Project acronym ENSURE
Project Exploring the New Science and engineering unveiled by Ultraintense ultrashort Radiation interaction with mattEr
Researcher (PI) Matteo Passoni
Host Institution (HI) POLITECNICO DI MILANO
Country Italy
Call Details Consolidator Grant (CoG), PE8, ERC-2014-CoG
Summary With the ENSURE project I aim at attaining ground-breaking results in the field of superintense laser-driven ion acceleration, proposing a multidisciplinary research program in which theoretical, numerical and experimental research will be coherently developed in a team integrating in an unprecedented way advanced expertise from materials engineering and nanotechnology, laser-plasma physics, computational science. The aim will be to bring this topic from the realm of fundamental basic science into a subject having realistic engineering applications.
The discovery in 2000 of brilliant, multi-MeV, collimated ion sources from targets irradiated by intense laser pulses stimulated great interest worldwide, due to the ultra-compact spatial scale of the accelerator and ion beam properties. The laser-target system provides unique appealing features to fundamental physics which can be studied in a small lab. At the same time, laser-ion beams could have future potential in many technological areas. This is boosting the development of new labs and facilities all over Europe, but to support these efforts, crucial challenges need to be faced to make these applications a reality.
The goals of ENSURE are: i) design and production of nanoengineered targets, with properties tailored to achieve optimized ion acceleration regimes. This will be pursued exploiting advanced techniques of material science & nanotechnology ii) design of laser-ion beams for novel, key applications in nuclear and materials engineering iii) realization of engineering-oriented ion acceleration experiments, in advanced facilities iv) synergic development of all the required theoretical support for i,ii,iii).
The results of the project can determine a unique impact in the research on laser-driven ion acceleration in Europe, providing new directions to support the attainment, in the next future, of concrete applications of great societal relevance, in medical, energy and materials areas.
Summary
With the ENSURE project I aim at attaining ground-breaking results in the field of superintense laser-driven ion acceleration, proposing a multidisciplinary research program in which theoretical, numerical and experimental research will be coherently developed in a team integrating in an unprecedented way advanced expertise from materials engineering and nanotechnology, laser-plasma physics, computational science. The aim will be to bring this topic from the realm of fundamental basic science into a subject having realistic engineering applications.
The discovery in 2000 of brilliant, multi-MeV, collimated ion sources from targets irradiated by intense laser pulses stimulated great interest worldwide, due to the ultra-compact spatial scale of the accelerator and ion beam properties. The laser-target system provides unique appealing features to fundamental physics which can be studied in a small lab. At the same time, laser-ion beams could have future potential in many technological areas. This is boosting the development of new labs and facilities all over Europe, but to support these efforts, crucial challenges need to be faced to make these applications a reality.
The goals of ENSURE are: i) design and production of nanoengineered targets, with properties tailored to achieve optimized ion acceleration regimes. This will be pursued exploiting advanced techniques of material science & nanotechnology ii) design of laser-ion beams for novel, key applications in nuclear and materials engineering iii) realization of engineering-oriented ion acceleration experiments, in advanced facilities iv) synergic development of all the required theoretical support for i,ii,iii).
The results of the project can determine a unique impact in the research on laser-driven ion acceleration in Europe, providing new directions to support the attainment, in the next future, of concrete applications of great societal relevance, in medical, energy and materials areas.
