Project acronym 0MSPIN
Project Spintronics based on relativistic phenomena in systems with zero magnetic moment
Researcher (PI) Tomáš Jungwirth
Host Institution (HI) FYZIKALNI USTAV AV CR V.V.I
Call Details Advanced Grant (AdG), PE3, ERC-2010-AdG_20100224
Summary The 0MSPIN project consists of an extensive integrated theoretical, experimental and device development programme of research opening a radical new approach to spintronics. Spintronics has the potential to supersede existing storage and memory applications, and to provide alternatives to current CMOS technology. Ferromagnetic matels used in all current spintronics applications may make it impractical to realise the full potential of spintronics. Metals are unsuitable for transistor and information processing applications, for opto-electronics, or for high-density integration. The 0MSPIN project aims to remove the major road-block holding back the development of spintronics in a radical way: removing the ferromagnetic component from key active parts or from the whole of the spintronic devices. This approach is based on exploiting the combination of exchange and spin-orbit coupling phenomena and material systems with zero macroscopic moment. The goal of the 0MSPIN is to provide a new paradigm by which spintronics can enter the realms of conventional semiconductors in both fundamental condensed matter research and in information technologies. In the central part of the proposal, the research towards this goal is embedded within a materials science project whose aim is to introduce into physics and microelectronics an entirely new class of semiconductors. 0MSPIN seeks to exploit three classes of material systems: (1) Antiferromagnetic bi-metallic 3d-5d alloys (e.g. Mn2Au). (2) Antiferromagnetic I-II-V semiconductors (e.g. LiMnAs). (3) Non-magnetic spin-orbit coupled semiconductors with injected spin-polarized currents (e.g. 2D III-V structures). Proof of concept devices operating at high temperatures will be fabricated to show-case new functionalities offered by zero-moment systems for sensing and memory applications, information processing, and opto-electronics technologies.
Summary
The 0MSPIN project consists of an extensive integrated theoretical, experimental and device development programme of research opening a radical new approach to spintronics. Spintronics has the potential to supersede existing storage and memory applications, and to provide alternatives to current CMOS technology. Ferromagnetic matels used in all current spintronics applications may make it impractical to realise the full potential of spintronics. Metals are unsuitable for transistor and information processing applications, for opto-electronics, or for high-density integration. The 0MSPIN project aims to remove the major road-block holding back the development of spintronics in a radical way: removing the ferromagnetic component from key active parts or from the whole of the spintronic devices. This approach is based on exploiting the combination of exchange and spin-orbit coupling phenomena and material systems with zero macroscopic moment. The goal of the 0MSPIN is to provide a new paradigm by which spintronics can enter the realms of conventional semiconductors in both fundamental condensed matter research and in information technologies. In the central part of the proposal, the research towards this goal is embedded within a materials science project whose aim is to introduce into physics and microelectronics an entirely new class of semiconductors. 0MSPIN seeks to exploit three classes of material systems: (1) Antiferromagnetic bi-metallic 3d-5d alloys (e.g. Mn2Au). (2) Antiferromagnetic I-II-V semiconductors (e.g. LiMnAs). (3) Non-magnetic spin-orbit coupled semiconductors with injected spin-polarized currents (e.g. 2D III-V structures). Proof of concept devices operating at high temperatures will be fabricated to show-case new functionalities offered by zero-moment systems for sensing and memory applications, information processing, and opto-electronics technologies.
Max ERC Funding
1 938 000 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym ARMOS
Project Advanced multifunctional Reactors for green Mobility and Solar fuels
Researcher (PI) Athanasios Konstandopoulos
Host Institution (HI) ETHNIKO KENTRO EREVNAS KAI TECHNOLOGIKIS ANAPTYXIS
Call Details Advanced Grant (AdG), PE8, ERC-2010-AdG_20100224
Summary Green Mobility requires an integrated approach to the chain fuel/engine/emissions. The present project aims at ground breaking advances in the area of Green Mobility by (a) enabling the production of affordable, carbon-neutral, clean, solar fuels using exclusively renewable/recyclable raw materials, namely solar energy, water and captured Carbon Dioxide from combustion power plants (b) developing a highly compact, multifunctional reactor, able to eliminate gaseous and particulate emissions from the exhaust of engines operated on such clean fuels.
