Project acronym B-INNATE
Project Innate signaling networks in B cell antibody production: new targets for vaccine development
Researcher (PI) Andrea Cerutti
Host Institution (HI) FUNDACIO INSTITUT MAR D INVESTIGACIONS MEDIQUES IMIM
Call Details Advanced Grant (AdG), LS6, ERC-2011-ADG_20110310
Summary The long-term goal of this proposal is to explore a novel immune pathway that involves an unexpected interplay between marginal zone (MZ) B cells and neutrophils. MZ B cells are strategically positioned at the interface between the immune system and the circulation and rapidly produce protective antibodies to blood-borne pathogens through a T cell-independent pathway that remains poorly understood. We recently found that the human spleen contains a novel subset of B cell helper neutrophils (NBH cells) with a phenotype and gene expression profile distinct from those of conventional circulating neutrophils (NC cells). In this proposal, we hypothesize that NC cells undergo splenic reprogramming into NBH cells through an IL-10-dependent pathway involving perifollicular sinusoidal endothelial cells. We contend that these unique endothelial cells release NC cell-attracting chemokines and IL-10 upon sensing blood-borne bacteria through Toll-like receptors. We also argue that IL-10 from sinusoidal endothelial cells stimulates NC cells to differentiate into NBH cells equipped with powerful MZ B cell-stimulating activity. The following three aims will be pursued. Aim 1 is to determine the mechanisms by which splenic sinusoidal endothelial cells induce reprogramming of NC cells into NBH cells upon sensing bacteria through Toll-like receptors. Aim 2 is to elucidate the mechanisms by which NBH cells induce IgM production, IgG and IgA class switching, and plasma cell differentiation in MZ B cells. Aim 3 is to evaluate the mechanisms by which NBH cells induce V(D)J gene somatic hypermutation and high-affinity antibody production in MZ B cells. These studies will uncover previously unknown facets of the immunological function of neutrophils by taking advantage of unique cells and tissues from patients with rare primary immunodeficiencies and by making use of selected mouse models. Results from these studies may also lead to the identification of novel vaccine strategies.
Summary
The long-term goal of this proposal is to explore a novel immune pathway that involves an unexpected interplay between marginal zone (MZ) B cells and neutrophils. MZ B cells are strategically positioned at the interface between the immune system and the circulation and rapidly produce protective antibodies to blood-borne pathogens through a T cell-independent pathway that remains poorly understood. We recently found that the human spleen contains a novel subset of B cell helper neutrophils (NBH cells) with a phenotype and gene expression profile distinct from those of conventional circulating neutrophils (NC cells). In this proposal, we hypothesize that NC cells undergo splenic reprogramming into NBH cells through an IL-10-dependent pathway involving perifollicular sinusoidal endothelial cells. We contend that these unique endothelial cells release NC cell-attracting chemokines and IL-10 upon sensing blood-borne bacteria through Toll-like receptors. We also argue that IL-10 from sinusoidal endothelial cells stimulates NC cells to differentiate into NBH cells equipped with powerful MZ B cell-stimulating activity. The following three aims will be pursued. Aim 1 is to determine the mechanisms by which splenic sinusoidal endothelial cells induce reprogramming of NC cells into NBH cells upon sensing bacteria through Toll-like receptors. Aim 2 is to elucidate the mechanisms by which NBH cells induce IgM production, IgG and IgA class switching, and plasma cell differentiation in MZ B cells. Aim 3 is to evaluate the mechanisms by which NBH cells induce V(D)J gene somatic hypermutation and high-affinity antibody production in MZ B cells. These studies will uncover previously unknown facets of the immunological function of neutrophils by taking advantage of unique cells and tissues from patients with rare primary immunodeficiencies and by making use of selected mouse models. Results from these studies may also lead to the identification of novel vaccine strategies.