Max ERC Funding
1 887 500 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym INTERACT
Project Intelligent Non-woven Textiles and Elastomeric Responsive materials by Advancing liquid Crystal Technology
Researcher (PI) Jan Peter Felix Lagerwall
Host Institution (HI) UNIVERSITE DU LUXEMBOURG
Country Luxembourg
Call Details Consolidator Grant (CoG), PE8, ERC-2014-CoG
Summary A grand challenge in today’s materials research is the realization of flexible materials that are also intelligent and functional. They will be the enablers of true breakthroughs in the hot trends of soft robotics and wearable technology. The standard approach to the latter is to decorate rubber sheets with electronic components, yielding two serious flaws: rubber is uncomfortable as it does not breath and solid state electronics will eventually fail as a garment is flexed and stretched when worn. While the softness of rubber is ideal it must be used in the form of textile fibers to provide breathability, and for long-term failure resistance we need intelligent components that are soft. A solution to this conundrum was recently presented by the PI with the concept of liquid crystal (LC) electrospinning. The extreme responsiveness of LCs is transferred to a non-woven textile by incorporating the LC in the fiber core, yielding a smart flexible mat with sensory function. Moreover, it consumes no power, providing a further advantage over electronics-based approaches. In a second research line he uses microfluidics to make LC rubber microshells, functioning as autonomous actuators which may serve as innovative components for soft robotics, and photonic crystal shells. This interdisciplinary project presents an ambitious agenda to advance these new concepts to the realization of soft, stretchable intelligent materials of revolutionary character. Five specific objectives are in focus: 1) develop understanding of the dynamic response of LCs in these unconventional configurations; 2) establish interaction dynamics during polymerisation of an LC precursor; 3) elucidate LC response to gas exposure; 4) establish correlation between actuation response and internal order of curved LCE rubbers; and 5) assess usefulness of LC-functionalized fibers and polymerized LC shells, tubes and Janus particles in wearable sensors, soft robotic actuators and high-security identification tags.
Summary
A grand challenge in today’s materials research is the realization of flexible materials that are also intelligent and functional. They will be the enablers of true breakthroughs in the hot trends of soft robotics and wearable technology. The standard approach to the latter is to decorate rubber sheets with electronic components, yielding two serious flaws: rubber is uncomfortable as it does not breath and solid state electronics will eventually fail as a garment is flexed and stretched when worn. While the softness of rubber is ideal it must be used in the form of textile fibers to provide breathability, and for long-term failure resistance we need intelligent components that are soft. A solution to this conundrum was recently presented by the PI with the concept of liquid crystal (LC) electrospinning. The extreme responsiveness of LCs is transferred to a non-woven textile by incorporating the LC in the fiber core, yielding a smart flexible mat with sensory function. Moreover, it consumes no power, providing a further advantage over electronics-based approaches. In a second research line he uses microfluidics to make LC rubber microshells, functioning as autonomous actuators which may serve as innovative components for soft robotics, and photonic crystal shells. This interdisciplinary project presents an ambitious agenda to advance these new concepts to the realization of soft, stretchable intelligent materials of revolutionary character. Five specific objectives are in focus: 1) develop understanding of the dynamic response of LCs in these unconventional configurations; 2) establish interaction dynamics during polymerisation of an LC precursor; 3) elucidate LC response to gas exposure; 4) establish correlation between actuation response and internal order of curved LCE rubbers; and 5) assess usefulness of LC-functionalized fibers and polymerized LC shells, tubes and Janus particles in wearable sensors, soft robotic actuators and high-security identification tags.
Max ERC Funding
1 929 976 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym NICHOID
Project Mechanobiology of nuclear import of transcription factors modeled within a bioengineered stem cell niche.
Researcher (PI) Manuela Teresa Raimondi
Host Institution (HI) POLITECNICO DI MILANO
Country Italy
Call Details Consolidator Grant (CoG), PE8, ERC-2014-CoG
Summary Many therapeutic applications of stem cells require accurate control of their differentiation. To this purpose there is a major ongoing effort in the development of advanced culture substrates to be used as “synthetic niches” for the cells, mimicking the native ones. The goal of this project is to use a synthetic niche cell culture model to test my revolutionary hypothesis that in stem cell differentiation, nuclear import of gene-regulating transcription factors is controlled by the stretch of the nuclear pore complexes. If verified, this idea could lead to a breakthrough in biomimetic approaches to engineering stem cell differentiation.
I investigate this question specifically in mesenchymal stem cells (MSC), because they are adherent and highly mechano-sensitive to architectural cues of the microenvironment. To verify my hypothesis I will use a combined experimental-computational model of mechanotransduction. I will a) scale-up an existing three-dimensional synthetic niche culture substrate, fabricated by two-photon laser polymerization, b) characterize the effect of tridimensionality on the differentiation fate of MSC cultured in the niches, c) develop a multiphysics/multiscale computational model of nuclear import of transcription factors within differentially-spread cultured cells, and d) integrate the numerical predictions with experimentally-measured import of fluorescently-labelled transcription factors.
