Euclidean space
Researcher (PI) Xavier Tolsa Domenech
Host Institution (HI) UNIVERSITAT AUTONOMA DE BARCELONA
Call Details Advanced Grant (AdG), PE1, ERC-2012-ADG_20120216
Summary "We propose to study different questions in the area of the so called geometric analysis. Most of the topics we are interested in deal with the connection between the behavior of singular integrals and the geometry of sets and measures. The study of this connection has been shown to be extremely helpful in the solution of certain long standing problems in the last years, such as the solution of the Painlev\'e problem or the obtaining of the optimal distortion bounds for quasiconformal mappings by Astala.
More specifically, we would like to study the relationship between the L^2 boundedness of singular integrals associated with Riesz and other related kernels, and rectifiability and other geometric notions. The so called David-Semmes problem is probably the main open problem in this area. Up to now, the techniques used to deal with this problem come from multiscale analysis and involve ideas from Littlewood-Paley theory and quantitative techniques of rectifiability. We propose to apply new ideas that combine variational arguments with other techniques which have connections with mass transportation. Further, we think that it is worth to explore in more detail the connection among mass transportation, singular integrals, and uniform rectifiability.
We are also interested in the field of quasiconformal mappings. We plan to study a problem regarding the quasiconformal distortion of quasicircles. This problem consists in proving that the bounds obtained recently by S. Smirnov on the dimension of K-quasicircles are optimal. We want to apply techniques from quantitative geometric measure theory to deal with this question.
Another question that we intend to explore lies in the interplay of harmonic analysis, geometric measure theory and partial differential equations. This concerns an old problem on the unique continuation of harmonic functions at the boundary open C^1 or Lipschitz domain. All the results known by now deal with smoother Dini domains."
Summary
"We propose to study different questions in the area of the so called geometric analysis. Most of the topics we are interested in deal with the connection between the behavior of singular integrals and the geometry of sets and measures. The study of this connection has been shown to be extremely helpful in the solution of certain long standing problems in the last years, such as the solution of the Painlev\'e problem or the obtaining of the optimal distortion bounds for quasiconformal mappings by Astala.
More specifically, we would like to study the relationship between the L^2 boundedness of singular integrals associated with Riesz and other related kernels, and rectifiability and other geometric notions. The so called David-Semmes problem is probably the main open problem in this area. Up to now, the techniques used to deal with this problem come from multiscale analysis and involve ideas from Littlewood-Paley theory and quantitative techniques of rectifiability. We propose to apply new ideas that combine variational arguments with other techniques which have connections with mass transportation. Further, we think that it is worth to explore in more detail the connection among mass transportation, singular integrals, and uniform rectifiability.
We are also interested in the field of quasiconformal mappings. We plan to study a problem regarding the quasiconformal distortion of quasicircles. This problem consists in proving that the bounds obtained recently by S. Smirnov on the dimension of K-quasicircles are optimal. We want to apply techniques from quantitative geometric measure theory to deal with this question.
Another question that we intend to explore lies in the interplay of harmonic analysis, geometric measure theory and partial differential equations. This concerns an old problem on the unique continuation of harmonic functions at the boundary open C^1 or Lipschitz domain. All the results known by now deal with smoother Dini domains."
Max ERC Funding
1 105 930 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym AnoPath
Project Genetics of mosquito resistance to pathogens
Researcher (PI) Kenneth Du Souchet Vernick
Host Institution (HI) INSTITUT PASTEUR
Call Details Advanced Grant (AdG), LS2, ERC-2012-ADG_20120314
Summary Malaria parasite infection in humans has been called “the strongest known force for evolutionary selection in the recent history of the human genome”, and I hypothesize that a similar statement may apply to the mosquito vector, which is the definitive host of the malaria parasite. We previously discovered efficient malaria-resistance mechanisms in natural populations of the African malaria vector, Anopheles gambiae. Aim 1 of the proposed project will implement a novel genetic mapping design to systematically survey the mosquito population for common and rare genetic variants of strong effect against the human malaria parasite, Plasmodium falciparum. A product of the mapping design will be living mosquito families carrying the resistance loci. Aim 2 will use the segregating families to functionally dissect the underlying molecular mechanisms controlled by the loci, including determination of the pathogen specificity spectra of the host-defense traits. Aim 3 targets arbovirus transmission, where Anopheles mosquitoes transmit human malaria but not arboviruses such as Dengue and Chikungunya, even though the two mosquitoes bite the same people and are exposed to the same pathogens, often in malaria-arbovirus co-infections. We will use deep-sequencing to detect processing of the arbovirus dsRNA intermediates of replication produced by the RNAi pathway of the mosquitoes. The results will reveal important new information about differences in the efficiency and quality of the RNAi response between mosquitoes, which is likely to underlie at least part of the host specificity of arbovirus transmission. The 3 Aims will make significant contributions to understanding malaria and arbovirus transmission, major global public health problems, will aid the development of a next generation of vector surveillance and control tools, and will produce a definitive description of the major genetic factors influencing host-pathogen interactions in mosquito immunity.
Summary
Malaria parasite infection in humans has been called “the strongest known force for evolutionary selection in the recent history of the human genome”, and I hypothesize that a similar statement may apply to the mosquito vector, which is the definitive host of the malaria parasite. We previously discovered efficient malaria-resistance mechanisms in natural populations of the African malaria vector, Anopheles gambiae. Aim 1 of the proposed project will implement a novel genetic mapping design to systematically survey the mosquito population for common and rare genetic variants of strong effect against the human malaria parasite, Plasmodium falciparum. A product of the mapping design will be living mosquito families carrying the resistance loci. Aim 2 will use the segregating families to functionally dissect the underlying molecular mechanisms controlled by the loci, including determination of the pathogen specificity spectra of the host-defense traits. Aim 3 targets arbovirus transmission, where Anopheles mosquitoes transmit human malaria but not arboviruses such as Dengue and Chikungunya, even though the two mosquitoes bite the same people and are exposed to the same pathogens, often in malaria-arbovirus co-infections. We will use deep-sequencing to detect processing of the arbovirus dsRNA intermediates of replication produced by the RNAi pathway of the mosquitoes. The results will reveal important new information about differences in the efficiency and quality of the RNAi response between mosquitoes, which is likely to underlie at least part of the host specificity of arbovirus transmission. The 3 Aims will make significant contributions to understanding malaria and arbovirus transmission, major global public health problems, will aid the development of a next generation of vector surveillance and control tools, and will produce a definitive description of the major genetic factors influencing host-pathogen interactions in mosquito immunity.
Max ERC Funding
2 307 800 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym Anti-Virome
Project A combined evolutionary and proteomics approach to the discovery, induction and application of antiviral immunity factors
Researcher (PI) Frank Kirchhoff
Host Institution (HI) UNIVERSITAET ULM
Call Details Advanced Grant (AdG), LS6, ERC-2012-ADG_20120314
Summary "Humans are equipped with a variety of intrinsic immunity or host restriction factors. These evolved under positive selection pressure for diversification and represent a first line of defence against invading viruses. Unfortunately, however, many pathogens have evolved effective antagonists against our defences. For example, the capability of HIV-1 to counteract human restriction factors that interfere with reverse transcription, uncoating and virion release has been a prerequisite for the global spread of AIDS. We are just beginning to understand the diversity and induction of antiretroviral factors and how pandemic HIV-1 group M (major) strains evolved to counteract all of them. Here, I propose to use a genetics, proteomics and evolutionary approach to discover and define as-yet-unknown antiviral effectors and their inducers. To identify novel antiviral factors, we will examine the capability of all primate genes that are under strong positive selection pressure to inhibit HIV and its simian (SIV) precursors. This examination from the evolutionary perspective of the invading pathogen will also reveal which adaptations allowed HIV-1 to cause the AIDS pandemic. Furthermore, complex peptide-protein libraries representing essentially the entire human peptidome, will be utilized to identify novel specific inducers of antiviral restriction factors. My ultimate aim is to unravel the network of inducers and effectors of antiviral immunity - the ""Anti-Virome"" - and to use this knowledge to develop novel effective preventive and therapeutic approaches based on the induction of combinations of antiviral factors targeting different steps of the viral life cycle. The results of this innovative and interdisciplinary program will provide fundamental new insights into intrinsic immunity and may offer alternatives to conventional vaccine and therapeutic approaches because most restriction factors have broad antiviral activity and are thus effective against various pathogens."
Summary
"Humans are equipped with a variety of intrinsic immunity or host restriction factors. These evolved under positive selection pressure for diversification and represent a first line of defence against invading viruses. Unfortunately, however, many pathogens have evolved effective antagonists against our defences. For example, the capability of HIV-1 to counteract human restriction factors that interfere with reverse transcription, uncoating and virion release has been a prerequisite for the global spread of AIDS. We are just beginning to understand the diversity and induction of antiretroviral factors and how pandemic HIV-1 group M (major) strains evolved to counteract all of them. Here, I propose to use a genetics, proteomics and evolutionary approach to discover and define as-yet-unknown antiviral effectors and their inducers. To identify novel antiviral factors, we will examine the capability of all primate genes that are under strong positive selection pressure to inhibit HIV and its simian (SIV) precursors. This examination from the evolutionary perspective of the invading pathogen will also reveal which adaptations allowed HIV-1 to cause the AIDS pandemic. Furthermore, complex peptide-protein libraries representing essentially the entire human peptidome, will be utilized to identify novel specific inducers of antiviral restriction factors. My ultimate aim is to unravel the network of inducers and effectors of antiviral immunity - the ""Anti-Virome"" - and to use this knowledge to develop novel effective preventive and therapeutic approaches based on the induction of combinations of antiviral factors targeting different steps of the viral life cycle. The results of this innovative and interdisciplinary program will provide fundamental new insights into intrinsic immunity and may offer alternatives to conventional vaccine and therapeutic approaches because most restriction factors have broad antiviral activity and are thus effective against various pathogens."
Max ERC Funding
1 915 200 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym Antivessel-T-Cells
Project Development of Vascular-Disrupting Lymphocyte Therapy for Tumours
Researcher (PI) Georgios Coukos
Host Institution (HI) CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS
Call Details Advanced Grant (AdG), LS7, ERC-2012-ADG_20120314
Summary T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory.
I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.
Summary
T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory.
I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-08-01, End date: 2018-07-31
Project acronym ANTS
Project Attine ANT SymbiomeS
Researcher (PI) Jacobus Jan Boomsma
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), LS8, ERC-2012-ADG_20120314
Summary "The attine fungus-growing ants are prime models for understanding phenotypic adaptations in social evolution and symbiosis. The mutualism has many hallmarks of advanced cooperation in its mating system commitments and functional complementarity between multiple symbiont partners, but potential conflicts between sexes and castes over reproductive priorities, and between hosts and symbionts over symbiont mixing have also been documented. With collaborators at BGI-Shenzhen and the Smithsonian Institution my group has obtained six reference genomes representing all genus-level branches of the higher attine ants and a lower attine outgroup. With collaborators in Denmark and Australia we have pioneered proteomic approaches to understand the preservation of sperm viability in spite of sperm competition and the enzymatic decomposition of plant substrates that the ants use to make their fungus gardens grow.
Here, I propose an integrated study focusing on four major areas of attine ant biology that are particularly inviting for in depth molecular approaches: 1. The protein-level networks that secure life-time (up to 20 years) sperm storage in specialized ant-queen organs and the genetic mechanisms that shape and adjust these “sexual symbiome” networks. 2. The ant-fungal symbiome, i.e. the dynamics of fungal enzyme production for plant substrate degradation and the redistribution of these enzymes in fungus gardens through fecal deposition after they are ingested but not digested by the ants. 3. The microbial symbiome of ant guts and other tissues with obligate bacterial mutualists, of which we have identified some and will characterize a wider collection across the different branches of the attine ant phylogeny. 4. The genome-wide frequency of genomic imprinting and the significance of these imprints for the expression of caste phenotypes and the regulation of potential reproductive conflicts."
Summary
"The attine fungus-growing ants are prime models for understanding phenotypic adaptations in social evolution and symbiosis. The mutualism has many hallmarks of advanced cooperation in its mating system commitments and functional complementarity between multiple symbiont partners, but potential conflicts between sexes and castes over reproductive priorities, and between hosts and symbionts over symbiont mixing have also been documented. With collaborators at BGI-Shenzhen and the Smithsonian Institution my group has obtained six reference genomes representing all genus-level branches of the higher attine ants and a lower attine outgroup. With collaborators in Denmark and Australia we have pioneered proteomic approaches to understand the preservation of sperm viability in spite of sperm competition and the enzymatic decomposition of plant substrates that the ants use to make their fungus gardens grow.
Here, I propose an integrated study focusing on four major areas of attine ant biology that are particularly inviting for in depth molecular approaches: 1. The protein-level networks that secure life-time (up to 20 years) sperm storage in specialized ant-queen organs and the genetic mechanisms that shape and adjust these “sexual symbiome” networks. 2. The ant-fungal symbiome, i.e. the dynamics of fungal enzyme production for plant substrate degradation and the redistribution of these enzymes in fungus gardens through fecal deposition after they are ingested but not digested by the ants. 3. The microbial symbiome of ant guts and other tissues with obligate bacterial mutualists, of which we have identified some and will characterize a wider collection across the different branches of the attine ant phylogeny. 4. The genome-wide frequency of genomic imprinting and the significance of these imprints for the expression of caste phenotypes and the regulation of potential reproductive conflicts."
Max ERC Funding
2 290 102 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym APMPAL
Project Asset Prices and Macro Policy when Agents Learn
Researcher (PI) Albert Marcet Torrens
Host Institution (HI) FUNDACIÓ MARKETS, ORGANIZATIONS AND VOTES IN ECONOMICS
Call Details Advanced Grant (AdG), SH1, ERC-2012-ADG_20120411
Summary "A conventional assumption in dynamic models is that agents form their expectations in a very sophisticated manner. In particular, that they have Rational Expectations (RE). We develop some tools to relax this assumption while retaining fully optimal behaviour by agents. We study implications for asset pricing and macro policy.
We assume that agents have a consistent set of beliefs that is close, but not equal, to RE. Agents are ""Internally Rational"", that is, they behave rationally given their system of beliefs. Thus, it is conceptually a small deviation from RE. It provides microfoundations for models of adaptive learning, since the learning algorithm is determined by agents’ optimal behaviour. In previous work we have shown that this framework can match stock price and housing price fluctuations, and that policy implications are quite different.
In this project we intend to: i) develop further the foundations of internally rational (IR) learning, ii) apply this to explain observed asset price price behavior, such as stock prices, bond prices, inflation, commodity derivatives, and exchange rates, iii) extend the IR framework to the case when agents entertain various models, iv) optimal policy under IR learning and under private information when some hidden shocks are not revealed ex-post. Along the way we will address policy issues such as: effects of creating derivative markets, sovereign spread as a signal of sovereign default risk, tests of fiscal sustainability, fiscal policy when agents learn, monetary policy (more specifically, QE measures and interest rate policy), and the role of credibility in macro policy."
