Project acronym B-response
Project Memory and innate-like B-cell subsets: deciphering a multi-layered B-cell response in mice and humans
Researcher (PI) Claude-Agnes REYNAUD
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Advanced Grant (AdG), LS6, ERC-2015-AdG
Summary B cells are the main actors of successful vaccines, and their protective capacity relies on several subsets with innate-like and memory properties that fulfill different effector functions. In the present project, we wish to develop approaches in both mice and humans, to confront the similarities and the differences of their B cell responses.
The three aims proposed are:
1) To study the different B cell subsets and TFH cells engaged in a memory response through the use of a new mouse reporter line allowing their irreversible labeling (inducible Cre recombinase under the control of the Bcl6 gene): this will be performed in different conditions of TH1 vs. TH2 polarization, as well as during a chronic viral infection, in which virus-specific antibodies have been shown to be required to control the disease (in collaboration with D. Pinschewer, Basel)
2) To study whether the lifelong persistence of B cell memory, as occurs for memory B cells against smallpox that we can obtain at high purity from aged donor's spleens, corresponds to a specific transcriptional program at the miRNA, lncRNA or mRNA level, as well as a specific cell homeostasis
3) To discriminate the specific effector function of human marginal zone and IgM memory B cells in, respectively, T-independent and T-dependent responses, as well as their specific differentiation/diversification pathway.
The general goal is to delineate the regulatory pathways leading to the activation and persistence of the different B cell subsets, allowing for a better understanding of the conditions leading to their pathological or beneficial mobilization.
Summary
B cells are the main actors of successful vaccines, and their protective capacity relies on several subsets with innate-like and memory properties that fulfill different effector functions. In the present project, we wish to develop approaches in both mice and humans, to confront the similarities and the differences of their B cell responses.
The three aims proposed are:
1) To study the different B cell subsets and TFH cells engaged in a memory response through the use of a new mouse reporter line allowing their irreversible labeling (inducible Cre recombinase under the control of the Bcl6 gene): this will be performed in different conditions of TH1 vs. TH2 polarization, as well as during a chronic viral infection, in which virus-specific antibodies have been shown to be required to control the disease (in collaboration with D. Pinschewer, Basel)
2) To study whether the lifelong persistence of B cell memory, as occurs for memory B cells against smallpox that we can obtain at high purity from aged donor's spleens, corresponds to a specific transcriptional program at the miRNA, lncRNA or mRNA level, as well as a specific cell homeostasis
3) To discriminate the specific effector function of human marginal zone and IgM memory B cells in, respectively, T-independent and T-dependent responses, as well as their specific differentiation/diversification pathway.
The general goal is to delineate the regulatory pathways leading to the activation and persistence of the different B cell subsets, allowing for a better understanding of the conditions leading to their pathological or beneficial mobilization.
Max ERC Funding
2 098 750 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym CHAMPAGNE
Project Charge orders, Magnetism and Pairings in High Temperature Superconductors
Researcher (PI) Catherine, Marie, Elisabeth PEPIN
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Advanced Grant (AdG), PE3, ERC-2015-AdG
Summary For nearly thirty years, the search for a room-temperature superconductor has focused on exotic materials known as cuprates, obtained by doping a parent Mott insulator, and which can carry currents without losing energy as heat at temperatures up to 164 Kelvin. Conventionally three main players were identified as being crucial i) the Mott insulating phase, ii) the anti-ferromagnetic order and iii) the superconducting (SC) phase. Recently a body of experimental probes suggested the presence of a fourth forgotten player, charge ordering-, as a direct competitor for superconductivity. In this project we propose that the relationship between charge ordering and superconductivity is more intimate than previously thought and is protected by an emerging SU(2) symmetry relating the two. The beauty of our theory resides in that it can be encapsulated in one simple and universal “gap equation”, which in contrast to strong coupling approaches used up to now, can easily be connected to experiments. In the first part of this work, we will refine the theoretical model in order to shape it for comparison with experiments and consistently test the SU(2) symmetry. In the second part of the work, we will search for the experimental signatures of our theory through a back and forth interaction with experimental groups. We expect our theory to generate new insights and experimental developments, and to lead to a major breakthrough if it correctly explains the origin of anomalous superconductivity in these materials.