This project requires the synergic combination of several advanced bioengineering technologies, including micro/nano fabrication and biomimetics. The use of two-photon laser polymerization for controlling the geometry of the synthetic cell niches is very innovative and will highly impact the fields of bioengineering and biomaterial technology. A successful outcome will lead to a deeper understanding of bioengineering methods to direct stem cell fate and have therefore a significant impact in tissue repair technologies and regenerative medicine.
Summary
Many therapeutic applications of stem cells require accurate control of their differentiation. To this purpose there is a major ongoing effort in the development of advanced culture substrates to be used as “synthetic niches” for the cells, mimicking the native ones. The goal of this project is to use a synthetic niche cell culture model to test my revolutionary hypothesis that in stem cell differentiation, nuclear import of gene-regulating transcription factors is controlled by the stretch of the nuclear pore complexes. If verified, this idea could lead to a breakthrough in biomimetic approaches to engineering stem cell differentiation.
I investigate this question specifically in mesenchymal stem cells (MSC), because they are adherent and highly mechano-sensitive to architectural cues of the microenvironment. To verify my hypothesis I will use a combined experimental-computational model of mechanotransduction. I will a) scale-up an existing three-dimensional synthetic niche culture substrate, fabricated by two-photon laser polymerization, b) characterize the effect of tridimensionality on the differentiation fate of MSC cultured in the niches, c) develop a multiphysics/multiscale computational model of nuclear import of transcription factors within differentially-spread cultured cells, and d) integrate the numerical predictions with experimentally-measured import of fluorescently-labelled transcription factors.
This project requires the synergic combination of several advanced bioengineering technologies, including micro/nano fabrication and biomimetics. The use of two-photon laser polymerization for controlling the geometry of the synthetic cell niches is very innovative and will highly impact the fields of bioengineering and biomaterial technology. A successful outcome will lead to a deeper understanding of bioengineering methods to direct stem cell fate and have therefore a significant impact in tissue repair technologies and regenerative medicine.
Max ERC Funding
1 903 330 €
Duration
Start date: 2015-05-01, End date: 2020-07-31
Project acronym POLITICALMIND
Project Explaining Politicians' and Voters' Behavior
Researcher (PI) Tommaso Nannicini
Host Institution (HI) UNIVERSITA COMMERCIALE LUIGI BOCCONI
Country Italy
Call Details Consolidator Grant (CoG), SH1, ERC-2014-CoG
Summary Theoretical models and empirical studies in political economy aim at explaining both the beliefs and the choices of voters and politicians, so as to assess their impact on economic policy. In particular, a recent literature has recognized the crucial relevance of the identity of politicians in taking policy decisions and ultimately in shaping the fate of their country (Besley 2005; Jones and Olken 2005). In this project, we will address two neglected elements in the existing literature: the role of political parties as organizational structures that shape political careers (i.e., who gets on top in democracies); and the nature of social preferences, personality traits, and cognitive biases in understanding the beliefs and the choices of both politicians and voters.
To make this research agenda operational, we will cover a set of related topics, which will range from the analysis of networks and career trajectories within political parties to the impact of emotions on protests, from the cognitive biases and personality traits of elected officials to the impact of violence on long-term political attitudes, from cognitive dissonance in voting to the contamination between political and judicial elections.
From a methodological perspective, the project will tackle these issues empirically by combining the collection of original individual-level datasets (mainly in Italy) with the implementation of design-based identification strategies (Angrist and Pischke 2010). In particular, based on a careful institutional analysis of the topics under investigation, the empirical strategies will range from randomized controlled trials to instrumental variables, from laboratory experiments with elected officials (i.e., taking politicians to the lab) to regression discontinuity designs.
Summary
Theoretical models and empirical studies in political economy aim at explaining both the beliefs and the choices of voters and politicians, so as to assess their impact on economic policy. In particular, a recent literature has recognized the crucial relevance of the identity of politicians in taking policy decisions and ultimately in shaping the fate of their country (Besley 2005; Jones and Olken 2005). In this project, we will address two neglected elements in the existing literature: the role of political parties as organizational structures that shape political careers (i.e., who gets on top in democracies); and the nature of social preferences, personality traits, and cognitive biases in understanding the beliefs and the choices of both politicians and voters.