Summary
"A conventional assumption in dynamic models is that agents form their expectations in a very sophisticated manner. In particular, that they have Rational Expectations (RE). We develop some tools to relax this assumption while retaining fully optimal behaviour by agents. We study implications for asset pricing and macro policy.
We assume that agents have a consistent set of beliefs that is close, but not equal, to RE. Agents are ""Internally Rational"", that is, they behave rationally given their system of beliefs. Thus, it is conceptually a small deviation from RE. It provides microfoundations for models of adaptive learning, since the learning algorithm is determined by agents’ optimal behaviour. In previous work we have shown that this framework can match stock price and housing price fluctuations, and that policy implications are quite different.
In this project we intend to: i) develop further the foundations of internally rational (IR) learning, ii) apply this to explain observed asset price price behavior, such as stock prices, bond prices, inflation, commodity derivatives, and exchange rates, iii) extend the IR framework to the case when agents entertain various models, iv) optimal policy under IR learning and under private information when some hidden shocks are not revealed ex-post. Along the way we will address policy issues such as: effects of creating derivative markets, sovereign spread as a signal of sovereign default risk, tests of fiscal sustainability, fiscal policy when agents learn, monetary policy (more specifically, QE measures and interest rate policy), and the role of credibility in macro policy."
Max ERC Funding
1 970 260 €
Duration
Start date: 2013-06-01, End date: 2018-08-31
Project acronym ARIPHYHIMO
Project Arithmetic and physics of Higgs moduli spaces
Researcher (PI) Tamas Hausel
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Advanced Grant (AdG), PE1, ERC-2012-ADG_20120216
Summary The proposal studies problems concerning the geometry and topology of moduli spaces of Higgs bundles on a Riemann surface motivated by parallel considerations in number theory and mathematical physics. In this way the proposal bridges various duality theories in string theory with the Langlands program in number theory.
The heart of the proposal is a circle of precise conjectures relating to the topology of the moduli space of Higgs bundles. The formulation and motivations of the conjectures make direct contact with the Langlands program in number theory, various duality conjectures in string theory, algebraic combinatorics, knot theory and low dimensional topology and representation theory of quivers, finite groups and algebras of Lie type and Cherednik algebras.
Summary
The proposal studies problems concerning the geometry and topology of moduli spaces of Higgs bundles on a Riemann surface motivated by parallel considerations in number theory and mathematical physics. In this way the proposal bridges various duality theories in string theory with the Langlands program in number theory.
The heart of the proposal is a circle of precise conjectures relating to the topology of the moduli space of Higgs bundles. The formulation and motivations of the conjectures make direct contact with the Langlands program in number theory, various duality conjectures in string theory, algebraic combinatorics, knot theory and low dimensional topology and representation theory of quivers, finite groups and algebras of Lie type and Cherednik algebras.
Max ERC Funding
1 304 945 €
Duration
Start date: 2013-04-01, End date: 2018-08-31
Project acronym ARISYS
Project Engineering an artificial immune system with functional components assembled from prokaryotic parts and modules
Researcher (PI) Víctor De Lorenzo Prieto
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), LS9, ERC-2012-ADG_20120314
Summary The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.
Summary
The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.
Max ERC Funding
2 422 271 €
Duration
Start date: 2013-05-01, End date: 2019-04-30
Project acronym ARITHQUANTUMCHAOS
Project Arithmetic and Quantum Chaos
Researcher (PI) Zeev Rudnick
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Advanced Grant (AdG), PE1, ERC-2012-ADG_20120216
Summary Quantum Chaos is an emerging discipline which is crossing over from Physics into Pure Mathematics. The recent crossover is driven in part by a connection with Number Theory. This project explores several aspects of this interrelationship and is composed of a number of sub-projects. The sub-projects deal with: statistics of energy levels and wave functions of pseudo-integrable systems, a hitherto unexplored subject in the mathematical community which is not well understood in the physics community; with statistics of zeros of zeta functions over function fields, a purely number theoretic topic which is linked to the subproject on Quantum Chaos through the mysterious connections to Random Matrix Theory and an analogy between energy levels and zeta zeros; and with spatial statistics in arithmetic.
Summary
Quantum Chaos is an emerging discipline which is crossing over from Physics into Pure Mathematics. The recent crossover is driven in part by a connection with Number Theory. This project explores several aspects of this interrelationship and is composed of a number of sub-projects. The sub-projects deal with: statistics of energy levels and wave functions of pseudo-integrable systems, a hitherto unexplored subject in the mathematical community which is not well understood in the physics community; with statistics of zeros of zeta functions over function fields, a purely number theoretic topic which is linked to the subproject on Quantum Chaos through the mysterious connections to Random Matrix Theory and an analogy between energy levels and zeta zeros; and with spatial statistics in arithmetic.
Max ERC Funding
1 714 000 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym ARTIMATTER
Project "Lego-Style Materials, Structures and Devices Assembled on Demand from Isolated Atomic Planes"
Researcher (PI) Andre Geim
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Advanced Grant (AdG), PE3, ERC-2012-ADG_20120216
Summary "Following the advent of graphene with its wide range of unique properties, several other one-atom-thick crystals have been isolated and their preliminary studies have been undertaken. They range from semiconducting monolayers of MoS2 and NbSe2, which similar to graphene exhibit the electric field effect and relatively high electronic quality, to wide-gap insulators such as boron-nitride monolayers that can serve as atomically-thin tunnel barriers.
This library of two-dimensional crystals opens a possibility to construct various 3D structures with on-demand properties, which do not exist in nature but can be assembled in Lego style by stacking individual atomic planes on top of each other in a desired sequence. This project is to explore this new avenue.
We will design, fabricate and study multilayer materials ranging from basic heterostructures that consist of a few alternating layers of graphene and boron nitride and already exhibit a rich spectrum of new phenomena, as recently demonstrated by the applicant’s group, to complex artificial materials containing many layers of different 2D crystals and mimicking, for example, layered superconductors. In a similar manner, various electronic, optoelectronic, micromechanical and other devices will be developed and investigated. The applicant’s aim is to search for new materials with unique properties, novel devices with better characteristics and new physics that is likely to emerge along the way.
The proposed research offers many exciting opportunities and can lead to the development of a large unexplored field with impact exceeding even that of graphene research. This presents a unique, once-in-decade, opportunity to make a very significant breakthrough in condensed matter physics and materials science."
Summary
"Following the advent of graphene with its wide range of unique properties, several other one-atom-thick crystals have been isolated and their preliminary studies have been undertaken. They range from semiconducting monolayers of MoS2 and NbSe2, which similar to graphene exhibit the electric field effect and relatively high electronic quality, to wide-gap insulators such as boron-nitride monolayers that can serve as atomically-thin tunnel barriers.
This library of two-dimensional crystals opens a possibility to construct various 3D structures with on-demand properties, which do not exist in nature but can be assembled in Lego style by stacking individual atomic planes on top of each other in a desired sequence. This project is to explore this new avenue.
We will design, fabricate and study multilayer materials ranging from basic heterostructures that consist of a few alternating layers of graphene and boron nitride and already exhibit a rich spectrum of new phenomena, as recently demonstrated by the applicant’s group, to complex artificial materials containing many layers of different 2D crystals and mimicking, for example, layered superconductors. In a similar manner, various electronic, optoelectronic, micromechanical and other devices will be developed and investigated. The applicant’s aim is to search for new materials with unique properties, novel devices with better characteristics and new physics that is likely to emerge along the way.
The proposed research offers many exciting opportunities and can lead to the development of a large unexplored field with impact exceeding even that of graphene research. This presents a unique, once-in-decade, opportunity to make a very significant breakthrough in condensed matter physics and materials science."
Max ERC Funding
2 200 000 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym ASES
Project "Advancing computational chemistry with new accurate, robust and scalable electronic structure methods"
Researcher (PI) Hans-Joachim Werner
Host Institution (HI) UNIVERSITAET STUTTGART
Call Details Advanced Grant (AdG), PE4, ERC-2012-ADG_20120216
Summary "The objective of this proposal is to tackle two of the greatest challenges in quantum chemistry: (i) extending the applicability of highly accurate wave function methods to large molecular systems, and (ii) developing accurate and robust multi-reference methods that can be used for studying important but very difficult problems in transition metal chemistry, catalysis, and photochemistry. Solutions to these problems have now come within reach due to three advances we recently reported: first, the steep scaling of the computational cost with molecular size can be reduced to linear by exploiting the short-range character of electron correlation (local correlation methods). Second, the accuracy, efficiency, and robustness of these local correlation methods can be strongly improved by new tensor decomposition approaches and the inclusion of terms depending explicitly on the inter-electronic distances (F12 methods). Third, the development of highly complex electronic structure theories can be greatly facilitated and accelerated by new automated tensor network evaluation techniques. We are certain that by combining and generalizing these advances the long-standing problems (i) and (ii) can be solved. We will focus especially on highly scalable algorithms in order to use massively parallel computer systems efficiently. For linear-scaling methods this means that the size of the molecules that can be treated in a fixed time will grow linearly with the number of available processors. We will furthermore explore new multi-reference ansätze and implement analytical energy gradients and response properties for local methods. Hybrid and embedding methods to account for solvent and environment effects will also be investigated. It is our priority to make our new methods as easy to use, robust, and widely applicable as possible. We believe that they will open entirely new horizons for innumerable applications in chemistry, physics, biology, and materials science."
Summary
"The objective of this proposal is to tackle two of the greatest challenges in quantum chemistry: (i) extending the applicability of highly accurate wave function methods to large molecular systems, and (ii) developing accurate and robust multi-reference methods that can be used for studying important but very difficult problems in transition metal chemistry, catalysis, and photochemistry. Solutions to these problems have now come within reach due to three advances we recently reported: first, the steep scaling of the computational cost with molecular size can be reduced to linear by exploiting the short-range character of electron correlation (local correlation methods). Second, the accuracy, efficiency, and robustness of these local correlation methods can be strongly improved by new tensor decomposition approaches and the inclusion of terms depending explicitly on the inter-electronic distances (F12 methods). Third, the development of highly complex electronic structure theories can be greatly facilitated and accelerated by new automated tensor network evaluation techniques. We are certain that by combining and generalizing these advances the long-standing problems (i) and (ii) can be solved. We will focus especially on highly scalable algorithms in order to use massively parallel computer systems efficiently. For linear-scaling methods this means that the size of the molecules that can be treated in a fixed time will grow linearly with the number of available processors. We will furthermore explore new multi-reference ansätze and implement analytical energy gradients and response properties for local methods. Hybrid and embedding methods to account for solvent and environment effects will also be investigated. It is our priority to make our new methods as easy to use, robust, and widely applicable as possible. We believe that they will open entirely new horizons for innumerable applications in chemistry, physics, biology, and materials science."
Max ERC Funding
2 454 000 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym ATMMACHINE
Project Structural mechanism of recognition, signaling and resection of DNA double-strand breaks
Researcher (PI) Karl-Peter Hopfner
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS1, ERC-2012-ADG_20120314
Summary DNA double-strand breaks are perhaps the most harmful DNA damages and result in carcinogenic chromosome aberrations. Cells protect their genome by activating a complex signaling and repair network, collectively denoted DNA damage response (DDR). A key initial step of the DDR is the activation of the 360 kDa checkpoint kinase ATM (ataxia telangiectasia mutated) by the multifunctional DSB repair factor Mre11-Rad50-Nbs1 (MRN). MRN senses and tethers DSBs, processes DSBs for further resection, and recruits and activates ATM to trigger the DDR. A mechanistic basis for the activities of the core DDR sensor MRN has not been established, despite intense research over the past decade. Our recent breakthroughs on structures of core Mre11-Rad50 and Mre11-Nbs1 complexes enable us now address three central questions to finally clarify the mechanism of MRN in the DDR:
- How does MRN interact with DNA or DNA ends in an ATP dependent manner?
- How do MRN and associated factors such as CtIP process blocked DNA ends?
- How do MRN and DNA activate ATM?
We will employ an innovative structural biology hybrid methods approach by combining X-ray crystallography, electron microscopy and small angle scattering with crosslink mass spectrometry and combine the structure-oriented techniques with validating in vitro and in vivo functional studies. The anticipated outcome will clarify the structural mechanism of one of the most important but enigmatic molecular machineries in maintaining genome stability and also help understand the molecular defects associated with several prominent cancer predisposition and neurodegenerative disorders.
Summary
DNA double-strand breaks are perhaps the most harmful DNA damages and result in carcinogenic chromosome aberrations. Cells protect their genome by activating a complex signaling and repair network, collectively denoted DNA damage response (DDR). A key initial step of the DDR is the activation of the 360 kDa checkpoint kinase ATM (ataxia telangiectasia mutated) by the multifunctional DSB repair factor Mre11-Rad50-Nbs1 (MRN). MRN senses and tethers DSBs, processes DSBs for further resection, and recruits and activates ATM to trigger the DDR. A mechanistic basis for the activities of the core DDR sensor MRN has not been established, despite intense research over the past decade. Our recent breakthroughs on structures of core Mre11-Rad50 and Mre11-Nbs1 complexes enable us now address three central questions to finally clarify the mechanism of MRN in the DDR:
- How does MRN interact with DNA or DNA ends in an ATP dependent manner?
- How do MRN and associated factors such as CtIP process blocked DNA ends?
- How do MRN and DNA activate ATM?
We will employ an innovative structural biology hybrid methods approach by combining X-ray crystallography, electron microscopy and small angle scattering with crosslink mass spectrometry and combine the structure-oriented techniques with validating in vitro and in vivo functional studies. The anticipated outcome will clarify the structural mechanism of one of the most important but enigmatic molecular machineries in maintaining genome stability and also help understand the molecular defects associated with several prominent cancer predisposition and neurodegenerative disorders.
Max ERC Funding
2 498 019 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym Attoclock
Project Clocking fundamental attosecond electron dynamics
Researcher (PI) Ursula Keller
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE2, ERC-2012-ADG_20120216
Summary The attoclock is a powerful, new, and unconventional tool to study fundamental attosecond dynamics on an atomic scale. We established its potential by using the first attoclock to measure the tunneling delay time in laser-induced ionization of helium and argon atoms, with surprising results. Building on these first proof-of-principle measurements, I propose to amplify and expand this tool concept to explore the following key questions: How fast can light liberate electrons from a single atom, a single molecule, or a solid-state system? Related are more questions: How fast can an electron tunnel through a potential barrier? How fast is a multi-photon absorption process? How fast is single-photon photoemission? Many of these questions will undoubtedly spark more questions – revealing deeper and more detailed insights on the dynamics of some of the most fundamental and relevant optoelectronic processes.
There are still many unknown and unexplored areas here. Theory has failed to offer definitive answers. Simulations based on the exact time-dependent Schrödinger equation have not been possible in most cases. Therefore one uses approximations and simpler models to capture the essential physics. Such semi-classical models potentially will help to understand attosecond energy and charge transport in larger molecular systems. Indeed the attoclock provides a unique tool to explore different semi-classical models.
