Project acronym TREATSKIN
Project Tissue engineering to evaluate novel treatments for skin cancer and genetic disease
Researcher (PI) Irene May Leigh
Host Institution (HI) UNIVERSITY OF DUNDEE
Call Details Advanced Grant (AdG), LS7, ERC-2009-AdG
Summary As our understanding of disease translates from basic science to clinical application there is a need for robust preclinical models to test interventions and therapies, which mirror the clinical situation and likely outcomes. This will assist key stage decision making before costly clinical trials are commenced. Skin diseases represent a significant health burden. Non-melanoma skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common human malignancies. Genetic skin diseases, or genodermatoses, are heritable conditions comprising nearly 300 distinct often rare clinical entities, which affect ~30M people in Europe i.e. ~7% of the entire population (http://geneskin.idi.it/homepgs/rareg.php). Thus, genodermatoses have important medical and social implications and have very limited therapeutic possibilities. This proposal will develop preclinical models which can be used to identify therapeutic targets for the treatment of skin cancer and to explore novel approaches to gene and cell therapy. Organotypical tissue engineered skin constructs combining normal, malignant and diseased epithelial, mesenchymal and connective tissue elements will first be used to examine the effect of tumour microenvironment on cancer cell invasion. Then constructs mimicking 1. intraepithelial, 2. well and 3. poorly differentiated SCCs will be used as surface xenotransplants. Optimisation will examine the contribution of adipocyte and mesenchymal stem cells. A set of genes identified as a characteristic SCC signature by extensive previous studies will then be genetically manipulated to examine the effects of up and down regulation of these genes in tumour progression and invasion. The effects of novel small molecules will also be tested. Surface xenotransplants of organotypical cultures of genetically diseased keratinocytes will be established to assess the long term outcomes of comparing ex vivo gene therapy with protein and cell therapy.
Summary
As our understanding of disease translates from basic science to clinical application there is a need for robust preclinical models to test interventions and therapies, which mirror the clinical situation and likely outcomes. This will assist key stage decision making before costly clinical trials are commenced. Skin diseases represent a significant health burden. Non-melanoma skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common human malignancies. Genetic skin diseases, or genodermatoses, are heritable conditions comprising nearly 300 distinct often rare clinical entities, which affect ~30M people in Europe i.e. ~7% of the entire population (http://geneskin.idi.it/homepgs/rareg.php). Thus, genodermatoses have important medical and social implications and have very limited therapeutic possibilities. This proposal will develop preclinical models which can be used to identify therapeutic targets for the treatment of skin cancer and to explore novel approaches to gene and cell therapy. Organotypical tissue engineered skin constructs combining normal, malignant and diseased epithelial, mesenchymal and connective tissue elements will first be used to examine the effect of tumour microenvironment on cancer cell invasion. Then constructs mimicking 1. intraepithelial, 2. well and 3. poorly differentiated SCCs will be used as surface xenotransplants. Optimisation will examine the contribution of adipocyte and mesenchymal stem cells. A set of genes identified as a characteristic SCC signature by extensive previous studies will then be genetically manipulated to examine the effects of up and down regulation of these genes in tumour progression and invasion. The effects of novel small molecules will also be tested. Surface xenotransplants of organotypical cultures of genetically diseased keratinocytes will be established to assess the long term outcomes of comparing ex vivo gene therapy with protein and cell therapy.
Max ERC Funding
1 999 999 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym UNITEDWESTAND
Project The dynamics and consequences of institutions for collective action in pre-industrial Europe
Researcher (PI) Martina De Moor
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Starting Grant (StG), SH6, ERC-2009-StG
Summary Europe s economic development in the centuries leading up to the Industrial Revolution, continues to fascinate scholars. In recent debates, institutionalised forms of collective action have been put forward as a key feature of Europe s precocious development. This project examines that connection between institutions and economic development in detail. It also harks back to the origins of such institutions, teasing out the impact of changing family patterns that emerged in Western Europe in the Late Middle Ages, which are often described as the European Marriage Pattern . Together with such factors as the absence of a strong state, and a helpful legal framework, the weakening of family relations may have created opportunities for other, non-kin social organisations to emerge, explaining the strength of institutions for collective action in this part of the world. Interactions between economic growth, marriage patterns and collective action institutions will be examined on several levels. A European wide-analysis, using specific indicators for institutional development and demographic patterns, should help clarify our understanding of their temporal and geographical co-evolution. Regulations for several types of collective action institutions will be analysed for Western Europe and Southern Europe to study the impact of household constitution and marriage patterns on institutional arrangements. A third level of the project, to be subdivided in an urban and a rural study, will look into the application of such regulations in everyday practices, through the analysis of several case-studies of guilds, commons and beguinages in the Low Countries. Finally, a sub-project is will promote dissemination and exchange of the project s data among the wider academic community. Several events will be organised to stimulate debates about the topics raised by the project.
