Project acronym 2D–SYNETRA
Project Two-dimensional colloidal nanostructures - Synthesis and electrical transport
Researcher (PI) Christian Klinke
Host Institution (HI) UNIVERSITAET HAMBURG
Call Details Starting Grant (StG), PE4, ERC-2012-StG_20111012
Summary We propose to develop truly two-dimensional continuous materials and two-dimensional monolayer films composed of individual nanocrystals by the comparatively fast, inexpensive, and scalable colloidal synthesis method. The materials’ properties will be studied in detail, especially regarding their (photo-) electrical transport. This will allow developing new types of device structures, such as Coulomb blockade and field enhancement based transistors.
Recently, we demonstrated the possibility to synthesize in a controlled manner truly two-dimensional colloidal nanostructures. We will investigate their formation mechanism, synthesize further materials as “nanosheets”, develop methodologies to tune their geometrical properties, and study their (photo-) electrical properties.
Furthermore, we will use the Langmuir-Blodgett method to deposit highly ordered monolayers of monodisperse nanoparticles. Such structures show interesting transport properties governed by Coulomb blockade effects known from individual nanoparticles. This leads to semiconductor-like behavior in metal nanoparticle films. The understanding of the electric transport in such “multi-tunnel devices” is still very limited. Thus, we will investigate this concept in detail and take it to its limits. Beside improvement of quality and exchange of material we will tune the nanoparticles’ size and shape in order to gain a deeper understanding of the electrical properties of supercrystallographic assemblies. Furthermore, we will develop device concepts for diode and transistor structures which take into account the novel properties of the low-dimensional assemblies.
Nanosheets and monolayers of nanoparticles truly follow the principle of building devices by the bottom-up approach and allow electric transport measurements in a 2D regime. Highly ordered nanomaterial systems possess easy and reliably to manipulate electronic properties what make them interesting for future (inexpensive) electronic devices.
Summary
We propose to develop truly two-dimensional continuous materials and two-dimensional monolayer films composed of individual nanocrystals by the comparatively fast, inexpensive, and scalable colloidal synthesis method. The materials’ properties will be studied in detail, especially regarding their (photo-) electrical transport. This will allow developing new types of device structures, such as Coulomb blockade and field enhancement based transistors.
Recently, we demonstrated the possibility to synthesize in a controlled manner truly two-dimensional colloidal nanostructures. We will investigate their formation mechanism, synthesize further materials as “nanosheets”, develop methodologies to tune their geometrical properties, and study their (photo-) electrical properties.
Furthermore, we will use the Langmuir-Blodgett method to deposit highly ordered monolayers of monodisperse nanoparticles. Such structures show interesting transport properties governed by Coulomb blockade effects known from individual nanoparticles. This leads to semiconductor-like behavior in metal nanoparticle films. The understanding of the electric transport in such “multi-tunnel devices” is still very limited. Thus, we will investigate this concept in detail and take it to its limits. Beside improvement of quality and exchange of material we will tune the nanoparticles’ size and shape in order to gain a deeper understanding of the electrical properties of supercrystallographic assemblies. Furthermore, we will develop device concepts for diode and transistor structures which take into account the novel properties of the low-dimensional assemblies.
Nanosheets and monolayers of nanoparticles truly follow the principle of building devices by the bottom-up approach and allow electric transport measurements in a 2D regime. Highly ordered nanomaterial systems possess easy and reliably to manipulate electronic properties what make them interesting for future (inexpensive) electronic devices.
Max ERC Funding
1 497 200 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym 3D_Tryps
Project The role of three-dimensional genome architecture in antigenic variation
Researcher (PI) Tim Nicolai SIEGEL
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism.
The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression.
I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen.
The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.
Summary
Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism.
The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression.
I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen.
The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.
Max ERC Funding
1 498 175 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym a SMILE
Project analyse Soluble + Membrane complexes with Improved LILBID Experiments
Researcher (PI) Nina Morgner
Host Institution (HI) JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN
Call Details Starting Grant (StG), PE4, ERC-2013-StG
Summary Crucial processes within cells depend on specific non-covalent interactions which mediate the assembly of proteins and other biomolecules. Deriving structural information to understand the function of these complex systems is the primary goal of Structural Biology.
In this application, the recently developed LILBID method (Laser Induced Liquid Bead Ion Desorption) will be optimized for investigation of macromolecular complexes with a mass accuracy two orders of magnitude better than in 1st generation spectrometers.