The overall research approach will be based on material science, engineering and simulation technology developed by the PI over the past 20 years in the area of Diesel Emission Control Reactors, which will be further extended and cross-fertilized in the area of Solar Thermochemical Reactors, an emerging discipline of high importance for sustainable development, where the PI’s research group has already made significant contributions, and received the 2006 European Commission’s Descartes Prize for the development of the first ever solar reactor, holding the potential to produce on a large scale, pure renewable Hydrogen from the thermochemical splitting of water, also known as the HYDROSOL technology.
Summary
Green Mobility requires an integrated approach to the chain fuel/engine/emissions. The present project aims at ground breaking advances in the area of Green Mobility by (a) enabling the production of affordable, carbon-neutral, clean, solar fuels using exclusively renewable/recyclable raw materials, namely solar energy, water and captured Carbon Dioxide from combustion power plants (b) developing a highly compact, multifunctional reactor, able to eliminate gaseous and particulate emissions from the exhaust of engines operated on such clean fuels.
The overall research approach will be based on material science, engineering and simulation technology developed by the PI over the past 20 years in the area of Diesel Emission Control Reactors, which will be further extended and cross-fertilized in the area of Solar Thermochemical Reactors, an emerging discipline of high importance for sustainable development, where the PI’s research group has already made significant contributions, and received the 2006 European Commission’s Descartes Prize for the development of the first ever solar reactor, holding the potential to produce on a large scale, pure renewable Hydrogen from the thermochemical splitting of water, also known as the HYDROSOL technology.
Max ERC Funding
1 750 000 €
Duration
Start date: 2011-02-01, End date: 2017-01-31
Project acronym ATMOPACS
Project Atmospheric Organic Particulate Matter, Air Quality and Climate Change Studies
Researcher (PI) Spyridon Pandis
Host Institution (HI) FOUNDATION FOR RESEARCH AND TECHNOLOGY HELLAS
Call Details Advanced Grant (AdG), PE10, ERC-2010-AdG_20100224
Summary Despite its importance for human health and climate change organic aerosol (OA) remains one of the least understood aspects of atmospheric chemistry. We propose to develop an innovative new framework for the description of OA in chemical transport and climate models that will be able to overcome the challenges posed by the chemical complexity of OA while capturing its essential features.
The objectives of ATMOPACS are: (i) The development of a new unified framework for the description of OA based on its two most important parameters: volatility and oxygen content. (ii) The development of measurement techniques for the volatility distribution and oxygen content distribution of OA. This will allow the experimental characterization of OA in this new “coordinate system”. (iii) The study of the major OA processes (partitioning, chemical aging, hygroscopicity, CCN formation, nucleation) in this new framework combining lab and field measurements. (iv) The development and evaluation of the next generation of regional and global CTMs using the above framework. (v) The quantification of the importance of the various sources and formation pathways of OA in Europe and the world, of the sensitivity of OA to emission control strategies, and its role in the direct and indirect effects of aerosols on climate.
The proposed work involves a combination of laboratory measurements, field measurements including novel “atmospheric perturbation experiments”, OA model development, and modelling in urban, regional, and global scales. Therefore, it will span the system scales starting from the nanoscale to the global. The modelling tools that will be developed will be made available to all other research groups.
Summary
Despite its importance for human health and climate change organic aerosol (OA) remains one of the least understood aspects of atmospheric chemistry. We propose to develop an innovative new framework for the description of OA in chemical transport and climate models that will be able to overcome the challenges posed by the chemical complexity of OA while capturing its essential features.
The objectives of ATMOPACS are: (i) The development of a new unified framework for the description of OA based on its two most important parameters: volatility and oxygen content. (ii) The development of measurement techniques for the volatility distribution and oxygen content distribution of OA. This will allow the experimental characterization of OA in this new “coordinate system”. (iii) The study of the major OA processes (partitioning, chemical aging, hygroscopicity, CCN formation, nucleation) in this new framework combining lab and field measurements. (iv) The development and evaluation of the next generation of regional and global CTMs using the above framework. (v) The quantification of the importance of the various sources and formation pathways of OA in Europe and the world, of the sensitivity of OA to emission control strategies, and its role in the direct and indirect effects of aerosols on climate.
The proposed work involves a combination of laboratory measurements, field measurements including novel “atmospheric perturbation experiments”, OA model development, and modelling in urban, regional, and global scales. Therefore, it will span the system scales starting from the nanoscale to the global. The modelling tools that will be developed will be made available to all other research groups.