For example, the question of whether electron tunneling through an energetically forbidden region takes a finite time or is instantaneous has been subject to ongoing debate for the last sixty years. The tunnelling process, charge transfer, and energy transport all play key roles in electronics, energy conversion, chemical and biological reactions, and fundamental processes important for improved information, health, and energy technologies. We believe the attoclock can help refine and resolve key models for many of these important underlying attosecond processes.
Summary
The attoclock is a powerful, new, and unconventional tool to study fundamental attosecond dynamics on an atomic scale. We established its potential by using the first attoclock to measure the tunneling delay time in laser-induced ionization of helium and argon atoms, with surprising results. Building on these first proof-of-principle measurements, I propose to amplify and expand this tool concept to explore the following key questions: How fast can light liberate electrons from a single atom, a single molecule, or a solid-state system? Related are more questions: How fast can an electron tunnel through a potential barrier? How fast is a multi-photon absorption process? How fast is single-photon photoemission? Many of these questions will undoubtedly spark more questions – revealing deeper and more detailed insights on the dynamics of some of the most fundamental and relevant optoelectronic processes.
There are still many unknown and unexplored areas here. Theory has failed to offer definitive answers. Simulations based on the exact time-dependent Schrödinger equation have not been possible in most cases. Therefore one uses approximations and simpler models to capture the essential physics. Such semi-classical models potentially will help to understand attosecond energy and charge transport in larger molecular systems. Indeed the attoclock provides a unique tool to explore different semi-classical models.
For example, the question of whether electron tunneling through an energetically forbidden region takes a finite time or is instantaneous has been subject to ongoing debate for the last sixty years. The tunnelling process, charge transfer, and energy transport all play key roles in electronics, energy conversion, chemical and biological reactions, and fundamental processes important for improved information, health, and energy technologies. We believe the attoclock can help refine and resolve key models for many of these important underlying attosecond processes.
Max ERC Funding
2 319 796 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym AUTHORITARIANGLOBAL
Project Authoritarianism in a Global Age: Controlling Information and Communication, Association and People Movement
Researcher (PI) Marlies Glasius
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), SH2, ERC-2012-ADG_20120411
Summary The overarching research question of this project is: how is authoritarian rule affected by and responding to globalisation of (a) information and communication, (b) association, and (c) people movement? The wholly unpredicted series of revolts that recently spread across the Arab world suggests that the nature and sustainability of contemporary authoritarian rule are not well-understood. Openness to global ICT and media, international NGOs, and inflow and outflow of people have thrown up new challenges for authoritarian rulers in terms of how to control citizens. This project investigates changes in both the nature and the sustainability of authoritarian rule in relation to the erosion of decision-making autonomy at the state level posited by globalisation theorists.
In four sub-projects, this project will investigate:
1. Whether, how and to what extent globalisation of information and communication, association, and people movement affect authoritarian persistence (longitudinal quantitative study, 1970-2011)
2. How, i.e. with what policy mechanisms, authoritarian states respond to globalisation of information and communication, association, and people movement (qualitative multi-sited studies relating to Belarus, China, Iran and Zimbabwe)
3. How to understand the phenomenon of subnational authoritarianism in its engagement with the democratic state and the wider world in relation to information and communication, association, and people movement (mixed method subnational studies of states within India and Mexico)
4. What authoritarianism is in a global age: reconsidering authoritarianism’s defining characteristics of low accountability and high coercion, and whether these still relate exclusively to statehood (theory study)
The project will transcend the theoretical and empirical separation between globalisation studies (which have neglected authoritarian contexts) and authoritarianism studies(which have taken relatively little notice of effects of globalisation)
Summary
The overarching research question of this project is: how is authoritarian rule affected by and responding to globalisation of (a) information and communication, (b) association, and (c) people movement? The wholly unpredicted series of revolts that recently spread across the Arab world suggests that the nature and sustainability of contemporary authoritarian rule are not well-understood. Openness to global ICT and media, international NGOs, and inflow and outflow of people have thrown up new challenges for authoritarian rulers in terms of how to control citizens. This project investigates changes in both the nature and the sustainability of authoritarian rule in relation to the erosion of decision-making autonomy at the state level posited by globalisation theorists.
In four sub-projects, this project will investigate:
1. Whether, how and to what extent globalisation of information and communication, association, and people movement affect authoritarian persistence (longitudinal quantitative study, 1970-2011)
2. How, i.e. with what policy mechanisms, authoritarian states respond to globalisation of information and communication, association, and people movement (qualitative multi-sited studies relating to Belarus, China, Iran and Zimbabwe)
3. How to understand the phenomenon of subnational authoritarianism in its engagement with the democratic state and the wider world in relation to information and communication, association, and people movement (mixed method subnational studies of states within India and Mexico)
4. What authoritarianism is in a global age: reconsidering authoritarianism’s defining characteristics of low accountability and high coercion, and whether these still relate exclusively to statehood (theory study)
The project will transcend the theoretical and empirical separation between globalisation studies (which have neglected authoritarian contexts) and authoritarianism studies(which have taken relatively little notice of effects of globalisation)
Max ERC Funding
2 451 179 €
Duration
Start date: 2013-10-01, End date: 2019-02-28
Project acronym AXONSURVIVAL
Project Axon survival: the role of protein synthesis
Researcher (PI) Christine Elizabeth Holt
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), LS5, ERC-2012-ADG_20120314
Summary Neurons make long-distance connections with synaptic targets via axons. These axons survive throughout the lifetime of an organism, often many years in mammals, yet how axons are maintained is not fully understood. Recently, we provided in vivo evidence that local mRNA translation in mature axons is required for their maintenance. This new finding, along with in vitro work from other groups, indicates that promoting axonal protein synthesis is a key mechanism by which trophic factors act to prevent axon degeneration. Here we propose a program of research to investigate the importance of ribosomal proteins (RPs) in axon maintenance and degeneration. The rationale for this is fourfold. First, recent genome-wide studies of axonal transcriptomes have revealed that protein synthesis (including RP mRNAs) is the highest functional category in several neuronal types. Second, some RPs have evolved extra-ribosomal functions that include signalling, such as 67LR which acts both as a cell surface receptor for laminin and as a RP. Third, mutations in different RPs in vertebrates cause unexpectedly specific defects, such as the loss of optic axons. Fourth, preliminary results show that RP mRNAs are translated in optic axons in response to trophic factors. Collectively these findings lead us to propose that locally synthesized RPs play a role in axon maintenance through either ribosomal or extra-ribosomal function. To pursue this proposal, we will perform unbiased screens and functional assays using an array of experimental approaches and animal models. By gaining an understanding of how local RP synthesis contributes to axon survival, our studies have the potential to provide novel insights into how components conventionally associated with a housekeeping role (translation) are linked to axon degeneration. Our findings could provide new directions for developing therapeutic tools for neurodegenerative disorders and may have an impact on more diverse areas of biology and disease.
Summary
Neurons make long-distance connections with synaptic targets via axons. These axons survive throughout the lifetime of an organism, often many years in mammals, yet how axons are maintained is not fully understood. Recently, we provided in vivo evidence that local mRNA translation in mature axons is required for their maintenance. This new finding, along with in vitro work from other groups, indicates that promoting axonal protein synthesis is a key mechanism by which trophic factors act to prevent axon degeneration. Here we propose a program of research to investigate the importance of ribosomal proteins (RPs) in axon maintenance and degeneration. The rationale for this is fourfold. First, recent genome-wide studies of axonal transcriptomes have revealed that protein synthesis (including RP mRNAs) is the highest functional category in several neuronal types. Second, some RPs have evolved extra-ribosomal functions that include signalling, such as 67LR which acts both as a cell surface receptor for laminin and as a RP. Third, mutations in different RPs in vertebrates cause unexpectedly specific defects, such as the loss of optic axons. Fourth, preliminary results show that RP mRNAs are translated in optic axons in response to trophic factors. Collectively these findings lead us to propose that locally synthesized RPs play a role in axon maintenance through either ribosomal or extra-ribosomal function. To pursue this proposal, we will perform unbiased screens and functional assays using an array of experimental approaches and animal models. By gaining an understanding of how local RP synthesis contributes to axon survival, our studies have the potential to provide novel insights into how components conventionally associated with a housekeeping role (translation) are linked to axon degeneration. Our findings could provide new directions for developing therapeutic tools for neurodegenerative disorders and may have an impact on more diverse areas of biology and disease.
Max ERC Funding
2 426 573 €
Duration
Start date: 2013-03-01, End date: 2018-09-30
Project acronym BabMed
Project Fragments of cuneiform medicine in the Babylonian Talmud: Knowledge Transfer in Late Antiquity
Researcher (PI) Markham Judah Geller
Host Institution (HI) FREIE UNIVERSITAET BERLIN
Call Details Advanced Grant (AdG), SH5, ERC-2012-ADG_20120411
Summary BabMed represents the first ever comprehensive study of ancient Babylonian medical science since the decipherment of cuneiform, comprising the largest ancient collection of medical data before Hippocrates. The latest phase of Babylonian medicine, as preserved in Aramaic in the Babylonian Talmud, has never been systematically studied in the light of older cuneiform materials. The absence of accessible cuneiform medical literature has forced recent medical histories to bypass Babylonian medicine, while Aramaic medicine in the Babylonian Talmud has simply been ignored. BabMed tests a number of 'high risk' propositions, including two key hypotheses: 1) cuneiform survived much longer than previously suspected, and 2) Aramaic medicine in the Babylonian Talmud mostly derives from Akkadian medicine. BabMed's methodology relies upon native taxonomies rather than modern biomedical disease classifications, countering flawed retrospective diagnoses that obviate the entire history of medicine. Comparisons with neighbouring medical systems challenge the prevalent Eurocentricity of current histories, in which Greek medicine has become the standard for all ancient medicine. BabMed will introduce a new paradigm for knowledge transfer which will recognise the barriers between ancient arts of medicine and how they were overcome in antiquity. One such barrier was script and language, and BabMed proposes that Babylonian medicine survived the death of cuneiform script and was preserved in part in the local Aramaic of the Babylonian Talmud, a unique text which straddles the borders of Greco-Roman Palestine and Persian Babylonia and mirrors the scientific thinking of both worlds.
Summary
BabMed represents the first ever comprehensive study of ancient Babylonian medical science since the decipherment of cuneiform, comprising the largest ancient collection of medical data before Hippocrates. The latest phase of Babylonian medicine, as preserved in Aramaic in the Babylonian Talmud, has never been systematically studied in the light of older cuneiform materials. The absence of accessible cuneiform medical literature has forced recent medical histories to bypass Babylonian medicine, while Aramaic medicine in the Babylonian Talmud has simply been ignored. BabMed tests a number of 'high risk' propositions, including two key hypotheses: 1) cuneiform survived much longer than previously suspected, and 2) Aramaic medicine in the Babylonian Talmud mostly derives from Akkadian medicine. BabMed's methodology relies upon native taxonomies rather than modern biomedical disease classifications, countering flawed retrospective diagnoses that obviate the entire history of medicine. Comparisons with neighbouring medical systems challenge the prevalent Eurocentricity of current histories, in which Greek medicine has become the standard for all ancient medicine. BabMed will introduce a new paradigm for knowledge transfer which will recognise the barriers between ancient arts of medicine and how they were overcome in antiquity. One such barrier was script and language, and BabMed proposes that Babylonian medicine survived the death of cuneiform script and was preserved in part in the local Aramaic of the Babylonian Talmud, a unique text which straddles the borders of Greco-Roman Palestine and Persian Babylonia and mirrors the scientific thinking of both worlds.
Max ERC Funding
2 233 747 €
Duration
Start date: 2013-07-01, End date: 2018-06-30
Project acronym BACNK
Project Recognition of bacteria by NK cells
Researcher (PI) Ofer Mandelboim
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Advanced Grant (AdG), LS6, ERC-2012-ADG_20120314
Summary NK cells that are well known by their ability to recognize and eliminate virus infected and tumor cells were also implicated in the defence against bacteria. However, the recognition of bacteria by NK cells is only poorly understood. we do not know how bacteria are recognized and the functional consequences of such recognition are also weakly understood. In the current proposal we aimed at determining the “NK cell receptor-bacterial interactome”. We will examine the hypothesis that NK inhibitory and activating receptors are directly involved in bacterial recognition. This ground breaking hypothesis is based on our preliminary results in which we show that several NK cell receptors directly recognize various bacterial strains as well as on a few other publications. We will generate various mice knockouts for NCR1 (a major NK killer receptor) and determine their microbiota to understand the physiological function of NCR1 and whether certain bacterial strains affects its activity. We will use different human and mouse NK killer and inhibitory receptors fused to IgG1 to pull-down bacteria from saliva and fecal samples and then use 16S rRNA analysis and next generation sequencing to determine the nature of the bacteria species isolated. We will identify the bacterial ligands that are recognized by the relevant NK cell receptors, using bacterial random transposon insertion mutagenesis approach. We will end this research with functional assays. In the wake of the emerging threat of bacterial drug resistance and the involvement of bacteria in the pathogenesis of many different chronic diseases and in shaping the immune response, the completion of this study will open a new field of research; the direct recognition of bacteria by NK cell receptors.
Summary
NK cells that are well known by their ability to recognize and eliminate virus infected and tumor cells were also implicated in the defence against bacteria. However, the recognition of bacteria by NK cells is only poorly understood. we do not know how bacteria are recognized and the functional consequences of such recognition are also weakly understood. In the current proposal we aimed at determining the “NK cell receptor-bacterial interactome”. We will examine the hypothesis that NK inhibitory and activating receptors are directly involved in bacterial recognition. This ground breaking hypothesis is based on our preliminary results in which we show that several NK cell receptors directly recognize various bacterial strains as well as on a few other publications. We will generate various mice knockouts for NCR1 (a major NK killer receptor) and determine their microbiota to understand the physiological function of NCR1 and whether certain bacterial strains affects its activity. We will use different human and mouse NK killer and inhibitory receptors fused to IgG1 to pull-down bacteria from saliva and fecal samples and then use 16S rRNA analysis and next generation sequencing to determine the nature of the bacteria species isolated. We will identify the bacterial ligands that are recognized by the relevant NK cell receptors, using bacterial random transposon insertion mutagenesis approach. We will end this research with functional assays. In the wake of the emerging threat of bacterial drug resistance and the involvement of bacteria in the pathogenesis of many different chronic diseases and in shaping the immune response, the completion of this study will open a new field of research; the direct recognition of bacteria by NK cell receptors.