Summary
Europe s economic development in the centuries leading up to the Industrial Revolution, continues to fascinate scholars. In recent debates, institutionalised forms of collective action have been put forward as a key feature of Europe s precocious development. This project examines that connection between institutions and economic development in detail. It also harks back to the origins of such institutions, teasing out the impact of changing family patterns that emerged in Western Europe in the Late Middle Ages, which are often described as the European Marriage Pattern . Together with such factors as the absence of a strong state, and a helpful legal framework, the weakening of family relations may have created opportunities for other, non-kin social organisations to emerge, explaining the strength of institutions for collective action in this part of the world. Interactions between economic growth, marriage patterns and collective action institutions will be examined on several levels. A European wide-analysis, using specific indicators for institutional development and demographic patterns, should help clarify our understanding of their temporal and geographical co-evolution. Regulations for several types of collective action institutions will be analysed for Western Europe and Southern Europe to study the impact of household constitution and marriage patterns on institutional arrangements. A third level of the project, to be subdivided in an urban and a rural study, will look into the application of such regulations in everyday practices, through the analysis of several case-studies of guilds, commons and beguinages in the Low Countries. Finally, a sub-project is will promote dissemination and exchange of the project s data among the wider academic community. Several events will be organised to stimulate debates about the topics raised by the project.
Max ERC Funding
1 199 721 €
Duration
Start date: 2010-01-01, End date: 2014-12-31
Project acronym UPGAL
Project Understanding the Physics of Galaxy Formation and Evolution at High Redshift
Researcher (PI) Emanuele Daddi
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Starting Grant (StG), PE9, ERC-2009-StG
Summary Understanding the processes regulating galaxy formation is a major open issue in observational cosmology. We now have a fairly detailed census of the diverse high-z galaxy populations, hence time is ripe for fundamental advances in understanding galaxy formation and evolution in the crucial first few billion years. This requires to observationally constrain and clarify the physical processes that operated at those early epochs. Thanks to a new galaxy selection technique that I recently introduced, I have been leading research projects that have now provided major new results on high redshift z~2 galaxies. These include molecular gas first seen in typical high-z galaxies; the major phase of star formation at very high rates; widespread presence of previously unknown Compton-thick AGNs inside massive galaxies; and the existence of evolved galaxy clusters containing X-ray emitting gas already at z~2. Building on the legacy of these discoveries and critical results, I ask for support to fund the establishment of a new research team to lead research aimed at exploring the physics of galaxy formation in the distant Universe. With three postdocs each year for a total of 5 years, we will pave new avenues towards understanding the relation between black holes and galaxies at the time of their major mass growth and assembly. In a full multiwavelength approach, by obtaining and using data from all major observational facilities (both in space and on the ground) we will aim to clarify the physical trigger of downsizing, catch AGN feedback in action and assess its role in galaxy transformations, along with the effects of the environment, gas accretion, star formation and merging in driving galaxy formation.
Summary
Understanding the processes regulating galaxy formation is a major open issue in observational cosmology. We now have a fairly detailed census of the diverse high-z galaxy populations, hence time is ripe for fundamental advances in understanding galaxy formation and evolution in the crucial first few billion years. This requires to observationally constrain and clarify the physical processes that operated at those early epochs. Thanks to a new galaxy selection technique that I recently introduced, I have been leading research projects that have now provided major new results on high redshift z~2 galaxies. These include molecular gas first seen in typical high-z galaxies; the major phase of star formation at very high rates; widespread presence of previously unknown Compton-thick AGNs inside massive galaxies; and the existence of evolved galaxy clusters containing X-ray emitting gas already at z~2. Building on the legacy of these discoveries and critical results, I ask for support to fund the establishment of a new research team to lead research aimed at exploring the physics of galaxy formation in the distant Universe. With three postdocs each year for a total of 5 years, we will pave new avenues towards understanding the relation between black holes and galaxies at the time of their major mass growth and assembly. In a full multiwavelength approach, by obtaining and using data from all major observational facilities (both in space and on the ground) we will aim to clarify the physical trigger of downsizing, catch AGN feedback in action and assess its role in galaxy transformations, along with the effects of the environment, gas accretion, star formation and merging in driving galaxy formation.