Max ERC Funding
2 214 035 €
Duration
Start date: 2012-04-01, End date: 2017-09-30
Project acronym BacRafts
Project Architecture of bacterial lipid rafts; inhibition of virulence and antibiotic resistance using raft-disassembling small molecules
Researcher (PI) Daniel López Serrano
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Starting Grant (StG), LS6, ERC-2013-StG
Summary Membranes of eukaryotic cells organize signal transduction proteins into microdomains or lipid rafts whose integrity is essential for numerous cellular processes. Lipid rafts has been considered a fundamental step to define the cellular complexity of eukaryotes, assuming that bacteria do not require such a sophisticated organization of their signaling networks. However, I have discovered that bacteria organize many signaling pathways in membrane microdomains similar to the eukaryotic lipid rafts. Perturbation of bacterial lipid rafts leads to a potent and simultaneous impairment of all raft-harbored signaling pathways. Consequently, the disassembly of lipid rafts in pathogens like Staphylococcus aureus generates a simultaneous inhibition of numerous infection-related processes that can be further explored to control bacterial infections. This unexpected sophistication in membrane organization is unprecedented in bacteria and hence, this proposal will explore the molecular basis of the assembly of bacterial lipid rafts and their role in the infection-related processes. These questions will be addressed in three main goals: First, I will elucidate the molecular components and the mechanism of assembly of bacterial lipid rafts using S. aureus as model organism. Second, I will dissect the molecular basis that links the functionality of the infection-related processes to the integrity of bacterial lipid rafts. Third, my collection of anti-raft small molecules that are able to disrupt lipid rafts will be tested as antimicrobial agents to prevent hospital-acquired infections, abrogate pre-existing infections and develop bacteria-free materials that can be used in clinical settings. I will use a number of molecular approaches in combination with cutting-edge techniques in flow cytometry, cell-imaging and transcriptomics to clarify the architecture and functionality of lipid rafts and demonstrate the feasibility of targeting lipid a new strategy for anti-microbial therapy.
Summary
Membranes of eukaryotic cells organize signal transduction proteins into microdomains or lipid rafts whose integrity is essential for numerous cellular processes. Lipid rafts has been considered a fundamental step to define the cellular complexity of eukaryotes, assuming that bacteria do not require such a sophisticated organization of their signaling networks. However, I have discovered that bacteria organize many signaling pathways in membrane microdomains similar to the eukaryotic lipid rafts. Perturbation of bacterial lipid rafts leads to a potent and simultaneous impairment of all raft-harbored signaling pathways. Consequently, the disassembly of lipid rafts in pathogens like Staphylococcus aureus generates a simultaneous inhibition of numerous infection-related processes that can be further explored to control bacterial infections. This unexpected sophistication in membrane organization is unprecedented in bacteria and hence, this proposal will explore the molecular basis of the assembly of bacterial lipid rafts and their role in the infection-related processes. These questions will be addressed in three main goals: First, I will elucidate the molecular components and the mechanism of assembly of bacterial lipid rafts using S. aureus as model organism. Second, I will dissect the molecular basis that links the functionality of the infection-related processes to the integrity of bacterial lipid rafts. Third, my collection of anti-raft small molecules that are able to disrupt lipid rafts will be tested as antimicrobial agents to prevent hospital-acquired infections, abrogate pre-existing infections and develop bacteria-free materials that can be used in clinical settings. I will use a number of molecular approaches in combination with cutting-edge techniques in flow cytometry, cell-imaging and transcriptomics to clarify the architecture and functionality of lipid rafts and demonstrate the feasibility of targeting lipid a new strategy for anti-microbial therapy.
Max ERC Funding
1 493 126 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym BILITERACY
Project Bi-literacy: Learning to read in L1 and in L2
Researcher (PI) Manuel Francisco Carreiras Valiña
Host Institution (HI) BCBL BASQUE CENTER ON COGNITION BRAIN AND LANGUAGE
Call Details Advanced Grant (AdG), SH4, ERC-2011-ADG_20110406
Summary Learning to read is probably one of the most exciting discoveries in our life. Using a longitudinal approach, the research proposed examines how the human brain responds to two major challenges: (a) the instantiation a complex cognitive function for which there is no genetic blueprint (learning to read in a first language, L1), and (b) the accommodation to new statistical regularities when learning to read in a second language (L2). The aim of the present research project is to identify the neural substrates of the reading process and its constituent cognitive components, with specific attention to individual differences and reading disabilities; as well as to investigate the relationship between specific cognitive functions and the changes in neural activity that take place in the course of learning to read in L1 and in L2. The project will employ a longitudinal design. We will recruit children before they learn to read in L1 and in L2 and track reading development with both cognitive and neuroimaging measures over 24 months. The findings from this project will provide a deeper understanding of (a) how general neurocognitive factors and language specific factors underlie individual differences – and reading disabilities– in reading acquisition in L1 and in L2; (b) how the neuro-cognitive circuitry changes and brain mechanisms synchronize while instantiating reading in L1 and in L2; (c) what the limitations and the extent of brain plasticity are in young readers. An interdisciplinary and multi-methodological approach is one of the keys to success of the present project, along with strong theory-driven investigation. By combining both we will generate breakthroughs to advance our understanding of how literacy in L1 and in L2 is acquired and mastered. The research proposed will also lay the foundations for more applied investigations of best practice in teaching reading in first and subsequent languages, and devising intervention methods for reading disabilities.