Max ERC Funding
2 499 800 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym BEAM-ME-UP
Project From Radio-Frequency to Giga-Bit
Optical- and Quantum-Wireless
Researcher (PI) Lajos Hanzo
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Call Details Advanced Grant (AdG), PE7, ERC-2012-ADG_20120216
Summary The majority of the globe's population carries a mobile phone, but with the increasing proliferation of smart phones and tablet-computers the tele-traffic is predicted to grow 1000-fold over the next decade, especially, when aiming for creating the impression of ubiquitous and flawless 'tele-presence' based on crisp, three-dimensional (3D) video with its sense of joy and wonder. For tele-presence to become a reality requires a further quantum-leap from the popular 3G/4G smart phones and tablet-computers. This project will create the link-level enabling techniques of this transformational quantum leap to immersive Giga-bit 3D video communications, relying on Optical Wireless (OW) hotspots and their ad hoc networking.
As a result, the Beam-Me-Up project will contribute to job- and wealth-creation in numeorus ways, as exemplified by the often-quoted economic benefits of 3G/4G phones on businesses. From an environmental perspective, flawless tele-presence has the potential of eliminating millions of flights/trips and hence will considerably reduce CO2 emissions, whilst reducing the related business-costs as well as saving precious time for the work-force. However, the transfiguration of the voice-only phone into today's intelligent smart phone was facilitated by a 1000-fold transmission-rate increase, which would result in a proportionally increased power consumption, CO2 emissions and in a soaring energy-bill. Tele-presence based on crisp Avatar-style 3D video has even higher bitrates and energy consumption. These radically new high-rate 3D tele-presence services can no longer be accommodated in the severely congested Radio Frequency (RF) band.
Hence the project will create a suite of new OW system components, operating in the visible-light domain and will conceive low-power, low-complexity OW solutions to enable immersive Giga-bit 3D wireless video communications over heterogeneous networks.
Summary
The majority of the globe's population carries a mobile phone, but with the increasing proliferation of smart phones and tablet-computers the tele-traffic is predicted to grow 1000-fold over the next decade, especially, when aiming for creating the impression of ubiquitous and flawless 'tele-presence' based on crisp, three-dimensional (3D) video with its sense of joy and wonder. For tele-presence to become a reality requires a further quantum-leap from the popular 3G/4G smart phones and tablet-computers. This project will create the link-level enabling techniques of this transformational quantum leap to immersive Giga-bit 3D video communications, relying on Optical Wireless (OW) hotspots and their ad hoc networking.
As a result, the Beam-Me-Up project will contribute to job- and wealth-creation in numeorus ways, as exemplified by the often-quoted economic benefits of 3G/4G phones on businesses. From an environmental perspective, flawless tele-presence has the potential of eliminating millions of flights/trips and hence will considerably reduce CO2 emissions, whilst reducing the related business-costs as well as saving precious time for the work-force. However, the transfiguration of the voice-only phone into today's intelligent smart phone was facilitated by a 1000-fold transmission-rate increase, which would result in a proportionally increased power consumption, CO2 emissions and in a soaring energy-bill. Tele-presence based on crisp Avatar-style 3D video has even higher bitrates and energy consumption. These radically new high-rate 3D tele-presence services can no longer be accommodated in the severely congested Radio Frequency (RF) band.
Hence the project will create a suite of new OW system components, operating in the visible-light domain and will conceive low-power, low-complexity OW solutions to enable immersive Giga-bit 3D wireless video communications over heterogeneous networks.
Max ERC Funding
2 470 416 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym BI-DSC
Project Building Integrated Dye Sensitized Solar Cells
Researcher (PI) Adélio Miguel Magalhaes Mendes
Host Institution (HI) UNIVERSIDADE DO PORTO
Call Details Advanced Grant (AdG), PE8, ERC-2012-ADG_20120216
Summary In the last decade, solar and photovoltaic (PV) technologies have emerged as a potentially major technology for power generation in the world. So far the PV field has been dominated by silicon devices, even though this technology is still expensive.Dye-sensitized solar cells (DSC) are an important type of thin-film photovoltaics due to their potential for low-cost fabrication and versatile applications, and because their aesthetic appearance, semi-transparency and different color possibilities.This advantageous characteristic makes DSC the first choice for building integrated photovoltaics.Despite their great potential, DSCs for building applications are still not available at commercial level. However, to bring DSCs to a marketable product several developments are still needed and the present project targets to give relevant answers to three key limitations: encapsulation, glass substrate enhanced electrical conductivity and more efficient and low-cost raw-materials. Recently, the proponent successfully addressed the hermetic devices sealing by developing a laser-assisted glass sealing procedure.Thus, BI-DSC proposal envisages the development of DSC modules 30x30cm2, containing four individual cells, and their incorporation in a 1m2 double glass sheet arrangement for BIPV with an energy efficiency of at least 9% and a lifetime of 20 years. Additionally, aiming at enhanced efficiency of the final device and decreased total costs of DSCs manufacturing, new materials will be also pursued. The following inner-components were identified as critical: carbon-based counter-electrode; carbon quantum-dots and hierarchically TiO2 photoelectrode. It is then clear that this project is divided into two research though parallel directions: a fundamental research line, contributing to the development of the new generation DSC technology; while a more applied research line targets the development of a DSC functional module that can be used to pave the way for its industrialization.
Summary
In the last decade, solar and photovoltaic (PV) technologies have emerged as a potentially major technology for power generation in the world. So far the PV field has been dominated by silicon devices, even though this technology is still expensive.Dye-sensitized solar cells (DSC) are an important type of thin-film photovoltaics due to their potential for low-cost fabrication and versatile applications, and because their aesthetic appearance, semi-transparency and different color possibilities.This advantageous characteristic makes DSC the first choice for building integrated photovoltaics.Despite their great potential, DSCs for building applications are still not available at commercial level. However, to bring DSCs to a marketable product several developments are still needed and the present project targets to give relevant answers to three key limitations: encapsulation, glass substrate enhanced electrical conductivity and more efficient and low-cost raw-materials. Recently, the proponent successfully addressed the hermetic devices sealing by developing a laser-assisted glass sealing procedure.Thus, BI-DSC proposal envisages the development of DSC modules 30x30cm2, containing four individual cells, and their incorporation in a 1m2 double glass sheet arrangement for BIPV with an energy efficiency of at least 9% and a lifetime of 20 years. Additionally, aiming at enhanced efficiency of the final device and decreased total costs of DSCs manufacturing, new materials will be also pursued. The following inner-components were identified as critical: carbon-based counter-electrode; carbon quantum-dots and hierarchically TiO2 photoelectrode. It is then clear that this project is divided into two research though parallel directions: a fundamental research line, contributing to the development of the new generation DSC technology; while a more applied research line targets the development of a DSC functional module that can be used to pave the way for its industrialization.
Max ERC Funding
1 989 300 €
Duration
Start date: 2013-03-01, End date: 2018-08-31
Project acronym BIMPC
Project Biologically-Inspired Massively-Parallel Computation
Researcher (PI) Stephen Byram Furber
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Advanced Grant (AdG), PE6, ERC-2012-ADG_20120216
Summary "We aim to establish a world-leading research capability in Europe for advancing novel models of asynchronous computation based upon principles inspired by brain function. This work will accelerate progress towards an understanding of how the potential of brain-inspired many-core architectures may be harnessed. The results will include new brain-inspired models of asynchronous computation and new brain- inspired approaches to fault-tolerance and reliability in complex computer systems.
Many-core processors are now established as the way forward for computing from embedded systems to supercomputers. An emerging problem with leading-edge silicon technology is a reduction in the yield and reliability of modern processors due to high variability in the manufacture of the components and interconnect as transistor geometries shrink towards atomic scales. We are faced with the longstanding problem of how to make use of a potentially large array of parallel processors, but with the new constraint that the individual elements are the system are inherently unreliable.
The human brain remains as one of the great frontiers of science – how does this organ upon which we all depend so critically actually do its job? A great deal is known about the underlying technology – the neuron – and we can observe large-scale brain activity through techniques such as magnetic resonance imaging, but this knowledge barely starts to tell us how the brain works. Something is happening at the intermediate levels of processing that we have yet to begin to understand, but the essence of the brain's massively-parallel information processing capabilities and robustness to component failure lies in these intermediate levels.
These two issues draws us towards two high-level research questions:
• Can our growing understanding of brain function point the way to more efficient parallel, fault-tolerant computing?
• Can massively parallel computing resources accelerate our understanding of brain function"
Summary
"We aim to establish a world-leading research capability in Europe for advancing novel models of asynchronous computation based upon principles inspired by brain function. This work will accelerate progress towards an understanding of how the potential of brain-inspired many-core architectures may be harnessed. The results will include new brain-inspired models of asynchronous computation and new brain- inspired approaches to fault-tolerance and reliability in complex computer systems.
Many-core processors are now established as the way forward for computing from embedded systems to supercomputers. An emerging problem with leading-edge silicon technology is a reduction in the yield and reliability of modern processors due to high variability in the manufacture of the components and interconnect as transistor geometries shrink towards atomic scales. We are faced with the longstanding problem of how to make use of a potentially large array of parallel processors, but with the new constraint that the individual elements are the system are inherently unreliable.
The human brain remains as one of the great frontiers of science – how does this organ upon which we all depend so critically actually do its job? A great deal is known about the underlying technology – the neuron – and we can observe large-scale brain activity through techniques such as magnetic resonance imaging, but this knowledge barely starts to tell us how the brain works. Something is happening at the intermediate levels of processing that we have yet to begin to understand, but the essence of the brain's massively-parallel information processing capabilities and robustness to component failure lies in these intermediate levels.
These two issues draws us towards two high-level research questions:
• Can our growing understanding of brain function point the way to more efficient parallel, fault-tolerant computing?
• Can massively parallel computing resources accelerate our understanding of brain function"
Max ERC Funding
2 399 761 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym BIOMECAMORPH
Project The Biomechanics of Epithelial Cell and Tissue Morphogenesis
Researcher (PI) Thomas Marie Michel Lecuit
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), LS3, ERC-2012-ADG_20120314
Summary Tissue morphogenesis is a complex process that emerges from spatially controlled patterns of cell shape changes. Dedicated genetic programmes regulate cell behaviours, exemplified in animals by the specification of apical constriction in invaginating epithelial tissues, or the orientation of cell intercalation during tissue extension. This genetic control is constrained by physical properties of cells that dictate how they can modify their shape. A major challenge is to understand how biochemical pathways control subcellular mechanics in epithelia, such as how forces are produced by interactions between actin filaments and myosin motors, and how these forces are transmitted at cell junctions. The major objective of our project is to investigate the fundamental principles of epithelial mechanics and to understand how intercellular signals and mechanical coupling between cells coordinate individual behaviours at the tissue level.
We will study early Drosophila embryogenesis and combine quantitative cell biological studies of cell dynamics, biophysical characterization of cell mechanics and genetic control of cell signalling to answer the following questions: i) how are forces generated, in particular what underlies deformation and stabilization of cell shape by actomyosin networks, and pulsatile contractility; ii) how are forces transmitted at junctions, what are the feedback interactions between tension generation and transmission; iii) how are individual cell mechanics orchestrated at the tissue level to yield collective tissue morphogenesis?
We expect to encapsulate the information-based, cell biological and physical descriptions of morphogenesis in a single, coherent framework. The project should impact more broadly on morphogenesis in other organisms and shed light on the mechanisms underlying robustness and plasticity in epithelia.
Summary
Tissue morphogenesis is a complex process that emerges from spatially controlled patterns of cell shape changes. Dedicated genetic programmes regulate cell behaviours, exemplified in animals by the specification of apical constriction in invaginating epithelial tissues, or the orientation of cell intercalation during tissue extension. This genetic control is constrained by physical properties of cells that dictate how they can modify their shape. A major challenge is to understand how biochemical pathways control subcellular mechanics in epithelia, such as how forces are produced by interactions between actin filaments and myosin motors, and how these forces are transmitted at cell junctions. The major objective of our project is to investigate the fundamental principles of epithelial mechanics and to understand how intercellular signals and mechanical coupling between cells coordinate individual behaviours at the tissue level.
We will study early Drosophila embryogenesis and combine quantitative cell biological studies of cell dynamics, biophysical characterization of cell mechanics and genetic control of cell signalling to answer the following questions: i) how are forces generated, in particular what underlies deformation and stabilization of cell shape by actomyosin networks, and pulsatile contractility; ii) how are forces transmitted at junctions, what are the feedback interactions between tension generation and transmission; iii) how are individual cell mechanics orchestrated at the tissue level to yield collective tissue morphogenesis?
We expect to encapsulate the information-based, cell biological and physical descriptions of morphogenesis in a single, coherent framework. The project should impact more broadly on morphogenesis in other organisms and shed light on the mechanisms underlying robustness and plasticity in epithelia.
Max ERC Funding
2 473 313 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym BIOMECHTOOLS
Project Biomechanical diagnostic, pre-planning and outcome tools to improve musculoskeletal surgery
Researcher (PI) Nicolaas Verdonschot
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Advanced Grant (AdG), LS7, ERC-2012-ADG_20120314
Summary The aetiology of many musculoskeletal (MS) diseases is related to biomechanical factors. However, the tools to assess the biomechanical condition of patients used by clinicians and researchers are often crude and subjective leading to non-optimal patient analyses and care. In this project innovations related to imaging, sensor technology and biomechanical modelling are utilized to generate versatile, accurate and objective methods to quantify the (pathological) MS condition of the lower extremity of patients in a unique manner. The project will produce advanced diagnostic, pre-planning and outcome tools which allow clinicians and researchers for detailed biomechanical analysis about abnormal tissue deformations, pathological loading of the joints, abnormal stresses in the hard and soft tissues, and aberrant joint kinematics.
The key objectives of this proposal are:
1) Develop and validate image-based 3-D volumetric elastographic diagnostic methods that can quantify normal and pathological conditions under dynamic loading and which can be linked to biomechanical modelling tools.
2) Create an ultrasound (US)-based system to assess internal joint kinematics which can be used as a diagnostic tool for clinicians and researchers and is a validation tool for biomechanical modelling.
3) Generate and validate an ambulant functional (force and kinematic) diagnostic system which is easy to use and which can be used to provide input data for biomechanical models.
4) Create and validate a new modelling approach that integrates muscle-models with finite element models at a highly personalized level.
5) Generate biomechanical models which have personalized mechanical properties of the hard and soft tissues.
6) Demonstrate the applicability of the personalized diagnostic and pre-planning platform by application to healthy individuals and patient subjects.
Support from the ERC will open new research fields related to biomechanical patient assessment and modeling of MS pathologies.
Summary
The aetiology of many musculoskeletal (MS) diseases is related to biomechanical factors. However, the tools to assess the biomechanical condition of patients used by clinicians and researchers are often crude and subjective leading to non-optimal patient analyses and care. In this project innovations related to imaging, sensor technology and biomechanical modelling are utilized to generate versatile, accurate and objective methods to quantify the (pathological) MS condition of the lower extremity of patients in a unique manner. The project will produce advanced diagnostic, pre-planning and outcome tools which allow clinicians and researchers for detailed biomechanical analysis about abnormal tissue deformations, pathological loading of the joints, abnormal stresses in the hard and soft tissues, and aberrant joint kinematics.