Max ERC Funding
939 600 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym VIP
Project Voxel Imaging PET Pathfinder
Researcher (PI) Mokhtar Chmeissani Raad
Host Institution (HI) INSTITUTO DE FISICA DE ALTAS ENERGIAS
Call Details Advanced Grant (AdG), LS7, ERC-2009-AdG
Summary Positron-Emission-Tomography (PET) scanners play an important role in cancer diagnosis and molecular imaging. Their accuracy overtakes that of the conventional diagnostics systems. They are used, alone or in combination with other imaging systems, such as CT or MRI. The current best detectors for PET are based on LSO crystals that are usually made of 4mm x 4mm x 10mm coupled to PMT, APD, or similar photon-sensitive device. At best, the FWHM that can be achieved at 511keV is around 10%. This limited energy resolution limits the ability to remove scattered events which are a significant noise contribution to the reconstructed image. The typical length (in the radial direction) of the LSO crystals is about 10mm, which implies a significant uncertainty of the impact point in the radial direction and this induces an error in the projection of the Line of Response. This error deteriorates the quality of the reconstructed image. Pixel-PET uses pixel solid-state-detector coupled to front end electronics. With this novel detector one can achieve the followings: 1- millimeter-size voxel, this means no more parallax effect and hence precise LOR; 2-FWHM energy resolution of less than 1% for 511keV photons. This allows us to eliminate most of the scattered events and thus keep the golden events; 3- Have adequate depth of absorption to achieve high detection efficiency (90%) for 511keV photon; 4- The modular detector has trapezoidal parallelepiped shape thus making it seamless compared to the existing PET system; 5- The conceptual design can be modified to construct a Flat panel detector (Gamma Camera); 6-The design is compatible with MRI making it ideal for Brain imaging. Preliminary Geant4 simulation results, using Derenzo Phantom with Pixel-PET detector suggests that one can achieve the same image quality of the current PET devices but using 25 times less dose.
Summary
Positron-Emission-Tomography (PET) scanners play an important role in cancer diagnosis and molecular imaging. Their accuracy overtakes that of the conventional diagnostics systems. They are used, alone or in combination with other imaging systems, such as CT or MRI. The current best detectors for PET are based on LSO crystals that are usually made of 4mm x 4mm x 10mm coupled to PMT, APD, or similar photon-sensitive device. At best, the FWHM that can be achieved at 511keV is around 10%. This limited energy resolution limits the ability to remove scattered events which are a significant noise contribution to the reconstructed image. The typical length (in the radial direction) of the LSO crystals is about 10mm, which implies a significant uncertainty of the impact point in the radial direction and this induces an error in the projection of the Line of Response. This error deteriorates the quality of the reconstructed image. Pixel-PET uses pixel solid-state-detector coupled to front end electronics. With this novel detector one can achieve the followings: 1- millimeter-size voxel, this means no more parallax effect and hence precise LOR; 2-FWHM energy resolution of less than 1% for 511keV photons. This allows us to eliminate most of the scattered events and thus keep the golden events; 3- Have adequate depth of absorption to achieve high detection efficiency (90%) for 511keV photon; 4- The modular detector has trapezoidal parallelepiped shape thus making it seamless compared to the existing PET system; 5- The conceptual design can be modified to construct a Flat panel detector (Gamma Camera); 6-The design is compatible with MRI making it ideal for Brain imaging. Preliminary Geant4 simulation results, using Derenzo Phantom with Pixel-PET detector suggests that one can achieve the same image quality of the current PET devices but using 25 times less dose.
Max ERC Funding
2 044 400 €
Duration
Start date: 2010-07-01, End date: 2015-06-30
Project acronym VOICE
Project """Hearing voices"" - From cognition to brain systems"
Researcher (PI) Kenneth Hugdahl
Host Institution (HI) UNIVERSITETET I BERGEN
Call Details Advanced Grant (AdG), SH4, ERC-2009-AdG
Summary The experience of "hearing voices", i. e. auditory hallucinations in the absence of an external acoustic input is a perplexing phenomenon. In addition to being a defining characteristic of schizophrenia, experiences of "hearing voices" may be more common in the general population than what we normally think, which poses a theoretical challenge from a neuropsychological point of view. The overall goal is to track auditory hallucinations from the cognitive (phenomenological) to the neuronal (brain systems and synaptic) levels of explanation, by drawing on my previous research on hemispheric asymmetry and attention-modulation of dichotic listening and functional neuroimaging. I now suggest a new model for explaining "hearing voices" in patients and in healthy individuals. From the phenomenology of what patients and healthy individuals "hearing voices" actually report led me to question current models and theories that auditory hallucinations are "inner speech" or "traumatic memories". Since both patients and healthy individuals "hearing voices" subjectively report experiencing someone "speaking to them" it seems that a perceptual model would better fit the actual phenomenology. A perceptual model can however not explain why patients and healthy individuals differ in the way they cope with and interpret the "voice". An expanded model is therefore advanced that sees auditory hallucinations as a break-down of the dynamic interplay between bottom-up (perceptual) and top-down (inhibitory control) cognitive processes. It is suggested that while both groups show deficient perceptual processing, the patients in addition have impaired inhibitory control functions which prevents them from interpreting the "voices" as coming from inner thought processes. A series of experiments are proposed to test the model.