Controlled disassembly of the multiprotein complexes in the mass spectrometric analysis while keeping the 3D structure intact, will allow for the determination of complex stoichiometry and connectivity of the constituting proteins. Methods for such controlled disassembly will be developed in two separate units of the proposed LILBID spectrometer, in a collision chamber and in a laser dissociation chamber, enabling gas phase dissociation of protein complexes and removal of excess water/buffer molecules. As a third unit, a chamber allowing determination of ion mobility (IM) will be integrated to determine collisional cross sections (CCS). From CCS, unique information regarding the spatial arrangement of proteins in complexes or subcomplexes will then be obtainable from LILBID.
The proposed design of the new spectrometer will offer fundamentally new possibilities for the investigation of non-covalent RNA, soluble and membrane protein complexes, as well as broadening the applicability of non-covalent MS towards supercomplexes.
Summary
Crucial processes within cells depend on specific non-covalent interactions which mediate the assembly of proteins and other biomolecules. Deriving structural information to understand the function of these complex systems is the primary goal of Structural Biology.
In this application, the recently developed LILBID method (Laser Induced Liquid Bead Ion Desorption) will be optimized for investigation of macromolecular complexes with a mass accuracy two orders of magnitude better than in 1st generation spectrometers.
Controlled disassembly of the multiprotein complexes in the mass spectrometric analysis while keeping the 3D structure intact, will allow for the determination of complex stoichiometry and connectivity of the constituting proteins. Methods for such controlled disassembly will be developed in two separate units of the proposed LILBID spectrometer, in a collision chamber and in a laser dissociation chamber, enabling gas phase dissociation of protein complexes and removal of excess water/buffer molecules. As a third unit, a chamber allowing determination of ion mobility (IM) will be integrated to determine collisional cross sections (CCS). From CCS, unique information regarding the spatial arrangement of proteins in complexes or subcomplexes will then be obtainable from LILBID.
The proposed design of the new spectrometer will offer fundamentally new possibilities for the investigation of non-covalent RNA, soluble and membrane protein complexes, as well as broadening the applicability of non-covalent MS towards supercomplexes.
Max ERC Funding
1 264 477 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym ACDC
Project Algorithms and Complexity of Highly Decentralized Computations
Researcher (PI) Fabian Daniel Kuhn
Host Institution (HI) ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
Call Details Starting Grant (StG), PE6, ERC-2013-StG
Summary "Many of today's and tomorrow's computer systems are built on top of large-scale networks such as, e.g., the Internet, the world wide web, wireless ad hoc and sensor networks, or peer-to-peer networks. Driven by technological advances, new kinds of networks and applications have become possible and we can safely assume that this trend is going to continue. Often modern systems are envisioned to consist of a potentially large number of individual components that are organized in a completely decentralized way. There is no central authority that controls the topology of the network, how nodes join or leave the system, or in which way nodes communicate with each other. Also, many future distributed applications will be built using wireless devices that communicate via radio.
The general objective of the proposed project is to improve our understanding of the algorithmic and theoretical foundations of decentralized distributed systems. From an algorithmic point of view, decentralized networks and computations pose a number of fascinating and unique challenges that are not present in sequential or more standard distributed systems. As communication is limited and mostly between nearby nodes, each node of a large network can only maintain a very restricted view of the global state of the system. This is particularly true if the network can change dynamically, either by nodes joining or leaving the system or if the topology changes over time, e.g., because of the mobility of the devices in case of a wireless network. Nevertheless, the nodes of a network need to coordinate in order to achieve some global goal.
In particular, we plan to study algorithms and lower bounds for basic computation and information dissemination tasks in such systems. In addition, we are particularly interested in the complexity of distributed computations in dynamic and wireless networks."
Summary
"Many of today's and tomorrow's computer systems are built on top of large-scale networks such as, e.g., the Internet, the world wide web, wireless ad hoc and sensor networks, or peer-to-peer networks. Driven by technological advances, new kinds of networks and applications have become possible and we can safely assume that this trend is going to continue. Often modern systems are envisioned to consist of a potentially large number of individual components that are organized in a completely decentralized way. There is no central authority that controls the topology of the network, how nodes join or leave the system, or in which way nodes communicate with each other. Also, many future distributed applications will be built using wireless devices that communicate via radio.