To make this research agenda operational, we will cover a set of related topics, which will range from the analysis of networks and career trajectories within political parties to the impact of emotions on protests, from the cognitive biases and personality traits of elected officials to the impact of violence on long-term political attitudes, from cognitive dissonance in voting to the contamination between political and judicial elections.
From a methodological perspective, the project will tackle these issues empirically by combining the collection of original individual-level datasets (mainly in Italy) with the implementation of design-based identification strategies (Angrist and Pischke 2010). In particular, based on a careful institutional analysis of the topics under investigation, the empirical strategies will range from randomized controlled trials to instrumental variables, from laboratory experiments with elected officials (i.e., taking politicians to the lab) to regression discontinuity designs.
Max ERC Funding
1 375 869 €
Duration
Start date: 2015-10-01, End date: 2021-07-31
Project acronym rEnDOx
Project REDOX SIGNALING AND METABOLIC STATES IN ANGIOGENESIS IN HEALTH AND DISEASE
Researcher (PI) Massimo Santoro
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Country Italy
Call Details Consolidator Grant (CoG), LS4, ERC-2014-CoG
Summary Endothelial cells (ECs) exhibit a remarkable and unique plasticity in terms of redox biology and metabolism. They can quickly adapt to oxygen, nitric oxide and metabolic variations. Therefore, EC must be equipped with a selective and unique repertoire of redox and metabolic mechanisms, that play a crucial role to preserve redox balance, and adjust metabolic conditions in both normal and pathological angiogenesis. The identification of such redox signaling and metabolic pathways is crucial to the gaining of better insights in endothelial biology and dysfunction. More importantly, these insights could be used to establish innovative therapeutic approaches for the treatment of those conditions where aberrant or excessive angiogenesis is the underlying cause of the disease itself. However, the formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. Here, by using cutting-edge real-time redox imaging platforms, and innovative molecular and genetic approaches in different in vivo animal models, we will (1) reveal the working of redox signaling in EC in health and disease, (2) shed light on the novel role for the mevalonate metabolic pathway in angiogenesis and (3) provide solid evidence, that manipulation of endothelial redox and metabolic state by genetic alteration of the redox rheostat UBIAD1, is a valuable strategy by which to block pathological angiogenesis in vivo.
The ultimate objective is to open the way for the development of innovative (cancer) therapeutic strategies and complement the existing ones based on genetic or pharmacological manipulation of redox rheostats to balance oxidative or reductive stress in angiogenic processes. The success of this project is built upon our major expertise in the field of angiogenesis in small vertebrate animal models as well as on the collaborations with leading laboratories that are active in research on the pre-clinical stages for angiogenesis-rel
Summary
Endothelial cells (ECs) exhibit a remarkable and unique plasticity in terms of redox biology and metabolism. They can quickly adapt to oxygen, nitric oxide and metabolic variations. Therefore, EC must be equipped with a selective and unique repertoire of redox and metabolic mechanisms, that play a crucial role to preserve redox balance, and adjust metabolic conditions in both normal and pathological angiogenesis. The identification of such redox signaling and metabolic pathways is crucial to the gaining of better insights in endothelial biology and dysfunction. More importantly, these insights could be used to establish innovative therapeutic approaches for the treatment of those conditions where aberrant or excessive angiogenesis is the underlying cause of the disease itself. However, the formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. Here, by using cutting-edge real-time redox imaging platforms, and innovative molecular and genetic approaches in different in vivo animal models, we will (1) reveal the working of redox signaling in EC in health and disease, (2) shed light on the novel role for the mevalonate metabolic pathway in angiogenesis and (3) provide solid evidence, that manipulation of endothelial redox and metabolic state by genetic alteration of the redox rheostat UBIAD1, is a valuable strategy by which to block pathological angiogenesis in vivo.
