Project acronym ContentMAP
Project Contentotopic mapping: the topographical organization of object knowledge in the brain
Researcher (PI) Jorge ALMEIDA
Host Institution (HI) UNIVERSIDADE DE COIMBRA
Call Details Starting Grant (StG), SH4, ERC-2018-STG
Summary Our ability to recognize an object amongst many others is one of the most important features of the human mind. However, object recognition requires tremendous computational effort, as we need to solve a complex and recursive environment with ease and proficiency. This challenging feat is dependent on the implementation of an effective organization of knowledge in the brain. In ContentMAP I will put forth a novel understanding of how object knowledge is organized in the brain, by proposing that this knowledge is topographically laid out in the cortical surface according to object-related dimensions that code for different types of representational content – I will call this contentotopic mapping. To study this fine-grain topography, I will use a combination of fMRI, behavioral, and neuromodulation approaches. I will first obtain patterns of neural and cognitive similarity between objects, and from these extract object-related dimensions using a dimensionality reduction technique. I will then parametrically manipulate these dimensions with an innovative use of a visual field mapping technique, and test how functional selectivity changes across the cortical surface according to an object’s score on a target dimension. Moreover, I will test the tuning function of these contentotopic maps. Finally, to mirror the complexity of implementing a high-dimensional manifold onto a 2D cortical sheet, I will aggregate the topographies for the different dimensions into a composite map, and develop an encoding model to predict neural signatures for each object. To sum up, ContentMAP will have a dramatic impact in the cognitive sciences by describing how the stuff of concepts is represented in the brain, and providing a complete description of how fine-grain representations and functional selectivity within high-level complex processes are topographically implemented.
Summary
Our ability to recognize an object amongst many others is one of the most important features of the human mind. However, object recognition requires tremendous computational effort, as we need to solve a complex and recursive environment with ease and proficiency. This challenging feat is dependent on the implementation of an effective organization of knowledge in the brain. In ContentMAP I will put forth a novel understanding of how object knowledge is organized in the brain, by proposing that this knowledge is topographically laid out in the cortical surface according to object-related dimensions that code for different types of representational content – I will call this contentotopic mapping. To study this fine-grain topography, I will use a combination of fMRI, behavioral, and neuromodulation approaches. I will first obtain patterns of neural and cognitive similarity between objects, and from these extract object-related dimensions using a dimensionality reduction technique. I will then parametrically manipulate these dimensions with an innovative use of a visual field mapping technique, and test how functional selectivity changes across the cortical surface according to an object’s score on a target dimension. Moreover, I will test the tuning function of these contentotopic maps. Finally, to mirror the complexity of implementing a high-dimensional manifold onto a 2D cortical sheet, I will aggregate the topographies for the different dimensions into a composite map, and develop an encoding model to predict neural signatures for each object. To sum up, ContentMAP will have a dramatic impact in the cognitive sciences by describing how the stuff of concepts is represented in the brain, and providing a complete description of how fine-grain representations and functional selectivity within high-level complex processes are topographically implemented.
Max ERC Funding
1 816 004 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym CORKtheCAMBIA
Project Thickening of plant organs by nested stem cells
Researcher (PI) Ari Pekka MÄHÖNEN
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Consolidator Grant (CoG), LS3, ERC-2018-COG
Summary Growth originates from meristems, where stem cells are located. Lateral meristems, which provide thickness to tree stems and other plant organs, include vascular cambium (produces xylem [wood] and phloem); and cork cambium (forms cork, a tough protective layer).
We recently identified the molecular mechanism that specifies stem cells of vascular cambium. Unexpectedly, this same set of experiments revealed also novel aspects of the regulation of cork cambium, a meristem whose development has remained unknown. CORKtheCAMBIA aims to identify the stem cells of cork cambium and reveal how they mechanistically regulate plant organ thickening. Thus, stemming from these novel unpublished findings and my matching expertise on plant stem cells and lateral growth, the timing is perfect to discover the molecular mechanism underlying specification of stem cells of cork cambium.