The key objectives of this proposal are:
1) Develop and validate image-based 3-D volumetric elastographic diagnostic methods that can quantify normal and pathological conditions under dynamic loading and which can be linked to biomechanical modelling tools.
2) Create an ultrasound (US)-based system to assess internal joint kinematics which can be used as a diagnostic tool for clinicians and researchers and is a validation tool for biomechanical modelling.
3) Generate and validate an ambulant functional (force and kinematic) diagnostic system which is easy to use and which can be used to provide input data for biomechanical models.
4) Create and validate a new modelling approach that integrates muscle-models with finite element models at a highly personalized level.
5) Generate biomechanical models which have personalized mechanical properties of the hard and soft tissues.
6) Demonstrate the applicability of the personalized diagnostic and pre-planning platform by application to healthy individuals and patient subjects.
Support from the ERC will open new research fields related to biomechanical patient assessment and modeling of MS pathologies.
Max ERC Funding
2 456 400 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym BRONZEAGETIN
Project Tin Isotopes and the Sources of Bronze Age Tin in the Old World
Researcher (PI) Ernst Pernicka
Host Institution (HI) RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Call Details Advanced Grant (AdG), SH6, ERC-2012-ADG_20120411
Summary "This multidisciplinary project comprising archaeology, history, geochemistry, and geology aims at the decipherment of the enigma of the origin of a material that emerged in the third millennium BCE and gave an entire cultural epoch its name, namely the alloy of copper and tin called bronze. While copper deposits are relatively widely distributed there are only very few tin deposits known in the Old World (Europe, the Mediterranean basin and southwest Asia). Since the late 19th century archaeologists have discussed the question of the provenance of tin for the production of the earliest bronzes without any definite answer. The enigma has even grown over the past decades, because it turned out that the earliest bronzes appear in a wide area stretching from the Aegean to the Persian Gulf that is geologically devoid of any tin deposits. There is tin in western and central Europe and there is also tin in central Asia. Thus, tin or bronze seems to have been traded over large distances but it is unknown in which direction.
Now a new method has become available that offers the chance to trace ancient tin via tin isotope signatures. It was found that the isotope ratios of tin exhibit small but measurable variations in nature making different tin deposits identifiable so that bronze objects can in principle be related to specific ore deposits. It is proposed to apply for the first time this new technology to characterize all known tin deposits in the Old World and relate them to bronze and tin artefacts of the third and second millennia BCE. This groundbreaking interdisciplinary study will increase our understanding of Bronze Age metal trade beyond surmise and speculation with vast implications for the reconstruction of socio-economic relations within and between Bronze Age societies. The impact will be a major advance in our understanding of the earliest complex societies with craft specialization and the formation of cities and empires."
Summary
"This multidisciplinary project comprising archaeology, history, geochemistry, and geology aims at the decipherment of the enigma of the origin of a material that emerged in the third millennium BCE and gave an entire cultural epoch its name, namely the alloy of copper and tin called bronze. While copper deposits are relatively widely distributed there are only very few tin deposits known in the Old World (Europe, the Mediterranean basin and southwest Asia). Since the late 19th century archaeologists have discussed the question of the provenance of tin for the production of the earliest bronzes without any definite answer. The enigma has even grown over the past decades, because it turned out that the earliest bronzes appear in a wide area stretching from the Aegean to the Persian Gulf that is geologically devoid of any tin deposits. There is tin in western and central Europe and there is also tin in central Asia. Thus, tin or bronze seems to have been traded over large distances but it is unknown in which direction.
Now a new method has become available that offers the chance to trace ancient tin via tin isotope signatures. It was found that the isotope ratios of tin exhibit small but measurable variations in nature making different tin deposits identifiable so that bronze objects can in principle be related to specific ore deposits. It is proposed to apply for the first time this new technology to characterize all known tin deposits in the Old World and relate them to bronze and tin artefacts of the third and second millennia BCE. This groundbreaking interdisciplinary study will increase our understanding of Bronze Age metal trade beyond surmise and speculation with vast implications for the reconstruction of socio-economic relations within and between Bronze Age societies. The impact will be a major advance in our understanding of the earliest complex societies with craft specialization and the formation of cities and empires."
Max ERC Funding
2 340 800 €
Duration
Start date: 2013-08-01, End date: 2018-07-31
Project acronym CALENDARS
Project Calendars in late Antiquity and the Middle Ages: standardization and fixation
Researcher (PI) Sacha David Stern
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Advanced Grant (AdG), SH6, ERC-2012-ADG_20120411
Summary This project will study how calendars evolved in late antique and medieval societies towards ever increasing standardization and fixation. The study of calendars has been neglected by historians as a technical curiosity; but in fact, the calendar was at the heart of ancient and medieval culture, as a structured concept of time, and as an organizing principle of social life.
The history of calendars in late Antiquity and the Middle Ages was a complex social and cultural process, closely related to politics, science, and religion. The standardization and fixation of calendars was related in Antiquity to the rise of large, centralized empires in the Mediterranean and Near East, and in the Middle Ages, to the rise of the monotheistic, universalist religions of Christianity and Islam. The standardization and fixation of calendars contributed also, more widely, to the formation of a unified and universal culture in the ancient and medieval worlds.
The standardization and fixation of ancient and medieval calendars will be analyzed by focusing on four, specific manifestations of this process: (1) the diffusion and standardization of the seven-day week in the Roman Empire; (2) the production of hemerologia (comparative calendar tables) in late Antiquity; (3) the use of Jewish calendar fixed cycles in medieval manuscripts; (4) the production and diffusion of monographs on the calendar by medieval Muslim, Christian, and Jewish scholars, especially al-Biruni’s Chronology of the Ancient Nations and Isaac Israeli’s Yesod Olam. Study of these four research areas will enable us to formulate a general interpretation and explanation of how and why calendars became increasingly standardized and fixed.
This will be the first ever study of calendars on this scale, covering a wide range of historical periods and cultures, and involving a wide range of disciplines: social history, ancient and medieval astronomy and mathematics, study of religions, literature, epigraphy, and codicology.
Summary
This project will study how calendars evolved in late antique and medieval societies towards ever increasing standardization and fixation. The study of calendars has been neglected by historians as a technical curiosity; but in fact, the calendar was at the heart of ancient and medieval culture, as a structured concept of time, and as an organizing principle of social life.
The history of calendars in late Antiquity and the Middle Ages was a complex social and cultural process, closely related to politics, science, and religion. The standardization and fixation of calendars was related in Antiquity to the rise of large, centralized empires in the Mediterranean and Near East, and in the Middle Ages, to the rise of the monotheistic, universalist religions of Christianity and Islam. The standardization and fixation of calendars contributed also, more widely, to the formation of a unified and universal culture in the ancient and medieval worlds.
The standardization and fixation of ancient and medieval calendars will be analyzed by focusing on four, specific manifestations of this process: (1) the diffusion and standardization of the seven-day week in the Roman Empire; (2) the production of hemerologia (comparative calendar tables) in late Antiquity; (3) the use of Jewish calendar fixed cycles in medieval manuscripts; (4) the production and diffusion of monographs on the calendar by medieval Muslim, Christian, and Jewish scholars, especially al-Biruni’s Chronology of the Ancient Nations and Isaac Israeli’s Yesod Olam. Study of these four research areas will enable us to formulate a general interpretation and explanation of how and why calendars became increasingly standardized and fixed.
This will be the first ever study of calendars on this scale, covering a wide range of historical periods and cultures, and involving a wide range of disciplines: social history, ancient and medieval astronomy and mathematics, study of religions, literature, epigraphy, and codicology.
Max ERC Funding
2 499 006 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym CANBUILD
Project Building a Human Tumour Microenvironment
Researcher (PI) Frances Rosemary Balkwill
Host Institution (HI) QUEEN MARY UNIVERSITY OF LONDON
Call Details Advanced Grant (AdG), LS4, ERC-2012-ADG_20120314
Summary Even at their earliest stages, human cancers are more than just cells with malignant potential. Cells and extracellular matrix components that normally support and protect the body are coerced into a tumour microenvironment that is central to disease progression. My hypothesis is that recent advances in tissue engineering, biomechanics and stem cell biology make it possible to engineer, for the first time, a complex 3D human tumour microenvironment in which individual cell lineages of malignant, haemopoietic and mesenchymal origin will communicate, evolve and grow in vitro. The ultimate aim is to build this cancerous tissue with autologous cells: there is an urgent need for models in which we can study the interaction of human immune cells with malignant cells from the same individual in an appropriate 3D biomechanical microenvironment.
To achieve the objectives of the CANBUILD project, I have assembled a multi-disciplinary team of collaborators with international standing in tumour microenvironment research, cancer treatment, tissue engineering, mechanobiology, stem cell research and 3D computer-assisted imaging.
The goal is to recreate the microenvironment of high-grade serous ovarian cancer metastases in the omentum. This is a major clinical problem, my lab has extensive knowledge of this microenvironment and we have already established simple 3D models of these metastases.
The research plan involves:
Deconstruction of this specific tumour microenvironment
Construction of artificial scaffold, optimising growth of cell lineages, assembly of the model
Comparison to fresh tissue
Investigating the role of individual cell lineages
Testing therapies that target the tumour microenvironment
My vision is that this project will revolutionise the practice of human malignant cell research, replacing misleading systems based on cancer cell monoculture on plastic surfaces and allowing us to better test new treatments that target the human tumour microenvironment.
Summary
Even at their earliest stages, human cancers are more than just cells with malignant potential. Cells and extracellular matrix components that normally support and protect the body are coerced into a tumour microenvironment that is central to disease progression. My hypothesis is that recent advances in tissue engineering, biomechanics and stem cell biology make it possible to engineer, for the first time, a complex 3D human tumour microenvironment in which individual cell lineages of malignant, haemopoietic and mesenchymal origin will communicate, evolve and grow in vitro. The ultimate aim is to build this cancerous tissue with autologous cells: there is an urgent need for models in which we can study the interaction of human immune cells with malignant cells from the same individual in an appropriate 3D biomechanical microenvironment.
To achieve the objectives of the CANBUILD project, I have assembled a multi-disciplinary team of collaborators with international standing in tumour microenvironment research, cancer treatment, tissue engineering, mechanobiology, stem cell research and 3D computer-assisted imaging.
The goal is to recreate the microenvironment of high-grade serous ovarian cancer metastases in the omentum. This is a major clinical problem, my lab has extensive knowledge of this microenvironment and we have already established simple 3D models of these metastases.
The research plan involves:
Deconstruction of this specific tumour microenvironment
Construction of artificial scaffold, optimising growth of cell lineages, assembly of the model
Comparison to fresh tissue
Investigating the role of individual cell lineages
Testing therapies that target the tumour microenvironment
My vision is that this project will revolutionise the practice of human malignant cell research, replacing misleading systems based on cancer cell monoculture on plastic surfaces and allowing us to better test new treatments that target the human tumour microenvironment.
Max ERC Funding
2 431 035 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym CARDIONECT
Project Cardiac Connective Tissue: Beat-by-Beat Relevance for Heart Function in Health and Disease
Researcher (PI) Peter Kohl
Host Institution (HI) UNIVERSITAETSKLINIKUM FREIBURG
Call Details Advanced Grant (AdG), LS4, ERC-2012-ADG_20120314
Summary Cardiac connective tissue is regarded as passive in terms of cardiac electro-mechanics. However, recent evidence confirms that fibroblasts interact directly with cardiac muscle cells in a way that is likely to affect their beat-by-beat activity.
To overcome limitations of traditional approaches to exploring these interactions in native tissue, we will build and explore murine models that express functional reporters (membrane potential, Vm; calcium concentration, [Ca2+]i) in fibroblasts, to identify how they are functionally integrated in native heart (myocyte => fibroblast effects). Next, we will express light-gated ion channels in murine fibroblast, to selectively interfere with their Vm (fibroblast => myocyte effects). Fibroblast-specific observation and interference will be conducted in normal and pathologically remodelled tissue, to characterise fibroblast relevance for heart function in health & disease.
Based on these studies, we will generate 2 transgenic rabbits (fibroblast Vm reporting / interfering). Rabbit cardiac structure-function is more amenable to translational work, e.g. to study fibroblast involvement in normal origin & spread of excitation across the heart, in pathological settings such as arrhythmogenicity of post-infarct scars (a leading causes of sudden death), or as a determinant of therapeutic outcomes such as in healing of atrial ablation lines (interfering with a key interventions to treat atrial fibrillation).
The final ‘blue-skies’ study will assess whether modulation of cardiac activity, from ‘tuning’ of biological pacemaker rates to ‘unpinning’ / termination of re-entrant excitation waves, can be achieved by targeting not myocytes, but fibroblasts.
The study integrates basic-science-driven discovery research into mechanisms and dynamics of biophysical myocyte-fibroblast interactions, generation of novel transgenic models useful for a broad range of studies, and elucidation of conceptually new approaches to heart rhythm management.
Summary
Cardiac connective tissue is regarded as passive in terms of cardiac electro-mechanics. However, recent evidence confirms that fibroblasts interact directly with cardiac muscle cells in a way that is likely to affect their beat-by-beat activity.
To overcome limitations of traditional approaches to exploring these interactions in native tissue, we will build and explore murine models that express functional reporters (membrane potential, Vm; calcium concentration, [Ca2+]i) in fibroblasts, to identify how they are functionally integrated in native heart (myocyte => fibroblast effects). Next, we will express light-gated ion channels in murine fibroblast, to selectively interfere with their Vm (fibroblast => myocyte effects). Fibroblast-specific observation and interference will be conducted in normal and pathologically remodelled tissue, to characterise fibroblast relevance for heart function in health & disease.
Based on these studies, we will generate 2 transgenic rabbits (fibroblast Vm reporting / interfering). Rabbit cardiac structure-function is more amenable to translational work, e.g. to study fibroblast involvement in normal origin & spread of excitation across the heart, in pathological settings such as arrhythmogenicity of post-infarct scars (a leading causes of sudden death), or as a determinant of therapeutic outcomes such as in healing of atrial ablation lines (interfering with a key interventions to treat atrial fibrillation).
The final ‘blue-skies’ study will assess whether modulation of cardiac activity, from ‘tuning’ of biological pacemaker rates to ‘unpinning’ / termination of re-entrant excitation waves, can be achieved by targeting not myocytes, but fibroblasts.
The study integrates basic-science-driven discovery research into mechanisms and dynamics of biophysical myocyte-fibroblast interactions, generation of novel transgenic models useful for a broad range of studies, and elucidation of conceptually new approaches to heart rhythm management.