Max ERC Funding
2 496 000 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym CODAMODA
Project Controlling Data Movement in the Digital Age
Researcher (PI) Aggelos Kiayias
Host Institution (HI) ETHNIKO KAI KAPODISTRIAKO PANEPISTIMIO ATHINON
Call Details Starting Grant (StG), PE6, ERC-2010-StG_20091028
Summary Nowadays human intellectual product is increasingly produced and disseminated solely in digital form. The capability of digital data for effortless reproduction and transfer has lead to a true revolution that impacts every aspect of human creativity. Nevertheless, as with every technological revolution, this digital media revolution comes with a dark side that, if left unaddressed, it will limit its impact and may counter its potential advantages. In particular, the way we produce and disseminate digital content today does not lend itself to controlling the way data move and change. It turns out that the power of being digital can be a double-edged sword: the ease of production, dissemination and editing also implies the ease of misappropriation, plagiarism and improper modification.
To counter the above problems, the proposed research activity will focus on the development of a new generation of enabling cryptographic technologies that have the power to facilitate the appropriate controls for data movement. Using the techniques developed in this project it will be feasible to build digital content distribution systems where content producers will have the full possible control on the dissemination of their intellectual product, while at the same time the rights of the end-users in terms of privacy and fair use can be preserved. The PI is uniquely qualified to carry out the proposed research activity as he has extensive prior experience in making innovations in the area of digital content distribution as well as in the management of research projects. As part of the project activities, the PI will establish the CODAMODA laboratory in the University of Athens and will seek opportunities for technology transfer and interdisciplinary work with the legal science community.
Summary
Nowadays human intellectual product is increasingly produced and disseminated solely in digital form. The capability of digital data for effortless reproduction and transfer has lead to a true revolution that impacts every aspect of human creativity. Nevertheless, as with every technological revolution, this digital media revolution comes with a dark side that, if left unaddressed, it will limit its impact and may counter its potential advantages. In particular, the way we produce and disseminate digital content today does not lend itself to controlling the way data move and change. It turns out that the power of being digital can be a double-edged sword: the ease of production, dissemination and editing also implies the ease of misappropriation, plagiarism and improper modification.
To counter the above problems, the proposed research activity will focus on the development of a new generation of enabling cryptographic technologies that have the power to facilitate the appropriate controls for data movement. Using the techniques developed in this project it will be feasible to build digital content distribution systems where content producers will have the full possible control on the dissemination of their intellectual product, while at the same time the rights of the end-users in terms of privacy and fair use can be preserved. The PI is uniquely qualified to carry out the proposed research activity as he has extensive prior experience in making innovations in the area of digital content distribution as well as in the management of research projects. As part of the project activities, the PI will establish the CODAMODA laboratory in the University of Athens and will seek opportunities for technology transfer and interdisciplinary work with the legal science community.
Max ERC Funding
1 212 960 €
Duration
Start date: 2011-04-01, End date: 2017-03-31
Project acronym DOGPSYCH
Project Canine models of human psychiatric disease: identifying novel anxiety genes with the help of man's best friend
Researcher (PI) Hannes Tapani Lohi
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary Anxiety disorders include different forms of pathological fear and anxiety and rank among the most common health concerns in human medicine. Millions of people become affected every year, and many of them do not respond to treatments. Anxiety disorders are heritable, but genetically complex. As a result, traditional gene mapping methods in the human population with prominent locus and allelic heterogeneity have not succeeded. Similarly, rodents have provided some insights into the circuitry of anxiety, but naturally occurring versions do not exist and gene deletion studies have not provided adequate models. To break through and identify new anxiety genes, I propose a novel and unique approach that resorts to man s best friend, dog. Taking advantage of the exaggerated genetic homogeneity characteristic of purebred dogs, recent genomics tools and the existence of naturally occurring heritable behaviour disorders in dogs can remedy the current lack of a suitable animal model of human psychiatric disorders. I propose to collect and perform a genome-wide association study in four breed-specific anxiety traits in dogs representing the three major forms of human anxiety: compulsive pacing and tail-chasing, noise phobia, and shyness corresponding to human OCD, panic disorder and social phobia, respectively. Canine anxiety disorders respond to human medications and other phenomenological studies suggest a share biological mechanism in both species. The proposed research has the potential to discover new genetic risk factors, which eventually will shed light on the biological basis of common neuropsychiatric disorders in both dog and human, provide insight into etiological mechanisms, enable identification of individuals at high-risk for adverse health outcomes, and facilitate development of tailored treatments.
