Project acronym 1D-Engine
Project 1D-electrons coupled to dissipation: a novel approach for understanding and engineering superconducting materials and devices
Researcher (PI) Adrian KANTIAN
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary Correlated electrons are at the forefront of condensed matter theory. Interacting quasi-1D electrons have seen vast progress in analytical and numerical theory, and thus in fundamental understanding and quantitative prediction. Yet, in the 1D limit fluctuations preclude important technological use, particularly of superconductors. In contrast, high-Tc superconductors in 2D/3D are not precluded by fluctuations, but lack a fundamental theory, making prediction and engineering of their properties, a major goal in physics, very difficult. This project aims to combine the advantages of both areas by making major progress in the theory of quasi-1D electrons coupled to an electron bath, in part building on recent breakthroughs (with the PIs extensive involvement) in simulating 1D and 2D electrons with parallelized density matrix renormalization group (pDMRG) numerics. Such theory will fundamentally advance the study of open electron systems, and show how to use 1D materials as elements of new superconducting (SC) devices and materials: 1) It will enable a new state of matter, 1D electrons with true SC order. Fluctuations from the electronic liquid, such as graphene, could also enable nanoscale wires to appear SC at high temperatures. 2) A new approach for the deliberate engineering of a high-Tc superconductor. In 1D, how electrons pair by repulsive interactions is understood and can be predicted. Stabilization by reservoir - formed by a parallel array of many such 1D systems - offers a superconductor for which all factors setting Tc are known and can be optimized. 3) Many existing superconductors with repulsive electron pairing, all presently not understood, can be cast as 1D electrons coupled to a bath. Developing chain-DMFT theory based on pDMRG will allow these materials SC properties to be simulated and understood for the first time. 4) The insights gained will be translated to 2D superconductors to study how they could be enhanced by contact with electronic liquids.
Summary
Correlated electrons are at the forefront of condensed matter theory. Interacting quasi-1D electrons have seen vast progress in analytical and numerical theory, and thus in fundamental understanding and quantitative prediction. Yet, in the 1D limit fluctuations preclude important technological use, particularly of superconductors. In contrast, high-Tc superconductors in 2D/3D are not precluded by fluctuations, but lack a fundamental theory, making prediction and engineering of their properties, a major goal in physics, very difficult. This project aims to combine the advantages of both areas by making major progress in the theory of quasi-1D electrons coupled to an electron bath, in part building on recent breakthroughs (with the PIs extensive involvement) in simulating 1D and 2D electrons with parallelized density matrix renormalization group (pDMRG) numerics. Such theory will fundamentally advance the study of open electron systems, and show how to use 1D materials as elements of new superconducting (SC) devices and materials: 1) It will enable a new state of matter, 1D electrons with true SC order. Fluctuations from the electronic liquid, such as graphene, could also enable nanoscale wires to appear SC at high temperatures. 2) A new approach for the deliberate engineering of a high-Tc superconductor. In 1D, how electrons pair by repulsive interactions is understood and can be predicted. Stabilization by reservoir - formed by a parallel array of many such 1D systems - offers a superconductor for which all factors setting Tc are known and can be optimized. 3) Many existing superconductors with repulsive electron pairing, all presently not understood, can be cast as 1D electrons coupled to a bath. Developing chain-DMFT theory based on pDMRG will allow these materials SC properties to be simulated and understood for the first time. 4) The insights gained will be translated to 2D superconductors to study how they could be enhanced by contact with electronic liquids.
Max ERC Funding
1 491 013 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym 3DMOSHBOND
Project Three-Dimensional Mapping Of a Single Hydrogen Bond
Researcher (PI) Adam Marc SWEETMAN
Host Institution (HI) UNIVERSITY OF LEEDS
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary All properties of matter are ultimately governed by the forces between single atoms, but our knowledge of interatomic, and intermolecular, potentials is often derived indirectly.
In 3DMOSHBOND, I outline a program of work designed to create a paradigm shift in the direct measurement of complex interatomic potentials via a fundamental reimagining of how atomic resolution imaging, and force measurement, techniques are applied.
To provide a clear proof of principle demonstration of the power of this concept, I propose to map the strength, shape and extent of single hydrogen bonding (H-bonding) interactions in 3D with sub-Angstrom precision. H-bonding is a key component governing intermolecular interactions, particularly for biologically important molecules. Despite its critical importance, H-bonding is relatively poorly understood, and the IUPAC definition of the H-bond was changed as recently as 2011- highlighting the relevance of a new means to engage with these fundamental interactions.