Max ERC Funding
2 498 612 €
Duration
Start date: 2013-07-01, End date: 2019-06-30
Project acronym CarnoMorph
Project The Evolution and Development of Complex Morphologies
Researcher (PI) Enrico Coen
Host Institution (HI) JOHN INNES CENTRE
Call Details Advanced Grant (AdG), LS3, ERC-2012-ADG_20120314
Summary Plant and animal organs display a remarkable diversity of shapes. A major challenge in developmental and evolutionary biology is to understand how this diversity of forms is generated. Recent advances in imaging, computational modelling and genomics now make it possible to address this challenge effectively for the first time. Leaf development is a particularly tractable system because of its accessibility to imaging and preservation of connectivity during growth. Leaves also display remarkable diversity in shape and form, with perhaps the most complex form being the pitcher-shaped (epiascidiate) leaves of carnivorous plants. This form has evolved four times independently, raising the question of whether its seeming complexity may have arisen through simple modulations in underlying morphogenetic mechanisms. To test this hypothesis, I aim to develop a model system for carnivorous plants based on Utricularia gibba (humped bladderwort), which has the advantage of having one of the smallest genomes known in plants (~2/3 the size of the Arabidopsis genome) and small transparent pitcher-shaped leaves amenable to imaging. I will use this system to define the morphogenetic events underlying the formation of pitcher-shaped leaves and their molecular genetic control. I will also develop and apply computational modelling to explore hypotheses that may account for the development of U. gibba bladders and further test these hypotheses experimentally. In addition, I will investigate the relationship between U. gibba bladder development and species with simpler leaf shapes, such as Arabidopsis, or species where the epiascidiate form has evolved independently. Taken together, these studies should show how developmental rules elucidated in current model systems might be extended and built upon to account for the diversity and complexity of tissue forms, integrating evo-devo approaches with a mechanistic understanding of morphogenesis.
Summary
Plant and animal organs display a remarkable diversity of shapes. A major challenge in developmental and evolutionary biology is to understand how this diversity of forms is generated. Recent advances in imaging, computational modelling and genomics now make it possible to address this challenge effectively for the first time. Leaf development is a particularly tractable system because of its accessibility to imaging and preservation of connectivity during growth. Leaves also display remarkable diversity in shape and form, with perhaps the most complex form being the pitcher-shaped (epiascidiate) leaves of carnivorous plants. This form has evolved four times independently, raising the question of whether its seeming complexity may have arisen through simple modulations in underlying morphogenetic mechanisms. To test this hypothesis, I aim to develop a model system for carnivorous plants based on Utricularia gibba (humped bladderwort), which has the advantage of having one of the smallest genomes known in plants (~2/3 the size of the Arabidopsis genome) and small transparent pitcher-shaped leaves amenable to imaging. I will use this system to define the morphogenetic events underlying the formation of pitcher-shaped leaves and their molecular genetic control. I will also develop and apply computational modelling to explore hypotheses that may account for the development of U. gibba bladders and further test these hypotheses experimentally. In addition, I will investigate the relationship between U. gibba bladder development and species with simpler leaf shapes, such as Arabidopsis, or species where the epiascidiate form has evolved independently. Taken together, these studies should show how developmental rules elucidated in current model systems might be extended and built upon to account for the diversity and complexity of tissue forms, integrating evo-devo approaches with a mechanistic understanding of morphogenesis.
Max ERC Funding
2 499 997 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym CATGOLD
Project ADVANCING GOLD CATALYSIS
Researcher (PI) Antonio María Echavarren Pablos
Host Institution (HI) FUNDACIO PRIVADA INSTITUT CATALA D'INVESTIGACIO QUIMICA
Call Details Advanced Grant (AdG), PE5, ERC-2012-ADG_20120216
Summary We plan to chase new goals by exploring the limits of gold chemistry and organic synthesis. A major goal is to promote copper to the level of gold as the catalyst of choice for the activation of alkynes under homogeneous conditions. Another major goal is to develop enantioselective reactions based on a new chiral catalyst design to overcome the inherent limitations of the linear coordination of d10 M(I) coinage metals. We whish to contribute to bridge the gap between homogeneous and heterogeneous gold catalysis discovering new reactions for C-C bond formation via cross-coupling and C-H activation. We will apply new methods based on Au catalysis to fill the gap that exists between chemical synthesis and physical methods such as graphite exfoliation or laser ablation for the synthesis of nanographenes and other large acenes.
Summary
We plan to chase new goals by exploring the limits of gold chemistry and organic synthesis. A major goal is to promote copper to the level of gold as the catalyst of choice for the activation of alkynes under homogeneous conditions. Another major goal is to develop enantioselective reactions based on a new chiral catalyst design to overcome the inherent limitations of the linear coordination of d10 M(I) coinage metals. We whish to contribute to bridge the gap between homogeneous and heterogeneous gold catalysis discovering new reactions for C-C bond formation via cross-coupling and C-H activation. We will apply new methods based on Au catalysis to fill the gap that exists between chemical synthesis and physical methods such as graphite exfoliation or laser ablation for the synthesis of nanographenes and other large acenes.
Max ERC Funding
2 499 060 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym CBM-INNATE
Project Regulation and Function of CARD9 / BCL10 / MALT1 Signalosomes in Innate Immunity and Inflammation
Researcher (PI) Jürgen Maximilian Ruland
Host Institution (HI) KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN
Call Details Advanced Grant (AdG), LS6, ERC-2012-ADG_20120314
Summary Acute inflammation is a response to infection or tissue damage that is critical for host protection and tissue homeostasis. However, deregulated or chronic inflammation is harmful to the host and can cause multiple diseases including inflammatory bowel disease, rheumatoid arthritis, cardiovascular diseases, neuroinflammatory disease and cancer. Cells of the innate immune system sense microbial or sterile danger via pattern recognition receptors (PRRs). Subsequently, these PRRs engage intracellular signalling modules to elicit inflammatory effector mechanisms. We have recently identified the CARD9 / BCL10 / MALT1 (CBM) signalosome as a central proinflammatory signalling complex in innate immune cells. This molecular platform responds to stimuli from transmembrane SYK-coupled C-type lectin receptors and from intracellular danger sensors such as RIG-I-like helicases, NOD2 and presumably others to robustly activate NF-κB and MAPK pathways. Innate CBM signalling is engaged upon fungal, bacterial or viral recognition and upon sterile cell injury and it is essential for host protection in humans and mice. Still, it is unclear how the CARD9 / BCL10 / MALT1 signalosome is activated on a molecular level and how CBM responses are transduced to effector cascades. Moreover, although CARD9 polymorphisms are linked to various human inflammatory diseases, the cell type- and signal-specific roles of CBM signalosomes in complex diseases in vivo are unknown. Here we aim to take an integrated genetic, biochemical and in vivo approach to comprehensively dissect the regulation of the CARD9 / BCL10 / MALT1 complex in innate immunity and to define the role of this signalosome in clinically relevant inflammatory diseases. Mechanistic in vitro studies will be combined with the in vivo analysis of CBM function in genetically defined mouse models to gain better insights into the regulation of innate immunity and to pave the way to novel therapeutics for inflammatory diseases.
Summary
Acute inflammation is a response to infection or tissue damage that is critical for host protection and tissue homeostasis. However, deregulated or chronic inflammation is harmful to the host and can cause multiple diseases including inflammatory bowel disease, rheumatoid arthritis, cardiovascular diseases, neuroinflammatory disease and cancer. Cells of the innate immune system sense microbial or sterile danger via pattern recognition receptors (PRRs). Subsequently, these PRRs engage intracellular signalling modules to elicit inflammatory effector mechanisms. We have recently identified the CARD9 / BCL10 / MALT1 (CBM) signalosome as a central proinflammatory signalling complex in innate immune cells. This molecular platform responds to stimuli from transmembrane SYK-coupled C-type lectin receptors and from intracellular danger sensors such as RIG-I-like helicases, NOD2 and presumably others to robustly activate NF-κB and MAPK pathways. Innate CBM signalling is engaged upon fungal, bacterial or viral recognition and upon sterile cell injury and it is essential for host protection in humans and mice. Still, it is unclear how the CARD9 / BCL10 / MALT1 signalosome is activated on a molecular level and how CBM responses are transduced to effector cascades. Moreover, although CARD9 polymorphisms are linked to various human inflammatory diseases, the cell type- and signal-specific roles of CBM signalosomes in complex diseases in vivo are unknown. Here we aim to take an integrated genetic, biochemical and in vivo approach to comprehensively dissect the regulation of the CARD9 / BCL10 / MALT1 complex in innate immunity and to define the role of this signalosome in clinically relevant inflammatory diseases. Mechanistic in vitro studies will be combined with the in vivo analysis of CBM function in genetically defined mouse models to gain better insights into the regulation of innate immunity and to pave the way to novel therapeutics for inflammatory diseases.
Max ERC Funding
2 440 200 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym CCFIB
Project Cardiac Control of Fear in Brain
Researcher (PI) Hugo Dyfrig Critchley
Host Institution (HI) THE UNIVERSITY OF SUSSEX
Call Details Advanced Grant (AdG), SH4, ERC-2012-ADG_20120411
Summary "Imagine what might be possible if you can turn fear on and off. In exploring the contribution of bodily arousal to emotions, we uncovered a specific mechanism whereby the brain’s processing of threatening / fear stimuli is ‘gated’ by the occurrence of heartbeats: Fear stimuli presented when the heart has just made a beat are processed more effectively than at other times, modulating their emotional impact. We term this effect the Cardiac Control of Fear in Brain (CCFIB). Specifically, I wish to refine, develop and exploit CCFIB as; 1) a clinical screening tool for drugs and patients; 2) as the basis of an intervention to accelerate unlearning of fear, e.g. for treatment of anxiety disorders; 3) as a means to optimise and enrich human-machine interactions, in anticipation of the rapid development of virtual or augmented reality (VR/AR) as a therapeutic tool, and to open possibilities for improving machine operation. This ground-breaking project will have impact in many areas, notably in the clinical management of anxiety disorders, which affect 69.1 million European Union citizens at an annual cost of €74.4 billion, and in the educational, recreational and occupational realms of human-machine interaction. The proposal 1) will refine knowledge about the neurochemistry and stimulus-specificity of CCFIB for implementation as a clinical screening tool, using pharmacological and neuroimaging methods. 2) Test in clinical anxiety patients the power of CCFIB to predict symptom profile and response to psychological and pharmacological treatment. 3) Optimize CCFIB to augment psychological and behavioural treatments and validate this in phobic individuals. 4) Instantiate CCFIB in VR/AR settings to enhance engagement with virtual environments, develop VR/AR as a ‘training platform’ in clinical and recreational contexts and to demonstrate how reactions to rapid threats fluctuate with cardiac cycle, motivating corresponding changes in sensitivity of user interfaces (e.g. brakes)."
Summary
"Imagine what might be possible if you can turn fear on and off. In exploring the contribution of bodily arousal to emotions, we uncovered a specific mechanism whereby the brain’s processing of threatening / fear stimuli is ‘gated’ by the occurrence of heartbeats: Fear stimuli presented when the heart has just made a beat are processed more effectively than at other times, modulating their emotional impact. We term this effect the Cardiac Control of Fear in Brain (CCFIB). Specifically, I wish to refine, develop and exploit CCFIB as; 1) a clinical screening tool for drugs and patients; 2) as the basis of an intervention to accelerate unlearning of fear, e.g. for treatment of anxiety disorders; 3) as a means to optimise and enrich human-machine interactions, in anticipation of the rapid development of virtual or augmented reality (VR/AR) as a therapeutic tool, and to open possibilities for improving machine operation. This ground-breaking project will have impact in many areas, notably in the clinical management of anxiety disorders, which affect 69.1 million European Union citizens at an annual cost of €74.4 billion, and in the educational, recreational and occupational realms of human-machine interaction. The proposal 1) will refine knowledge about the neurochemistry and stimulus-specificity of CCFIB for implementation as a clinical screening tool, using pharmacological and neuroimaging methods. 2) Test in clinical anxiety patients the power of CCFIB to predict symptom profile and response to psychological and pharmacological treatment. 3) Optimize CCFIB to augment psychological and behavioural treatments and validate this in phobic individuals. 4) Instantiate CCFIB in VR/AR settings to enhance engagement with virtual environments, develop VR/AR as a ‘training platform’ in clinical and recreational contexts and to demonstrate how reactions to rapid threats fluctuate with cardiac cycle, motivating corresponding changes in sensitivity of user interfaces (e.g. brakes)."
Max ERC Funding
1 912 383 €
Duration
Start date: 2013-06-01, End date: 2017-05-31
Project acronym CD-LINK
Project Celiac disease: from lincRNAs to disease mechanism
Researcher (PI) Tjitske Nienke Wijmenga
Host Institution (HI) ACADEMISCH ZIEKENHUIS GRONINGEN
Call Details Advanced Grant (AdG), LS2, ERC-2012-ADG_20120314
Summary Celiac disease affects at least 1% of the world population. Its onset is triggered by gluten, a common dietary protein, however, its etiology is poorly understood. More than 80% of patients are not properly diagnosed and they therefore do not follow a gluten-free diet, thereby increasing their risk for disease-associated complications and early death. A better understanding of the disease biology would improve the diagnosis, prevention, and treatment of celiac disease.
This project investigates the disease mechanisms in celiac disease by using predisposing genes and genetic variants as disease initiating factors. Specifically, it will investigate if long, intergenic non-coding RNAs (lincRNAs) are causally involved in celiac disease pathogenesis by regulating protein-coding genes and pathways associated with the disease.
This project is based on two important observations by my group: (1) Our genetic studies, which led to identifying 39 celiac disease risk loci, suggest that the mechanism underlying the disease is largely governed by dysregulation of gene expression. (2) We uncovered a previously unrecognized role for lincRNAs that provides clues as to exactly how genetic variation causes disease, as this class of biologically important RNA molecules regulate gene expression.
The research will be performed in CD4+ T cells, a severely affected cell type in disease pathology. I will first use celiac disease-associated protein-coding genes to delineate their regulatory pathways and then study the transcriptional programs of lincRNAs present in celiac disease loci. Next I will combine the information and investigate if the expressed lincRNAs modulate the pathways and affect T cell function, thereby discovering if lincRNAs are a missing link between non-coding genetic variation and protein-coding genes. Our findings may well lead to potential therapeutic targets and provide a solid scientific basis for new diagnostic markers, particularly biomarkers, based on genetics.
Summary
Celiac disease affects at least 1% of the world population. Its onset is triggered by gluten, a common dietary protein, however, its etiology is poorly understood. More than 80% of patients are not properly diagnosed and they therefore do not follow a gluten-free diet, thereby increasing their risk for disease-associated complications and early death. A better understanding of the disease biology would improve the diagnosis, prevention, and treatment of celiac disease.
This project investigates the disease mechanisms in celiac disease by using predisposing genes and genetic variants as disease initiating factors. Specifically, it will investigate if long, intergenic non-coding RNAs (lincRNAs) are causally involved in celiac disease pathogenesis by regulating protein-coding genes and pathways associated with the disease.
This project is based on two important observations by my group: (1) Our genetic studies, which led to identifying 39 celiac disease risk loci, suggest that the mechanism underlying the disease is largely governed by dysregulation of gene expression. (2) We uncovered a previously unrecognized role for lincRNAs that provides clues as to exactly how genetic variation causes disease, as this class of biologically important RNA molecules regulate gene expression.