Summary
Anxiety disorders include different forms of pathological fear and anxiety and rank among the most common health concerns in human medicine. Millions of people become affected every year, and many of them do not respond to treatments. Anxiety disorders are heritable, but genetically complex. As a result, traditional gene mapping methods in the human population with prominent locus and allelic heterogeneity have not succeeded. Similarly, rodents have provided some insights into the circuitry of anxiety, but naturally occurring versions do not exist and gene deletion studies have not provided adequate models. To break through and identify new anxiety genes, I propose a novel and unique approach that resorts to man s best friend, dog. Taking advantage of the exaggerated genetic homogeneity characteristic of purebred dogs, recent genomics tools and the existence of naturally occurring heritable behaviour disorders in dogs can remedy the current lack of a suitable animal model of human psychiatric disorders. I propose to collect and perform a genome-wide association study in four breed-specific anxiety traits in dogs representing the three major forms of human anxiety: compulsive pacing and tail-chasing, noise phobia, and shyness corresponding to human OCD, panic disorder and social phobia, respectively. Canine anxiety disorders respond to human medications and other phenomenological studies suggest a share biological mechanism in both species. The proposed research has the potential to discover new genetic risk factors, which eventually will shed light on the biological basis of common neuropsychiatric disorders in both dog and human, provide insight into etiological mechanisms, enable identification of individuals at high-risk for adverse health outcomes, and facilitate development of tailored treatments.
Max ERC Funding
1 381 807 €
Duration
Start date: 2010-10-01, End date: 2015-09-30
Project acronym GEDA
Project Global Environmental Decision Analysis
Researcher (PI) Atte Jaakko Moilanen
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary Habitat degradation and climate change are generally considered the greatest threats to biodiversity globally. Together, these processes pose an urgent challenge to conservation science, requiring ever increasing efficiency in ecologically-based decision making, to slow down, and hopefully eventually reverse, the ongoing global loss of biodiversity. In responding to this challenge, I am proposing a project in which the over-arching goal is to provide improved conservation-oriented analytical methods and tools to underpin knowledge-based land-use planning and associated political decision making. The proposed work builds on a broad established history of research in the field of spatial ecology and conservation prioritization.
Specific components of the proposal include: (i) developing the general conceptual, ecological, methodological and statistical basis of environmental and conservation resource allocation: (ii) combining species and community-level prioritization approaches for data-poor areas of the world; (iii) developing methods for alleviating the negative ecological consequences of climate change, based on connectivity both in geographic and environmental space; (iv) developing an uncertainty-analytic method for the planning of habitat restoration and calculation of compensation ratios for habitat that will be impacted due to economic activity, (v) developing methods for allocating alternative conservation actions (protection, maintenance, restoration) in combination with habitat-specific loss rates in spatial conservation prioritization, and (vi) implementing the proposed methods as publicly available, efficient and well-documented software packages. Particular emphasis will be placed on solving the algorithmic challenges involved in analyzing the large data sets that are becoming increasingly available as the distributions of environmental conditions and biodiversity features are derived from large-scale high-resolution remote-sensing data.
Summary
Habitat degradation and climate change are generally considered the greatest threats to biodiversity globally. Together, these processes pose an urgent challenge to conservation science, requiring ever increasing efficiency in ecologically-based decision making, to slow down, and hopefully eventually reverse, the ongoing global loss of biodiversity. In responding to this challenge, I am proposing a project in which the over-arching goal is to provide improved conservation-oriented analytical methods and tools to underpin knowledge-based land-use planning and associated political decision making. The proposed work builds on a broad established history of research in the field of spatial ecology and conservation prioritization.
Specific components of the proposal include: (i) developing the general conceptual, ecological, methodological and statistical basis of environmental and conservation resource allocation: (ii) combining species and community-level prioritization approaches for data-poor areas of the world; (iii) developing methods for alleviating the negative ecological consequences of climate change, based on connectivity both in geographic and environmental space; (iv) developing an uncertainty-analytic method for the planning of habitat restoration and calculation of compensation ratios for habitat that will be impacted due to economic activity, (v) developing methods for allocating alternative conservation actions (protection, maintenance, restoration) in combination with habitat-specific loss rates in spatial conservation prioritization, and (vi) implementing the proposed methods as publicly available, efficient and well-documented software packages. Particular emphasis will be placed on solving the algorithmic challenges involved in analyzing the large data sets that are becoming increasingly available as the distributions of environmental conditions and biodiversity features are derived from large-scale high-resolution remote-sensing data.