Hitherto unprecedented resolution and accuracy will be achieved via a creation of a novel layer of vertically oriented H-bonding molecules, functionalisation of the tip of a scanning probe microscope with a single complementary H-bonding molecule, and by complete characterisation of the position of all atoms in the junction. This will place two H-bonding groups “end on” and map the extent, and magnitude, of the H-bond with sub-Angstrom precision for a variety of systems. This investigation of the H-bond will present us with an unparalleled level of information regarding its properties.
Experimental results will be compared with ab initio density functional theory (DFT) simulations, to investigate the extent to which state-of-the-art simulations are able to reproduce the behaviour of the H-bonding interaction. The project will create a new generalised probe for the study of single atomic and molecular interactions.
Summary
All properties of matter are ultimately governed by the forces between single atoms, but our knowledge of interatomic, and intermolecular, potentials is often derived indirectly.
In 3DMOSHBOND, I outline a program of work designed to create a paradigm shift in the direct measurement of complex interatomic potentials via a fundamental reimagining of how atomic resolution imaging, and force measurement, techniques are applied.
To provide a clear proof of principle demonstration of the power of this concept, I propose to map the strength, shape and extent of single hydrogen bonding (H-bonding) interactions in 3D with sub-Angstrom precision. H-bonding is a key component governing intermolecular interactions, particularly for biologically important molecules. Despite its critical importance, H-bonding is relatively poorly understood, and the IUPAC definition of the H-bond was changed as recently as 2011- highlighting the relevance of a new means to engage with these fundamental interactions.
Hitherto unprecedented resolution and accuracy will be achieved via a creation of a novel layer of vertically oriented H-bonding molecules, functionalisation of the tip of a scanning probe microscope with a single complementary H-bonding molecule, and by complete characterisation of the position of all atoms in the junction. This will place two H-bonding groups “end on” and map the extent, and magnitude, of the H-bond with sub-Angstrom precision for a variety of systems. This investigation of the H-bond will present us with an unparalleled level of information regarding its properties.
Experimental results will be compared with ab initio density functional theory (DFT) simulations, to investigate the extent to which state-of-the-art simulations are able to reproduce the behaviour of the H-bonding interaction. The project will create a new generalised probe for the study of single atomic and molecular interactions.
Max ERC Funding
1 971 468 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym ANTIViR
Project Molecular mechanisms of interferon-induced antiviral restriction and signalling
Researcher (PI) Caroline GOUJON
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Starting Grant (StG), LS6, ERC-2017-STG
Summary Interferons (IFNs), which are signalling proteins produced by infected cells, are the first line of defence against viral infections. IFNs induce, in infected and neighbouring cells, the expression of hundreds of IFN-stimulated genes (ISGs). The ISGs in turn induce in cells a potent antiviral state, capable of preventing replication of most viruses, including Human Immunodeficiency Virus type 1 (HIV-1) and influenza A virus (FLUAV). Identifying the antiviral ISGs and understanding their mechanisms of action is therefore crucial to progress in the fight against viruses.
ISGs playing a role in the antiviral state have been identified, such as human MX1, a well-known antiviral factor able to restrict numerous viruses including FLUAV, and MX2, an HIV-1 inhibitor. Both proteins bind to viral components but their detailed mechanisms of action, as well as the consequences of restriction on the activation of the innate immune system, remain unclear. Moreover, our preliminary work shows that additional anti-HIV-1 and anti-FLUAV ISGs remain to identify.
In this context, this proposal seeks an ERC StG funding to explore 3 major aims: 1) unravelling the mechanisms of antiviral action of MX proteins, by taking advantage of their similar structure and engineered chimeric proteins, and by using functional genetic screens to identify their cofactors; 2) investigating the consequences of incoming virus recognition by MX proteins on innate immune signalling, by altering their expression in target cells and measuring the cell response in terms of gene induction and cytokine production; 3) identifying and characterizing new ISGs able to inhibit viral replication with a combination of powerful approaches, including a whole-genome CRISPR/Cas9 knock-out screen.
Overall, this proposal will provide a better understanding of the molecular mechanisms involved in the antiviral effect of IFN, and may guide future efforts to identify novel therapeutic targets against major pathogenic viruses.
