Project acronym CBCD
Project Understanding the basis of cerebellar and brainstem congenital defects: from clinical and molecular characterisation to the development of a novel neuroembryonic in vitro model
Researcher (PI) Enza Maria Valente
Host Institution (HI) FONDAZIONE SANTA LUCIA
Call Details Starting Grant (StG), LS7, ERC-2010-StG_20091118
Summary Cerebellar and brainstem congenital defects (CBCDs) are heterogeneous disorders with high pre-and post-natal mortality and morbidity. Their genetic basis and pathogenetic mechanisms are largely unknown, hampering patients’ diagnosis and management and family counselling. This project aims at improve current understanding of primary CBCDs through a multidisciplinary approach combining innovative clinical, neuroimaging, molecular and functional studies, that will be articulated in four workpackages:
WP1- Clinical and neuroimaging studies: collection of detailed data and biological samples from a large cohort of patients covering a broad spectrum of CBCDs, neuroimaging classification based on magnetic resonance imaging and tractography, genotype-phenotype correlates and follow-up studies.
WP2 - Molecular studies on mendelian CBCDs: high-throughput resequencing of ciliary genes to identify pathogenic mutations and genetic modifiers in patients with ciliopathies, identification of novel disease genes, mutation analysis of genes causative of other mendelian CBCDs.
WP3 - Molecular studies on sporadic CBCDs: identification of cryptic chromosomal rearrangements by high resolution SNP-array analysis, selection and mutation analysis of candidate genes mapping to the rearranged regions.
WP4 - Functional studies: optimisation of a novel neuroembryonic in vitro model derived from mouse embryonic stem cells, to test the role of known and candidate disease genes (from WP2 and 3) on cerebellar and brainstem development, define the pathways in which they are involved and the effect of disease-causative mutations.
This project is expected to improve the current CBCD nosology, identify novel genes and mechanisms involved in cerebellar and brainstem development that are responsible for mendelian or sporadic defects, expand the available tools for pre- and post-natal diagnosis and identify clinical-genetic correlates and prognostic indexes.
Summary
Cerebellar and brainstem congenital defects (CBCDs) are heterogeneous disorders with high pre-and post-natal mortality and morbidity. Their genetic basis and pathogenetic mechanisms are largely unknown, hampering patients’ diagnosis and management and family counselling. This project aims at improve current understanding of primary CBCDs through a multidisciplinary approach combining innovative clinical, neuroimaging, molecular and functional studies, that will be articulated in four workpackages:
WP1- Clinical and neuroimaging studies: collection of detailed data and biological samples from a large cohort of patients covering a broad spectrum of CBCDs, neuroimaging classification based on magnetic resonance imaging and tractography, genotype-phenotype correlates and follow-up studies.
WP2 - Molecular studies on mendelian CBCDs: high-throughput resequencing of ciliary genes to identify pathogenic mutations and genetic modifiers in patients with ciliopathies, identification of novel disease genes, mutation analysis of genes causative of other mendelian CBCDs.
WP3 - Molecular studies on sporadic CBCDs: identification of cryptic chromosomal rearrangements by high resolution SNP-array analysis, selection and mutation analysis of candidate genes mapping to the rearranged regions.
WP4 - Functional studies: optimisation of a novel neuroembryonic in vitro model derived from mouse embryonic stem cells, to test the role of known and candidate disease genes (from WP2 and 3) on cerebellar and brainstem development, define the pathways in which they are involved and the effect of disease-causative mutations.
This project is expected to improve the current CBCD nosology, identify novel genes and mechanisms involved in cerebellar and brainstem development that are responsible for mendelian or sporadic defects, expand the available tools for pre- and post-natal diagnosis and identify clinical-genetic correlates and prognostic indexes.