The research will be performed in CD4+ T cells, a severely affected cell type in disease pathology. I will first use celiac disease-associated protein-coding genes to delineate their regulatory pathways and then study the transcriptional programs of lincRNAs present in celiac disease loci. Next I will combine the information and investigate if the expressed lincRNAs modulate the pathways and affect T cell function, thereby discovering if lincRNAs are a missing link between non-coding genetic variation and protein-coding genes. Our findings may well lead to potential therapeutic targets and provide a solid scientific basis for new diagnostic markers, particularly biomarkers, based on genetics.
Max ERC Funding
2 319 914 €
Duration
Start date: 2013-02-01, End date: 2018-11-30
Project acronym cdGMP
Project Time, space and speed: cdGMP signaling in cell behavior and reproduction
Researcher (PI) Urs Jenal
Host Institution (HI) UNIVERSITAT BASEL
Call Details Advanced Grant (AdG), LS6, ERC-2012-ADG_20120314
Summary Bacterial biofilms are the primary cause of chronic infections and of resulting infection relapses. To be able to interfere with bacterial persistence it is vital to understand the molecular details of biofilm formation and to define how motile planktonic cells transit into surface-grown communities. The nucleotide second messenger cyclic di-guanosinemonophosphate (cdGMP) has emerged as a central regulatory factor governing bacterial surface adaptation and biofilm formation. Although cdGMP signaling may well represent the Achilles heel of bacterial communities, cdGMP networks in bacterial pathogens are exquisitely complex and an integrated cellular system to uncover the details of cdGMP dynamics is missing.
To quantitatively describe cdGMP signaling we propose to exploit Caulobacter crescentus, an organism with a simple bimodal life-style that integrates the sessile-motile switch into its asymmetric division cycle. We aim to: 1) identify the role and regulation of all diguanylate cyclases and phosphodiesterases that contribute to the asymmetric cellular program with the goal to model the temporal and spatial distribution of cdGMP during development; 2) identify and characterize cdGMP effectors, their downstream targets and cellular pathways; 3) elucidate how cdGMP coordinates cell differentiation with cell growth and propagation; 4) unravel the role of cdGMP as an allosteric regulator in mechanosensation and in rapid adaptation of bacteria to growth on surfaces; 5) develop novel tools to quantitatively describe cdGMP network dynamics as the basis for mathematical modeling that provides the predictive power to experimentally test and refine important network parameters. We propose a multidisciplinary research program at the forefront of bacterial signal transduction that will provide the molecular and conceptual framework for a rapidly growing research field of second messenger signaling in pathogenic bacteria.
Summary
Bacterial biofilms are the primary cause of chronic infections and of resulting infection relapses. To be able to interfere with bacterial persistence it is vital to understand the molecular details of biofilm formation and to define how motile planktonic cells transit into surface-grown communities. The nucleotide second messenger cyclic di-guanosinemonophosphate (cdGMP) has emerged as a central regulatory factor governing bacterial surface adaptation and biofilm formation. Although cdGMP signaling may well represent the Achilles heel of bacterial communities, cdGMP networks in bacterial pathogens are exquisitely complex and an integrated cellular system to uncover the details of cdGMP dynamics is missing.
To quantitatively describe cdGMP signaling we propose to exploit Caulobacter crescentus, an organism with a simple bimodal life-style that integrates the sessile-motile switch into its asymmetric division cycle. We aim to: 1) identify the role and regulation of all diguanylate cyclases and phosphodiesterases that contribute to the asymmetric cellular program with the goal to model the temporal and spatial distribution of cdGMP during development; 2) identify and characterize cdGMP effectors, their downstream targets and cellular pathways; 3) elucidate how cdGMP coordinates cell differentiation with cell growth and propagation; 4) unravel the role of cdGMP as an allosteric regulator in mechanosensation and in rapid adaptation of bacteria to growth on surfaces; 5) develop novel tools to quantitatively describe cdGMP network dynamics as the basis for mathematical modeling that provides the predictive power to experimentally test and refine important network parameters. We propose a multidisciplinary research program at the forefront of bacterial signal transduction that will provide the molecular and conceptual framework for a rapidly growing research field of second messenger signaling in pathogenic bacteria.
Max ERC Funding
2 496 000 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym CDREG
Project Carbon dioxide regulation of Earth’s ecological weathering engine: from microorganisms to ecosystems
Researcher (PI) David Beerling
Host Institution (HI) THE UNIVERSITY OF SHEFFIELD
Call Details Advanced Grant (AdG), LS8, ERC-2012-ADG_20120314
Summary CDREG develops the major new Earth system science research hypothesis that tectonic-related variations in Earth’s atmospheric CO2 concentration ([CO2]a) drive negative ecological feedbacks on terrestrial silicate weathering rates that stabilise further [CO2]a change and regulate climate. This paradigm-changing hypothesis integrates ecological and abiotic controls on silicate weathering to understand how terrestrial ecosystems have shaped past Earth system dynamics. The proposed ecological feedbacks are mechanistically linked to the extent and activities of forested ecosystems and their symbiotic fungal partners as the primary engines of biological weathering.
CDREG’s core hypothesis establishes an exciting cross-disciplinary Research Programme that offers novel opportunities for major breakthroughs implemented through four linked hypothesis-driven work packages (WPs) employing experimental, geochemical and numerical modelling approaches. WP1 quantitatively characterises [CO2]a-driven tree/grass-fungal mineral weathering by coupling metabolic profiling with advanced nanometre scale surface metrological techniques for investigating hyphal-mineral interactions. WP2 quantifies the role [CO2]a-drought interactions on savanna tree mortality and C4 grass survivorship, plus symbiotic fungal-driven mineral weathering. WP3 exploits the past 8 Ma of marine sediment archives to investigate the links between forest to savanna transition, terrestrial weathering, fire, and climate in Africa. WP4 integrates findings from WP1-3 into a new Earth system modelling framework to rigorously investigate the biogeochemical feedbacks of [CO2]a-regulated ecological weathering on [CO2]a via marine carbonate deposition and organic C burial.
The ultimate goal is to provide a new synthesis in which the role of [CO2]a in regulating the ecological weathering engine across scales from root-associated microorganisms to terrestrial ecosystems is mechanistically understood and assessed.
Summary
CDREG develops the major new Earth system science research hypothesis that tectonic-related variations in Earth’s atmospheric CO2 concentration ([CO2]a) drive negative ecological feedbacks on terrestrial silicate weathering rates that stabilise further [CO2]a change and regulate climate. This paradigm-changing hypothesis integrates ecological and abiotic controls on silicate weathering to understand how terrestrial ecosystems have shaped past Earth system dynamics. The proposed ecological feedbacks are mechanistically linked to the extent and activities of forested ecosystems and their symbiotic fungal partners as the primary engines of biological weathering.
CDREG’s core hypothesis establishes an exciting cross-disciplinary Research Programme that offers novel opportunities for major breakthroughs implemented through four linked hypothesis-driven work packages (WPs) employing experimental, geochemical and numerical modelling approaches. WP1 quantitatively characterises [CO2]a-driven tree/grass-fungal mineral weathering by coupling metabolic profiling with advanced nanometre scale surface metrological techniques for investigating hyphal-mineral interactions. WP2 quantifies the role [CO2]a-drought interactions on savanna tree mortality and C4 grass survivorship, plus symbiotic fungal-driven mineral weathering. WP3 exploits the past 8 Ma of marine sediment archives to investigate the links between forest to savanna transition, terrestrial weathering, fire, and climate in Africa. WP4 integrates findings from WP1-3 into a new Earth system modelling framework to rigorously investigate the biogeochemical feedbacks of [CO2]a-regulated ecological weathering on [CO2]a via marine carbonate deposition and organic C burial.
The ultimate goal is to provide a new synthesis in which the role of [CO2]a in regulating the ecological weathering engine across scales from root-associated microorganisms to terrestrial ecosystems is mechanistically understood and assessed.
Max ERC Funding
2 271 980 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym CELLO
Project From Cells to Organs on Chips: Development of an Integrative Microfluidic Platform
Researcher (PI) Jean-Louis Viovy
Host Institution (HI) INSTITUT CURIE
Call Details Advanced Grant (AdG), PE3, ERC-2012-ADG_20120216
Summary We shall develop a microfluidic and microsystems toolbox allowing the construction and study of complex cellular assemblies (“tissue or organ mimics on chip”), in a highly controlled and parallelized way. This platform will allow the selection of specific cells from one or several populations, their deterministic positioning and/or connection relative to each other, yielding functional assemblies with a degree of complexity, determinism and physiological realism unavailable to current in vitro systems We shall in particular develop “semi-3D” architectures, reproducing the local 3D arrangement of tissues, but presenting at mesoscale a planar and periodic arrangement facilitating high resolution stimulation and recording. This will provide biologists and clinicians with new experimental models able to bridge the gap between current in vitro systems, in which cells can be observed in parallel at high resolution, but lack the highly ordered architecture present in living systems, and in vivo models, in which observation and stimulation means are more limited. This development will follow a functional approach, and gather competences and concepts from micr-nano-systems, surface science, hydrodynamics, soft matter and biology. We shall validate it on three specific applications, the sorting and study of circulating tumour cells for understanding metastases, the creation of “miniguts”, artificial intestinal tissue, for applications in developmental biology and cancerogenesis, and the in vitro construction of active and connected neuron arrays, for studying the molecular mechanisms of Alzheimer, and signal processing by neuron networks. This platform will also open new routes for drug testing, replacing animal models and reducing the health and economic risk of clinical tests, developmental biology , stem cells research. and regenerative medicine.
Summary
We shall develop a microfluidic and microsystems toolbox allowing the construction and study of complex cellular assemblies (“tissue or organ mimics on chip”), in a highly controlled and parallelized way. This platform will allow the selection of specific cells from one or several populations, their deterministic positioning and/or connection relative to each other, yielding functional assemblies with a degree of complexity, determinism and physiological realism unavailable to current in vitro systems We shall in particular develop “semi-3D” architectures, reproducing the local 3D arrangement of tissues, but presenting at mesoscale a planar and periodic arrangement facilitating high resolution stimulation and recording. This will provide biologists and clinicians with new experimental models able to bridge the gap between current in vitro systems, in which cells can be observed in parallel at high resolution, but lack the highly ordered architecture present in living systems, and in vivo models, in which observation and stimulation means are more limited. This development will follow a functional approach, and gather competences and concepts from micr-nano-systems, surface science, hydrodynamics, soft matter and biology. We shall validate it on three specific applications, the sorting and study of circulating tumour cells for understanding metastases, the creation of “miniguts”, artificial intestinal tissue, for applications in developmental biology and cancerogenesis, and the in vitro construction of active and connected neuron arrays, for studying the molecular mechanisms of Alzheimer, and signal processing by neuron networks. This platform will also open new routes for drug testing, replacing animal models and reducing the health and economic risk of clinical tests, developmental biology , stem cells research. and regenerative medicine.
Max ERC Funding
2 260 000 €
Duration
Start date: 2013-07-01, End date: 2018-06-30
Project acronym CFRFSS
Project Chromatin Fiber and Remodeling Factor Structural Studies
Researcher (PI) Timothy John Richmond
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), LS1, ERC-2012-ADG_20120314
Summary "DNA in higher organisms is organized in a nucleoprotein complex called chromatin. The structure of chromatin is responsible for compacting DNA to fit within the nucleus and for governing its access in nuclear processes. Epigenetic information is encoded chiefly via chromatin modifications. Readout of the genetic code depends on chromatin remodeling, a process actively altering chromatin structure. An understanding of the hierarchical structure of chromatin and of structurally based, remodeling mechanisms will have enormous impact for developments in medicine.
Following our high resolution structure of the nucleosome core particle, the fundamental repeating unit of chromatin, we have endeavored to determine the structure of the chromatin fiber. We showed with our X-ray structure of a tetranucleosome how nucleosomes could be organized in the fiber. Further progress has been limited by structural polymorphism and crystal disorder, but new evidence on the in vivo spacing of nucleosomes in chromatin should stimulate more advances. Part A of this application describes how we would apply these new findings to our cryo-electron microscopy study of the chromatin fiber and to our crystallographic study of a tetranucleosome containing linker histone.
Recently, my laboratory succeeded in providing the first structurally based mechanism for nucleosome spacing by a chromatin remodeling factor. We combined the X-ray structure of ISW1a(ATPase) bound to DNA with cryo-EM structures of the factor bound to two different nucleosomes to build a model showing how this remodeler uses a dinucleosome, not a mononucleosome, as its substrate. Our results from a functional assay using ISW1a further justified this model. Part B of this application describes how we would proceed to the relevant cryo-EM and X-ray structures incorporating dinucleosomes. Our recombinant ISW1a allows us to study in addition the interaction of the ATPase domain with nucleosome substrates."
Summary
"DNA in higher organisms is organized in a nucleoprotein complex called chromatin. The structure of chromatin is responsible for compacting DNA to fit within the nucleus and for governing its access in nuclear processes. Epigenetic information is encoded chiefly via chromatin modifications. Readout of the genetic code depends on chromatin remodeling, a process actively altering chromatin structure. An understanding of the hierarchical structure of chromatin and of structurally based, remodeling mechanisms will have enormous impact for developments in medicine.
Following our high resolution structure of the nucleosome core particle, the fundamental repeating unit of chromatin, we have endeavored to determine the structure of the chromatin fiber. We showed with our X-ray structure of a tetranucleosome how nucleosomes could be organized in the fiber. Further progress has been limited by structural polymorphism and crystal disorder, but new evidence on the in vivo spacing of nucleosomes in chromatin should stimulate more advances. Part A of this application describes how we would apply these new findings to our cryo-electron microscopy study of the chromatin fiber and to our crystallographic study of a tetranucleosome containing linker histone.
Recently, my laboratory succeeded in providing the first structurally based mechanism for nucleosome spacing by a chromatin remodeling factor. We combined the X-ray structure of ISW1a(ATPase) bound to DNA with cryo-EM structures of the factor bound to two different nucleosomes to build a model showing how this remodeler uses a dinucleosome, not a mononucleosome, as its substrate. Our results from a functional assay using ISW1a further justified this model. Part B of this application describes how we would proceed to the relevant cryo-EM and X-ray structures incorporating dinucleosomes. Our recombinant ISW1a allows us to study in addition the interaction of the ATPase domain with nucleosome substrates."