Summary
Learning to read is probably one of the most exciting discoveries in our life. Using a longitudinal approach, the research proposed examines how the human brain responds to two major challenges: (a) the instantiation a complex cognitive function for which there is no genetic blueprint (learning to read in a first language, L1), and (b) the accommodation to new statistical regularities when learning to read in a second language (L2). The aim of the present research project is to identify the neural substrates of the reading process and its constituent cognitive components, with specific attention to individual differences and reading disabilities; as well as to investigate the relationship between specific cognitive functions and the changes in neural activity that take place in the course of learning to read in L1 and in L2. The project will employ a longitudinal design. We will recruit children before they learn to read in L1 and in L2 and track reading development with both cognitive and neuroimaging measures over 24 months. The findings from this project will provide a deeper understanding of (a) how general neurocognitive factors and language specific factors underlie individual differences – and reading disabilities– in reading acquisition in L1 and in L2; (b) how the neuro-cognitive circuitry changes and brain mechanisms synchronize while instantiating reading in L1 and in L2; (c) what the limitations and the extent of brain plasticity are in young readers. An interdisciplinary and multi-methodological approach is one of the keys to success of the present project, along with strong theory-driven investigation. By combining both we will generate breakthroughs to advance our understanding of how literacy in L1 and in L2 is acquired and mastered. The research proposed will also lay the foundations for more applied investigations of best practice in teaching reading in first and subsequent languages, and devising intervention methods for reading disabilities.
Max ERC Funding
2 487 000 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym BUBPOL
Project Monetary Policy and Asset Price Bubbles
Researcher (PI) Jordi Galí Garreta
Host Institution (HI) Centre de Recerca en Economia Internacional (CREI)
Call Details Advanced Grant (AdG), SH1, ERC-2013-ADG
Summary "The proposed research project seeks to further our understanding on two important questions for the design of monetary policy:
(a) What are the effects of monetary policy interventions on asset price bubbles?
(b) How should monetary policy be conducted in the presence of asset price bubbles?
The first part of the project will focus on the development of a theoretical framework that can be used to analyze rigorously the implications of alternative monetary policy rules in the presence of asset price bubbles, and to characterize the optimal monetary policy. In particular, I plan to use such a framework to assess the merits of a “leaning against the wind” strategy, which calls for a systematic rise in interest rates in response to the development of a bubble.
The second part of the project will seek to produce evidence, both empirical and experimental, regarding the effects of monetary policy on asset price bubbles. The empirical evidence will seek to identify and estimate the sign and response of asset price bubbles to interest rate changes, exploiting the potential differences in the joint behavior of interest rates and asset prices during “bubbly” episodes, in comparison to “normal” times. In addition, I plan to conduct some lab experiments in order to shed some light on the link between monetary policy and bubbles. Participants will trade two assets, a one-period riskless asset and a long-lived stock, in an environment consistent with the existence of asset price bubbles in equilibrium. Monetary policy interventions will take the form of changes in the short-term interest rate, engineered by the experimenter. The experiments will allow us to evaluate some of the predictions of the theoretical models regarding the impact of monetary policy on the dynamics of bubbles, as well as the effectiveness of “leaning against the wind” policies."
Summary
"The proposed research project seeks to further our understanding on two important questions for the design of monetary policy:
(a) What are the effects of monetary policy interventions on asset price bubbles?