To identify the origin of stem cells of cork cambium, 1st-we will combine lineage tracing with a detailed molecular marker analysis. To deduce the cell dynamics of cork cambium, 2nd-we will follow regeneration of the stem cells after ablation of this meristem. To discover the molecular factors regulating the stem cell specification of cork cambium, 3rd-we will utilize molecular genetics and a novel method (inducible CRISPR/Cas9 mutant targeting) being developed in my lab. Since the lateral growth is orchestrated by two adjacent, nested meristems, cork and vascular cambia, the growth process must be tightly co-regulated. Thus, 4th-an in silico model of the intertwined growth process will be generated. By combining modelling with experimentation, we will uncover mechanistically how cork and vascular cambium coordinate lateral growth.
CORKtheCAMBIA will thus provide long-awaited insight into the regulatory mechanisms specifying the stem cells of lateral meristem as whole, lay the foundation for studies on radial thickening and facilitate rational manipulation of lateral meristems of crop plants and trees.
Summary
Growth originates from meristems, where stem cells are located. Lateral meristems, which provide thickness to tree stems and other plant organs, include vascular cambium (produces xylem [wood] and phloem); and cork cambium (forms cork, a tough protective layer).
We recently identified the molecular mechanism that specifies stem cells of vascular cambium. Unexpectedly, this same set of experiments revealed also novel aspects of the regulation of cork cambium, a meristem whose development has remained unknown. CORKtheCAMBIA aims to identify the stem cells of cork cambium and reveal how they mechanistically regulate plant organ thickening. Thus, stemming from these novel unpublished findings and my matching expertise on plant stem cells and lateral growth, the timing is perfect to discover the molecular mechanism underlying specification of stem cells of cork cambium.
To identify the origin of stem cells of cork cambium, 1st-we will combine lineage tracing with a detailed molecular marker analysis. To deduce the cell dynamics of cork cambium, 2nd-we will follow regeneration of the stem cells after ablation of this meristem. To discover the molecular factors regulating the stem cell specification of cork cambium, 3rd-we will utilize molecular genetics and a novel method (inducible CRISPR/Cas9 mutant targeting) being developed in my lab. Since the lateral growth is orchestrated by two adjacent, nested meristems, cork and vascular cambia, the growth process must be tightly co-regulated. Thus, 4th-an in silico model of the intertwined growth process will be generated. By combining modelling with experimentation, we will uncover mechanistically how cork and vascular cambium coordinate lateral growth.
CORKtheCAMBIA will thus provide long-awaited insight into the regulatory mechanisms specifying the stem cells of lateral meristem as whole, lay the foundation for studies on radial thickening and facilitate rational manipulation of lateral meristems of crop plants and trees.
Max ERC Funding
1 999 752 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym CROME
Project Crossed Memories, Politics of Silence: The Colonial-Liberation Wars in Postcolonial Times
Researcher (PI) Miguel Gonçalo CARDINA
Host Institution (HI) CENTRO DE ESTUDOS SOCIAIS
Call Details Starting Grant (StG), SH6, ERC-2016-STG
Summary Colonial-Liberation Wars generate plural memories, conflicting evocations and persisting amnesias. The project’s main challenge is to produce innovative knowledge about the memories of the wars fought by the Portuguese state and pro-independence African movements between 1961 and 1974/5. The approach chosen is simultaneously diachronic and comparative, inasmuch as it contrasts changes that took place between the end of the conflicts and nowadays, regarding how wars, colonial pasts and anticolonial legacies have been remembered and silenced in Portugal, Angola, Mozambique, Guinea-Bissau, Cape Verde and São Tomé and Principe. The key hypothesis is that wars - as pivotal moments that ended the cycle of Empire in Portugal and started the cycle of African independences in the former Portuguese colonies - triggered memorialisation and silencing processes which had their own historicity.
CROME is divided into two strands. The first one, named ‘Colonial Wars, Postcolonial States’, looks at the role played by the states under consideration in mobilising, articulating and recognising the past, but also in actively generating selective representations. ‘Memory as a battlefield’ is the second strand, which will highlight distinct uses of the past and dynamics between social memories and individual memories.
