Project acronym 3D-FABRIC
Project 3D Flow Analysis in Bijels Reconfigured for Interfacial Catalysis
Researcher (PI) Martin F. HAASE
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Starting Grant (StG), PE8, ERC-2018-STG
Summary The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Summary
The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Max ERC Funding
1 905 000 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
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 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 AGGLONANOCOAT
Project The interplay between agglomeration and coating of nanoparticles in the gas phase
Researcher (PI) Jan Rudolf Van Ommen
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Starting Grant (StG), PE8, ERC-2011-StG_20101014
Summary This proposal aims to develop a generic synthesis approach for core-shell nanoparticles by unravelling the relevant mechanisms. Core-shell nanoparticles have high potential in heterogeneous catalysis, energy storage, and medical applications. However, on a fundamental level there is currently a poor understanding of how to produce such nanostructured particles in a controllable and scalable manner.
The main barriers to achieving this goal are understanding how nanoparticles agglomerate to loose dynamic clusters and controlling the agglomeration process in gas flows during coating, such that uniform coatings can be made. This is very challenging because of the two-way coupling between agglomeration and coating. During the coating we change the particle surfaces and thus the way the particles stick together. Correspondingly, the stickiness of particles determines how easy reactants can reach the surface.
Innovatively the project will be the first systematic study into this multi-scale phenomenon with investigations at all relevant length scales. Current synthesis approaches – mostly carried out in the liquid phase – are typically developed case by case. I will coat nanoparticles in the gas phase with atomic layer deposition (ALD): a technique from the semi-conductor industry that can deposit a wide range of materials. ALD applied to flat substrates offers excellent control over layer thickness. I will investigate the modification of single particle surfaces, particle-particle interaction, the structure of agglomerates, and the flow behaviour of large number of agglomerates. To this end, I will apply a multidisciplinary approach, combining disciplines as physical chemistry, fluid dynamics, and reaction engineering.
Summary
This proposal aims to develop a generic synthesis approach for core-shell nanoparticles by unravelling the relevant mechanisms. Core-shell nanoparticles have high potential in heterogeneous catalysis, energy storage, and medical applications. However, on a fundamental level there is currently a poor understanding of how to produce such nanostructured particles in a controllable and scalable manner.
The main barriers to achieving this goal are understanding how nanoparticles agglomerate to loose dynamic clusters and controlling the agglomeration process in gas flows during coating, such that uniform coatings can be made. This is very challenging because of the two-way coupling between agglomeration and coating. During the coating we change the particle surfaces and thus the way the particles stick together. Correspondingly, the stickiness of particles determines how easy reactants can reach the surface.
Innovatively the project will be the first systematic study into this multi-scale phenomenon with investigations at all relevant length scales. Current synthesis approaches – mostly carried out in the liquid phase – are typically developed case by case. I will coat nanoparticles in the gas phase with atomic layer deposition (ALD): a technique from the semi-conductor industry that can deposit a wide range of materials. ALD applied to flat substrates offers excellent control over layer thickness. I will investigate the modification of single particle surfaces, particle-particle interaction, the structure of agglomerates, and the flow behaviour of large number of agglomerates. To this end, I will apply a multidisciplinary approach, combining disciplines as physical chemistry, fluid dynamics, and reaction engineering.
Max ERC Funding
1 409 952 €
Duration
Start date: 2011-12-01, End date: 2016-11-30
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 ANISOGEL
Project Injectable anisotropic microgel-in-hydrogel matrices for spinal cord repair
Researcher (PI) Laura De Laporte
Host Institution (HI) DWI LEIBNIZ-INSTITUT FUR INTERAKTIVE MATERIALIEN EV
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary This project will engineer an injectable biomaterial that forms an anisotropic microheterogeneous structure in vivo. Injectable hydrogels enable a minimal invasive in situ generation of matrices for the regeneration of tissues and organs, but currently lack structural organization and unidirectional orientation. The anisotropic, injectable hydrogels to be developed will mimic local extracellular matrix architectures that cells encounter in complex tissues (e.g. nerves, muscles). This project aims for the development of a biomimetic scaffold for spinal cord regeneration.
To realize such a major breakthrough, my group will focus on three research objectives. i) Poly(ethylene glycol) microgel-in-hydrogel matrices will be fabricated with the ability to create macroscopic order due to microgel shape anisotropy and magnetic alignment. Barrel-like microgels will be prepared using an in-mold polymerization technique. Their ability to self-assemble will be investigated in function of their dimensions, aspect ratio, crosslinking density, and volume fraction. Superparamagnetic nanoparticles will be included into the microgels to enable unidirectional orientation by means of a magnetic field. Subsequently, the oriented microgels will be interlocked within a master hydrogel. ii) The microgel-in-hydrogel matrices will be equipped with (bio)functional properties for spinal cord regeneration, i.e., to control and optimize mechanical anisotropy and biological signaling by in vitro cell growth experiments. iii) Selected hydrogel composites will be injected after rat spinal cord injury and directional tissue growth and animal functional behavior will be analyzed.
Succesful fabrication of the proposed microgel-in-hydrogel matrix will provide a new type of biomaterial, which enables investigating the effect of an anisotropic structure on physiological and pathological processes in vivo. This is a decisive step towards creating a clinical healing matrix for anisotropic tissue repair.
Summary
This project will engineer an injectable biomaterial that forms an anisotropic microheterogeneous structure in vivo. Injectable hydrogels enable a minimal invasive in situ generation of matrices for the regeneration of tissues and organs, but currently lack structural organization and unidirectional orientation. The anisotropic, injectable hydrogels to be developed will mimic local extracellular matrix architectures that cells encounter in complex tissues (e.g. nerves, muscles). This project aims for the development of a biomimetic scaffold for spinal cord regeneration.
To realize such a major breakthrough, my group will focus on three research objectives. i) Poly(ethylene glycol) microgel-in-hydrogel matrices will be fabricated with the ability to create macroscopic order due to microgel shape anisotropy and magnetic alignment. Barrel-like microgels will be prepared using an in-mold polymerization technique. Their ability to self-assemble will be investigated in function of their dimensions, aspect ratio, crosslinking density, and volume fraction. Superparamagnetic nanoparticles will be included into the microgels to enable unidirectional orientation by means of a magnetic field. Subsequently, the oriented microgels will be interlocked within a master hydrogel. ii) The microgel-in-hydrogel matrices will be equipped with (bio)functional properties for spinal cord regeneration, i.e., to control and optimize mechanical anisotropy and biological signaling by in vitro cell growth experiments. iii) Selected hydrogel composites will be injected after rat spinal cord injury and directional tissue growth and animal functional behavior will be analyzed.
Succesful fabrication of the proposed microgel-in-hydrogel matrix will provide a new type of biomaterial, which enables investigating the effect of an anisotropic structure on physiological and pathological processes in vivo. This is a decisive step towards creating a clinical healing matrix for anisotropic tissue repair.
Max ERC Funding
1 435 396 €
Duration
Start date: 2015-03-01, End date: 2020-02-29
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