(b) How should monetary policy be conducted in the presence of asset price bubbles?
The first part of the project will focus on the development of a theoretical framework that can be used to analyze rigorously the implications of alternative monetary policy rules in the presence of asset price bubbles, and to characterize the optimal monetary policy. In particular, I plan to use such a framework to assess the merits of a “leaning against the wind” strategy, which calls for a systematic rise in interest rates in response to the development of a bubble.
The second part of the project will seek to produce evidence, both empirical and experimental, regarding the effects of monetary policy on asset price bubbles. The empirical evidence will seek to identify and estimate the sign and response of asset price bubbles to interest rate changes, exploiting the potential differences in the joint behavior of interest rates and asset prices during “bubbly” episodes, in comparison to “normal” times. In addition, I plan to conduct some lab experiments in order to shed some light on the link between monetary policy and bubbles. Participants will trade two assets, a one-period riskless asset and a long-lived stock, in an environment consistent with the existence of asset price bubbles in equilibrium. Monetary policy interventions will take the form of changes in the short-term interest rate, engineered by the experimenter. The experiments will allow us to evaluate some of the predictions of the theoretical models regarding the impact of monetary policy on the dynamics of bubbles, as well as the effectiveness of “leaning against the wind” policies."
Max ERC Funding
799 200 €
Duration
Start date: 2014-01-01, End date: 2017-12-31
Project acronym CANCERLINC
Project Functional and Mecahnistic Roles of Large Intergenic Non-coding RNAs in Cancer
Researcher (PI) Maite Huarte Martinez
Host Institution (HI) FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary Mammalian cells express thousands of RNA molecules structurally similar to protein coding genes –they are large, spliced, poly-adenylated, transcribed by RNA Pol II, with conserved promoters and exonic structures –however lack coding capacity. Although thousands exist, only few of these large intergenic non-coding RNAs (lincRNAs) have been characterized. The few that have, show powerful biological roles as regulators of gene expression by diverse epigenetic and non-epigenetic mechanisms. Significantly, their expression patterns suggest that some lincRNAs are involved in cellular pathways critical in cancer, like the p53 pathway. I explored this association demonstrating that p53 induces the expression of many lincRNAs. One them, named lincRNA-p21, is directly induced by p53 to play a critical role in the p53 response, being required for the global repression of genes that interfere with p53 induction of apoptosis. My results, together with the emerging evidence in the field, suggest that lincRNAs may play key roles in numerous tumor-suppressor and oncogenic pathways, representing an unknown paradigm in cellular transformation. However, their mechanisms of function and biological roles remain largely unexplored.
The goal of this project is to decipher the functional and biological roles of lincRNAs in the context of oncogenic pathways to better understand the cellular mechanisms of gene regulation at the epigenetic and non-epigenetic levels, and be able to implement lincRNA use for diagnostics and therapies. In order to accomplish these goals we will integrate molecular and cell biology techniques with functional genomics approaches and in vivo studies. Importantly, the profiling of patient samples will reveal the relevance of our findings in human disease. Together, the functional study of lincRNAs will not only be crucial for developing improved diagnostics and therapies, but also will help a better understanding of the mechanisms that govern cellular network.
Summary
Mammalian cells express thousands of RNA molecules structurally similar to protein coding genes –they are large, spliced, poly-adenylated, transcribed by RNA Pol II, with conserved promoters and exonic structures –however lack coding capacity. Although thousands exist, only few of these large intergenic non-coding RNAs (lincRNAs) have been characterized. The few that have, show powerful biological roles as regulators of gene expression by diverse epigenetic and non-epigenetic mechanisms. Significantly, their expression patterns suggest that some lincRNAs are involved in cellular pathways critical in cancer, like the p53 pathway. I explored this association demonstrating that p53 induces the expression of many lincRNAs. One them, named lincRNA-p21, is directly induced by p53 to play a critical role in the p53 response, being required for the global repression of genes that interfere with p53 induction of apoptosis. My results, together with the emerging evidence in the field, suggest that lincRNAs may play key roles in numerous tumor-suppressor and oncogenic pathways, representing an unknown paradigm in cellular transformation. However, their mechanisms of function and biological roles remain largely unexplored.