Summary
Interferons (IFNs), which are signalling proteins produced by infected cells, are the first line of defence against viral infections. IFNs induce, in infected and neighbouring cells, the expression of hundreds of IFN-stimulated genes (ISGs). The ISGs in turn induce in cells a potent antiviral state, capable of preventing replication of most viruses, including Human Immunodeficiency Virus type 1 (HIV-1) and influenza A virus (FLUAV). Identifying the antiviral ISGs and understanding their mechanisms of action is therefore crucial to progress in the fight against viruses.
ISGs playing a role in the antiviral state have been identified, such as human MX1, a well-known antiviral factor able to restrict numerous viruses including FLUAV, and MX2, an HIV-1 inhibitor. Both proteins bind to viral components but their detailed mechanisms of action, as well as the consequences of restriction on the activation of the innate immune system, remain unclear. Moreover, our preliminary work shows that additional anti-HIV-1 and anti-FLUAV ISGs remain to identify.
In this context, this proposal seeks an ERC StG funding to explore 3 major aims: 1) unravelling the mechanisms of antiviral action of MX proteins, by taking advantage of their similar structure and engineered chimeric proteins, and by using functional genetic screens to identify their cofactors; 2) investigating the consequences of incoming virus recognition by MX proteins on innate immune signalling, by altering their expression in target cells and measuring the cell response in terms of gene induction and cytokine production; 3) identifying and characterizing new ISGs able to inhibit viral replication with a combination of powerful approaches, including a whole-genome CRISPR/Cas9 knock-out screen.
Overall, this proposal will provide a better understanding of the molecular mechanisms involved in the antiviral effect of IFN, and may guide future efforts to identify novel therapeutic targets against major pathogenic viruses.
Max ERC Funding
1 499 794 €
Duration
Start date: 2017-12-01, End date: 2022-11-30
Project acronym AUTISMS
Project Decomposing Heterogeneity in Autism Spectrum Disorders
Researcher (PI) Michael LOMBARDO
Host Institution (HI) FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Call Details Starting Grant (StG), SH4, ERC-2017-STG
Summary Autism spectrum disorders (ASD) affect 1-2% of the population and are a major public health issue. Heterogeneity between affected ASD individuals is substantial both at clinical and etiological levels, thus warranting the idea that we should begin characterizing the ASD population as multiple kinds of ‘autisms’. Without an advanced understanding of how heterogeneity manifests in ASD, it is likely that we will not make pronounced progress towards translational research goals that can have real impact on patient’s lives. This research program is focused on decomposing heterogeneity in ASD at multiple levels of analysis. Using multiple ‘big data’ resources that are both ‘broad’ (large sample size) and ‘deep’ (multiple levels of analysis measured within each individual), I will examine how known variables such as sex, early language development, early social preferences, and early intervention treatment response may be important stratification variables that differentiate ASD subgroups at phenotypic, neural systems/circuits, and genomic levels of analysis. In addition to examining known stratification variables, this research program will engage in data-driven discovery via application of advanced unsupervised computational techniques that can highlight novel multivariate distinctions in the data that signal important ASD subgroups. These data-driven approaches may hold promise for discovering novel ASD subgroups at biological and phenotypic levels of analysis that may be valuable for prioritization in future work developing personalized assessment, monitoring, and treatment strategies for subsets of the ASD population. By enhancing the precision of our understanding about multiple subtypes of ASD this work will help accelerate progress towards the ideals of personalized medicine and help to reduce the burden of ASD on individuals, families, and society.
Summary
Autism spectrum disorders (ASD) affect 1-2% of the population and are a major public health issue. Heterogeneity between affected ASD individuals is substantial both at clinical and etiological levels, thus warranting the idea that we should begin characterizing the ASD population as multiple kinds of ‘autisms’. Without an advanced understanding of how heterogeneity manifests in ASD, it is likely that we will not make pronounced progress towards translational research goals that can have real impact on patient’s lives. This research program is focused on decomposing heterogeneity in ASD at multiple levels of analysis. Using multiple ‘big data’ resources that are both ‘broad’ (large sample size) and ‘deep’ (multiple levels of analysis measured within each individual), I will examine how known variables such as sex, early language development, early social preferences, and early intervention treatment response may be important stratification variables that differentiate ASD subgroups at phenotypic, neural systems/circuits, and genomic levels of analysis. In addition to examining known stratification variables, this research program will engage in data-driven discovery via application of advanced unsupervised computational techniques that can highlight novel multivariate distinctions in the data that signal important ASD subgroups. These data-driven approaches may hold promise for discovering novel ASD subgroups at biological and phenotypic levels of analysis that may be valuable for prioritization in future work developing personalized assessment, monitoring, and treatment strategies for subsets of the ASD population. By enhancing the precision of our understanding about multiple subtypes of ASD this work will help accelerate progress towards the ideals of personalized medicine and help to reduce the burden of ASD on individuals, families, and society.