Summary
For nearly thirty years, the search for a room-temperature superconductor has focused on exotic materials known as cuprates, obtained by doping a parent Mott insulator, and which can carry currents without losing energy as heat at temperatures up to 164 Kelvin. Conventionally three main players were identified as being crucial i) the Mott insulating phase, ii) the anti-ferromagnetic order and iii) the superconducting (SC) phase. Recently a body of experimental probes suggested the presence of a fourth forgotten player, charge ordering-, as a direct competitor for superconductivity. In this project we propose that the relationship between charge ordering and superconductivity is more intimate than previously thought and is protected by an emerging SU(2) symmetry relating the two. The beauty of our theory resides in that it can be encapsulated in one simple and universal “gap equation”, which in contrast to strong coupling approaches used up to now, can easily be connected to experiments. In the first part of this work, we will refine the theoretical model in order to shape it for comparison with experiments and consistently test the SU(2) symmetry. In the second part of the work, we will search for the experimental signatures of our theory through a back and forth interaction with experimental groups. We expect our theory to generate new insights and experimental developments, and to lead to a major breakthrough if it correctly explains the origin of anomalous superconductivity in these materials.
Max ERC Funding
1 318 145 €
Duration
Start date: 2016-08-01, End date: 2021-07-31
Project acronym chemech
Project From Chemical Bond Forces and Breakage to Macroscopic Fracture of Soft Materials
Researcher (PI) Costantino CRETON
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), PE5, ERC-2015-AdG
Summary Soft materials are irreplaceable in engineering applications where large reversible deformations are needed, and in life sciences to mimic ever more closely or replace a variety of living tissues. While mechanical strength may not be essential for all applications, excessive brittleness is a strong limitation. Yet predicting if a soft material will be tough or brittle from its molecular composition or structure relies on empirical concepts due to the lack of proper tools to detect the damage occurring to the material before it breaks. Taking advantage of the recent advances in materials science and mechanochemistry, we propose a ground-breaking method to investigate the mechanisms of fracture of tough soft materials. To achieve this objective we will use a series of model materials containing a variable population of internal sacrificial bonds that break before the material fails macroscopically, and use a combination of advanced characterization techniques and molecular probes to map stress, strain, bond breakage and structure in a region ~100 µm in size ahead of the propagating crack. By using mechanoluminescent and mechanophore molecules incorporated in the model material in selected positions, confocal laser microscopy, digital image correlation and small-angle X-ray scattering we will gain an unprecedented molecular understanding of where and when bonds break as the material fails and the crack propagates, and will then be able to establish a direct relation between the architecture of soft polymer networks and their fracture energy, leading to a new molecular and multi-scale vision of macroscopic fracture of soft materials. Such advances will be invaluable to guide materials chemists to design and develop better and more finely tuned soft but tough and sometimes self-healing materials to replace living tissues (in bio engineering) and make lightweight tough and flexible parts for energy efficient transport.
Summary
Soft materials are irreplaceable in engineering applications where large reversible deformations are needed, and in life sciences to mimic ever more closely or replace a variety of living tissues. While mechanical strength may not be essential for all applications, excessive brittleness is a strong limitation. Yet predicting if a soft material will be tough or brittle from its molecular composition or structure relies on empirical concepts due to the lack of proper tools to detect the damage occurring to the material before it breaks. Taking advantage of the recent advances in materials science and mechanochemistry, we propose a ground-breaking method to investigate the mechanisms of fracture of tough soft materials. To achieve this objective we will use a series of model materials containing a variable population of internal sacrificial bonds that break before the material fails macroscopically, and use a combination of advanced characterization techniques and molecular probes to map stress, strain, bond breakage and structure in a region ~100 µm in size ahead of the propagating crack. By using mechanoluminescent and mechanophore molecules incorporated in the model material in selected positions, confocal laser microscopy, digital image correlation and small-angle X-ray scattering we will gain an unprecedented molecular understanding of where and when bonds break as the material fails and the crack propagates, and will then be able to establish a direct relation between the architecture of soft polymer networks and their fracture energy, leading to a new molecular and multi-scale vision of macroscopic fracture of soft materials. Such advances will be invaluable to guide materials chemists to design and develop better and more finely tuned soft but tough and sometimes self-healing materials to replace living tissues (in bio engineering) and make lightweight tough and flexible parts for energy efficient transport.