The goal of this project is to decipher the functional and biological roles of lincRNAs in the context of oncogenic pathways to better understand the cellular mechanisms of gene regulation at the epigenetic and non-epigenetic levels, and be able to implement lincRNA use for diagnostics and therapies. In order to accomplish these goals we will integrate molecular and cell biology techniques with functional genomics approaches and in vivo studies. Importantly, the profiling of patient samples will reveal the relevance of our findings in human disease. Together, the functional study of lincRNAs will not only be crucial for developing improved diagnostics and therapies, but also will help a better understanding of the mechanisms that govern cellular network.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-01-01, End date: 2017-12-31
Project acronym CANCERMETAB
Project Metabolic requirements for prostate cancer cell fitness
Researcher (PI) Arkaitz Carracedo Perez
Host Institution (HI) ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOCIENCIAS
Call Details Starting Grant (StG), LS4, ERC-2013-StG
Summary The actual view of cellular transformation and cancer progression supports the notion that cancer cells must undergo metabolic reprogramming in order to survive in a hostile environment. This field has experienced a renaissance in recent years, with the discovery of cancer genes regulating metabolic homeostasis, in turn being accepted as an emergent hallmark of cancer. Prostate cancer presents one of the highest incidences in men mostly in developed societies and exhibits a significant association with lifestyle environmental factors. Prostate cancer recurrence is thought to rely on a subpopulation of cancer cells with low-androgen requirements, high self-renewal potential and multidrug resistance, defined as cancer-initiating cells. However, whether this cancer cell fraction presents genuine metabolic properties that can be therapeutically relevant remains undefined. In CancerMetab, we aim to understand the potential benefit of monitoring and manipulating metabolism for prostate cancer prevention, detection and therapy. My group will carry out a multidisciplinary strategy, comprising cellular systems, genetic mouse models of prostate cancer, human epidemiological and clinical studies and bioinformatic analysis. The singularity of this proposal stems from the approach to the three key aspects that we propose to study. For prostate cancer prevention, we will use our faithful mouse model of prostate cancer to shed light on the contribution of obesity to prostate cancer. For prostate cancer detection, we will overcome the consistency issues of previously reported metabolic biomarkers by adding robustness to the human studies with mouse data integration. For prostate cancer therapy, we will focus on a cell population for which the metabolic requirements and the potential of targeting them for therapy have been overlooked to date, that is the prostate cancer-initiating cell compartment.
Summary
The actual view of cellular transformation and cancer progression supports the notion that cancer cells must undergo metabolic reprogramming in order to survive in a hostile environment. This field has experienced a renaissance in recent years, with the discovery of cancer genes regulating metabolic homeostasis, in turn being accepted as an emergent hallmark of cancer. Prostate cancer presents one of the highest incidences in men mostly in developed societies and exhibits a significant association with lifestyle environmental factors. Prostate cancer recurrence is thought to rely on a subpopulation of cancer cells with low-androgen requirements, high self-renewal potential and multidrug resistance, defined as cancer-initiating cells. However, whether this cancer cell fraction presents genuine metabolic properties that can be therapeutically relevant remains undefined. In CancerMetab, we aim to understand the potential benefit of monitoring and manipulating metabolism for prostate cancer prevention, detection and therapy. My group will carry out a multidisciplinary strategy, comprising cellular systems, genetic mouse models of prostate cancer, human epidemiological and clinical studies and bioinformatic analysis. The singularity of this proposal stems from the approach to the three key aspects that we propose to study. For prostate cancer prevention, we will use our faithful mouse model of prostate cancer to shed light on the contribution of obesity to prostate cancer. For prostate cancer detection, we will overcome the consistency issues of previously reported metabolic biomarkers by adding robustness to the human studies with mouse data integration. For prostate cancer therapy, we will focus on a cell population for which the metabolic requirements and the potential of targeting them for therapy have been overlooked to date, that is the prostate cancer-initiating cell compartment.