Max ERC Funding
1 499 444 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym BETLIV
Project Returning to a Better Place: The (Re)assessment of the ‘Good Life’ in Times of Crisis
Researcher (PI) Valerio SIMONI RIBA
Host Institution (HI) FONDATION POUR L INSTITUT DE HAUTES ETUDES INTERNATIONALES ET DU DEVELOPPEMENT
Call Details Starting Grant (StG), SH5, ERC-2017-STG
Summary What makes for a valuable and good life is a question that many people in the contemporary world ask themselves, yet it is one that social science research has seldom addressed. Only recently have scholars started undertaking inductive comparative research on different notions of the ‘good life’, highlighting socio-cultural variations and calling for a better understanding of the different imaginaries, aspirations and values that guide people in their quest for better living conditions. Research is still lacking, however, on how people themselves evaluate, compare, and put into perspective different visions of good living and their socio-cultural anchorage. This project addresses such questions from an anthropological perspective, proposing an innovative study of how ideals of the good life are articulated, (re)assessed, and related to specific places and contexts as a result of the experience of crisis and migration. The case studies chosen to operationalize these lines of enquiry focus on the phenomenon of return migration, and consist in an analysis of the imaginaries and experience of return by Ecuadorian and Cuban men and women who migrated to Spain, are dissatisfied with their life there, and envisage/carry out the project of going back to their countries of origin (Ecuador and Cuba respectively). The project’s ambition is to bring together and contribute to three main scholarly areas of enquiry: 1) the study of morality, ethics and what counts as ‘good life’, 2) the study of the field of economic practice, its definition, value regimes, and ‘crises’, and 3) the study of migratory aspirations, projects, and trajectories. A multi-sited endeavour, the research is designed in three subprojects carried out in Spain (PhD student), Ecuador (Post-Doc), and Cuba (PI), in which ethnographic methods will be used to provide the first empirically grounded study of the links between notions and experiences of crisis, return migration, and the (re)assessment of good living.
Summary
What makes for a valuable and good life is a question that many people in the contemporary world ask themselves, yet it is one that social science research has seldom addressed. Only recently have scholars started undertaking inductive comparative research on different notions of the ‘good life’, highlighting socio-cultural variations and calling for a better understanding of the different imaginaries, aspirations and values that guide people in their quest for better living conditions. Research is still lacking, however, on how people themselves evaluate, compare, and put into perspective different visions of good living and their socio-cultural anchorage. This project addresses such questions from an anthropological perspective, proposing an innovative study of how ideals of the good life are articulated, (re)assessed, and related to specific places and contexts as a result of the experience of crisis and migration. The case studies chosen to operationalize these lines of enquiry focus on the phenomenon of return migration, and consist in an analysis of the imaginaries and experience of return by Ecuadorian and Cuban men and women who migrated to Spain, are dissatisfied with their life there, and envisage/carry out the project of going back to their countries of origin (Ecuador and Cuba respectively). The project’s ambition is to bring together and contribute to three main scholarly areas of enquiry: 1) the study of morality, ethics and what counts as ‘good life’, 2) the study of the field of economic practice, its definition, value regimes, and ‘crises’, and 3) the study of migratory aspirations, projects, and trajectories. A multi-sited endeavour, the research is designed in three subprojects carried out in Spain (PhD student), Ecuador (Post-Doc), and Cuba (PI), in which ethnographic methods will be used to provide the first empirically grounded study of the links between notions and experiences of crisis, return migration, and the (re)assessment of good living.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym Brain2Bee
Project How dopamine affects social and motor ability - from the human brain to the honey bee
Researcher (PI) Jennifer COOK
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Call Details Starting Grant (StG), SH4, ERC-2017-STG
Summary Parkinson’s Disease is usually characterised by motor impairment, and Autism by social difficulties. However, the co-occurrence of social and motor symptoms is critically underappreciated; Parkinson’s Disease patients exhibit social symptoms, and motor difficulties are common in Autism. At present, the biological basis of co-occurring social and motor impairment is unclear. Notably, both Autism and Parkinson’s Disease have been associated with dopamine (DA) system dysfunction and, in non-clinical populations, DA has been linked with social and motor ability. These disparate strands of research have never been combined.