The project intends to demonstrate how wars gave rise to multiple memories and conflicting historical judgements, mostly in Portugal, but also to examine how the specific nature of the (post-)colonial histories of each African country has generated different ways to summon war memories and (anti-)colonial legacies. CROME will, thus, put forward a ground-breaking perspective in terms of colonial-liberation war studies, and will be instrumental in dealing with such traumatic experience, for its comparative approach might help overcoming everlasting constraints still at play today, caused by the historical burden European colonialism left behind.
Summary
Colonial-Liberation Wars generate plural memories, conflicting evocations and persisting amnesias. The project’s main challenge is to produce innovative knowledge about the memories of the wars fought by the Portuguese state and pro-independence African movements between 1961 and 1974/5. The approach chosen is simultaneously diachronic and comparative, inasmuch as it contrasts changes that took place between the end of the conflicts and nowadays, regarding how wars, colonial pasts and anticolonial legacies have been remembered and silenced in Portugal, Angola, Mozambique, Guinea-Bissau, Cape Verde and São Tomé and Principe. The key hypothesis is that wars - as pivotal moments that ended the cycle of Empire in Portugal and started the cycle of African independences in the former Portuguese colonies - triggered memorialisation and silencing processes which had their own historicity.
CROME is divided into two strands. The first one, named ‘Colonial Wars, Postcolonial States’, looks at the role played by the states under consideration in mobilising, articulating and recognising the past, but also in actively generating selective representations. ‘Memory as a battlefield’ is the second strand, which will highlight distinct uses of the past and dynamics between social memories and individual memories.
The project intends to demonstrate how wars gave rise to multiple memories and conflicting historical judgements, mostly in Portugal, but also to examine how the specific nature of the (post-)colonial histories of each African country has generated different ways to summon war memories and (anti-)colonial legacies. CROME will, thus, put forward a ground-breaking perspective in terms of colonial-liberation war studies, and will be instrumental in dealing with such traumatic experience, for its comparative approach might help overcoming everlasting constraints still at play today, caused by the historical burden European colonialism left behind.
Max ERC Funding
1 478 249 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym CROSSLOCATIONS
Project Crosslocations in the Mediterranean: rethinking the socio-cultural dynamics of relative positioning
Researcher (PI) Sarah Francesca Green
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Advanced Grant (AdG), SH5, ERC-2015-AdG
Summary The Mediterranean, a key socio-cultural, economic and political crossroads, has shifted its relative position recently, with profound effects for relations between the peoples associated with its diverse parts. Crosslocations is a groundbreaking theoretical approach that goes beyond current borders research to analyse the significance of the changes in relations between places and peoples that this involves. It does this through explaining shifts in the relative positioning of the Mediterranean’s many locations – i.e. the changing values of where people are rather than who they are. Approaches focusing on people’s identities, statecraft or networks do not provide a way to research how the relative value of ‘being somewhere in particular’ is changing and diversifying.
The approach builds on the idea that in socio-cultural terms, location is a form of political, social, economic, and technical relative positioning, involving diverse scales that calibrate relative values (here called ‘locating regimes’). This means locations are both multiple and historically variable, so different types of location may overlap in the same geographical space, particularly in crossroads regions such as the Mediterranean. The dynamics between them alter relations between places, significantly affecting people’s daily lives, including their life chances, wellbeing, environmental, social and political conditions and status.
The project will first research the locating regimes crossing the Mediterranean region (border regimes, infrastructures; digital technologies; fiscal, financial and trading systems; environmental policies; and social and religious structures); then intensively ethnographically study the socio-cultural dynamics of relative positioning that these regimes generate in selected parts of the Mediterranean region. Through explaining the dynamics of relative location, Crosslocations will transform our understanding of trans-local, socio-cultural relations and separations.
Summary
The Mediterranean, a key socio-cultural, economic and political crossroads, has shifted its relative position recently, with profound effects for relations between the peoples associated with its diverse parts. Crosslocations is a groundbreaking theoretical approach that goes beyond current borders research to analyse the significance of the changes in relations between places and peoples that this involves. It does this through explaining shifts in the relative positioning of the Mediterranean’s many locations – i.e. the changing values of where people are rather than who they are. Approaches focusing on people’s identities, statecraft or networks do not provide a way to research how the relative value of ‘being somewhere in particular’ is changing and diversifying.
