Project acronym 2O2ACTIVATION
Project Development of Direct Dehydrogenative Couplings mediated by Dioxygen
Researcher (PI) Frederic William Patureau
Host Institution (HI) RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Call Details Starting Grant (StG), PE5, ERC-2016-STG
Summary The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research.
The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation.
The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event.
Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.
Summary
The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research.
The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation.
The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event.
Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.
Max ERC Funding
1 489 823 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym 3D-FNPWriting
Project Unprecedented spatial control of porosity and functionality in nanoporous membranes through 3D printing and microscopy for polymer writing
Researcher (PI) Annette ANDRIEU-BRUNSEN
Host Institution (HI) TECHNISCHE UNIVERSITAT DARMSTADT
Call Details Starting Grant (StG), PE5, ERC-2018-STG
Summary Membranes are key materials in our life. Nature offers high performance membranes relying on a parallel local regulation of nanopore structure, functional placement, membrane composition and architecture. Existing technological membranes are key materials in separation, recycling, sensing, energy conversion, being essential components for a sustainable future. But their performance is far away from their natural counterparts. One reason for this performance gap is the lack of 3D nanolocal control in membrane design. This applies to each individual nanopore but as well to the membrane architecture. This proposal aims to implement 3D printing (additive manufacturing, top down) and complex near-field and total internal reflection (TIR) high resolution microscopy induced polymer writing (bottom up) to nanolocally control in hierarchical nanoporous membranes spatially and independent of each other: porosity, pore functionalization, membrane architecture, composition. This disruptive technology platform will make accessible to date unachieved, highly accurate asymmetric nanopores and multifunctional, hierarchical membrane architecture/ composition and thus highly selective, directed, transport with tuneable rates. 3D-FNPWriting will demonstrate this for the increasing class of metal nanoparticle/ salt pollutants aiming for tuneable, selective, directed transport based monitoring and recycling instead of size-based filtration, accumulation into sewerage and distribution into nature. Specifically, the potential of this disruptive technology with respect to transport design will be demonstrated for a) a 3D-printed in-situ functionalized nanoporous fiber architecture and b) a printed, nanolocally near-field and TIR-microscopy polymer functionalized membrane representing a thin separation layer. This will open systematic understanding of nanolocal functional control on transport and new perspectives in water/ energy management for future smart industry/ homes.
Summary
Membranes are key materials in our life. Nature offers high performance membranes relying on a parallel local regulation of nanopore structure, functional placement, membrane composition and architecture. Existing technological membranes are key materials in separation, recycling, sensing, energy conversion, being essential components for a sustainable future. But their performance is far away from their natural counterparts. One reason for this performance gap is the lack of 3D nanolocal control in membrane design. This applies to each individual nanopore but as well to the membrane architecture. This proposal aims to implement 3D printing (additive manufacturing, top down) and complex near-field and total internal reflection (TIR) high resolution microscopy induced polymer writing (bottom up) to nanolocally control in hierarchical nanoporous membranes spatially and independent of each other: porosity, pore functionalization, membrane architecture, composition. This disruptive technology platform will make accessible to date unachieved, highly accurate asymmetric nanopores and multifunctional, hierarchical membrane architecture/ composition and thus highly selective, directed, transport with tuneable rates. 3D-FNPWriting will demonstrate this for the increasing class of metal nanoparticle/ salt pollutants aiming for tuneable, selective, directed transport based monitoring and recycling instead of size-based filtration, accumulation into sewerage and distribution into nature. Specifically, the potential of this disruptive technology with respect to transport design will be demonstrated for a) a 3D-printed in-situ functionalized nanoporous fiber architecture and b) a printed, nanolocally near-field and TIR-microscopy polymer functionalized membrane representing a thin separation layer. This will open systematic understanding of nanolocal functional control on transport and new perspectives in water/ energy management for future smart industry/ homes.