Brain2Bee will use psychopharmacology in typical individuals to develop a model of the relationship between DA, Motor, and Social behaviour – the DAMS model. Brain2Bee will use sophisticated genetic analysis to refine DAMS, elucidating the contributions of DA-related biological processes (e.g. synthesis, receptor expression, reuptake). Brain2Bee will then test DAMS’ predictions in patients with Parkinson’s Disease and Autism. Finally, Brain2Bee will investigate whether DAMS generalises to an animal model, the honey bee, enabling future research to unpack the cascade of biological events linking DA-related genes with social and motor behaviour.
Brain2Bee will unite disparate research fields and establish the DAMS model. The causal structure of DAMS will identify the impact of dopaminergic variation on social and motor function in clinical and non-clinical populations, elucidating, for example, whether social difficulties in Parkinson’s Disease are a product of the motor difficulties caused by DA dysfunction. DAMS’ biological specificity will provide unique insight into the DA-related processes linking social and motor difficulties in Autism. Thus, Brain2Bee will determine the type of dopaminergic drugs (e.g. receptor blockers, reuptake inhibitors) most likely to improve both social and motor function.
Summary
Parkinson’s Disease is usually characterised by motor impairment, and Autism by social difficulties. However, the co-occurrence of social and motor symptoms is critically underappreciated; Parkinson’s Disease patients exhibit social symptoms, and motor difficulties are common in Autism. At present, the biological basis of co-occurring social and motor impairment is unclear. Notably, both Autism and Parkinson’s Disease have been associated with dopamine (DA) system dysfunction and, in non-clinical populations, DA has been linked with social and motor ability. These disparate strands of research have never been combined.
Brain2Bee will use psychopharmacology in typical individuals to develop a model of the relationship between DA, Motor, and Social behaviour – the DAMS model. Brain2Bee will use sophisticated genetic analysis to refine DAMS, elucidating the contributions of DA-related biological processes (e.g. synthesis, receptor expression, reuptake). Brain2Bee will then test DAMS’ predictions in patients with Parkinson’s Disease and Autism. Finally, Brain2Bee will investigate whether DAMS generalises to an animal model, the honey bee, enabling future research to unpack the cascade of biological events linking DA-related genes with social and motor behaviour.
Brain2Bee will unite disparate research fields and establish the DAMS model. The causal structure of DAMS will identify the impact of dopaminergic variation on social and motor function in clinical and non-clinical populations, elucidating, for example, whether social difficulties in Parkinson’s Disease are a product of the motor difficulties caused by DA dysfunction. DAMS’ biological specificity will provide unique insight into the DA-related processes linking social and motor difficulties in Autism. Thus, Brain2Bee will determine the type of dopaminergic drugs (e.g. receptor blockers, reuptake inhibitors) most likely to improve both social and motor function.
Max ERC Funding
1 783 147 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym CALLIOPE
Project voCAL articuLations Of Parliamentary Identity and Empire
Researcher (PI) Josephine HOEGAERTS
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), SH5, ERC-2017-STG
Summary What did politicians sound like before they were on the radio and television? The fascination with politicians’ vocal characteristics and quirks is often connected to the rise of audio-visual media. But in the age of the printed press, political representatives also had to ‘speak well’ – without recourse to amplification.
Historians and linguists have provided sophisticated understandings of the discursive and aesthetic aspects of politicians’ language, but have largely ignored the importance of the acoustic character of their speech. CALLIOPE studies how vocal performances in parliament have influenced the course of political careers and political decision making in the 19th century. It shows how politicians’ voices helped to define the diverse identities they articulated. In viewing parliament through the lens of audibility, the project offers a new perspective on political representation by reframing how authority was embodied (through performances that were heard, rather than seen). It does so for the Second Chamber in Britain and France, and in dialogue with ‘colonial’ modes of speech in Kolkata and Algiers, which, we argue, exerted considerable influence on European vocal culture.