The general objective of the proposed project is to improve our understanding of the algorithmic and theoretical foundations of decentralized distributed systems. From an algorithmic point of view, decentralized networks and computations pose a number of fascinating and unique challenges that are not present in sequential or more standard distributed systems. As communication is limited and mostly between nearby nodes, each node of a large network can only maintain a very restricted view of the global state of the system. This is particularly true if the network can change dynamically, either by nodes joining or leaving the system or if the topology changes over time, e.g., because of the mobility of the devices in case of a wireless network. Nevertheless, the nodes of a network need to coordinate in order to achieve some global goal.
In particular, we plan to study algorithms and lower bounds for basic computation and information dissemination tasks in such systems. In addition, we are particularly interested in the complexity of distributed computations in dynamic and wireless networks."
Max ERC Funding
1 148 000 €
Duration
Start date: 2013-11-01, End date: 2018-10-31
Project acronym ADIPODIF
Project Adipocyte Differentiation and Metabolic Functions in Obesity and Type 2 Diabetes
Researcher (PI) Christian Wolfrum
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary Obesity associated disorders such as T2D, hypertension and CVD, commonly referred to as the “metabolic syndrome”, are prevalent diseases of industrialized societies. Deranged adipose tissue proliferation and differentiation contribute significantly to the development of these metabolic disorders. Comparatively little however is known, about how these processes influence the development of metabolic disorders. Using a multidisciplinary approach, I plan to elucidate molecular mechanisms underlying the altered adipocyte differentiation and maturation in different models of obesity associated metabolic disorders. Special emphasis will be given to the analysis of gene expression, postranslational modifications and lipid molecular species composition. To achieve this goal, I am establishing several novel methods to isolate pure primary preadipocytes including a new animal model that will allow me to monitor preadipocytes, in vivo and track their cellular fate in the context of a complete organism. These systems will allow, for the first time to study preadipocyte biology, in an in vivo setting. By monitoring preadipocyte differentiation in vivo, I will also be able to answer the key questions regarding the development of preadipocytes and examine signals that induce or inhibit their differentiation. Using transplantation techniques, I will elucidate the genetic and environmental contributions to the progression of obesity and its associated metabolic disorders. Furthermore, these studies will integrate a lipidomics approach to systematically analyze lipid molecular species composition in different models of metabolic disorders. My studies will provide new insights into the mechanisms and dynamics underlying adipocyte differentiation and maturation, and relate them to metabolic disorders. Detailed knowledge of these mechanisms will facilitate development of novel therapeutic approaches for the treatment of obesity and associated metabolic disorders.
Summary
Obesity associated disorders such as T2D, hypertension and CVD, commonly referred to as the “metabolic syndrome”, are prevalent diseases of industrialized societies. Deranged adipose tissue proliferation and differentiation contribute significantly to the development of these metabolic disorders. Comparatively little however is known, about how these processes influence the development of metabolic disorders. Using a multidisciplinary approach, I plan to elucidate molecular mechanisms underlying the altered adipocyte differentiation and maturation in different models of obesity associated metabolic disorders. Special emphasis will be given to the analysis of gene expression, postranslational modifications and lipid molecular species composition. To achieve this goal, I am establishing several novel methods to isolate pure primary preadipocytes including a new animal model that will allow me to monitor preadipocytes, in vivo and track their cellular fate in the context of a complete organism. These systems will allow, for the first time to study preadipocyte biology, in an in vivo setting. By monitoring preadipocyte differentiation in vivo, I will also be able to answer the key questions regarding the development of preadipocytes and examine signals that induce or inhibit their differentiation. Using transplantation techniques, I will elucidate the genetic and environmental contributions to the progression of obesity and its associated metabolic disorders. Furthermore, these studies will integrate a lipidomics approach to systematically analyze lipid molecular species composition in different models of metabolic disorders. My studies will provide new insights into the mechanisms and dynamics underlying adipocyte differentiation and maturation, and relate them to metabolic disorders. Detailed knowledge of these mechanisms will facilitate development of novel therapeutic approaches for the treatment of obesity and associated metabolic disorders.
Max ERC Funding
1 607 105 €
Duration
Start date: 2008-07-01, End date: 2013-06-30
Project acronym AIM2 INFLAMMASOME
Project Cytosolic recognition of foreign nucleic acids: Molecular and functional characterization of AIM2, a central player in DNA-triggered inflammasome activation
Researcher (PI) Veit Hornung
Host Institution (HI) UNIVERSITAETSKLINIKUM BONN
Call Details Starting Grant (StG), LS6, ERC-2009-StG
Summary Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.