Max ERC Funding
1 495 213 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym IMMA
Project Integrating the Multiple Meta-Analysis: a framework for evaluating and ranking multiple health care technologies
Researcher (PI) Georgia Salanti
Host Institution (HI) PANEPISTIMIO IOANNINON
Call Details Starting Grant (StG), LS7, ERC-2010-StG_20091118
Summary Health care practitioners face daily questions and make choices regarding the effectiveness and quality of several health technologies (e.g. alternative interventions). On this regard they usually consider meta-analysis; the statistical synthesis of results from relevant experiments. The main drawback of the current state of the art is that meta-analysis focuses on comparing only two alternatives. However, clinicians and scientists need to know the relative ranking of a set of alternative options and not only whether option A is better than B. There is an urgent need to establish and disseminate a robust framework for selecting among many treatment options, possibly after taking into account environmental and genetic interactions. The goal of the proposed project is to provide this by establishing and disseminating a revolutionary evidence synthesis toolkit. Its main methodological vehicle is a flexible statistical framework using Bayesian techniques for multiple-treatments meta-analysis. This will enable the relative ranking of all alternative health care options, will allow comprehensive use of all available data, will improve precision and confidence in the conclusions and will answer methodological questions related to bias. Once established in clinical epidemiology, the tool will be extended to genetic epidemiology to account for multiple genetic markers, environmental factors and effects of treatments. Based on ongoing collaborations with teams undertaking applied health care research I plan to evaluate the new tool empirically in real-life health care problems such as ranking the pharmacological treatments for osteoarthritis, indicating the best treatments for multiple sclerosis and ranking the vaccines for influenza.
Summary
Health care practitioners face daily questions and make choices regarding the effectiveness and quality of several health technologies (e.g. alternative interventions). On this regard they usually consider meta-analysis; the statistical synthesis of results from relevant experiments. The main drawback of the current state of the art is that meta-analysis focuses on comparing only two alternatives. However, clinicians and scientists need to know the relative ranking of a set of alternative options and not only whether option A is better than B. There is an urgent need to establish and disseminate a robust framework for selecting among many treatment options, possibly after taking into account environmental and genetic interactions. The goal of the proposed project is to provide this by establishing and disseminating a revolutionary evidence synthesis toolkit. Its main methodological vehicle is a flexible statistical framework using Bayesian techniques for multiple-treatments meta-analysis. This will enable the relative ranking of all alternative health care options, will allow comprehensive use of all available data, will improve precision and confidence in the conclusions and will answer methodological questions related to bias. Once established in clinical epidemiology, the tool will be extended to genetic epidemiology to account for multiple genetic markers, environmental factors and effects of treatments. Based on ongoing collaborations with teams undertaking applied health care research I plan to evaluate the new tool empirically in real-life health care problems such as ranking the pharmacological treatments for osteoarthritis, indicating the best treatments for multiple sclerosis and ranking the vaccines for influenza.
Max ERC Funding
592 500 €
Duration
Start date: 2010-10-01, End date: 2015-12-31
Project acronym INVPROB
Project Inverse Problems
Researcher (PI) Lassi Juhani Päivärinta
Host Institution (HI) TALLINNA TEHNIKAULIKOOL
Call Details Advanced Grant (AdG), PE1, ERC-2010-AdG_20100224
Summary Inverse problems constitute an interdisciplinary field of science concentrating on the mathematical theory and practical interpretation of indirect measurements. Their applications include medical imaging, atmospheric remote sensing, industrial process monitoring, and astronomical imaging. The common feature is extreme sensitivity to measurement noise. Computerized tomography, MRI, and exploration of the interior of earth by using earthquake data are typical inverse problems where mathematics has played an important role. By using the methods of inverse problems it is possible to bring modern mathematics to a vast number of applied fields. Genuine scientific innovations that are found in mathematical research, say in geometry, stochastics, or analysis, can be brought to real life applications through modelling. The solutions are often found by combining recent theoretical and computational advances. The study of inverse problems is one of the most active and fastest growing areas of modern applied mathematics, and the most interdisciplinary field of mathematics or even science in general.