The project devises an innovative methodological approach to include the sound of the human voice in studies of the past that precede acoustic recording. Adapting methods developed in sound studies and combining them with the tools of political history, the project proposes a new way to analyse parliamentary reporting, while also drawing on a variety of sources that are rarely connected to the history of politics.
The main source material for the study comprise transcripts of parliamentary speech (official reports and renditions by journalists). However, the project also mobilizes educational, satirical and fictional sources to elucidate the convoluted processes that led to the cultivation, exertion, reception and evaluation of a voice ‘fit’ for nineteenth-century politics.
Summary
What did politicians sound like before they were on the radio and television? The fascination with politicians’ vocal characteristics and quirks is often connected to the rise of audio-visual media. But in the age of the printed press, political representatives also had to ‘speak well’ – without recourse to amplification.
Historians and linguists have provided sophisticated understandings of the discursive and aesthetic aspects of politicians’ language, but have largely ignored the importance of the acoustic character of their speech. CALLIOPE studies how vocal performances in parliament have influenced the course of political careers and political decision making in the 19th century. It shows how politicians’ voices helped to define the diverse identities they articulated. In viewing parliament through the lens of audibility, the project offers a new perspective on political representation by reframing how authority was embodied (through performances that were heard, rather than seen). It does so for the Second Chamber in Britain and France, and in dialogue with ‘colonial’ modes of speech in Kolkata and Algiers, which, we argue, exerted considerable influence on European vocal culture.
The project devises an innovative methodological approach to include the sound of the human voice in studies of the past that precede acoustic recording. Adapting methods developed in sound studies and combining them with the tools of political history, the project proposes a new way to analyse parliamentary reporting, while also drawing on a variety of sources that are rarely connected to the history of politics.
The main source material for the study comprise transcripts of parliamentary speech (official reports and renditions by journalists). However, the project also mobilizes educational, satirical and fictional sources to elucidate the convoluted processes that led to the cultivation, exertion, reception and evaluation of a voice ‘fit’ for nineteenth-century politics.
Max ERC Funding
1 499 905 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym CANCER-DC
Project Dissecting Regulatory Networks That Mediate Dendritic Cell Suppression
Researcher (PI) Oren PARNAS
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), LS6, ERC-2017-STG
Summary Recent advances have shown that therapeutic manipulations of key cell-cell interactions can have dramatic clinical outcomes. Most notable are several early successes in cancer immunotherapy that target the tumor-T cell interface. However, these successes were only partial. This is likely because the few known interactions are just a few pieces of a much larger puzzle, involving additional signaling molecules and cell types. Dendritic cells (DCs), play critical roles in the induction/suppression of T cells. At early cancer stages, DCs capture tumor antigens and present them to T cells. However, in advanced cancers, the tumor microenvironment (TME) disrupts the crosstalk between DCs and T cells.
We will take a multi-step approach to explore how the TME imposes a suppressive effect on DCs and how to reverse this hazardous effect. First, we will use single cell RNA-seq to search for genes in aggressive human and mouse ovarian tumors that are highly expressed in advanced tumors compared to early tumors and that encode molecules that suppress DC activity. Second, we will design a set of CRISPR screens to find genes that are expressed in DCs and regulate the transfer of the suppressive signals. The screens will be performed in the presence of suppressive molecules to mimic the TME and are expected to uncover many key genes in DCs biology. We will develop a new strategy to find synergistic combinations of genes to target (named Perturb-comb), thereby reversing the effect of local tumor immunosuppressive signals. Lastly, we will examine the effect of modified DCs on T cell activation and proliferation in-vivo, and on tumor growth.
We expect to find: (1) Signaling molecules in the TME that affect the immune system. (2) New cytokines and cell surface receptors that are expressed in DCs and signal to T cells. (3) New key regulators in DC biology and their mechanisms. (4) Combinations of genes to target in DCs that reverse the TME’s hazardous effects.
Summary
Recent advances have shown that therapeutic manipulations of key cell-cell interactions can have dramatic clinical outcomes. Most notable are several early successes in cancer immunotherapy that target the tumor-T cell interface. However, these successes were only partial. This is likely because the few known interactions are just a few pieces of a much larger puzzle, involving additional signaling molecules and cell types. Dendritic cells (DCs), play critical roles in the induction/suppression of T cells. At early cancer stages, DCs capture tumor antigens and present them to T cells. However, in advanced cancers, the tumor microenvironment (TME) disrupts the crosstalk between DCs and T cells.