Summary
Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.
Max ERC Funding
1 727 920 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym ALGILE
Project Foundations of Algebraic and Dynamic Data Management Systems
Researcher (PI) Christoph Koch
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE6, ERC-2011-StG_20101014
Summary "Contemporary database query languages are ultimately founded on logic and feature an additive operation – usually a form of (multi)set union or disjunction – that is asymmetric in that additions or updates do not always have an inverse. This asymmetry puts a greater part of the machinery of abstract algebra for equation solving outside the reach of databases. However, such equation solving would be a key functionality that problems such as query equivalence testing and data integration could be reduced to: In the current scenario of the presence of an asymmetric additive operation they are undecidable. Moreover, query languages with a symmetric additive operation (i.e., which has an inverse and is thus based on ring theory) would open up databases for a large range of new scientific and mathematical applications.
The goal of the proposed project is to reinvent database management systems with a foundation in abstract algebra and specifically in ring theory. The presence of an additive inverse allows to cleanly define differences between queries. This gives rise to a database analog of differential calculus that leads to radically new incremental and adaptive query evaluation algorithms that substantially outperform the state of the art techniques. These algorithms enable a new class of systems which I call Dynamic Data Management Systems. Such systems can maintain continuously fresh query views at extremely high update rates and have important applications in interactive Large-scale Data Analysis. There is a natural connection between differences and updates, motivating the group theoretic study of updates that will lead to better ways of creating out-of-core data processing algorithms for new storage devices. Basing queries on ring theory leads to a new class of systems, Algebraic Data Management Systems, which herald a convergence of database systems and computer algebra systems."
Summary
"Contemporary database query languages are ultimately founded on logic and feature an additive operation – usually a form of (multi)set union or disjunction – that is asymmetric in that additions or updates do not always have an inverse. This asymmetry puts a greater part of the machinery of abstract algebra for equation solving outside the reach of databases. However, such equation solving would be a key functionality that problems such as query equivalence testing and data integration could be reduced to: In the current scenario of the presence of an asymmetric additive operation they are undecidable. Moreover, query languages with a symmetric additive operation (i.e., which has an inverse and is thus based on ring theory) would open up databases for a large range of new scientific and mathematical applications.
The goal of the proposed project is to reinvent database management systems with a foundation in abstract algebra and specifically in ring theory. The presence of an additive inverse allows to cleanly define differences between queries. This gives rise to a database analog of differential calculus that leads to radically new incremental and adaptive query evaluation algorithms that substantially outperform the state of the art techniques. These algorithms enable a new class of systems which I call Dynamic Data Management Systems. Such systems can maintain continuously fresh query views at extremely high update rates and have important applications in interactive Large-scale Data Analysis. There is a natural connection between differences and updates, motivating the group theoretic study of updates that will lead to better ways of creating out-of-core data processing algorithms for new storage devices. Basing queries on ring theory leads to a new class of systems, Algebraic Data Management Systems, which herald a convergence of database systems and computer algebra systems."
Max ERC Funding
1 480 548 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym ALLERGUT
Project Mucosal Tolerance and Allergic Predisposition: Does it all start in the gut?
Researcher (PI) Caspar OHNMACHT
Host Institution (HI) HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Currently, more than 30% of all Europeans suffer from one or more allergic disorder but treatment is still mostly symptomatic due to a lack of understanding the underlying causality. Allergies are caused by type 2 immune responses triggered by recognition of harmless antigens. Both genetic and environmental factors have been proposed to favour allergic predisposition and both factors have a huge impact on the symbiotic microbiota and the intestinal immune system. Recently we and others showed that the transcription factor ROR(γt) seems to play a key role in mucosal tolerance in the gut and also regulates intestinal type 2 immune responses.