Max ERC Funding
2 251 026 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym ILC_REACTIVITY
Project Biological Determinants of ILC Reactivity for Immune Responses in Health and Disease
Researcher (PI) James DI SANTO
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Advanced Grant (AdG), LS6, ERC-2015-AdG
Summary Innate lymphoid cells (ILC) are a newly described family of hematopoietic cells that lack antigen-specific receptors but can be activated to promptly produce large amounts of cytokines (including interleukin (IL)-5, -13, -17A, -22, TNF-α and interferon-γ) and thereby contribute to the immediate, first-line immune defense against viral, bacterial, and parasitic infections. ILCs include the previously described natural killer (NK) cells and have a similar 'natural' effector function which is immediately available during immune responses and prior to that of adaptive immunity. Three groups of ILC (ILC1, ILC2, ILC3) have been described that share biological activities of T helper (Th)1, Th2 and Th17/22 subsets and CTL. ILCs are active during both fetal and adult life and play important roles in the homeostasis of mucosal and non-mucosal tissues. Nevertheless, how ILCs are integrated into ongoing immune responses remains unclear and this knowledge is a prerequisite for harnessing the clinical potential of these immune effector cells. This proposal will investigate critical checkpoints that can regulate ILC reactivity for immune responses in humans and mice. The four proposed objectives will be addressed using a combination of cutting-edge technologies including innovative mouse models that can report on ILC biology in vivo, single cell transcriptional and functional analysis of diverse circulating and tissue human and mouse ILC subsets, ‘digital’ pathogen-dependent ILC activation approaches and computational analysis of large immunological datasets from healthy, normal human individuals. Collectively, these complementary studies will shed new light on the biological determinants which condition ILC reactivity in humans and mice. Understanding how the threshold of ILC responsiveness is set prior to and during immune responses will have important implications for disease intervention.
Summary
Innate lymphoid cells (ILC) are a newly described family of hematopoietic cells that lack antigen-specific receptors but can be activated to promptly produce large amounts of cytokines (including interleukin (IL)-5, -13, -17A, -22, TNF-α and interferon-γ) and thereby contribute to the immediate, first-line immune defense against viral, bacterial, and parasitic infections. ILCs include the previously described natural killer (NK) cells and have a similar 'natural' effector function which is immediately available during immune responses and prior to that of adaptive immunity. Three groups of ILC (ILC1, ILC2, ILC3) have been described that share biological activities of T helper (Th)1, Th2 and Th17/22 subsets and CTL. ILCs are active during both fetal and adult life and play important roles in the homeostasis of mucosal and non-mucosal tissues. Nevertheless, how ILCs are integrated into ongoing immune responses remains unclear and this knowledge is a prerequisite for harnessing the clinical potential of these immune effector cells. This proposal will investigate critical checkpoints that can regulate ILC reactivity for immune responses in humans and mice. The four proposed objectives will be addressed using a combination of cutting-edge technologies including innovative mouse models that can report on ILC biology in vivo, single cell transcriptional and functional analysis of diverse circulating and tissue human and mouse ILC subsets, ‘digital’ pathogen-dependent ILC activation approaches and computational analysis of large immunological datasets from healthy, normal human individuals. Collectively, these complementary studies will shed new light on the biological determinants which condition ILC reactivity in humans and mice. Understanding how the threshold of ILC responsiveness is set prior to and during immune responses will have important implications for disease intervention.
Max ERC Funding
1 899 375 €
Duration
Start date: 2016-08-01, End date: 2021-07-31
Project acronym MONACAT
Project Magnetism and Optics for Nanoparticle Catalysis
Researcher (PI) Bruno CHAUDRET
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), PE5, ERC-2015-AdG
Summary MONACAT proposes a novel approach to address the challenge of intermittent energy storage. Specifically, the purpose is to conceive and synthesize novel complex nano-objects displaying both physical and chemical properties that enable catalytic transformations with a fast and optimum energy conversion. It follows over 20 years of research on “organometallic nanoparticles”, an approach of nanoparticles (NPs) synthesis where the first goal is to control the surface of the particles as in molecular organometallic species. Two families of NPs will be studied: 1) magnetic NPs that can be heated by excitation with an alternating magnetic field and 2) plasmonic NPs that absorb visible light and transform it into heat. In all cases, deposition of additional materials as islands or thin layers will improve the NPs catalytic activity. Iron carbides NPs have recently been shown to heat efficiently upon magnetic excitation and to catalyse CO hydrogenation into hydrocarbons. In order to transform this observation into a viable process, MONACAT will address the following challenges: determination and control of surface temperature using fluorophores or quantum dots, optimization of heating capacity (size, anisotropy of the material, crystallinity, phases: FeCo, FeNi, chemical order), optimization of catalytic properties (islands vs core-shell structures; Ru, Ni for methane, Cu/Zn for methanol), stability and optimization of energy efficiency. A similar approach will be used for direct light conversion using as first proofs of concept Au or Ag NPs coated with Ru. Catalytic tests will be performed on two heterogeneous reactions after deposition of the NPs onto a support: CO2 hydrogenation into methane and methanol synthesis. In addition, the potential of catalysis making use of self-heated and magnetically recoverable NPs will be studied in solution (reduction of arenes or oxygenated functions, hydrogenation and hydrogenolysis of biomass platform molecules, Fischer-Tropsch).