Max ERC Funding
1 367 960 €
Duration
Start date: 2011-08-01, End date: 2018-03-31
Project acronym CGT HEMOPHILIA A
Project Cell and gene therapy based strategies to correct the bleeding phenotype in Hemophilia A
Researcher (PI) Antonia Follenzi
Host Institution (HI) UNIVERSITA DEGLI STUDI DEL PIEMONTE ORIENTALE AMEDEO AVOGADRO
Call Details Starting Grant (StG), LS7, ERC-2010-StG_20091118
Summary Currently, haemophilia A cannot be cured. To prevent major bleeding episodes in haemophilia, human Factor VIII (FVIII) protein must be frequently administered as prophylaxis or on demand. This treatment is complicated by its high cost and development of antibodies that neutralize FVIII activity in 20 to 30% of the patients. Therefore, permanent solutions in the form of cell and gene therapy are very attractive for haemophilia A. Recently, we demonstrated in a murine model that liver sinusoidal endothelial cells (LSEC) produce and secrete FVIII, although not exclusively. We have also found that these mice can be treated by reconstitution with wild-type bone marrow, indicating that bone marrow-derived cells, of hematopoietic, mesenchymal or even endothelial origin, can produce and secrete FVIII. Based on these findings in mice, I propose that human LSEC, umbilical cord blood cells, and bone marrow cells might be suitable sources of FVIII to be used for cell replacement therapy for haemophilia A. To advance opportunities for cell and gene therapies in haemophilia A and for identifying additional cell sources of FVIII, I intend to explore whether replacement of liver endothelium and bone marrow in immnocompromised Haemophilia A mice with healthy human cells will provide therapeutic correction. Recently, the possibility of reprogramming mature somatic cells to generate induced pluripotent stem (iPS) cells has enabled the derivation of disease-specific pluripotent cells, thus providing unprecedented experimental platforms to treat human diseases. Therefore, I intend to study whether the generation of patient-specific iPS cells may be applied to cell and gene therapy of coagulation disorders and in particular for the treatment of Haemophilia A. Studies with these novel target cells may impact significantly the future course of Haemophilia A by providing proof-of feasibility of a novel therapy strategies.
Summary
Currently, haemophilia A cannot be cured. To prevent major bleeding episodes in haemophilia, human Factor VIII (FVIII) protein must be frequently administered as prophylaxis or on demand. This treatment is complicated by its high cost and development of antibodies that neutralize FVIII activity in 20 to 30% of the patients. Therefore, permanent solutions in the form of cell and gene therapy are very attractive for haemophilia A. Recently, we demonstrated in a murine model that liver sinusoidal endothelial cells (LSEC) produce and secrete FVIII, although not exclusively. We have also found that these mice can be treated by reconstitution with wild-type bone marrow, indicating that bone marrow-derived cells, of hematopoietic, mesenchymal or even endothelial origin, can produce and secrete FVIII. Based on these findings in mice, I propose that human LSEC, umbilical cord blood cells, and bone marrow cells might be suitable sources of FVIII to be used for cell replacement therapy for haemophilia A. To advance opportunities for cell and gene therapies in haemophilia A and for identifying additional cell sources of FVIII, I intend to explore whether replacement of liver endothelium and bone marrow in immnocompromised Haemophilia A mice with healthy human cells will provide therapeutic correction. Recently, the possibility of reprogramming mature somatic cells to generate induced pluripotent stem (iPS) cells has enabled the derivation of disease-specific pluripotent cells, thus providing unprecedented experimental platforms to treat human diseases. Therefore, I intend to study whether the generation of patient-specific iPS cells may be applied to cell and gene therapy of coagulation disorders and in particular for the treatment of Haemophilia A. Studies with these novel target cells may impact significantly the future course of Haemophilia A by providing proof-of feasibility of a novel therapy strategies.