The ultimate objective is to open the way for the development of innovative (cancer) therapeutic strategies and complement the existing ones based on genetic or pharmacological manipulation of redox rheostats to balance oxidative or reductive stress in angiogenic processes. The success of this project is built upon our major expertise in the field of angiogenesis in small vertebrate animal models as well as on the collaborations with leading laboratories that are active in research on the pre-clinical stages for angiogenesis-rel
Max ERC Funding
1 999 827 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym RENOIR
Project RENal prOgenItoRs as tools to understand kidney pathophysiology and treat kidney disorders
Researcher (PI) Paola Romagnani
Host Institution (HI) UNIVERSITA DEGLI STUDI DI FIRENZE
Country Italy
Call Details Consolidator Grant (CoG), LS4, ERC-2014-CoG
Summary Kidney disorders represent a major global health issue and new tools are needed to expand disease modeling and therapeutic options. The identification of renal progenitors (RPC) opens a wide range of possibilities to support progress in several fields of nephrology. Indeed, RPC have become a key player in the pathogenesis of kidney disorders, and their study is increasing knowledge about the mechanisms of kidney response to injury. In this project we propose new lineage tracing models to identify and characterize mouse RPC system. We then will use these models to establish RPC role in progression or resolution of glomerular and tubular injury, and the mechanisms involved in these processes. Furthermore, the role of abnormal RPC function in the pathogenesis of renal cell carcinoma will be established. We will proceed to validate RPC as therapeutic targets to improve podocyte regeneration and disease regression. Lineage tracing of the murine RPC system from development to adult life and characterization of the RPC niche will be performed through observation of RPC at various stages of nephron formation during development as well as during kidney growth, homeostasis and aging. RPC isolation and culture from kidney tissue being limited due to their inaccessibility, the recent development of a method for culturing them specifically from urine finally opens the perspective of personalized medicine of the kidney and the development of patient-specific treatment strategies. In addition, patient-specific RPC can be useful for screening of new drug compounds, developing disease-modifying assays, as well as for evaluation of drug toxicity, with particular regard to nephrotoxicity. Finally, RPC represent potential tools and/or targets for therapeutic purposes and to promote innovative renal replacement strategies for kidney disorders.
Summary
Kidney disorders represent a major global health issue and new tools are needed to expand disease modeling and therapeutic options. The identification of renal progenitors (RPC) opens a wide range of possibilities to support progress in several fields of nephrology. Indeed, RPC have become a key player in the pathogenesis of kidney disorders, and their study is increasing knowledge about the mechanisms of kidney response to injury. In this project we propose new lineage tracing models to identify and characterize mouse RPC system. We then will use these models to establish RPC role in progression or resolution of glomerular and tubular injury, and the mechanisms involved in these processes. Furthermore, the role of abnormal RPC function in the pathogenesis of renal cell carcinoma will be established. We will proceed to validate RPC as therapeutic targets to improve podocyte regeneration and disease regression. Lineage tracing of the murine RPC system from development to adult life and characterization of the RPC niche will be performed through observation of RPC at various stages of nephron formation during development as well as during kidney growth, homeostasis and aging. RPC isolation and culture from kidney tissue being limited due to their inaccessibility, the recent development of a method for culturing them specifically from urine finally opens the perspective of personalized medicine of the kidney and the development of patient-specific treatment strategies. In addition, patient-specific RPC can be useful for screening of new drug compounds, developing disease-modifying assays, as well as for evaluation of drug toxicity, with particular regard to nephrotoxicity. Finally, RPC represent potential tools and/or targets for therapeutic purposes and to promote innovative renal replacement strategies for kidney disorders.
Max ERC Funding
1 772 719 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym SalThApp
Project Psychology and Economic Behavior: Theory, Tests and Applications
Researcher (PI) Nicola Gennaioli
Host Institution (HI) UNIVERSITA COMMERCIALE LUIGI BOCCONI
Country Italy
Call Details Consolidator Grant (CoG), SH1, ERC-2014-CoG
Summary This proposal purports to develop psychologically founded models of economic decision making, test these models, and use them to shed light on several economic phenomena. The proposal builds on the psychology of selective attention. In particular, decision makers more easily retrieve from memory (precisely defined) representative events when making an inference, and they attach disproportionate attention and weighting to (precisely defined) salient choice options when making a choice. These ideas were modelled by the PI and his coauthors in previous work. The present grant proposal develops this research agenda in three stages. First, we plan to extend this approach to new theoretical problems such as the social psychology of stereotypes and the theory of consideration sets. Second, we plan to develop experimental tests dissecting the basic forces driving selective attention and decisions. Third, we plan to apply the theory to shed light on the following economic phenomena: a) investors’ risk perceptions in financial markets and asset price behavior, b) salient policy issues, voting behavior and political competition, c) consumer attention, product design and competition among firms, and d) discrimination in the labor market.