The approach builds on the idea that in socio-cultural terms, location is a form of political, social, economic, and technical relative positioning, involving diverse scales that calibrate relative values (here called ‘locating regimes’). This means locations are both multiple and historically variable, so different types of location may overlap in the same geographical space, particularly in crossroads regions such as the Mediterranean. The dynamics between them alter relations between places, significantly affecting people’s daily lives, including their life chances, wellbeing, environmental, social and political conditions and status.
The project will first research the locating regimes crossing the Mediterranean region (border regimes, infrastructures; digital technologies; fiscal, financial and trading systems; environmental policies; and social and religious structures); then intensively ethnographically study the socio-cultural dynamics of relative positioning that these regimes generate in selected parts of the Mediterranean region. Through explaining the dynamics of relative location, Crosslocations will transform our understanding of trans-local, socio-cultural relations and separations.
Max ERC Funding
2 433 234 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym CROWDED-PRO-LIPIDS
Project Computational Perspective to Dynamical Protein-Lipid Complexes under Crowded Conditions
Researcher (PI) Ilpo Tapio Vattulainen
Host Institution (HI) TTY-SAATIO
Call Details Advanced Grant (AdG), PE3, ERC-2011-ADG_20110209
Summary "One of the great challenges is to understand how cellular functions emerge in cell membrane systems. Unlocking this mystery is the key to the vast majority of human diseases. The current view is based on a static picture where membrane proteins in protein-poor membranes interact with a few specific lipids, while in reality the situation is much more complicated. This ambitious project aims for a breakthrough by changing the present paradigm. The objective is to focus on the dynamical interplay between lipids and proteins under crowded conditions, paving the way for understanding the dynamics of lipid-protein complexes and their resulting functions. The objectives are outstanding and contain a high risk, with exceptional gain. The main goal is better understanding of the physical principles that give rise to cellular functions, with a strong impact to clarify the relevance of dynamical lipid-protein interactions in cellular processes related to health and disease. For this purpose, the grand themes chosen for this project are lipoproteins coupled to cardiovascular disease (“good” and “bad” cholesterol) and the function of especially cholesterol and glycolipids with membrane proteins. In order to meet these goals, the applicant employs state-of-the-art simulation techniques that comprise quantum-mechanical, classical atomistic and coarse-grained simulation methods to elucidate the complex biological phenomena associated with lipid-protein systems. The simulations cover atomistic and molecular details, over time scales from femtoseconds up to milliseconds. The theory & simulation group lead by PI comprises expertise in a truly cross- and multi-disciplinary manner, and it strongly collaborates with some of the leading experimental teams in biomedical sciences, cell biology, structural biology, and membrane biophysics."
Summary
"One of the great challenges is to understand how cellular functions emerge in cell membrane systems. Unlocking this mystery is the key to the vast majority of human diseases. The current view is based on a static picture where membrane proteins in protein-poor membranes interact with a few specific lipids, while in reality the situation is much more complicated. This ambitious project aims for a breakthrough by changing the present paradigm. The objective is to focus on the dynamical interplay between lipids and proteins under crowded conditions, paving the way for understanding the dynamics of lipid-protein complexes and their resulting functions. The objectives are outstanding and contain a high risk, with exceptional gain. The main goal is better understanding of the physical principles that give rise to cellular functions, with a strong impact to clarify the relevance of dynamical lipid-protein interactions in cellular processes related to health and disease. For this purpose, the grand themes chosen for this project are lipoproteins coupled to cardiovascular disease (“good” and “bad” cholesterol) and the function of especially cholesterol and glycolipids with membrane proteins. In order to meet these goals, the applicant employs state-of-the-art simulation techniques that comprise quantum-mechanical, classical atomistic and coarse-grained simulation methods to elucidate the complex biological phenomena associated with lipid-protein systems. The simulations cover atomistic and molecular details, over time scales from femtoseconds up to milliseconds. The theory & simulation group lead by PI comprises expertise in a truly cross- and multi-disciplinary manner, and it strongly collaborates with some of the leading experimental teams in biomedical sciences, cell biology, structural biology, and membrane biophysics."