Max ERC Funding
1 499 844 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
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 ABRSEIST
Project Antibiotic Resistance: Socio-Economic Determinants and the Role of Information and Salience in Treatment Choice
Researcher (PI) Hannes ULLRICH
Host Institution (HI) DEUTSCHES INSTITUT FUR WIRTSCHAFTSFORSCHUNG DIW (INSTITUT FUR KONJUNKTURFORSCHUNG) EV
Call Details Starting Grant (StG), SH1, ERC-2018-STG
Summary Antibiotics have contributed to a tremendous increase in human well-being, saving many millions of lives. However, antibiotics become obsolete the more they are used as selection pressure promotes the development of resistant bacteria. The World Health Organization has proclaimed antibiotic resistance as a major global threat to public health. Today, 700,000 deaths per year are due to untreatable infections. To win the battle against antibiotic resistance, new policies affecting the supply and demand of existing and new drugs must be designed. I propose new research to identify and evaluate feasible and effective demand-side policy interventions targeting the relevant decision makers: physicians and patients. ABRSEIST will make use of a broad econometric toolset to identify mechanisms linking antibiotic resistance and consumption exploiting a unique combination of physician-patient-level antibiotic resistance, treatment, and socio-economic data. Using machine learning methods adapted for causal inference, theory-driven structural econometric analysis, and randomization in the field it will provide rigorous evidence on effective intervention designs. This research will improve our understanding of how prescribing, resistance, and the effect of antibiotic use on resistance, are distributed in the general population which has important implications for the design of targeted interventions. It will then estimate a structural model of general practitioners’ acquisition and use of information under uncertainty about resistance in prescription choice, allowing counterfactual analysis of information-improving policies such as mandatory diagnostic testing. The large-scale and structural econometric analyses allow flexible identification of physician heterogeneity, which ABRSEIST will exploit to design and evaluate targeted, randomized information nudges in the field. The result will be improved rational use and a toolset applicable in contexts of antibiotic prescribing.
Summary
Antibiotics have contributed to a tremendous increase in human well-being, saving many millions of lives. However, antibiotics become obsolete the more they are used as selection pressure promotes the development of resistant bacteria. The World Health Organization has proclaimed antibiotic resistance as a major global threat to public health. Today, 700,000 deaths per year are due to untreatable infections. To win the battle against antibiotic resistance, new policies affecting the supply and demand of existing and new drugs must be designed. I propose new research to identify and evaluate feasible and effective demand-side policy interventions targeting the relevant decision makers: physicians and patients. ABRSEIST will make use of a broad econometric toolset to identify mechanisms linking antibiotic resistance and consumption exploiting a unique combination of physician-patient-level antibiotic resistance, treatment, and socio-economic data. Using machine learning methods adapted for causal inference, theory-driven structural econometric analysis, and randomization in the field it will provide rigorous evidence on effective intervention designs. This research will improve our understanding of how prescribing, resistance, and the effect of antibiotic use on resistance, are distributed in the general population which has important implications for the design of targeted interventions. It will then estimate a structural model of general practitioners’ acquisition and use of information under uncertainty about resistance in prescription choice, allowing counterfactual analysis of information-improving policies such as mandatory diagnostic testing. The large-scale and structural econometric analyses allow flexible identification of physician heterogeneity, which ABRSEIST will exploit to design and evaluate targeted, randomized information nudges in the field. The result will be improved rational use and a toolset applicable in contexts of antibiotic prescribing.
Max ERC Funding
1 498 920 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ACTOMYO
Project Mechanisms of actomyosin-based contractility during cytokinesis
Researcher (PI) Ana Costa Xavier de Carvalho
Host Institution (HI) INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC
Call Details Starting Grant (StG), LS3, ERC-2014-STG
Summary Cytokinesis completes cell division by partitioning the contents of the mother cell to the two daughter cells. This process is accomplished through the assembly and constriction of a contractile ring, a complex actomyosin network that remains poorly understood on the molecular level. Research in cytokinesis has overwhelmingly focused on signaling mechanisms that dictate when and where the contractile ring is assembled. By contrast, the research I propose here addresses fundamental questions about the structural and functional properties of the contractile ring itself. We will use the nematode C. elegans to exploit the power of quantitative live imaging assays in an experimentally tractable metazoan organism. The early C. elegans embryo is uniquely suited to the study of the contractile ring, as cells dividing perpendicularly to the imaging plane provide a full end-on view of the contractile ring throughout constriction. This greatly facilitates accurate measurements of constriction kinetics, ring width and thickness, and levels as well as dynamics of fluorescently-tagged contractile ring components. Combining image-based assays with powerful molecular replacement technology for structure-function studies, we will 1) determine the contribution of branched and non-branched actin filament populations to contractile ring formation; 2) explore its ultra-structural organization in collaboration with a world expert in electron microcopy; 3) investigate how the contractile ring network is dynamically remodeled during constriction with the help of a novel laser microsurgery assay that has uncovered a remarkably robust ring repair mechanism; and 4) use a targeted RNAi screen and phenotype profiling to identify new components of actomyosin contractile networks. The results from this interdisciplinary project will significantly enhance our mechanistic understanding of cytokinesis and other cellular processes that involve actomyosin-based contractility.