Max ERC Funding
1 123 000 €
Duration
Start date: 2011-05-01, End date: 2017-04-30
Project acronym CHILDMOVE
Project The impact of flight experiences on the psychological wellbeing of unaccompanied refugee minors
Researcher (PI) Ilse DERLUYN
Host Institution (HI) UNIVERSITEIT GENT
Call Details Starting Grant (StG), SH3, ERC-2016-STG
Summary Since early 2015, the media continuously confront us with images of refugee children drowning in the Mediterranean, surviving in appalling conditions in camps or walking across Europe. Within this group of fleeing children, a considerable number is travelling without parents, the unaccompanied refugee minors.
While the media images testify to these flight experiences and their possible huge impact on unaccompanied minors’ wellbeing, there has been no systematic research to fully capture these experiences, nor their mental health impact. Equally, no evidence exists on whether the emotional impact of these flight experiences should be differentiated from the impact of the traumatic events these minors endured in their home country or from the daily stressors in the country of settlement.
This project aims to fundamentally increase our knowledge of the impact of experiences during the flight in relation to past trauma and current stressors. To achieve this aim, it is essential to set up a longitudinal follow-up of a large group of unaccompanied refugee minors, whereby our study starts from different transit countries, crosses several European countries, and uses innovative methodological and mixed-methods approaches. I will hereby not only document the psychological impact these flight experiences may have, but also the way in which care and reception structures for unaccompanied minors in both transit and settlement countries can contribute to reducing this mental health impact.
This proposal will fundamentally change the field of migration studies, by introducing a whole new area of study and novel methodological approaches to study these themes. Moreover, other fields, such as trauma studies, will be directly informed by the project, as also clinical, educational and social work interventions for victims of multiple trauma. Last, the findings on the impact of reception and care structures will be highly informative for policy makers and practitioners.
Summary
Since early 2015, the media continuously confront us with images of refugee children drowning in the Mediterranean, surviving in appalling conditions in camps or walking across Europe. Within this group of fleeing children, a considerable number is travelling without parents, the unaccompanied refugee minors.
While the media images testify to these flight experiences and their possible huge impact on unaccompanied minors’ wellbeing, there has been no systematic research to fully capture these experiences, nor their mental health impact. Equally, no evidence exists on whether the emotional impact of these flight experiences should be differentiated from the impact of the traumatic events these minors endured in their home country or from the daily stressors in the country of settlement.
This project aims to fundamentally increase our knowledge of the impact of experiences during the flight in relation to past trauma and current stressors. To achieve this aim, it is essential to set up a longitudinal follow-up of a large group of unaccompanied refugee minors, whereby our study starts from different transit countries, crosses several European countries, and uses innovative methodological and mixed-methods approaches. I will hereby not only document the psychological impact these flight experiences may have, but also the way in which care and reception structures for unaccompanied minors in both transit and settlement countries can contribute to reducing this mental health impact.
This proposal will fundamentally change the field of migration studies, by introducing a whole new area of study and novel methodological approaches to study these themes. Moreover, other fields, such as trauma studies, will be directly informed by the project, as also clinical, educational and social work interventions for victims of multiple trauma. Last, the findings on the impact of reception and care structures will be highly informative for policy makers and practitioners.
Max ERC Funding
1 432 500 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym CHIMERA
Project A novel instrument to identify chiral molecules for pharmaceutics and bio-chemistry.