Max ERC Funding
1 920 334 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym CUMTAS
Project Customized Micro Total Analysis Systems to Study Human Phase I Metabolism
Researcher (PI) Tiina Marjukka Sikanen
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS9, ERC-2012-StG_20111109
Summary The goal of this project is to develop inexpensive, high-throughput technology to screen the thus far unexplored metabolic interactions between environmental and household chemicals and clinically relevant drugs. The main influential focus will be on human phase I metabolism (redox reactions) of common toxicants like agrochemicals and plasticizers. On the basis of their structural resemblance to pharmaceuticals and endogenous compounds, many of these chemicals are suspected to have critical effects on cytochrome P450 metabolism which is the main detoxification route of pharmaceuticals in man. However, with the current analytical instrumentation, screening of such large chemical pool would take several years, and new chemicals would be introduced faster than the old ones are screened. Thus, the main technological goal of this project is to develop novel, practically zero-cost analytical instruments that enable characterization of a compound’s metabolic profile at very high speed (<1 min/sample). This goal is achieved through miniaturization and high degree of integration of analytical instrumentation by microfabrication means, an approach often called lab(oratory)-on-a-chip. The microfabricated arrays are envisioned to incorporate all analytical key functions required (i.e., sample pretreatment, metabolic reaction, separation of the reaction products, detection) on a single chip. Thanks to the reduced dimensions, the amount of chemical waste and consumption of expensive reagents are significantly reduced. In this project, several different microfabrication techniques, from delicate cleanroom processes to extremely simple printing techniques, will be exploited to produce smart microfluidic designs and multifunctional surfaces. Towards the end of the project, more focus will be put on “printable microfluidics” which provides a truly low-cost approach for fabrication of highly customized microfluidic assays. Numerical modelling is also an integral part of the work.
Summary
The goal of this project is to develop inexpensive, high-throughput technology to screen the thus far unexplored metabolic interactions between environmental and household chemicals and clinically relevant drugs. The main influential focus will be on human phase I metabolism (redox reactions) of common toxicants like agrochemicals and plasticizers. On the basis of their structural resemblance to pharmaceuticals and endogenous compounds, many of these chemicals are suspected to have critical effects on cytochrome P450 metabolism which is the main detoxification route of pharmaceuticals in man. However, with the current analytical instrumentation, screening of such large chemical pool would take several years, and new chemicals would be introduced faster than the old ones are screened. Thus, the main technological goal of this project is to develop novel, practically zero-cost analytical instruments that enable characterization of a compound’s metabolic profile at very high speed (<1 min/sample). This goal is achieved through miniaturization and high degree of integration of analytical instrumentation by microfabrication means, an approach often called lab(oratory)-on-a-chip. The microfabricated arrays are envisioned to incorporate all analytical key functions required (i.e., sample pretreatment, metabolic reaction, separation of the reaction products, detection) on a single chip. Thanks to the reduced dimensions, the amount of chemical waste and consumption of expensive reagents are significantly reduced. In this project, several different microfabrication techniques, from delicate cleanroom processes to extremely simple printing techniques, will be exploited to produce smart microfluidic designs and multifunctional surfaces. Towards the end of the project, more focus will be put on “printable microfluidics” which provides a truly low-cost approach for fabrication of highly customized microfluidic assays. Numerical modelling is also an integral part of the work.
Max ERC Funding
1 499 668 €
Duration
Start date: 2013-05-01, End date: 2019-02-28
Project acronym D-TECT
Project Does dust triboelectrification affect our climate?