The exciting but high risk problems in the research plan of the PI include mathematics of invisibility cloaking, invisible patterns, practical algorithms for imaging, and random quantum systems. Progress in these problems could have a considerable impact in applications such as construction of metamaterials for invisible optic fibre cables, scopes for MRI devices, and early screening for breast cancer. The progress here necessitates international collaboration. This will be realized in upcoming programs on inverse problems. The PI is involved in organizing semester programs in inverse problems at MSRI in 2010, Isaac Newton Institute in 2011, and Mittag-Leffler -institute in 2012.
Summary
Inverse problems constitute an interdisciplinary field of science concentrating on the mathematical theory and practical interpretation of indirect measurements. Their applications include medical imaging, atmospheric remote sensing, industrial process monitoring, and astronomical imaging. The common feature is extreme sensitivity to measurement noise. Computerized tomography, MRI, and exploration of the interior of earth by using earthquake data are typical inverse problems where mathematics has played an important role. By using the methods of inverse problems it is possible to bring modern mathematics to a vast number of applied fields. Genuine scientific innovations that are found in mathematical research, say in geometry, stochastics, or analysis, can be brought to real life applications through modelling. The solutions are often found by combining recent theoretical and computational advances. The study of inverse problems is one of the most active and fastest growing areas of modern applied mathematics, and the most interdisciplinary field of mathematics or even science in general.
The exciting but high risk problems in the research plan of the PI include mathematics of invisibility cloaking, invisible patterns, practical algorithms for imaging, and random quantum systems. Progress in these problems could have a considerable impact in applications such as construction of metamaterials for invisible optic fibre cables, scopes for MRI devices, and early screening for breast cancer. The progress here necessitates international collaboration. This will be realized in upcoming programs on inverse problems. The PI is involved in organizing semester programs in inverse problems at MSRI in 2010, Isaac Newton Institute in 2011, and Mittag-Leffler -institute in 2012.
Max ERC Funding
1 800 000 €
Duration
Start date: 2011-03-01, End date: 2016-02-29
Project acronym ISORI
Project Ion Spectroscopy of Reaction Intermediates
Researcher (PI) Jana Roithova
Host Institution (HI) UNIVERZITA KARLOVA
Call Details Starting Grant (StG), PE4, ERC-2010-StG_20091028
Summary Modern chemistry experiences a fast development of new reactions with dominance in organometallics and recently also organocatalysis. The massive synthetic progress however greatly foreruns mechanistic studies and the deeper insight is often rather limited. This large unexplored area accordingly challenges pioneering research and formulation of new concepts in chemistry. The present research project uses the most powerful tools of several research disciplines and aims towards the investigation of the elementary steps in organic reactions by means of mass spectrometry (MS) in combination with electrospray ionization (ESI) and quantum chemistry with a particular focus on ion spectroscopy.
The research will concentrate on elementary reactions in catalysis, e.g. the interaction of catalysts with substrates or bimolecular reactions of reactant/catalyst complexes. A major innovative contribution consists in applying ion spectroscopy for the structural characterization of reaction intermediates using a newly proposed tandem mass spectrometer with a cooled linear ion trap, which will allow two-photon experiments with IR and UV tunable lasers. The experiments will provide specific information about various intermediates and will help to disentangle even complicated mixtures or isomeric ions. In addition, an innovative experiment is designed, in which bimolecular reactivity of isobaric ions will be studied individually. Kinetics of selected reactions in solution will also be followed by ESI/MS. The combined efforts of these different approaches will provide a comprehensive understanding of the reaction mechanisms and will lead to the formulation of new general concepts in organic and organometallic reactivity.
Summary
Modern chemistry experiences a fast development of new reactions with dominance in organometallics and recently also organocatalysis. The massive synthetic progress however greatly foreruns mechanistic studies and the deeper insight is often rather limited. This large unexplored area accordingly challenges pioneering research and formulation of new concepts in chemistry. The present research project uses the most powerful tools of several research disciplines and aims towards the investigation of the elementary steps in organic reactions by means of mass spectrometry (MS) in combination with electrospray ionization (ESI) and quantum chemistry with a particular focus on ion spectroscopy.
The research will concentrate on elementary reactions in catalysis, e.g. the interaction of catalysts with substrates or bimolecular reactions of reactant/catalyst complexes. A major innovative contribution consists in applying ion spectroscopy for the structural characterization of reaction intermediates using a newly proposed tandem mass spectrometer with a cooled linear ion trap, which will allow two-photon experiments with IR and UV tunable lasers. The experiments will provide specific information about various intermediates and will help to disentangle even complicated mixtures or isomeric ions. In addition, an innovative experiment is designed, in which bimolecular reactivity of isobaric ions will be studied individually. Kinetics of selected reactions in solution will also be followed by ESI/MS. The combined efforts of these different approaches will provide a comprehensive understanding of the reaction mechanisms and will lead to the formulation of new general concepts in organic and organometallic reactivity.