Researcher (PI) Dario POLLI
Host Institution (HI) POLITECNICO DI MILANO
Call Details Proof of Concept (PoC), PC1, ERC-2016-PoC
Summary This proposal aims at bringing to the market a revolutionary device to uniquely identify the chirality of molecules. An object is chiral if it differs from its mirror image, like our left and right hands. Chirality plays an extremely important role in two main fields: (1) Many drugs are chiral and selecting one of the two forms often enables the pharma industry to extend patent franchise, thus increasing profitability, and to improve the quality, safety and efficacy of the drug. (2) Researchers in the chemistry and biophysics labs use chirality as an indication of the 3D structural conformation of proteins and DNA, to study e.g. their secondary structure and stability under external stimuli. Spectrometers for measuring chirality already exist in the market. Many customers in the two aforementioned sectors could be interested in the new product we propose because it presents several advantages, namely a 2-fold reduction of the price, a 4-fold shrinking of the footprint and an increased information content. The ground-breaking concept (under patenting) behind this new spectrometer is to employ an ultra-stable interferometer to measure the chiral spectrum of molecules via a Fourier-transform approach and a heterodyne amplification of the signal. A first working prototype has already been realized and tested. The CHIMERA project has two main goals. (1) We aim at unleashing the innovation potential of the approach, by technically validating two prototypes in a pharmaceutical company and a biochemistry research lab, thus pushing the Technology Readiness Level of the system to the ultimate maturity required to approach the market, corresponding to TRL9. (2) We will design a complete exploitation plan, performing a thorough analysis of the market, developing a financing strategy, benchmarking our instrument against the competitors’ ones, profiling strategic partners and drafting a first version of a Business Plan to decide on the opportunity to found a start-up company.
Summary
This proposal aims at bringing to the market a revolutionary device to uniquely identify the chirality of molecules. An object is chiral if it differs from its mirror image, like our left and right hands. Chirality plays an extremely important role in two main fields: (1) Many drugs are chiral and selecting one of the two forms often enables the pharma industry to extend patent franchise, thus increasing profitability, and to improve the quality, safety and efficacy of the drug. (2) Researchers in the chemistry and biophysics labs use chirality as an indication of the 3D structural conformation of proteins and DNA, to study e.g. their secondary structure and stability under external stimuli. Spectrometers for measuring chirality already exist in the market. Many customers in the two aforementioned sectors could be interested in the new product we propose because it presents several advantages, namely a 2-fold reduction of the price, a 4-fold shrinking of the footprint and an increased information content. The ground-breaking concept (under patenting) behind this new spectrometer is to employ an ultra-stable interferometer to measure the chiral spectrum of molecules via a Fourier-transform approach and a heterodyne amplification of the signal. A first working prototype has already been realized and tested. The CHIMERA project has two main goals. (1) We aim at unleashing the innovation potential of the approach, by technically validating two prototypes in a pharmaceutical company and a biochemistry research lab, thus pushing the Technology Readiness Level of the system to the ultimate maturity required to approach the market, corresponding to TRL9. (2) We will design a complete exploitation plan, performing a thorough analysis of the market, developing a financing strategy, benchmarking our instrument against the competitors’ ones, profiling strategic partners and drafting a first version of a Business Plan to decide on the opportunity to found a start-up company.
Max ERC Funding
149 375 €
Duration
Start date: 2017-05-01, End date: 2018-10-31
Project acronym cis-CONTROL
Project Decoding and controlling cell-state switching: A bottom-up approach based on enhancer logic
Researcher (PI) Stein Luc AERTS
Host Institution (HI) VIB
Call Details Consolidator Grant (CoG), LS2, ERC-2016-COG
Summary Cell-state switching in cancer allows cells to transition from a proliferative to an invasive and drug-resistant phenotype. This plasticity plays an important role in cancer progression and tumour heterogeneity. We have made a striking observation that cancer cells of different origin can switch to a common survival state. During this epigenomic reprogramming, cancer cells re-activate genomic enhancers from specific regulatory programs, such as wound repair and epithelial-to-mesenchymal transition.
The goal of my project is to decipher the enhancer logic underlying this canalization effect towards a common survival state. We will then employ this new understanding of enhancer logic to engineer synthetic enhancers that are able to monitor and manipulate cell-state switching in real time. Furthermore, we will use enhancer models to identify cis-regulatory mutations that have an impact on cell-state switching and drug resistance. Such applications are currently hampered because there is a significant gap in our understanding of how enhancers work.