Summary
MONACAT proposes a novel approach to address the challenge of intermittent energy storage. Specifically, the purpose is to conceive and synthesize novel complex nano-objects displaying both physical and chemical properties that enable catalytic transformations with a fast and optimum energy conversion. It follows over 20 years of research on “organometallic nanoparticles”, an approach of nanoparticles (NPs) synthesis where the first goal is to control the surface of the particles as in molecular organometallic species. Two families of NPs will be studied: 1) magnetic NPs that can be heated by excitation with an alternating magnetic field and 2) plasmonic NPs that absorb visible light and transform it into heat. In all cases, deposition of additional materials as islands or thin layers will improve the NPs catalytic activity. Iron carbides NPs have recently been shown to heat efficiently upon magnetic excitation and to catalyse CO hydrogenation into hydrocarbons. In order to transform this observation into a viable process, MONACAT will address the following challenges: determination and control of surface temperature using fluorophores or quantum dots, optimization of heating capacity (size, anisotropy of the material, crystallinity, phases: FeCo, FeNi, chemical order), optimization of catalytic properties (islands vs core-shell structures; Ru, Ni for methane, Cu/Zn for methanol), stability and optimization of energy efficiency. A similar approach will be used for direct light conversion using as first proofs of concept Au or Ag NPs coated with Ru. Catalytic tests will be performed on two heterogeneous reactions after deposition of the NPs onto a support: CO2 hydrogenation into methane and methanol synthesis. In addition, the potential of catalysis making use of self-heated and magnetically recoverable NPs will be studied in solution (reduction of arenes or oxygenated functions, hydrogenation and hydrogenolysis of biomass platform molecules, Fischer-Tropsch).
Max ERC Funding
2 472 223 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym TARICA
Project PoliTical And socioinstitutional change in NoRth AfrICA: competition of models and diversity of national trajectories
Researcher (PI) Alia GANA
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), SH2, ERC-2015-AdG
Summary While the “Arab spring” has been often analyzed as the sign of the world-wide expansion of the model of liberal democracy, almost five years after the Tunisian “revolution”, the geopolitical picture of North Africa (from Morocco to Egypt) shows very different configurations. The wave of protests and in some cases the collapse of authoritarian regimes have produced various outcomes and conducted to different political choices: « negotiated » political change in Morocco, containment of social unrest in Algeria, « national dialogue » and success of electoral processes in Tunisia, authoritarian restoration in Egypt and civil war in Libya. These varied situations have close links with the mobilizations of actors drawing on unequal resources and differentiated logics of action. Analyzing ongoing change in North Africa as part of the process of dissemination, confrontation and hybridization of various political and societal models, and as resulting from their appropriation and reinterpretation by social actors, this project aims at identifying the complex processes, which contribute to the diversity of the trajectories followed by the region in the aftermath of the “Arab revolts”. Our objective is to grasp how various actors position themselves in the space opened up by the collapse or the calling into question of authoritarian regimes and to analyze their strategies in connection with the reference models and normative repertoires, which guide their actions. Our purpose is to identify the factors and processes that make it possible (or prevent) the setting up of institutional arrangements able to manage social diversity, pluralism and conflicts, so as to avoid authoritarian restoration or civil war. Mobilizing a multidisciplinary team of 8 core researchers and a comparative approach centered on the actors, we will explore these processes through three thematic entrees: political regulation, management of the past and transitional justice, social injustice and development.
Summary
While the “Arab spring” has been often analyzed as the sign of the world-wide expansion of the model of liberal democracy, almost five years after the Tunisian “revolution”, the geopolitical picture of North Africa (from Morocco to Egypt) shows very different configurations. The wave of protests and in some cases the collapse of authoritarian regimes have produced various outcomes and conducted to different political choices: « negotiated » political change in Morocco, containment of social unrest in Algeria, « national dialogue » and success of electoral processes in Tunisia, authoritarian restoration in Egypt and civil war in Libya. These varied situations have close links with the mobilizations of actors drawing on unequal resources and differentiated logics of action. Analyzing ongoing change in North Africa as part of the process of dissemination, confrontation and hybridization of various political and societal models, and as resulting from their appropriation and reinterpretation by social actors, this project aims at identifying the complex processes, which contribute to the diversity of the trajectories followed by the region in the aftermath of the “Arab revolts”. Our objective is to grasp how various actors position themselves in the space opened up by the collapse or the calling into question of authoritarian regimes and to analyze their strategies in connection with the reference models and normative repertoires, which guide their actions. Our purpose is to identify the factors and processes that make it possible (or prevent) the setting up of institutional arrangements able to manage social diversity, pluralism and conflicts, so as to avoid authoritarian restoration or civil war. Mobilizing a multidisciplinary team of 8 core researchers and a comparative approach centered on the actors, we will explore these processes through three thematic entrees: political regulation, management of the past and transitional justice, social injustice and development.