Based on these results I postulate two major events in the gut for the development of an allergy in the lifetime of an individual: First, a failure to establish mucosal tolerance or anergy constitutes a necessity for the outbreak of allergic symptoms and allergic disease. Second, a certain ‘core’ microbiome or pathway of the intestinal microbiota predispose certain individuals for the later development of allergic disorders. Therefore, I will address the following aims:
1) Influence of ROR(γt) on mucosal tolerance induction and allergic disorders
2) Elucidate the T cell receptor repertoire of intestinal Th2 and ROR(γt)+ Tregs and assess the role of alternative NFκB pathway for induction of mucosal tolerance
3) Identification of ‘core’ microbiome signatures or metabolic pathways that favour allergic predisposition
ALLERGUT will provide ground-breaking knowledge on molecular mechanisms of the failure of mucosal tolerance in the gut and will prove if the resident ROR(γt)+ T(reg) cells can function as a mechanistic starting point for molecular intervention strategies on the background of the hygiene hypothesis. The vision of ALLERGUT is to diagnose mucosal disbalance, prevent and treat allergic disorders even before outbreak and thereby promote Public Health initiative for better living.
Summary
Currently, more than 30% of all Europeans suffer from one or more allergic disorder but treatment is still mostly symptomatic due to a lack of understanding the underlying causality. Allergies are caused by type 2 immune responses triggered by recognition of harmless antigens. Both genetic and environmental factors have been proposed to favour allergic predisposition and both factors have a huge impact on the symbiotic microbiota and the intestinal immune system. Recently we and others showed that the transcription factor ROR(γt) seems to play a key role in mucosal tolerance in the gut and also regulates intestinal type 2 immune responses.
Based on these results I postulate two major events in the gut for the development of an allergy in the lifetime of an individual: First, a failure to establish mucosal tolerance or anergy constitutes a necessity for the outbreak of allergic symptoms and allergic disease. Second, a certain ‘core’ microbiome or pathway of the intestinal microbiota predispose certain individuals for the later development of allergic disorders. Therefore, I will address the following aims:
1) Influence of ROR(γt) on mucosal tolerance induction and allergic disorders
2) Elucidate the T cell receptor repertoire of intestinal Th2 and ROR(γt)+ Tregs and assess the role of alternative NFκB pathway for induction of mucosal tolerance
3) Identification of ‘core’ microbiome signatures or metabolic pathways that favour allergic predisposition
ALLERGUT will provide ground-breaking knowledge on molecular mechanisms of the failure of mucosal tolerance in the gut and will prove if the resident ROR(γt)+ T(reg) cells can function as a mechanistic starting point for molecular intervention strategies on the background of the hygiene hypothesis. The vision of ALLERGUT is to diagnose mucosal disbalance, prevent and treat allergic disorders even before outbreak and thereby promote Public Health initiative for better living.
Max ERC Funding
1 498 175 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym ANTICIPATE
Project Anticipatory Human-Computer Interaction
Researcher (PI) Andreas BULLING
Host Institution (HI) UNIVERSITAET STUTTGART
Call Details Starting Grant (StG), PE6, ERC-2018-STG
Summary Even after three decades of research on human-computer interaction (HCI), current general-purpose user interfaces (UI) still lack the ability to attribute mental states to their users, i.e. they fail to understand users' intentions and needs and to anticipate their actions. This drastically restricts their interactive capabilities.
ANTICIPATE aims to establish the scientific foundations for a new generation of user interfaces that pro-actively adapt to users' future input actions by monitoring their attention and predicting their interaction intentions - thereby significantly improving the naturalness, efficiency, and user experience of the interactions. Realising this vision of anticipatory human-computer interaction requires groundbreaking advances in everyday sensing of user attention from eye and brain activity. We will further pioneer methods to predict entangled user intentions and forecast interactive behaviour with fine temporal granularity during interactions in everyday stationary and mobile settings. Finally, we will develop fundamental interaction paradigms that enable anticipatory UIs to pro-actively adapt to users' attention and intentions in a mindful way. The new capabilities will be demonstrated in four challenging cases: 1) mobile information retrieval, 2) intelligent notification management, 3) Autism diagnosis and monitoring, and 4) computer-based training.
Anticipatory human-computer interaction offers a strong complement to existing UI paradigms that only react to user input post-hoc. If successful, ANTICIPATE will deliver the first important building blocks for implementing Theory of Mind in general-purpose UIs. As such, the project has the potential to drastically improve the billions of interactions we perform with computers every day, to trigger a wide range of follow-up research in HCI as well as adjacent areas within and outside computer science, and to act as a key technical enabler for new applications, e.g. in healthcare and education.
Summary
Even after three decades of research on human-computer interaction (HCI), current general-purpose user interfaces (UI) still lack the ability to attribute mental states to their users, i.e. they fail to understand users' intentions and needs and to anticipate their actions. This drastically restricts their interactive capabilities.