To tackle this problem we will use a combination of in vivo massively parallel enhancer-reporter assays, single-cell genomics on microfluidic devices, computational modelling, and synthetic enhancer design. Using these approaches we will pursue the following aims: (1) to identify functional enhancers regulating cell-state switching by performing in vivo genetic screens in mice; (2) to elucidate the dynamic trajectories whereby cells of different cancer types switch to a common survival cell-state, at single-cell resolution; (3) to create synthetic enhancer circuits that specifically kill cancer cells undergoing cell-state switching.
Our findings will have an impact on genome research, characterizing how cellular decision making is implemented by the cis-regulatory code; and on cancer research, employing enhancer logic in the context of cancer therapy.
Summary
Cell-state switching in cancer allows cells to transition from a proliferative to an invasive and drug-resistant phenotype. This plasticity plays an important role in cancer progression and tumour heterogeneity. We have made a striking observation that cancer cells of different origin can switch to a common survival state. During this epigenomic reprogramming, cancer cells re-activate genomic enhancers from specific regulatory programs, such as wound repair and epithelial-to-mesenchymal transition.
The goal of my project is to decipher the enhancer logic underlying this canalization effect towards a common survival state. We will then employ this new understanding of enhancer logic to engineer synthetic enhancers that are able to monitor and manipulate cell-state switching in real time. Furthermore, we will use enhancer models to identify cis-regulatory mutations that have an impact on cell-state switching and drug resistance. Such applications are currently hampered because there is a significant gap in our understanding of how enhancers work.
To tackle this problem we will use a combination of in vivo massively parallel enhancer-reporter assays, single-cell genomics on microfluidic devices, computational modelling, and synthetic enhancer design. Using these approaches we will pursue the following aims: (1) to identify functional enhancers regulating cell-state switching by performing in vivo genetic screens in mice; (2) to elucidate the dynamic trajectories whereby cells of different cancer types switch to a common survival cell-state, at single-cell resolution; (3) to create synthetic enhancer circuits that specifically kill cancer cells undergoing cell-state switching.
Our findings will have an impact on genome research, characterizing how cellular decision making is implemented by the cis-regulatory code; and on cancer research, employing enhancer logic in the context of cancer therapy.
Max ERC Funding
1 999 660 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym ClustersXCosmo
Project Fundamental physics, Cosmology and Astrophysics: Galaxy Clusters at the Cross-roads
Researcher (PI) Alexandro SARO
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TRIESTE
Call Details Starting Grant (StG), PE9, ERC-2016-STG
Summary The ClustersXCosmo ERC Starting Grant proposal has the goal of investigating the role of Galaxy Clusters as a cosmological probe and of exploiting the strong synergies between observational cosmology, galaxy formation and fundamental physics related to the tracers of the extreme peaks in the matter density field. In the last decade, astronomical data-sets have started to be widely and quantitatively used by the scientific community to address important physical questions such as: the nature of the dark matter and dark energy components and their evolution; the physical properties of the baryonic matter; the variation of fundamental constants over cosmic time; the sum of neutrino masses; the interplay between the galaxy population and the intergalactic medium; the nature of gravity over megaparsec scales and over cosmic times; the temperature evolution of the Universe. Most of these results are based on well-established geometrical cosmological probes (e.g., galaxies, supernovae, cosmic microwave background). Galaxy clusters provide a complementary and necessary approach, as their distribution as a function of time and observables is sensitive to both the geometrical and the dynamical evolution of the Universe, driven by the growth of structures. Among different cluster surveys, Sunyaev Zel'Dovich effect (SZE) detected catalogs have registered the most dramatic improvement over the last ~5 years, yielding samples extending up to the earliest times these systems appeared. This proposal aims at using a combination of the best available SZE cluster surveys and to interpret them by means of state-of-the-art computational facilities in order to firmly establish the yet controversial role of Galaxy Clusters as a probe for cosmology, fundamental physics and astrophysics. The timely convergence of current and next generation multi-wavelength surveys (DES/SPT/Planck/eRosita/Euclid) will be important to establish the role of Galaxy Clusters as a cosmological tool.