Researcher (PI) Vasileios AMOIRIDIS
Host Institution (HI) NATIONAL OBSERVATORY OF ATHENS
Call Details Consolidator Grant (CoG), PE10, ERC-2016-COG
Summary The recent IPCC report identifies mineral dust and the associated uncertainties in climate projections as key topics for future research. Dust size distribution in climate models controls the dust-radiation-cloud interactions and is a major contributor to these uncertainties. Observations show that the coarse mode of dust can be sustained during long-range transport, while current understanding fails in explaining why the lifetime of large airborne dust particles is longer than expected from gravitational settling theories. This discrepancy between observations and theory suggests that other processes counterbalance the effect of gravity along transport. D-TECT envisages filling this knowledge gap by studying the contribution of the triboelectrification (contact electrification) on particle removal processes. Our hypothesis is that triboelectric charging generates adequate electric fields to hold large dust particles up in the atmosphere. D-TECT aims to (i) parameterize the physical mechanisms responsible for dust triboelectrification; (ii) assess the impact of electrification on dust settling; (iii) quantify the climatic impacts of the process, particularly the effect on the dust size evolution during transport, on dry deposition and on CCN/IN reservoirs, and the effect of the electric field on particle orientation and on radiative transfer. The approach involves the development of a novel specialized high-power lidar system to detect and characterize aerosol particle orientation and a large-scale field experiment in the Mediterranean Basin using unprecedented ground-based remote sensing and airborne in-situ observation synergies. Considering aerosol-electricity interactions, the observations will be used to improve theoretical understanding and simulations of dust lifecycle. The project will provide new fundamental understanding, able to open new horizons for weather and climate science, including biogeochemistry, volcanic ash and extraterrestrial dust research.
Summary
The recent IPCC report identifies mineral dust and the associated uncertainties in climate projections as key topics for future research. Dust size distribution in climate models controls the dust-radiation-cloud interactions and is a major contributor to these uncertainties. Observations show that the coarse mode of dust can be sustained during long-range transport, while current understanding fails in explaining why the lifetime of large airborne dust particles is longer than expected from gravitational settling theories. This discrepancy between observations and theory suggests that other processes counterbalance the effect of gravity along transport. D-TECT envisages filling this knowledge gap by studying the contribution of the triboelectrification (contact electrification) on particle removal processes. Our hypothesis is that triboelectric charging generates adequate electric fields to hold large dust particles up in the atmosphere. D-TECT aims to (i) parameterize the physical mechanisms responsible for dust triboelectrification; (ii) assess the impact of electrification on dust settling; (iii) quantify the climatic impacts of the process, particularly the effect on the dust size evolution during transport, on dry deposition and on CCN/IN reservoirs, and the effect of the electric field on particle orientation and on radiative transfer. The approach involves the development of a novel specialized high-power lidar system to detect and characterize aerosol particle orientation and a large-scale field experiment in the Mediterranean Basin using unprecedented ground-based remote sensing and airborne in-situ observation synergies. Considering aerosol-electricity interactions, the observations will be used to improve theoretical understanding and simulations of dust lifecycle. The project will provide new fundamental understanding, able to open new horizons for weather and climate science, including biogeochemistry, volcanic ash and extraterrestrial dust research.
Max ERC Funding
1 968 000 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym DAMAGECONTROL
Project Tissue Damage Control Regulates The Pathogenesis of Immune Mediated Inflammatory Diseases
Researcher (PI) Miguel Parreira Soares
Host Institution (HI) FUNDACAO CALOUSTE GULBENKIAN
Call Details Advanced Grant (AdG), LS6, ERC-2011-ADG_20110310
Summary "We propose to study evolutionarily conserved stress-responsive protective mechanisms that limit the extent of tissue damage caused by pathogens or by the innate as well as adaptive immune response elicited by those pathogens, which, without a countervailing response would lead to irreversible tissue damage and disease. We refer to these protective mechanisms as “tissue damage control”, and will argue they are an essential component of immunity that allows the effector mechanisms involved in pathogen clearance to operate without causing disease. This proposal aims at identifying and characterizing the mechanism of action of stress-induced genetic programs conferring tissue damage control and to relate those to the pathogenesis of different immune mediated inflammatory diseases. We hypothesize that these genetic programs share as a common denominator their regulation by a restricted number of evolutionary conserved transcription factors that act as “master regulators” of different protective responses to specific forms of stress. We will use “loss” and “gain” of function approaches targeting these master regulators in mice to characterize their function and identify stress-responsive genes conferring tissue metabolic adaptation, cytoprotection and/or tissue regeneration, all of which are components of tissue damage control. Expression of these master regulators likely impacts the pathogenesis of immune mediated inflammatory conditions, as tested under this proposal for infectious as well as autoimmune-like diseases. This proposal should unveil an essential component of immunity that uncouples pathogen clearance from tissue damage and disease, namely tissue damage control, providing new therapeutic targets to suppress the pathogenesis of a broad range of immune mediated inflammatory diseases."