ANTICIPATE aims to establish the scientific foundations for a new generation of user interfaces that pro-actively adapt to users' future input actions by monitoring their attention and predicting their interaction intentions - thereby significantly improving the naturalness, efficiency, and user experience of the interactions. Realising this vision of anticipatory human-computer interaction requires groundbreaking advances in everyday sensing of user attention from eye and brain activity. We will further pioneer methods to predict entangled user intentions and forecast interactive behaviour with fine temporal granularity during interactions in everyday stationary and mobile settings. Finally, we will develop fundamental interaction paradigms that enable anticipatory UIs to pro-actively adapt to users' attention and intentions in a mindful way. The new capabilities will be demonstrated in four challenging cases: 1) mobile information retrieval, 2) intelligent notification management, 3) Autism diagnosis and monitoring, and 4) computer-based training.
Anticipatory human-computer interaction offers a strong complement to existing UI paradigms that only react to user input post-hoc. If successful, ANTICIPATE will deliver the first important building blocks for implementing Theory of Mind in general-purpose UIs. As such, the project has the potential to drastically improve the billions of interactions we perform with computers every day, to trigger a wide range of follow-up research in HCI as well as adjacent areas within and outside computer science, and to act as a key technical enabler for new applications, e.g. in healthcare and education.
Max ERC Funding
1 499 625 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym ARCA
Project Analysis and Representation of Complex Activities in Videos
Researcher (PI) Juergen Gall
Host Institution (HI) RHEINISCHE FRIEDRICH-WILHELMS-UNIVERSITAT BONN
Call Details Starting Grant (StG), PE6, ERC-2015-STG
Summary The goal of the project is to automatically analyse human activities observed in videos. Any solution to this problem will allow the development of novel applications. It could be used to create short videos that summarize daily activities to support patients suffering from Alzheimer's disease. It could also be used for education, e.g., by providing a video analysis for a trainee in the hospital that shows if the tasks have been correctly executed.
The analysis of complex activities in videos, however, is very challenging since activities vary in temporal duration between minutes and hours, involve interactions with several objects that change their appearance and shape, e.g., food during cooking, and are composed of many sub-activities, which can happen at the same time or in various orders.
While the majority of recent works in action recognition focuses on developing better feature encoding techniques for classifying sub-activities in short video clips of a few seconds, this project moves forward and aims to develop a higher level representation of complex activities to overcome the limitations of current approaches. This includes the handling of large time variations and the ability to recognize and locate complex activities in videos. To this end, we aim to develop a unified model that provides detailed information about the activities and sub-activities in terms of time and spatial location, as well as involved pose motion, objects and their transformations.
Another aspect of the project is to learn a representation from videos that is not tied to a specific source of videos or limited to a specific application. Instead we aim to learn a representation that is invariant to a perspective change, e.g., from a third-person perspective to an egocentric perspective, and can be applied to various modalities like videos or depth data without the need of collecting massive training data for all modalities. In other words, we aim to learn the essence of activities.
Summary
The goal of the project is to automatically analyse human activities observed in videos. Any solution to this problem will allow the development of novel applications. It could be used to create short videos that summarize daily activities to support patients suffering from Alzheimer's disease. It could also be used for education, e.g., by providing a video analysis for a trainee in the hospital that shows if the tasks have been correctly executed.
The analysis of complex activities in videos, however, is very challenging since activities vary in temporal duration between minutes and hours, involve interactions with several objects that change their appearance and shape, e.g., food during cooking, and are composed of many sub-activities, which can happen at the same time or in various orders.
While the majority of recent works in action recognition focuses on developing better feature encoding techniques for classifying sub-activities in short video clips of a few seconds, this project moves forward and aims to develop a higher level representation of complex activities to overcome the limitations of current approaches. This includes the handling of large time variations and the ability to recognize and locate complex activities in videos. To this end, we aim to develop a unified model that provides detailed information about the activities and sub-activities in terms of time and spatial location, as well as involved pose motion, objects and their transformations.
Another aspect of the project is to learn a representation from videos that is not tied to a specific source of videos or limited to a specific application. Instead we aim to learn a representation that is invariant to a perspective change, e.g., from a third-person perspective to an egocentric perspective, and can be applied to various modalities like videos or depth data without the need of collecting massive training data for all modalities. In other words, we aim to learn the essence of activities.
Max ERC Funding
1 499 875 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