Summary
The ClustersXCosmo ERC Starting Grant proposal has the goal of investigating the role of Galaxy Clusters as a cosmological probe and of exploiting the strong synergies between observational cosmology, galaxy formation and fundamental physics related to the tracers of the extreme peaks in the matter density field. In the last decade, astronomical data-sets have started to be widely and quantitatively used by the scientific community to address important physical questions such as: the nature of the dark matter and dark energy components and their evolution; the physical properties of the baryonic matter; the variation of fundamental constants over cosmic time; the sum of neutrino masses; the interplay between the galaxy population and the intergalactic medium; the nature of gravity over megaparsec scales and over cosmic times; the temperature evolution of the Universe. Most of these results are based on well-established geometrical cosmological probes (e.g., galaxies, supernovae, cosmic microwave background). Galaxy clusters provide a complementary and necessary approach, as their distribution as a function of time and observables is sensitive to both the geometrical and the dynamical evolution of the Universe, driven by the growth of structures. Among different cluster surveys, Sunyaev Zel'Dovich effect (SZE) detected catalogs have registered the most dramatic improvement over the last ~5 years, yielding samples extending up to the earliest times these systems appeared. This proposal aims at using a combination of the best available SZE cluster surveys and to interpret them by means of state-of-the-art computational facilities in order to firmly establish the yet controversial role of Galaxy Clusters as a probe for cosmology, fundamental physics and astrophysics. The timely convergence of current and next generation multi-wavelength surveys (DES/SPT/Planck/eRosita/Euclid) will be important to establish the role of Galaxy Clusters as a cosmological tool.
Max ERC Funding
1 230 403 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym COD
Project The economic, social and political consequences of democratic reforms. A quantitative and qualitative comparative analysis
Researcher (PI) Giovanni Marco Carbone
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Call Details Starting Grant (StG), SH2, ERC-2010-StG_20091209
Summary The latter part of the twentieth century was a period of rapid democratisation on a global scale. The attention of comparative politics scholars followed the progression of so-called Third Wave democracies, and gradually progressed from the study of the causes of and the transitions to democracy to the problems of democratic consolidation, and then to more recent issues relating to the quality of democracy. A further, frontier step may now be added to such research path by focusing on a subject that has remained largely under-researched, if at all, namely the political, social and economic consequences that emerged in countries where real democratic change took place. The question of what democracy has been able to deliver will become ever more relevant to the future prospects of recent democratisation processes and of democracy at large.
In the study of the consequences of democratisation, the advent of democracy is thus no longer observed as an endpoint, or a dependent variable to be explained, but as a starting point, or an independent variable that allegedly contributes to the explanation of a wide range of political, economic and social effects. The question of the corollaries of democratisation also has crucial policy implications.
The goals of the proposed research are:
a) the definition of a theoretical framework that articulates, integrates and interrelates the different existing hypotheses and arguments on the consequences of democratization processes
b) the empirical investigation, through a combination and integration of quantitative and qualitative methods, of the validity of three specific such hypotheses, namely:
i. democratisation favours the consolidation of the state (as a political effect)
ii. democratisation favours economic liberalization (as an economic effect)
iii. democratisation improves social welfare (as a social effect)
c) the analysis of the specific forms that the effects of democratization assume in different world regions
Summary
The latter part of the twentieth century was a period of rapid democratisation on a global scale. The attention of comparative politics scholars followed the progression of so-called Third Wave democracies, and gradually progressed from the study of the causes of and the transitions to democracy to the problems of democratic consolidation, and then to more recent issues relating to the quality of democracy. A further, frontier step may now be added to such research path by focusing on a subject that has remained largely under-researched, if at all, namely the political, social and economic consequences that emerged in countries where real democratic change took place. The question of what democracy has been able to deliver will become ever more relevant to the future prospects of recent democratisation processes and of democracy at large.