Summary
"We propose to study evolutionarily conserved stress-responsive protective mechanisms that limit the extent of tissue damage caused by pathogens or by the innate as well as adaptive immune response elicited by those pathogens, which, without a countervailing response would lead to irreversible tissue damage and disease. We refer to these protective mechanisms as “tissue damage control”, and will argue they are an essential component of immunity that allows the effector mechanisms involved in pathogen clearance to operate without causing disease. This proposal aims at identifying and characterizing the mechanism of action of stress-induced genetic programs conferring tissue damage control and to relate those to the pathogenesis of different immune mediated inflammatory diseases. We hypothesize that these genetic programs share as a common denominator their regulation by a restricted number of evolutionary conserved transcription factors that act as “master regulators” of different protective responses to specific forms of stress. We will use “loss” and “gain” of function approaches targeting these master regulators in mice to characterize their function and identify stress-responsive genes conferring tissue metabolic adaptation, cytoprotection and/or tissue regeneration, all of which are components of tissue damage control. Expression of these master regulators likely impacts the pathogenesis of immune mediated inflammatory conditions, as tested under this proposal for infectious as well as autoimmune-like diseases. This proposal should unveil an essential component of immunity that uncouples pathogen clearance from tissue damage and disease, namely tissue damage control, providing new therapeutic targets to suppress the pathogenesis of a broad range of immune mediated inflammatory diseases."
Max ERC Funding
2 306 197 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym DAMOCLES
Project Simulating Non-Equilibrium Dynamics of Atmospheric Multicomponent Clusters
Researcher (PI) Hanna Vehkamäki
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Advanced Grant (AdG), PE10, ERC-2015-AdG
Summary Atmospheric aerosol particles play a key role in regulating the climate, and particulate matter is responsible for most of the 7 million deaths per year attributed to air pollution. Lack of understanding of aerosol processes, especially the formation of ice crystals and secondary particles from condensable trace gases, hampers the development of air quality modelling, and remains one of the major uncertainties in predicting climate.
The purpose of this project is to achieve a comprehensive understanding of atmospheric nanocluster and ice crystal formation based on fundamental physico-chemical principles. We will use a wide palette of theoretical methods including quantum chemistry, reaction kinetics, continuum solvent models, molecular dynamics, Monte Carlo simulations, Markov chain Monte Carlo methods, computational fluid dynamics, cluster kinetic and thermodynamic models. We will study non-equilibrium effects and kinetic barriers in atmospheric clustering, and use these to build cluster distribution models with genuine predictive capacity.
Chemical ionization mass spectrometers can, unlike any other instruments, detect the elemental composition of many of the smallest clusters at ambient low concentrations. However, the charging process and the environment inside the instrument change the composition of the clusters in hitherto unquantifiable ways. We will solve this problem by building an accurate model for the fate of clusters inside mass spectrometers, which will vastly improve the amount and quality of information that can be extracted from mass spectrometric measurements in atmospheric science and elsewhere.
DAMOCLES will produce reliable and consistent models for secondary aerosol and ice particle formation and growth. This will lead to improved predictions of aerosol concentrations and size distributions, leading to improved air quality forecasting, more accurate estimates of aerosol indirect climate forcing and other aerosol-cloud-climate interactions.
Summary
Atmospheric aerosol particles play a key role in regulating the climate, and particulate matter is responsible for most of the 7 million deaths per year attributed to air pollution. Lack of understanding of aerosol processes, especially the formation of ice crystals and secondary particles from condensable trace gases, hampers the development of air quality modelling, and remains one of the major uncertainties in predicting climate.
The purpose of this project is to achieve a comprehensive understanding of atmospheric nanocluster and ice crystal formation based on fundamental physico-chemical principles. We will use a wide palette of theoretical methods including quantum chemistry, reaction kinetics, continuum solvent models, molecular dynamics, Monte Carlo simulations, Markov chain Monte Carlo methods, computational fluid dynamics, cluster kinetic and thermodynamic models. We will study non-equilibrium effects and kinetic barriers in atmospheric clustering, and use these to build cluster distribution models with genuine predictive capacity.