Summary
Cytokinesis completes cell division by partitioning the contents of the mother cell to the two daughter cells. This process is accomplished through the assembly and constriction of a contractile ring, a complex actomyosin network that remains poorly understood on the molecular level. Research in cytokinesis has overwhelmingly focused on signaling mechanisms that dictate when and where the contractile ring is assembled. By contrast, the research I propose here addresses fundamental questions about the structural and functional properties of the contractile ring itself. We will use the nematode C. elegans to exploit the power of quantitative live imaging assays in an experimentally tractable metazoan organism. The early C. elegans embryo is uniquely suited to the study of the contractile ring, as cells dividing perpendicularly to the imaging plane provide a full end-on view of the contractile ring throughout constriction. This greatly facilitates accurate measurements of constriction kinetics, ring width and thickness, and levels as well as dynamics of fluorescently-tagged contractile ring components. Combining image-based assays with powerful molecular replacement technology for structure-function studies, we will 1) determine the contribution of branched and non-branched actin filament populations to contractile ring formation; 2) explore its ultra-structural organization in collaboration with a world expert in electron microcopy; 3) investigate how the contractile ring network is dynamically remodeled during constriction with the help of a novel laser microsurgery assay that has uncovered a remarkably robust ring repair mechanism; and 4) use a targeted RNAi screen and phenotype profiling to identify new components of actomyosin contractile networks. The results from this interdisciplinary project will significantly enhance our mechanistic understanding of cytokinesis and other cellular processes that involve actomyosin-based contractility.
Max ERC Funding
1 499 989 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
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
Project acronym ANYON
Project Engineering and exploring anyonic quantum gases
Researcher (PI) Christof WEITENBERG
Host Institution (HI) UNIVERSITAET HAMBURG
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary This project enters the experimental investigation of anyonic quantum gases. We will study anyons – conjectured particles with a statistical exchange phase anywhere between 0 and π – in different many-body systems. This progress will be enabled by a unique approach of bringing together artificial gauge fields and quantum gas microscopes for ultracold atoms.
Specifically, we will implement the 1D anyon Hubbard model via a lattice shaking protocol that imprints density-dependent Peierls phases. By engineering the statistical exchange phase, we can continuously tune between bosons and fermions and explore a statistically-induced quantum phase transition. We will monitor the continuous fermionization via the build-up of Friedel oscillations. Using state-of-the-art cold atom technology, we will thus open the physics of anyons to experimental research and address open questions related to their fractional exclusion statistics.
Secondly, we will create fractional quantum Hall systems in rapidly rotating microtraps. Using the quantum gas microscope, we will i) control the optical potentials at a level which allows approaching the centrifugal limit and ii) use small atom numbers equal to the inserted angular momentum quantum number. The strongly-correlated ground states such as the Laughlin state can be identified via their characteristic density correlations. Of particular interest are the quasihole excitations, whose predicted anyonic exchange statistics have not been directly observed to date. We will probe and test their statistics via the characteristic counting sequence in the excitation spectrum. Furthermore, we will test ideas to transfer anyonic properties of the excitations to a second tracer species. This approach will enable us to both probe the fractional exclusion statistics of the excitations and to create a 2D anyonic quantum gas.
In the long run, these techniques open a path to also study non-Abelian anyons with ultracold atoms.
Summary
This project enters the experimental investigation of anyonic quantum gases. We will study anyons – conjectured particles with a statistical exchange phase anywhere between 0 and π – in different many-body systems. This progress will be enabled by a unique approach of bringing together artificial gauge fields and quantum gas microscopes for ultracold atoms.
Specifically, we will implement the 1D anyon Hubbard model via a lattice shaking protocol that imprints density-dependent Peierls phases. By engineering the statistical exchange phase, we can continuously tune between bosons and fermions and explore a statistically-induced quantum phase transition. We will monitor the continuous fermionization via the build-up of Friedel oscillations. Using state-of-the-art cold atom technology, we will thus open the physics of anyons to experimental research and address open questions related to their fractional exclusion statistics.
Secondly, we will create fractional quantum Hall systems in rapidly rotating microtraps. Using the quantum gas microscope, we will i) control the optical potentials at a level which allows approaching the centrifugal limit and ii) use small atom numbers equal to the inserted angular momentum quantum number. The strongly-correlated ground states such as the Laughlin state can be identified via their characteristic density correlations. Of particular interest are the quasihole excitations, whose predicted anyonic exchange statistics have not been directly observed to date. We will probe and test their statistics via the characteristic counting sequence in the excitation spectrum. Furthermore, we will test ideas to transfer anyonic properties of the excitations to a second tracer species. This approach will enable us to both probe the fractional exclusion statistics of the excitations and to create a 2D anyonic quantum gas.
