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
Country United Kingdom
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
Country Germany
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
Country United Kingdom
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
Country France
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
Country United Kingdom
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 EN INFORMATIQUE ET AUTOMATIQUE
Country France
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
Country Germany
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
Country United Kingdom
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 Hedstroem
Host Institution (HI) LINKOPINGS UNIVERSITET
Country Sweden
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) UNIVERSIDAD AUTONOMA DE BARCELONA
Country Spain
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