Max ERC Funding
1 498 686 €
Duration
Start date: 2013-11-01, End date: 2019-10-31
Project acronym CARBONNEMS
Project NanoElectroMechanical Systems based on Carbon Nanotube and Graphene
Researcher (PI) Adrian Bachtold
Host Institution (HI) FUNDACIO INSTITUT DE CIENCIES FOTONIQUES
Call Details Starting Grant (StG), PE3, ERC-2011-StG_20101014
Summary Carbon nanotubes and graphene form a class of nanoscale objects with exceptional electrical, mechanical and structural properties. I propose to exploit these unique properties to fabricate and study various nanoelectromechanical systems (NEMS) based on graphene and nanotubes. Specifically, I will address two directions with major scientific interests:
1- I propose to study electromechanical resonators based on an individual nanotube or on a single layer of graphene. My group has a leading position in this recent research field and the idea is to take advantage of our expertise for two sets of experiments, one on inertial mass sensing and one on the exploration of quantum motion. These two topics are generating at present an intense activity in the NEMS community. Experiments are usually carried out using microfabricated silicon resonators but the ultra low mass of nanotubes and graphene has here an enormous asset. It drastically improves the sensitivity of mass sensing and it dramatically enhances the amplitude of the motion in the quantum regime.
2- My team will fabricate and exploit nanomotors based on nanotube and graphene. Only few man-made nanomotors have been demonstrated so far. Reasons are multiple. For instance, the fabrication of nanomotors is technically challenging. In addition, friction forces are often so strong that they hinder motion. Because of their unique properties, nanotubes and graphene represent a material of choice for the development of new nanomotors. We will construct nanomotors with different layouts and address how electrical, thermal or chemical energy can be transformed into mechanical energy in order to drive motion at the nanoscale.
Summary
Carbon nanotubes and graphene form a class of nanoscale objects with exceptional electrical, mechanical and structural properties. I propose to exploit these unique properties to fabricate and study various nanoelectromechanical systems (NEMS) based on graphene and nanotubes. Specifically, I will address two directions with major scientific interests:
1- I propose to study electromechanical resonators based on an individual nanotube or on a single layer of graphene. My group has a leading position in this recent research field and the idea is to take advantage of our expertise for two sets of experiments, one on inertial mass sensing and one on the exploration of quantum motion. These two topics are generating at present an intense activity in the NEMS community. Experiments are usually carried out using microfabricated silicon resonators but the ultra low mass of nanotubes and graphene has here an enormous asset. It drastically improves the sensitivity of mass sensing and it dramatically enhances the amplitude of the motion in the quantum regime.
2- My team will fabricate and exploit nanomotors based on nanotube and graphene. Only few man-made nanomotors have been demonstrated so far. Reasons are multiple. For instance, the fabrication of nanomotors is technically challenging. In addition, friction forces are often so strong that they hinder motion. Because of their unique properties, nanotubes and graphene represent a material of choice for the development of new nanomotors. We will construct nanomotors with different layouts and address how electrical, thermal or chemical energy can be transformed into mechanical energy in order to drive motion at the nanoscale.
Max ERC Funding
1 996 789 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym CDAC
Project "The role of consciousness in adaptive behavior: A combined empirical, computational and robot based approach"
Researcher (PI) Paulus Franciscus Maria Joseph Verschure
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Call Details Advanced Grant (AdG), SH4, ERC-2013-ADG
Summary "Understanding the nature of consciousness is one of the grand outstanding scientific challenges and two of its features stand out: consciousness is defined as the construction of one coherent scene but this scene is experienced with a delay relative to the action of the agent and not necessarily the cause of actions and thoughts. Did evolution render solutions to the challenge of survival that includes epiphenomenal processes? The Conscious Distributed Adaptive Control (CDAC) project aims at resolving this paradox by using a multi-disciplinary approach to show the functional role of consciousness in adaptive behaviour, to identify its underlying neuronal principles and to construct a neuromorphic robot based real-time conscious architecture. CDAC proposes that the shift from surviving in a physical world to one that is dominated by intentional agents requires radically different control architectures combining parallel and distributed control loops to assure real-time operation together with a second level of control that assures coherence through sequential coherent representation of self and the task domain, i.e. consciousness. This conscious scene is driving dedicated credit assignment and planning beyond the immediately given information. CDAC advances a comprehensive framework progressing beyond the state of the art and will be realized using system level models of a conscious architecture, detailed computational studies of its underlying neuronal substrate focusing, empirical validation with a humanoid robot and stroke patients and the advancement of beyond state of the art tools appropriate to the complexity of its objectives. The CDAC project directly addresses one of the main outstanding questions in science: the function and genesis of consciousness and will advance our understanding of mind and brain, provide radically new neurorehabilitation technologies and contribute to realizing a new generation of robots with advanced social competence."