Summary
This proposal purports to develop psychologically founded models of economic decision making, test these models, and use them to shed light on several economic phenomena. The proposal builds on the psychology of selective attention. In particular, decision makers more easily retrieve from memory (precisely defined) representative events when making an inference, and they attach disproportionate attention and weighting to (precisely defined) salient choice options when making a choice. These ideas were modelled by the PI and his coauthors in previous work. The present grant proposal develops this research agenda in three stages. First, we plan to extend this approach to new theoretical problems such as the social psychology of stereotypes and the theory of consideration sets. Second, we plan to develop experimental tests dissecting the basic forces driving selective attention and decisions. Third, we plan to apply the theory to shed light on the following economic phenomena: a) investors’ risk perceptions in financial markets and asset price behavior, b) salient policy issues, voting behavior and political competition, c) consumer attention, product design and competition among firms, and d) discrimination in the labor market.
Max ERC Funding
1 431 650 €
Duration
Start date: 2015-09-01, End date: 2021-02-28
Project acronym SEMICOMPLEX
Project Divide and conquer ab initio semiclassical molecular dynamics for spectroscopic calculations of complex systems
Researcher (PI) Michele Ceotto
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Country Italy
Call Details Consolidator Grant (CoG), PE4, ERC-2014-CoG
Summary Given the continuing revolution in “nano” and “bio” technologies, it is urgent for chemists to be able to carry out reliable quantum dynamics simulations of complex molecular systems. The goal of this project is to fill the gap between theory and experiment and provide the community with a user-friendly computational tool for nuclear spectra (IR, vibro-electronic, etc.) calculations of very complex systems.
Present theoretical methodologies are hampered either by artificial nuclear potential interactions or by local potential perturbation assumptions. The semiclassical molecular dynamics method that I have been pioneering is not affected by these limitations because it is based on ab initio classical trajectories. The nuclear forces can be calculated by any electronic structure software and trajectories can explore the entire potential surface. The remaining challenge is to overcome the exponential scaling of computational power.
I will adopt a divide-and-conquer strategy to beat the curse of dimensionality. Firstly, the ab initio classical molecular dynamics is performed for the entire complex system. Then, partial spectra are calculated by using the semiclassical information derived by the projection of the trajectories onto lower dimensional spaces. Vibrational modes are not artificially decoupled. Finally, the entire spectrum is reconstructed piece by piece. This method allows chemists to have a more reliable spectral interpretation in a wider context up to the nanoscale. With the help of my own previous experience and my collaborations, I will simulate pollutant photodegradation for environmental remediation and the vibro-electronic spectra of carcinogenic molecules adsorbed on TiO2. I will also reproduce the spectroscopic properties of molecular nano-texturing of titania films for outdoor cultural heritage preservation.
A new generation of semiclassical fellows will be educated to put Europe on the leading edge of quantum simulations for spectroscopy.
Summary
Given the continuing revolution in “nano” and “bio” technologies, it is urgent for chemists to be able to carry out reliable quantum dynamics simulations of complex molecular systems. The goal of this project is to fill the gap between theory and experiment and provide the community with a user-friendly computational tool for nuclear spectra (IR, vibro-electronic, etc.) calculations of very complex systems.
Present theoretical methodologies are hampered either by artificial nuclear potential interactions or by local potential perturbation assumptions. The semiclassical molecular dynamics method that I have been pioneering is not affected by these limitations because it is based on ab initio classical trajectories. The nuclear forces can be calculated by any electronic structure software and trajectories can explore the entire potential surface. The remaining challenge is to overcome the exponential scaling of computational power.
I will adopt a divide-and-conquer strategy to beat the curse of dimensionality. Firstly, the ab initio classical molecular dynamics is performed for the entire complex system. Then, partial spectra are calculated by using the semiclassical information derived by the projection of the trajectories onto lower dimensional spaces. Vibrational modes are not artificially decoupled. Finally, the entire spectrum is reconstructed piece by piece. This method allows chemists to have a more reliable spectral interpretation in a wider context up to the nanoscale. With the help of my own previous experience and my collaborations, I will simulate pollutant photodegradation for environmental remediation and the vibro-electronic spectra of carcinogenic molecules adsorbed on TiO2. I will also reproduce the spectroscopic properties of molecular nano-texturing of titania films for outdoor cultural heritage preservation.