Max ERC Funding
1 998 470 €
Duration
Start date: 2017-01-01, End date: 2020-12-31
Project acronym TILC
Project Targeting Innate Lymphoid Cells
Researcher (PI) Eric Vivier
Host Institution (HI) UNIVERSITE D'AIX MARSEILLE
Call Details Advanced Grant (AdG), LS6, ERC-2015-AdG
Summary TILC focuses on Innate Lymphoid Cells (ILCs). ILCs are a newly discovered type of lymphocyte, and their study opens up new perspectives for understanding and manipulating of immunity. ILCs include cytotoxic ILCs (NK cells) and helper-like ILCs (ILC1, ILC2 & ILC3). Studies of ILC2 cells have advanced considerably, but much remains unknown about the respective roles of NK, ILC1 and ILC3 cells. TILC aims to explore new frontiers in ILC biology, by focusing on these subsets of ILCs in mice and humans, through five specific aims.
1. NK cells, ILC1 & NCR+ILC3 are known to express NKp46 in humans and mice, but the nature of the NKp46 ligands remains unclear, limiting our understanding of the biology of these three major ILC subsets. We thus aim to identify the NKp46 ligands, building on our preliminary data showing that Complement Factor P (CFP, Properdin) is involved in NKp46 recognition, hence revealing an unprecedented mode of immune recognition.
2. We also aim to create new mouse models selectively targeting these ILC subsets in vivo. We will then use these models for dissecting out the selective roles of ILC subsets in two major immune functions: cancer surveillance and gut homeostasis.
3. In cancer, we will investigate the contribution of these cells to tumor editing.
4. In the intestine, we will focus on the homeostasis of the cecum and appendix. These organs were long considered to be vestiges of evolution, but our own recent findings and those of phylogenetic studies have challenged this notion. We thus aim to address the role of ILC subsets in the cecum/appendix, and determine whether these organs serve as a refuge for repopulation with commensals after dysbiosis.
5. Finally, we aim to identify patients with deficiencies in ILCs, to dissect the function of these cells in natura.
From the molecular scale to that of patients, we believe that TILC will provide answers to some of the most pressing questions concerning the role and clinical potential of NKp46+ ILCs
Summary
TILC focuses on Innate Lymphoid Cells (ILCs). ILCs are a newly discovered type of lymphocyte, and their study opens up new perspectives for understanding and manipulating of immunity. ILCs include cytotoxic ILCs (NK cells) and helper-like ILCs (ILC1, ILC2 & ILC3). Studies of ILC2 cells have advanced considerably, but much remains unknown about the respective roles of NK, ILC1 and ILC3 cells. TILC aims to explore new frontiers in ILC biology, by focusing on these subsets of ILCs in mice and humans, through five specific aims.
1. NK cells, ILC1 & NCR+ILC3 are known to express NKp46 in humans and mice, but the nature of the NKp46 ligands remains unclear, limiting our understanding of the biology of these three major ILC subsets. We thus aim to identify the NKp46 ligands, building on our preliminary data showing that Complement Factor P (CFP, Properdin) is involved in NKp46 recognition, hence revealing an unprecedented mode of immune recognition.
2. We also aim to create new mouse models selectively targeting these ILC subsets in vivo. We will then use these models for dissecting out the selective roles of ILC subsets in two major immune functions: cancer surveillance and gut homeostasis.
3. In cancer, we will investigate the contribution of these cells to tumor editing.
4. In the intestine, we will focus on the homeostasis of the cecum and appendix. These organs were long considered to be vestiges of evolution, but our own recent findings and those of phylogenetic studies have challenged this notion. We thus aim to address the role of ILC subsets in the cecum/appendix, and determine whether these organs serve as a refuge for repopulation with commensals after dysbiosis.
5. Finally, we aim to identify patients with deficiencies in ILCs, to dissect the function of these cells in natura.
From the molecular scale to that of patients, we believe that TILC will provide answers to some of the most pressing questions concerning the role and clinical potential of NKp46+ ILCs
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