Summary
The experience of "hearing voices", i. e. auditory hallucinations in the absence of an external acoustic input is a perplexing phenomenon. In addition to being a defining characteristic of schizophrenia, experiences of "hearing voices" may be more common in the general population than what we normally think, which poses a theoretical challenge from a neuropsychological point of view. The overall goal is to track auditory hallucinations from the cognitive (phenomenological) to the neuronal (brain systems and synaptic) levels of explanation, by drawing on my previous research on hemispheric asymmetry and attention-modulation of dichotic listening and functional neuroimaging. I now suggest a new model for explaining "hearing voices" in patients and in healthy individuals. From the phenomenology of what patients and healthy individuals "hearing voices" actually report led me to question current models and theories that auditory hallucinations are "inner speech" or "traumatic memories". Since both patients and healthy individuals "hearing voices" subjectively report experiencing someone "speaking to them" it seems that a perceptual model would better fit the actual phenomenology. A perceptual model can however not explain why patients and healthy individuals differ in the way they cope with and interpret the "voice". An expanded model is therefore advanced that sees auditory hallucinations as a break-down of the dynamic interplay between bottom-up (perceptual) and top-down (inhibitory control) cognitive processes. It is suggested that while both groups show deficient perceptual processing, the patients in addition have impaired inhibitory control functions which prevents them from interpreting the "voices" as coming from inner thought processes. A series of experiments are proposed to test the model.
Max ERC Funding
2 281 572 €
Duration
Start date: 2010-07-01, End date: 2015-06-30
Project acronym WORLDFAM
Project Towards a Unified Analysis of World Population: Family Patterns in Multilevel Perspective
Researcher (PI) Albert Esteve Palós
Host Institution (HI) CENTRO DE ESTUDIOS DEMOGRAFICOS
Call Details Starting Grant (StG), SH3, ERC-2009-StG
Summary The overarching aim of this proposal is to develop the conceptual and analytical instruments to establish a formal linkage between macro and micro level perspectives in demographic research, with an application to the study of worldwide patterns of family formation. Using census and survey microdata, we will conduct worldwide multilevel analyses that will allow us to investigate demographic trends at three levels of disaggregation: national, regional and individual. We will study the relationship between societal changes and three interrelated aspects of family formation: union formation, assortative mating, and intergenerational co-residence from the young cohort perspective. The societal effects will include phenomena such as educational expansion, women s economic activity, urbanization, as well as individual socio-economic characteristics. Analysis will be based on data from a vast new archive of international census microdata made available by the Integrated Public Use of Microdata Series international project (IPUMSi), with complementary use of Fertility and Family Surveys (FFS), Demographic Health Surveys (DHS) and Gender and Generations Surveys (GGS). The full dataset will amount to 124 countries, more than 1,400 regions and 305 million person records, statistically representing roughly 90% of the world population. This research raises complex theoretical and methodological questions. We do not contend that this project will be able to establish causality; rather, we will identify and illustrate differences between and within countries based on a rigorous and comprehensive set of variables exploiting microdata to develop systematic measures at different levels. Methodologically, the project will confront the challenges of combining datasets, providing meaningful measures of family formation, creating contextual variables, optimizing computational requirements, framing models that encompass different levels, time spans and regions.
Summary
The overarching aim of this proposal is to develop the conceptual and analytical instruments to establish a formal linkage between macro and micro level perspectives in demographic research, with an application to the study of worldwide patterns of family formation. Using census and survey microdata, we will conduct worldwide multilevel analyses that will allow us to investigate demographic trends at three levels of disaggregation: national, regional and individual. We will study the relationship between societal changes and three interrelated aspects of family formation: union formation, assortative mating, and intergenerational co-residence from the young cohort perspective. The societal effects will include phenomena such as educational expansion, women s economic activity, urbanization, as well as individual socio-economic characteristics. Analysis will be based on data from a vast new archive of international census microdata made available by the Integrated Public Use of Microdata Series international project (IPUMSi), with complementary use of Fertility and Family Surveys (FFS), Demographic Health Surveys (DHS) and Gender and Generations Surveys (GGS). The full dataset will amount to 124 countries, more than 1,400 regions and 305 million person records, statistically representing roughly 90% of the world population. This research raises complex theoretical and methodological questions. We do not contend that this project will be able to establish causality; rather, we will identify and illustrate differences between and within countries based on a rigorous and comprehensive set of variables exploiting microdata to develop systematic measures at different levels. Methodologically, the project will confront the challenges of combining datasets, providing meaningful measures of family formation, creating contextual variables, optimizing computational requirements, framing models that encompass different levels, time spans and regions.
Max ERC Funding
1 088 904 €
Duration
Start date: 2010-01-01, End date: 2015-06-30