Summary
"Understanding the nature of consciousness is one of the grand outstanding scientific challenges and two of its features stand out: consciousness is defined as the construction of one coherent scene but this scene is experienced with a delay relative to the action of the agent and not necessarily the cause of actions and thoughts. Did evolution render solutions to the challenge of survival that includes epiphenomenal processes? The Conscious Distributed Adaptive Control (CDAC) project aims at resolving this paradox by using a multi-disciplinary approach to show the functional role of consciousness in adaptive behaviour, to identify its underlying neuronal principles and to construct a neuromorphic robot based real-time conscious architecture. CDAC proposes that the shift from surviving in a physical world to one that is dominated by intentional agents requires radically different control architectures combining parallel and distributed control loops to assure real-time operation together with a second level of control that assures coherence through sequential coherent representation of self and the task domain, i.e. consciousness. This conscious scene is driving dedicated credit assignment and planning beyond the immediately given information. CDAC advances a comprehensive framework progressing beyond the state of the art and will be realized using system level models of a conscious architecture, detailed computational studies of its underlying neuronal substrate focusing, empirical validation with a humanoid robot and stroke patients and the advancement of beyond state of the art tools appropriate to the complexity of its objectives. The CDAC project directly addresses one of the main outstanding questions in science: the function and genesis of consciousness and will advance our understanding of mind and brain, provide radically new neurorehabilitation technologies and contribute to realizing a new generation of robots with advanced social competence."
Max ERC Funding
2 469 268 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym CHAI
Project Cardiovascular Health effects of Air pollution in Andhra Pradesh, India
Researcher (PI) Cathryn Tonne
Host Institution (HI) FUNDACION PRIVADA INSTITUTO DE SALUD GLOBAL BARCELONA
Call Details Starting Grant (StG), LS7, ERC-2013-StG
Summary While there is convincing evidence that exposure to particulate air pollution causes cardiovascular mortality and morbidity, nearly all of this evidence is based on populations in high-income countries where concentrations are relatively low. There is large uncertainty regarding the relationship between combustion particles and cardiovascular risk for concentrations higher than outdoor concentrations in urban areas of high-income countries and lower than active smoking. Exposures for our study population are likely to be in this range.
We will investigate the cardiovascular health effects of exposure to particles from outdoor and household sources within a prospective cohort in Andhra Pradesh, India. Firstly, we will characterise exposure of participants using an integrated approach utilising outdoor mobile monitoring, personal monitoring, and questionnaire data. We will then collect data on participants’ activities and location using ‘life-logging’ from which activities driving exposure can be identified. Finally, we will quantify the association between exposure to particles and biomarkers of atherosclerosis.
This research will shed light on the relationship between particles and cardiovascular risk at concentration ranges where there is the largest uncertainty. It will provide some of the first evidence of the cardiovascular health effects of medium-term exposure to particulate air pollution outside of a high-income country. The research will also provide evidence regarding the relative contribution of sources and activities linked to high exposure, forming the basis of recommendations for exposure reduction.
Summary
While there is convincing evidence that exposure to particulate air pollution causes cardiovascular mortality and morbidity, nearly all of this evidence is based on populations in high-income countries where concentrations are relatively low. There is large uncertainty regarding the relationship between combustion particles and cardiovascular risk for concentrations higher than outdoor concentrations in urban areas of high-income countries and lower than active smoking. Exposures for our study population are likely to be in this range.
We will investigate the cardiovascular health effects of exposure to particles from outdoor and household sources within a prospective cohort in Andhra Pradesh, India. Firstly, we will characterise exposure of participants using an integrated approach utilising outdoor mobile monitoring, personal monitoring, and questionnaire data. We will then collect data on participants’ activities and location using ‘life-logging’ from which activities driving exposure can be identified. Finally, we will quantify the association between exposure to particles and biomarkers of atherosclerosis.