In the study of the consequences of democratisation, the advent of democracy is thus no longer observed as an endpoint, or a dependent variable to be explained, but as a starting point, or an independent variable that allegedly contributes to the explanation of a wide range of political, economic and social effects. The question of the corollaries of democratisation also has crucial policy implications.
The goals of the proposed research are:
a) the definition of a theoretical framework that articulates, integrates and interrelates the different existing hypotheses and arguments on the consequences of democratization processes
b) the empirical investigation, through a combination and integration of quantitative and qualitative methods, of the validity of three specific such hypotheses, namely:
i. democratisation favours the consolidation of the state (as a political effect)
ii. democratisation favours economic liberalization (as an economic effect)
iii. democratisation improves social welfare (as a social effect)
c) the analysis of the specific forms that the effects of democratization assume in different world regions
Max ERC Funding
322 284 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
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 ContraNPM1AML
Project Dissecting to hit the therapeutic targets in nucleophosmin (NPM1)-mutated acute myeloid leukemia
Researcher (PI) Maria Paola MARTELLI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PERUGIA
Call Details Consolidator Grant (CoG), LS7, ERC-2016-COG
Summary Acute myeloid leukemia (AML) is a group of hematologic malignancies which, due to their molecular and clinical heterogeneity, have been traditionally difficult to classify and treat. Recently, next-generation, whole-genome sequencing has uncovered several recurrent somatic mutations that better define the landscape of AML genomics. Despite these advances in deciphering AML molecular subsets, there have been no concurrent improvements in AML therapy which still relies on the ‘antracycline+cytarabine’ scheme. Hereto, only about 40-50% of adult young patients are cured whilst most of the elderly succumb to their disease. Therefore, new therapeutic approaches which would take advantage of the new discoveries are clearly needed. In the past years, we discovered and characterized nucleophosmin (NPM1) mutations as the most frequent genetic alteration (about 30%) in AML, and today NPM1-mutated AML is a new entity in the WHO classification of myeloid neoplasms. However, mechanisms of leukemogenesis and a specific therapy for this leukemia are missing. Here, I aim to unravel the complex network of molecular interactions that take place in this distinct genetic subtype, and find their vulnerabilities to identify new targets for therapy. To address this issue, I will avail of relevant pre-clinical models developed in our laboratories and propose two complementary strategies: 1) a screening-based approach, focused either on the target, by analyzing synthetic lethal interactions through CRISPR-based genome-wide interference, or on the drug, by high-throughput chemical libraries screenings; 2) a hypothesis-driven approach, based on our recent gained novel insights on the role of specific intracellular pathways/genes in NPM1-mutated AML and on pharmacological studies with ‘old’ drugs, which we have revisited in the specific AML genetic context. I expect our discoveries will lead to find novel therapeutic approaches and make clinical trials available to patients as soon as possible.
Summary
Acute myeloid leukemia (AML) is a group of hematologic malignancies which, due to their molecular and clinical heterogeneity, have been traditionally difficult to classify and treat. Recently, next-generation, whole-genome sequencing has uncovered several recurrent somatic mutations that better define the landscape of AML genomics. Despite these advances in deciphering AML molecular subsets, there have been no concurrent improvements in AML therapy which still relies on the ‘antracycline+cytarabine’ scheme. Hereto, only about 40-50% of adult young patients are cured whilst most of the elderly succumb to their disease. Therefore, new therapeutic approaches which would take advantage of the new discoveries are clearly needed. In the past years, we discovered and characterized nucleophosmin (NPM1) mutations as the most frequent genetic alteration (about 30%) in AML, and today NPM1-mutated AML is a new entity in the WHO classification of myeloid neoplasms. However, mechanisms of leukemogenesis and a specific therapy for this leukemia are missing. Here, I aim to unravel the complex network of molecular interactions that take place in this distinct genetic subtype, and find their vulnerabilities to identify new targets for therapy. To address this issue, I will avail of relevant pre-clinical models developed in our laboratories and propose two complementary strategies: 1) a screening-based approach, focused either on the target, by analyzing synthetic lethal interactions through CRISPR-based genome-wide interference, or on the drug, by high-throughput chemical libraries screenings; 2) a hypothesis-driven approach, based on our recent gained novel insights on the role of specific intracellular pathways/genes in NPM1-mutated AML and on pharmacological studies with ‘old’ drugs, which we have revisited in the specific AML genetic context. I expect our discoveries will lead to find novel therapeutic approaches and make clinical trials available to patients as soon as possible.