In the long run, these techniques open a path to also study non-Abelian anyons with ultracold atoms.
Max ERC Funding
1 497 500 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ApoptoMDS
Project Hematopoietic stem cell Apoptosis in bone marrow failure and MyeloDysplastic Syndromes: Friend or foe?
Researcher (PI) Miriam Erlacher
Host Institution (HI) UNIVERSITAETSKLINIKUM FREIBURG
Call Details Starting Grant (StG), LS4, ERC-2014-STG
Summary Deregulated apoptotic signaling in hematopoietic stem and progenitor cells (HSPCs) strongly contributes to the pathogenesis and phenotypes of congenital bone marrow failure and myelodysplastic syndromes (MDS) and their progression to acute myeloid leukemia (AML). HSPCs are highly susceptible to apoptosis during bone marrow failure and early MDS, but AML evolution selects for apoptosis resistance. Little is known about the main apoptotic players and their regulators. ApoptoMDS will investigate the impact of apoptotic deregulation for pathogenesis, correlate apoptotic susceptibility with the kinetics of disease progression and characterize the mechanism by which apoptotic susceptibility turns into resistance. ApoptoMDS will draw on a large collection of patient-derived samples and genetically engineered mouse models to investigate disease progression in serially transplanted and xenotransplanted mice. How activated DNA damage checkpoint signaling contributes to syndrome phenotypes and HSPC hypersusceptibility to apoptosis will be assessed. Checkpoint activation confers a competitive disadvantage, and HSPCs undergoing malignant transformation are under high selective pressure to inactivate it. Checkpoint abrogation mitigates the hematological phenotype, but increases the risk of AML evolution. ApoptoMDS aims to analyze if inhibiting apoptosis in HSPCs from bone marrow failure and early-stage MDS can overcome the dilemma of checkpoint abrogation. Whether inhibiting apoptosis is sufficient to improve HSPC function will be tested on several levels and validated in patient-derived samples. How inhibiting apoptosis in the presence of functional checkpoint signaling influences malignant transformation kinetics will be assessed. If, as hypothesized, inhibiting apoptosis both mitigates hematological symptoms and delays AML evolution, ApoptoMDS will pave the way for novel therapeutic approaches to expand the less severe symptomatic period for patients with these syndromes.
Summary
Deregulated apoptotic signaling in hematopoietic stem and progenitor cells (HSPCs) strongly contributes to the pathogenesis and phenotypes of congenital bone marrow failure and myelodysplastic syndromes (MDS) and their progression to acute myeloid leukemia (AML). HSPCs are highly susceptible to apoptosis during bone marrow failure and early MDS, but AML evolution selects for apoptosis resistance. Little is known about the main apoptotic players and their regulators. ApoptoMDS will investigate the impact of apoptotic deregulation for pathogenesis, correlate apoptotic susceptibility with the kinetics of disease progression and characterize the mechanism by which apoptotic susceptibility turns into resistance. ApoptoMDS will draw on a large collection of patient-derived samples and genetically engineered mouse models to investigate disease progression in serially transplanted and xenotransplanted mice. How activated DNA damage checkpoint signaling contributes to syndrome phenotypes and HSPC hypersusceptibility to apoptosis will be assessed. Checkpoint activation confers a competitive disadvantage, and HSPCs undergoing malignant transformation are under high selective pressure to inactivate it. Checkpoint abrogation mitigates the hematological phenotype, but increases the risk of AML evolution. ApoptoMDS aims to analyze if inhibiting apoptosis in HSPCs from bone marrow failure and early-stage MDS can overcome the dilemma of checkpoint abrogation. Whether inhibiting apoptosis is sufficient to improve HSPC function will be tested on several levels and validated in patient-derived samples. How inhibiting apoptosis in the presence of functional checkpoint signaling influences malignant transformation kinetics will be assessed. If, as hypothesized, inhibiting apoptosis both mitigates hematological symptoms and delays AML evolution, ApoptoMDS will pave the way for novel therapeutic approaches to expand the less severe symptomatic period for patients with these syndromes.
Max ERC Funding
1 372 525 €
Duration
Start date: 2015-06-01, End date: 2020-05-31