A new generation of semiclassical fellows will be educated to put Europe on the leading edge of quantum simulations for spectroscopy.
Max ERC Funding
1 899 973 €
Duration
Start date: 2015-11-01, End date: 2022-04-30
Project acronym SPICE
Project Synthetic Lethal Phenotype Identification through Cancer Evolution Analysis
Researcher (PI) Francesca Demichelis
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TRENTO
Country Italy
Call Details Consolidator Grant (CoG), LS2, ERC-2014-CoG
Summary Prostate cancer (PCA) is a genetically heterogeneous disease. Advances in targeted hormonal therapy (second generation anti-androgens) have led to more effective management of castration-resistant prostate cancer (CRPC). Despite these highly potent drugs, disease recurs with new genomic and epigenetic alterations. In this ERC proposal, I will leverage my expertise in cancer genomics and a new computational methodology to unravel the landscape of lethal PCA, with a focus on determining the Achilles’ heel of these aggressive tumours. In Aim 1, I will take advantage of DNA sequencing data from over 1000 patient-derived tumour samples and use highly innovative mathematical algorithms to create a detailed evolution chart for each tumour and identify driver events leading to CRPC. After nominating candidate drivers, we propose testing 10 using in vitro gain- and loss-of-function validations experiments (i.e., CRISPR/Cas9, shRNA, and Tet-On assays) in PCA cell lines using migration, invasion, and cell cycle as readouts. In Aim 2, I will focus on genomic events that occur in recalcitrant CRPC, positing that genetic alterations occurring prior or secondary to treatment harbour clues into resistance. In vitro validations will be performed on the top 10 biomarkers. In Aim 3, I will nominate synthetic lethality combinations by mining CRPC genomic data taken from Stand Up 2 Cancer CRPC clinical trials. I will prioritize mutually exclusive genomic alterations in genes for which approved drugs exist. The top 5-10 candidates will be validated in a prostate lineage-specific manner. In summary, this ERC proposal will leverage my many years of expertise in PCA genomics and emerging public and private CRPC datasets to uncover driver mutations that will enhance our understanding of recalcitrant CRPC. Successful completion of this study should lead to novel treatment approaches for CRPC and to a computational model that may transform our approach to evaluating other cancers.
Summary
Prostate cancer (PCA) is a genetically heterogeneous disease. Advances in targeted hormonal therapy (second generation anti-androgens) have led to more effective management of castration-resistant prostate cancer (CRPC). Despite these highly potent drugs, disease recurs with new genomic and epigenetic alterations. In this ERC proposal, I will leverage my expertise in cancer genomics and a new computational methodology to unravel the landscape of lethal PCA, with a focus on determining the Achilles’ heel of these aggressive tumours. In Aim 1, I will take advantage of DNA sequencing data from over 1000 patient-derived tumour samples and use highly innovative mathematical algorithms to create a detailed evolution chart for each tumour and identify driver events leading to CRPC. After nominating candidate drivers, we propose testing 10 using in vitro gain- and loss-of-function validations experiments (i.e., CRISPR/Cas9, shRNA, and Tet-On assays) in PCA cell lines using migration, invasion, and cell cycle as readouts. In Aim 2, I will focus on genomic events that occur in recalcitrant CRPC, positing that genetic alterations occurring prior or secondary to treatment harbour clues into resistance. In vitro validations will be performed on the top 10 biomarkers. In Aim 3, I will nominate synthetic lethality combinations by mining CRPC genomic data taken from Stand Up 2 Cancer CRPC clinical trials. I will prioritize mutually exclusive genomic alterations in genes for which approved drugs exist. The top 5-10 candidates will be validated in a prostate lineage-specific manner. In summary, this ERC proposal will leverage my many years of expertise in PCA genomics and emerging public and private CRPC datasets to uncover driver mutations that will enhance our understanding of recalcitrant CRPC. Successful completion of this study should lead to novel treatment approaches for CRPC and to a computational model that may transform our approach to evaluating other cancers.
Max ERC Funding
1 996 428 €
Duration
Start date: 2015-10-01, End date: 2021-03-31