This research will shed light on the relationship between particles and cardiovascular risk at concentration ranges where there is the largest uncertainty. It will provide some of the first evidence of the cardiovascular health effects of medium-term exposure to particulate air pollution outside of a high-income country. The research will also provide evidence regarding the relative contribution of sources and activities linked to high exposure, forming the basis of recommendations for exposure reduction.
Max ERC Funding
1 200 000 €
Duration
Start date: 2015-01-01, End date: 2018-12-31
Project acronym Danger ATP
Project Regulation of inflammatory response by extracellular ATP and P2X7 receptor signalling: through and beyond the inflammasome
Researcher (PI) Pablo Pelegrin Vivancos
Host Institution (HI) FUNDACION PARA LA FORMACION E INVESTIGACION SANITARIAS DE LA REGION DE MURCIA
Call Details Consolidator Grant (CoG), LS6, ERC-2013-CoG
Summary Inflammatory diseases affect over 80 million people worldwide and accompany many diseases of industrialized countries, being the majority of them infection-free conditions. There are few efficient anti-inflammatory drugs to treat chronic inflammation and thus, there is an urgent need to validate novel targets. We now know that innate immunity is the main coordinator and driver of inflammation. Recently, we and others have shown that the activation of purinergic P2X7 receptors (P2X7R) in immune cells is a novel and increasingly validated pathway to initiate inflammation through the activation of the NLRP3 inflammasome and the release of IL-1β and IL-18 cytokines. However, how NLRP3 sense P2X7R activation is not fully understood. Furthermore, extracellular ATP, the physiological P2X7R agonist, is a crucial danger signal released by injured cells, and one of the most important mediators of infection-free inflammation. We have also identified novel signalling roles for P2X7R independent on the NLRP3 inflammasome, including the release of proteases or inflammatory lipids. Therefore, P2X7R has generated increasing interest as a therapeutic target in inflammatory diseases, being drug like P2X7R antagonist in clinical trials to treat inflammatory diseases. However, it is often questioned the functionality of P2X7R in vivo, where it is thought that extracellular ATP levels are below the threshold to activate P2X7R. The overall significance of this proposal relays to elucidate how extracellular ATP controls host-defence in vivo, ultimately depicting P2X7R signalling through and beyond inflammasome activation. We foresee that our results will generate a leading innovative knowledge about in vivo extracellular ATP signalling during the host response to infection and sterile danger.
Summary
Inflammatory diseases affect over 80 million people worldwide and accompany many diseases of industrialized countries, being the majority of them infection-free conditions. There are few efficient anti-inflammatory drugs to treat chronic inflammation and thus, there is an urgent need to validate novel targets. We now know that innate immunity is the main coordinator and driver of inflammation. Recently, we and others have shown that the activation of purinergic P2X7 receptors (P2X7R) in immune cells is a novel and increasingly validated pathway to initiate inflammation through the activation of the NLRP3 inflammasome and the release of IL-1β and IL-18 cytokines. However, how NLRP3 sense P2X7R activation is not fully understood. Furthermore, extracellular ATP, the physiological P2X7R agonist, is a crucial danger signal released by injured cells, and one of the most important mediators of infection-free inflammation. We have also identified novel signalling roles for P2X7R independent on the NLRP3 inflammasome, including the release of proteases or inflammatory lipids. Therefore, P2X7R has generated increasing interest as a therapeutic target in inflammatory diseases, being drug like P2X7R antagonist in clinical trials to treat inflammatory diseases. However, it is often questioned the functionality of P2X7R in vivo, where it is thought that extracellular ATP levels are below the threshold to activate P2X7R. The overall significance of this proposal relays to elucidate how extracellular ATP controls host-defence in vivo, ultimately depicting P2X7R signalling through and beyond inflammasome activation. We foresee that our results will generate a leading innovative knowledge about in vivo extracellular ATP signalling during the host response to infection and sterile danger.
Max ERC Funding
1 794 948 €
Duration
Start date: 2014-09-01, End date: 2019-08-31