Max ERC Funding
1 883 750 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym COPMAT
Project Full-scale COmputational design of Porous mesoscale MATerials
Researcher (PI) Sauro SUCCI
Host Institution (HI) FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Call Details Advanced Grant (AdG), PE8, ERC-2016-ADG
Summary The last decades have witnessed major progress in our understanding of the basic physics of soft matter materials. At the same time, microfluidics has also undergone spectacular theoretical and experimental progress. The confluence of such major advances spawns unprecedented opportunities for the design and manufacturing of new soft mesoscale materials, with promising applications in tissue engineering, photonics, catalysis and many others. COPMAT is targeted at making the most this opportunity through the pursuit of a single general goal: the full-scale simulation at nanometric resolution of micro-reactors for the design and synthesis of new tunable porous materials. In particular, we shall focus on the microfluidic design of: multi-jel materials, trabecular porous media and soft mesoscale molecules. We shall also explore new designs concepts based on unexplored microscale phenomena, such as the interaction between plasticity and nano-rugosity. The complex interplay between the highly non-linear rheology of soft materials and the major experimental control parameters leads to an engineering design of formidable complexity, characterized by a strong sensitivity of the macroscale material properties on the details of nanoscale interfacial interactions. COPMAT will tackle this formidable multiscale challenge through the deployment of an entirely new family of multiscale techniques, centered upon highly innovative extensions of the Lattice Boltzmann method and its combinations with Immersed Boundary Method, Dissipative Particle Dynamics and Dissipative Voronoi Dynamics. The success of COPMAT will be gauged by its capability of inspiring and realizing the design of microfluidic devices for the synthesis of novel families of porous materials for bio-engineering applications. The new paradigm established by COPMAT for the computational design of soft materials is expected to extend well beyond the time-horizon of the project.
Summary
The last decades have witnessed major progress in our understanding of the basic physics of soft matter materials. At the same time, microfluidics has also undergone spectacular theoretical and experimental progress. The confluence of such major advances spawns unprecedented opportunities for the design and manufacturing of new soft mesoscale materials, with promising applications in tissue engineering, photonics, catalysis and many others. COPMAT is targeted at making the most this opportunity through the pursuit of a single general goal: the full-scale simulation at nanometric resolution of micro-reactors for the design and synthesis of new tunable porous materials. In particular, we shall focus on the microfluidic design of: multi-jel materials, trabecular porous media and soft mesoscale molecules. We shall also explore new designs concepts based on unexplored microscale phenomena, such as the interaction between plasticity and nano-rugosity. The complex interplay between the highly non-linear rheology of soft materials and the major experimental control parameters leads to an engineering design of formidable complexity, characterized by a strong sensitivity of the macroscale material properties on the details of nanoscale interfacial interactions. COPMAT will tackle this formidable multiscale challenge through the deployment of an entirely new family of multiscale techniques, centered upon highly innovative extensions of the Lattice Boltzmann method and its combinations with Immersed Boundary Method, Dissipative Particle Dynamics and Dissipative Voronoi Dynamics. The success of COPMAT will be gauged by its capability of inspiring and realizing the design of microfluidic devices for the synthesis of novel families of porous materials for bio-engineering applications. The new paradigm established by COPMAT for the computational design of soft materials is expected to extend well beyond the time-horizon of the project.
Max ERC Funding
1 880 060 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