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym CHEMAGEB
Project CHEMometric and High-throughput Omics Analytical Methods for Assessment of Global Change Effects on Environmental and Biological Systems
Researcher (PI) Roman Tauler Ferrer
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), PE4, ERC-2012-ADG_20120216
Summary We propose to develop new chemometric and high-throughput analytical methods to assess the effects of environmental and climate changes on target biological systems which are representative of ecosystems. This project will combine powerful chemometric and analytical high-throughput methodologies with toxicological tests to examine the effects of environmental stressors (like chemical pollution) and of climate change (like temperature, water scarcity or food shortage), on genomic and metabonomic profiles of target biological systems. The complex nature of experimental data produced by high-throughput analytical techniques, such as DNA microarrays, hyphenated chromatography-mass spectrometry or multi-dimensional nuclear magnetic resonance spectroscopy, requires powerful data analysis tools to extract, summarize and interpret the large amount of information that such megavariate data sets may contain. There is a need to improve and automate every step in the analysis of the data generated from genomic and metabonomic studies using new chemometric and multi- and megavariate tools. The main purpose of this project is to develop such tools. As a result of the whole study, a detailed report on the effects of global change and chemical pollution on the genomic and metabonomic profiles of a selected set of representative target biological systems will be delivered and used for global risk assessment. The information acquired, data sets and computer software will be stored in public data bases using modern data compression and data management technologies. And all the methodologies developed in the project will be published.
Summary
We propose to develop new chemometric and high-throughput analytical methods to assess the effects of environmental and climate changes on target biological systems which are representative of ecosystems. This project will combine powerful chemometric and analytical high-throughput methodologies with toxicological tests to examine the effects of environmental stressors (like chemical pollution) and of climate change (like temperature, water scarcity or food shortage), on genomic and metabonomic profiles of target biological systems. The complex nature of experimental data produced by high-throughput analytical techniques, such as DNA microarrays, hyphenated chromatography-mass spectrometry or multi-dimensional nuclear magnetic resonance spectroscopy, requires powerful data analysis tools to extract, summarize and interpret the large amount of information that such megavariate data sets may contain. There is a need to improve and automate every step in the analysis of the data generated from genomic and metabonomic studies using new chemometric and multi- and megavariate tools. The main purpose of this project is to develop such tools. As a result of the whole study, a detailed report on the effects of global change and chemical pollution on the genomic and metabonomic profiles of a selected set of representative target biological systems will be delivered and used for global risk assessment. The information acquired, data sets and computer software will be stored in public data bases using modern data compression and data management technologies. And all the methodologies developed in the project will be published.
Max ERC Funding
2 454 280 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym ChemicalYouth
Project What chemicals do for youths in their everyday lives
Researcher (PI) Anita Petra Hardon
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), SH2, ERC-2012-ADG_20120411
Summary The everyday lives of contemporary youths are awash with chemicals and pharmaceutical compounds to boost pleasure, moods, sexual performance, vitality, appearance and health. Nevertheless, most studies of chemical use among young people have focused on the abuse of specific recreational drugs and their role within deviant youth sub-cultures. Instead of explaining drug abuse with the purpose of controlling it, this project aims to examine the pervasive use of chemicals from the perspectives of youths themselves. It aims to understand what chemical and pharmaceutical substances, and not only illicit narcotics, ‘do’ for youths. How are chemicals a part of their everyday lives? What role do they play in calming their fears or in achieving their dreams and aspirations? How can we understand the ways in which chemicals affect their bodies and minds?
The theoretical innovation promised by this project lies in its combining of disciplines – most notably medical anthropology, science and technology studies and youth studies – to formulate a new groundbreaking framework for understanding the complex sociality of chemicals in youths’ everyday lives. The framework will have both scientific and societal impact.
Ethnographic research will be conducted in four medium-sized cities: Marseille in France, Amsterdam in the Netherlands, Makassar in Indonesia, and Batangas in the Philippines.
Summary
The everyday lives of contemporary youths are awash with chemicals and pharmaceutical compounds to boost pleasure, moods, sexual performance, vitality, appearance and health. Nevertheless, most studies of chemical use among young people have focused on the abuse of specific recreational drugs and their role within deviant youth sub-cultures. Instead of explaining drug abuse with the purpose of controlling it, this project aims to examine the pervasive use of chemicals from the perspectives of youths themselves. It aims to understand what chemical and pharmaceutical substances, and not only illicit narcotics, ‘do’ for youths. How are chemicals a part of their everyday lives? What role do they play in calming their fears or in achieving their dreams and aspirations? How can we understand the ways in which chemicals affect their bodies and minds?
The theoretical innovation promised by this project lies in its combining of disciplines – most notably medical anthropology, science and technology studies and youth studies – to formulate a new groundbreaking framework for understanding the complex sociality of chemicals in youths’ everyday lives. The framework will have both scientific and societal impact.
Ethnographic research will be conducted in four medium-sized cities: Marseille in France, Amsterdam in the Netherlands, Makassar in Indonesia, and Batangas in the Philippines.
Max ERC Funding
2 489 967 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym CHESS
Project Challenges in Extraction and Separation of Sources
Researcher (PI) Christian Patrice Jutten
Host Institution (HI) UNIVERSITE GRENOBLE ALPES
Call Details Advanced Grant (AdG), PE7, ERC-2012-ADG_20120216
Summary Separation/extraction of sources are wide concepts in information sciences, since sensors provide information mixing and an essential step consists in separating or extracting useful information from unuseful one, called noise. In this project, we consider three challenges.
The first one is the multimodality. Indeed, with the multiplication of kinds of sensors, in many areas like biomedical signal processing, hyperspectral imaging, etc. there are many ways for recording the same physical phenomenon leading thus to multimodal data. Multimodality has been studied in the framework of human-computer interface or in data fusion, but never at the signal level. The objective is to provide a general framework for modeling classical multimodal properties, like complementarity, redundancy, equivalence, etc. as of function of source signals.
The second challenge is nonlinearity. Indeed, there exist a few cases where the mixtures are essentially nonlinear, e.g. with chemical sensors. The main objective is to enlarge results on identifiability conditions for new classes of nonlinearities and priors on sources.
The third challenge is the data size. For high-dimension data (e.g. EEG or MRI in brain imaging), separating all the sources is neither tractable nor relevant, since one would like to only extract the useful sources. Conversely, for a small number of sensors, especially smaller than the number of sources, it is again necessary to only focus on the useful signals. The main objective is to develop generic approaches able to only extract useful signals, based on simple reference signal, modeling weak properties of the useful signal.
Finally, validation and relevant modeling must be based on actual signals and problems. In this project, theoretical results and algorithms will be developed in interaction with applications in biomedical engineering (brain-computer interface, EEG, fMRI), chemical engineering, audio-visual scene analysis and hyperspectral imaging.
Summary
Separation/extraction of sources are wide concepts in information sciences, since sensors provide information mixing and an essential step consists in separating or extracting useful information from unuseful one, called noise. In this project, we consider three challenges.
The first one is the multimodality. Indeed, with the multiplication of kinds of sensors, in many areas like biomedical signal processing, hyperspectral imaging, etc. there are many ways for recording the same physical phenomenon leading thus to multimodal data. Multimodality has been studied in the framework of human-computer interface or in data fusion, but never at the signal level. The objective is to provide a general framework for modeling classical multimodal properties, like complementarity, redundancy, equivalence, etc. as of function of source signals.
The second challenge is nonlinearity. Indeed, there exist a few cases where the mixtures are essentially nonlinear, e.g. with chemical sensors. The main objective is to enlarge results on identifiability conditions for new classes of nonlinearities and priors on sources.
The third challenge is the data size. For high-dimension data (e.g. EEG or MRI in brain imaging), separating all the sources is neither tractable nor relevant, since one would like to only extract the useful sources. Conversely, for a small number of sensors, especially smaller than the number of sources, it is again necessary to only focus on the useful signals. The main objective is to develop generic approaches able to only extract useful signals, based on simple reference signal, modeling weak properties of the useful signal.
Finally, validation and relevant modeling must be based on actual signals and problems. In this project, theoretical results and algorithms will be developed in interaction with applications in biomedical engineering (brain-computer interface, EEG, fMRI), chemical engineering, audio-visual scene analysis and hyperspectral imaging.
Max ERC Funding
2 499 390 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym CHIRALLCARBON
Project Chiral Allotropes of Carbon
Researcher (PI) Nazario Martín
Host Institution (HI) UNIVERSIDAD COMPLUTENSE DE MADRID
Call Details Advanced Grant (AdG), PE5, ERC-2012-ADG_20120216
Summary The aim of the present project is to answer fundamental questions about how to introduce chirality into a variety of carbon nanostructures and how it modifies the properties in the search for new applications in materials science and nanotecnology. Thus, it describes a fundamental and technological research program designed to gain new knowledge for the development of novel covalent and supramolecular chiral carbon nanoforms, and their further chemical modification for the preparation of sophisticated supramolecular 3D nanoarchitectures. Our research activity should reinforce and integrate the strong position of Europe in the knowledge of carbon nanoforms.
This important scientific challenge has not been properly addressed so far due to the inherent difficulties to work on these materials and, particularly, to the lack of an efficient chemical protocol to prepare chiral carbon nanoforms.
Summary
The aim of the present project is to answer fundamental questions about how to introduce chirality into a variety of carbon nanostructures and how it modifies the properties in the search for new applications in materials science and nanotecnology. Thus, it describes a fundamental and technological research program designed to gain new knowledge for the development of novel covalent and supramolecular chiral carbon nanoforms, and their further chemical modification for the preparation of sophisticated supramolecular 3D nanoarchitectures. Our research activity should reinforce and integrate the strong position of Europe in the knowledge of carbon nanoforms.
This important scientific challenge has not been properly addressed so far due to the inherent difficulties to work on these materials and, particularly, to the lack of an efficient chemical protocol to prepare chiral carbon nanoforms.
Max ERC Funding
2 235 000 €
Duration
Start date: 2013-04-01, End date: 2019-03-31
Project acronym CHLIP
Project "Understanding Halogenated Lipids: Synthesis, Mode of Action, Structural Studies, and Applications"
Researcher (PI) Erick Moran Carreira
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE5, ERC-2012-ADG_20120216
Summary "Among the various toxins isolated, the chlorosulfolipids are particularly intriguing because of their structural and stereochemical complexity. The mechanism of biological activity remains unknown. The lack of availability of the natural products has impaired more in-depth studies aimed at pharmacological, biological, and chemical characterization for proper evaluation of the risk for human health and their role in nature. The proposal takes as its basis this unusual class of natural products and delineates a multifaceted program of inquiry involving: (1) structural characterization of the most complex chlorosulfolipid isolated to date, (2) conformational studies in solution of chlorinated lipids, (3) synthesis and study of brominated lipid analogs, (4) development of analytical methods for detection of these toxins in the environment, (5) the discovery and development of reagents and catalysts for asymmetric chlorination of olefins, (6) examination of lipid conformation in constrained media, (7) examination of the mechanism of anchimeric assistance by chlorides, and (8) applications to drug discovery."
Summary
"Among the various toxins isolated, the chlorosulfolipids are particularly intriguing because of their structural and stereochemical complexity. The mechanism of biological activity remains unknown. The lack of availability of the natural products has impaired more in-depth studies aimed at pharmacological, biological, and chemical characterization for proper evaluation of the risk for human health and their role in nature. The proposal takes as its basis this unusual class of natural products and delineates a multifaceted program of inquiry involving: (1) structural characterization of the most complex chlorosulfolipid isolated to date, (2) conformational studies in solution of chlorinated lipids, (3) synthesis and study of brominated lipid analogs, (4) development of analytical methods for detection of these toxins in the environment, (5) the discovery and development of reagents and catalysts for asymmetric chlorination of olefins, (6) examination of lipid conformation in constrained media, (7) examination of the mechanism of anchimeric assistance by chlorides, and (8) applications to drug discovery."
Max ERC Funding
2 233 240 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym CHOLINOMIRS
Project CholinomiRs: MicroRNA Regulators of Cholinergic Signalling in the Neuro-Immune Interface
Researcher (PI) Hermona Soreq
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Advanced Grant (AdG), LS5, ERC-2012-ADG_20120314
Summary "Communication between the nervous and the immune system is pivotal for maintaining homeostasis and ensuring rapid and efficient reaction to stress and infection insults. The emergence of microRNAs (miRs) as regulators of gene expression and of acetylcholine (ACh) signalling as regulator of anxiety and inflammation provides a model for studying this interaction. My hypothesis is that 1) a specific sub-group of miRs, designated ""CholinomiRs"", may silence multiple target genes in the neuro-immune interface; 2) these miRs compete with each other on the interaction with their targets, and 3) mutations interfering with miR binding lead to inherited susceptibility to anxiety and inflammation disorders by modifying these interactions. Our preliminary findings have shown that by targeting acetylcholinesterase (AChE), CholinomiR-132 can intensify acute stress, resolve intestinal inflammation and change post-ischemic stroke responses. Further, we have identified clustered single nucleotide polymorphisms (SNPs) interfering with AChE silencing by several miRs which associate with elevated trait anxiety, blood pressure and inflammation. To further study miR regulators of ACh signalling, I plan to: (1) Identify anxiety and inflammation-induced changes in CholinomiRs and their targets in challenged brain and immune cells. (2) Establish the roles of these targets for one selected CholinomiR by tissue-specific manipulations. (3) Study primate-specific CholinomiRs by continued human DNA screens to identify SNPs and in ""humanized"" mice with knocked-in human AChE and transgenic CholinomiR-608. (4) Test if therapeutic modulation of aberrant CholinomiR expression can restore homeostasis. This research will clarify how miRs interact with each other in health and disease, introduce the dimension of complexity of multi-target competition and miR interactions and make a conceptual change in miRs research while enhancing the ability to intervene with diseases involving impaired ACh signalling."
Summary
"Communication between the nervous and the immune system is pivotal for maintaining homeostasis and ensuring rapid and efficient reaction to stress and infection insults. The emergence of microRNAs (miRs) as regulators of gene expression and of acetylcholine (ACh) signalling as regulator of anxiety and inflammation provides a model for studying this interaction. My hypothesis is that 1) a specific sub-group of miRs, designated ""CholinomiRs"", may silence multiple target genes in the neuro-immune interface; 2) these miRs compete with each other on the interaction with their targets, and 3) mutations interfering with miR binding lead to inherited susceptibility to anxiety and inflammation disorders by modifying these interactions. Our preliminary findings have shown that by targeting acetylcholinesterase (AChE), CholinomiR-132 can intensify acute stress, resolve intestinal inflammation and change post-ischemic stroke responses. Further, we have identified clustered single nucleotide polymorphisms (SNPs) interfering with AChE silencing by several miRs which associate with elevated trait anxiety, blood pressure and inflammation. To further study miR regulators of ACh signalling, I plan to: (1) Identify anxiety and inflammation-induced changes in CholinomiRs and their targets in challenged brain and immune cells. (2) Establish the roles of these targets for one selected CholinomiR by tissue-specific manipulations. (3) Study primate-specific CholinomiRs by continued human DNA screens to identify SNPs and in ""humanized"" mice with knocked-in human AChE and transgenic CholinomiR-608. (4) Test if therapeutic modulation of aberrant CholinomiR expression can restore homeostasis. This research will clarify how miRs interact with each other in health and disease, introduce the dimension of complexity of multi-target competition and miR interactions and make a conceptual change in miRs research while enhancing the ability to intervene with diseases involving impaired ACh signalling."
Max ERC Funding
2 375 600 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