Chemical ionization mass spectrometers can, unlike any other instruments, detect the elemental composition of many of the smallest clusters at ambient low concentrations. However, the charging process and the environment inside the instrument change the composition of the clusters in hitherto unquantifiable ways. We will solve this problem by building an accurate model for the fate of clusters inside mass spectrometers, which will vastly improve the amount and quality of information that can be extracted from mass spectrometric measurements in atmospheric science and elsewhere.
DAMOCLES will produce reliable and consistent models for secondary aerosol and ice particle formation and growth. This will lead to improved predictions of aerosol concentrations and size distributions, leading to improved air quality forecasting, more accurate estimates of aerosol indirect climate forcing and other aerosol-cloud-climate interactions.
Max ERC Funding
2 390 450 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym DARE
Project Soil Foundation Structure Systems Beyond Conventional Seismic Failure Thresholds: Application to New or Existing Structures and Monuments
Researcher (PI) George Gazetas
Host Institution (HI) NATIONAL TECHNICAL UNIVERSITY OF ATHENS - NTUA
Call Details Advanced Grant (AdG), PE8, ERC-2008-AdG
Summary The main goal of the proposed research is to investigate the possibility of allowing below-ground support systems to respond to strong seismic shaking by going beyond a number of thresholds that would conventionally imply failure and are today forbidden by codes. Such thresholds include : (a) sliding at the soil-foundation interface ; (b) separation and uplifting of a shallow foundation from the soils ; (c) mobilization of bearing capacity failure mechanism for shallow foundations ; (d) structural yielding of pile foundations ; (e) combination of some of the above. Whereas under static loading conditions a slight exceedance of such thresholds leads to failure, the oscillatory nature of seismic shaking will allow such exceedances for a short period of time, with perhaps no detrimental or irreparable consequences. The latter take the form of permanent foundation displacements, rotations, or injuries , which the designer will aspire to confine within rational limits. The motivation and the need for this research has come from : (i) observations of actual behaviour in a variety of earthquakes ; conspicuous examples : the permanent tilting , overturning, and often survival of numerous buildings on extremely soft soil in Adapazari during the Kocaeli 1999 earthquake ; (ii) the foundation design of a number of critical structures (e.g., major bridge pier, air control tower, tall monuments, elevated water tanks,) against large seismic actions ; the disproportionately large overturning moment and/or base shear force of such slender structures can hardly be faced with today s conventional foundation methods, (iii) the need to seismically retrofit and rehabilitate older structures and historical monuments; (iv) structural yielding of pile foundations is now detectable (thanks to technological advances), thus eliminating one of the reasons for avoiding it.
Summary
The main goal of the proposed research is to investigate the possibility of allowing below-ground support systems to respond to strong seismic shaking by going beyond a number of thresholds that would conventionally imply failure and are today forbidden by codes. Such thresholds include : (a) sliding at the soil-foundation interface ; (b) separation and uplifting of a shallow foundation from the soils ; (c) mobilization of bearing capacity failure mechanism for shallow foundations ; (d) structural yielding of pile foundations ; (e) combination of some of the above. Whereas under static loading conditions a slight exceedance of such thresholds leads to failure, the oscillatory nature of seismic shaking will allow such exceedances for a short period of time, with perhaps no detrimental or irreparable consequences. The latter take the form of permanent foundation displacements, rotations, or injuries , which the designer will aspire to confine within rational limits. The motivation and the need for this research has come from : (i) observations of actual behaviour in a variety of earthquakes ; conspicuous examples : the permanent tilting , overturning, and often survival of numerous buildings on extremely soft soil in Adapazari during the Kocaeli 1999 earthquake ; (ii) the foundation design of a number of critical structures (e.g., major bridge pier, air control tower, tall monuments, elevated water tanks,) against large seismic actions ; the disproportionately large overturning moment and/or base shear force of such slender structures can hardly be faced with today s conventional foundation methods, (iii) the need to seismically retrofit and rehabilitate older structures and historical monuments; (iv) structural yielding of pile foundations is now detectable (thanks to technological advances), thus eliminating one of the reasons for avoiding it.
Max ERC Funding
2 399 992 €
Duration
Start date: 2008-12-01, End date: 2013-10-31