We will take a multi-step approach to explore how the TME imposes a suppressive effect on DCs and how to reverse this hazardous effect. First, we will use single cell RNA-seq to search for genes in aggressive human and mouse ovarian tumors that are highly expressed in advanced tumors compared to early tumors and that encode molecules that suppress DC activity. Second, we will design a set of CRISPR screens to find genes that are expressed in DCs and regulate the transfer of the suppressive signals. The screens will be performed in the presence of suppressive molecules to mimic the TME and are expected to uncover many key genes in DCs biology. We will develop a new strategy to find synergistic combinations of genes to target (named Perturb-comb), thereby reversing the effect of local tumor immunosuppressive signals. Lastly, we will examine the effect of modified DCs on T cell activation and proliferation in-vivo, and on tumor growth.
We expect to find: (1) Signaling molecules in the TME that affect the immune system. (2) New cytokines and cell surface receptors that are expressed in DCs and signal to T cells. (3) New key regulators in DC biology and their mechanisms. (4) Combinations of genes to target in DCs that reverse the TME’s hazardous effects.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym CASTLES
Project Charge And Spin in TopologicaL Edge States
Researcher (PI) ERWANN YANN EMILE BOCQUILLON
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary Topology provides mathematical tools to sort objects according to global properties regardless of local details, and manifests itself in various fields of physics. In solid-state physics, specific topological properties of the band structure, such as a band inversion, can for example robustly enforce the appearance of spin-polarized conducting states at the boundaries of the material, while its bulk remains insulating. The boundary states of these ‘topological insulators’ in fact provide a support system to encode information non-locally in ‘topological quantum bits’ robust to local perturbations. The emerging ‘topological quantum computation’ is as such an envisioned solution to decoherence problems in the realization of quantum computers. Despite immense theoretical and experimental efforts, the rise of these new materials has however been hampered by strong difficulties to observe robust and clear signatures of their predicted properties such as spin-polarization or perfect conductance.
These challenges strongly motivate my proposal to study two-dimensional topological insulators, and in particular explore the unknown dynamics of their topological edge states in normal and superconducting regimes. First it is possible to capture information both on charge and spin dynamics, and more clearly highlight the basic properties of topological edge states. Second, the dynamics reveals the effects of Coulomb interactions, an unexplored aspect that may explain the fragility of topological edge states. Finally, it enables the manipulation and characterization of quantum states on short time scales, relevant to quantum information processing. This project relies on the powerful toolbox offered by radiofrequency and current-correlations techniques and promises to open a new field of dynamical explorations of topological materials.
Summary
Topology provides mathematical tools to sort objects according to global properties regardless of local details, and manifests itself in various fields of physics. In solid-state physics, specific topological properties of the band structure, such as a band inversion, can for example robustly enforce the appearance of spin-polarized conducting states at the boundaries of the material, while its bulk remains insulating. The boundary states of these ‘topological insulators’ in fact provide a support system to encode information non-locally in ‘topological quantum bits’ robust to local perturbations. The emerging ‘topological quantum computation’ is as such an envisioned solution to decoherence problems in the realization of quantum computers. Despite immense theoretical and experimental efforts, the rise of these new materials has however been hampered by strong difficulties to observe robust and clear signatures of their predicted properties such as spin-polarization or perfect conductance.
These challenges strongly motivate my proposal to study two-dimensional topological insulators, and in particular explore the unknown dynamics of their topological edge states in normal and superconducting regimes. First it is possible to capture information both on charge and spin dynamics, and more clearly highlight the basic properties of topological edge states. Second, the dynamics reveals the effects of Coulomb interactions, an unexplored aspect that may explain the fragility of topological edge states. Finally, it enables the manipulation and characterization of quantum states on short time scales, relevant to quantum information processing. This project relies on the powerful toolbox offered by radiofrequency and current-correlations techniques and promises to open a new field of dynamical explorations of topological materials.
Max ERC Funding
1 499 940 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym COGNAP
Project To nap or not to nap? Why napping habits interfere with cognitive fitness in ageing
Researcher (PI) Christina Hildegard SCHMIDT
Host Institution (HI) UNIVERSITE DE LIEGE
Call Details Starting Grant (StG), SH4, ERC-2017-STG
Summary All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.
Summary
All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.
Max ERC Funding
1 499 125 €
Duration
Start date: 2018-01-01, End date: 2022-12-31