Max ERC Funding
1 294 800 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym KRASHIMPE
Project KRas mutation interactions with host immunity in malignant pleural effusion
Researcher (PI) Georgios Stathopoulos
Host Institution (HI) PANEPISTIMIO PATRON
Call Details Starting Grant (StG), LS4, ERC-2010-StG_20091118
Summary Malignant pleural effusion (MPE) is a significant problem most commonly caused by adenocarcinomas. Although tumors involving the pleura vary in their ability to produce MPE, pathways critical for MPE formation are poorly defined. We have found that mouse tumors harboring mutant (”)KRas produce MPE in mice while tumors without ”KRas do not. LLC and MC38 lung and colon adenocarcinomas, potent inducers of MPE in syngeneic mice, harbor ”KRas that drives constitutive Ras and alternative nuclear factor (NF)-ºB signaling, inflammatory gene expression, and recruitment of specific myeloid cells to the pleural space. In contrast, mouse B16 melanoma and AE17 mesothelioma have wtKRas, lack constitutive Ras/alternative NF-º’ signaling, and are incapable of forming MPE. RNAi-mediated silencing of KRas in MC38 tumors abrogated MPE formation and Ras/alternative NF-º’ activation, while these phenomena were reconstituted in B16 tumors after KRas overexpression. We hypothesize that Ras-activating mutations drive the inflammatory phenotype of adenocarcinomas critical for MPE formation, which is characterized by Ras/alternative NF-ºB activation, inflammatory signalling to host vasculature/immune system, and recruitment of specific myeloid cells, and results in endothelial proliferation/leakiness. To test this hypothesis, we propose to: 1) define the relationship between Ras-activating mutations (RAM) and MPE formation; 2) identify tumor cell Ras-dependent signalling pathways and gene expression signature critical for MPE formation; 3) investigate the host response to tumor cells with RAM that results in MPE; and 4) target Ras and dependent signalling pathways as potential therapy for MPE. Studies will be performed using delivery of mouse/human tumors with/without RAM into the pleura of syngeneic/immunocompromized mice and are likely to yield new insights into the mechanisms of pleural tumor progression and to identify novel approaches to treatment of cancer patients with MPE.
Summary
Malignant pleural effusion (MPE) is a significant problem most commonly caused by adenocarcinomas. Although tumors involving the pleura vary in their ability to produce MPE, pathways critical for MPE formation are poorly defined. We have found that mouse tumors harboring mutant (”)KRas produce MPE in mice while tumors without ”KRas do not. LLC and MC38 lung and colon adenocarcinomas, potent inducers of MPE in syngeneic mice, harbor ”KRas that drives constitutive Ras and alternative nuclear factor (NF)-ºB signaling, inflammatory gene expression, and recruitment of specific myeloid cells to the pleural space. In contrast, mouse B16 melanoma and AE17 mesothelioma have wtKRas, lack constitutive Ras/alternative NF-º’ signaling, and are incapable of forming MPE. RNAi-mediated silencing of KRas in MC38 tumors abrogated MPE formation and Ras/alternative NF-º’ activation, while these phenomena were reconstituted in B16 tumors after KRas overexpression. We hypothesize that Ras-activating mutations drive the inflammatory phenotype of adenocarcinomas critical for MPE formation, which is characterized by Ras/alternative NF-ºB activation, inflammatory signalling to host vasculature/immune system, and recruitment of specific myeloid cells, and results in endothelial proliferation/leakiness. To test this hypothesis, we propose to: 1) define the relationship between Ras-activating mutations (RAM) and MPE formation; 2) identify tumor cell Ras-dependent signalling pathways and gene expression signature critical for MPE formation; 3) investigate the host response to tumor cells with RAM that results in MPE; and 4) target Ras and dependent signalling pathways as potential therapy for MPE. Studies will be performed using delivery of mouse/human tumors with/without RAM into the pleura of syngeneic/immunocompromized mice and are likely to yield new insights into the mechanisms of pleural tumor progression and to identify novel approaches to treatment of cancer patients with MPE.
Max ERC Funding
1 995 000 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
