Project acronym FLEXOCOMP
Project Enabling flexoelectric engineering through modeling and computation
Researcher (PI) Irene Arias Vicente
Host Institution (HI) UNIVERSITAT POLITECNICA DE CATALUNYA
Call Details Starting Grant (StG), PE7, ERC-2015-STG
Summary Piezoelectric materials transduce electrical voltage into mechanical strain and vice-versa, which makes them ubiquitous in sensors, actuators, and energy harvesting systems. Flexoelectricity is a related but different effect, by which electric polarization is coupled to strain gradients, i.e. it requires inhomogeneous deformation. Flexoelectricity is present in a much wider variety of materials, including non-polar dielectrics and polymers, but is only significant at small length-scales. Flexoelectricity has demonstrated its potential in information technologies, by flexoelectric-mediated mechanical writing in ferroelectric thin films at the nanoscale, or in flexoelectric electromechanical transducers. It has been suggested that flexoelectricity could enable piezoelectric composites made out of non-piezoelectric components, including soft materials, which could be used in biocompatible and self-powered small-scale devices. Flexoelectricity is a nascent field with major open questions. Furthermore, experimental devices and material designs are limited by what we can understand and analyze, and unfortunately, we lack general engineering analysis tools for flexoelectricity. As a result, current flexoelectric devices are only minimal variations of configurations conceived within the uniform-strain mindset of piezoelectricity. Our main objective in this proposal is to develop an advanced computational infrastructure to quantify flexoelectricity in solids, focusing on continuum models but also exploring multiscale aspects. We plan to use it to (1) analyze accurately flexoelectricity accounting for general geometries, electrode configurations, and material behavior, (2) identify new physics emerging flexoelectricity, and (3) propose, build and test a new generation of thin-film devices, composites and metamaterials for electromechanical transduction, genuinely designed to exploit small-scale flexoelectricity and make it available at macroscopic scales.
Summary
Piezoelectric materials transduce electrical voltage into mechanical strain and vice-versa, which makes them ubiquitous in sensors, actuators, and energy harvesting systems. Flexoelectricity is a related but different effect, by which electric polarization is coupled to strain gradients, i.e. it requires inhomogeneous deformation. Flexoelectricity is present in a much wider variety of materials, including non-polar dielectrics and polymers, but is only significant at small length-scales. Flexoelectricity has demonstrated its potential in information technologies, by flexoelectric-mediated mechanical writing in ferroelectric thin films at the nanoscale, or in flexoelectric electromechanical transducers. It has been suggested that flexoelectricity could enable piezoelectric composites made out of non-piezoelectric components, including soft materials, which could be used in biocompatible and self-powered small-scale devices. Flexoelectricity is a nascent field with major open questions. Furthermore, experimental devices and material designs are limited by what we can understand and analyze, and unfortunately, we lack general engineering analysis tools for flexoelectricity. As a result, current flexoelectric devices are only minimal variations of configurations conceived within the uniform-strain mindset of piezoelectricity. Our main objective in this proposal is to develop an advanced computational infrastructure to quantify flexoelectricity in solids, focusing on continuum models but also exploring multiscale aspects. We plan to use it to (1) analyze accurately flexoelectricity accounting for general geometries, electrode configurations, and material behavior, (2) identify new physics emerging flexoelectricity, and (3) propose, build and test a new generation of thin-film devices, composites and metamaterials for electromechanical transduction, genuinely designed to exploit small-scale flexoelectricity and make it available at macroscopic scales.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym MYELOMANEXT
Project Integrated next-generation flow cytometry and sequencing to uncover the pathway of curability in multiple myeloma
Researcher (PI) Bruno David Lourenço Paiva
Host Institution (HI) UNIVERSIDAD DE NAVARRA
Call Details Starting Grant (StG), LS7, ERC-2015-STG
Summary Multiple myeloma (MM) represents a unique model to investigate cancer stem cells (CSCs), circulating tumour cells (CTCs), and the mechanisms of malignant transformation and chemoresistance. Despite the substantial improvement in MM patients’ outcome, the vast majority of patients eventually relapse and the disease remains largely incurable. For those patients failing to achieve deep remissions, biologically targeted research on the ultra-chemoresistant minimal residual disease (MRD) clone may allow us to understand the cellular mechanisms driving chemoresistance, and design novel therapeutic to overcome; importantly, such effort should be equally performed on two additional key players: CSCs and CTCs. On the opposite side, it is unquestionable that a selected group of patients does experience long-term survival irrespectively of the depth of response achieved, but we fail to understand the mechanisms driving sustained disease control. Is it because of persistent residual benign clones? Is it because of immune surveillance? Here, we will integrate next-generation flow cytometry and sequencing to define i) the signature of CTCs and ultra-chemoresistant MRD cells, ii) the hierarchical place of putative CSCs, iii) the genomic landscape of benign vs. malignant clones; and iv) the role of immune surveillance to achieve functional cures. Hence, we will characterize for the first-time-ever the highly-professional subclones responsible for malignant transformation, disease dissemination, and dramatic relapses after optimal response to therapy. Noteworthy, the innovative approach of this scientific proposal strongly relies on the use and expertise of highly-sensitive next-generation flow cytometry, coupled with optimized DNA- and RNA-sequencing for low-cell-numbers, and prospective patient samples longitudinally available within the scope of well-controlled clinical trials. Herein, we believe that all requirements are met to conduct this ground-breaking research program.
Summary
Multiple myeloma (MM) represents a unique model to investigate cancer stem cells (CSCs), circulating tumour cells (CTCs), and the mechanisms of malignant transformation and chemoresistance. Despite the substantial improvement in MM patients’ outcome, the vast majority of patients eventually relapse and the disease remains largely incurable. For those patients failing to achieve deep remissions, biologically targeted research on the ultra-chemoresistant minimal residual disease (MRD) clone may allow us to understand the cellular mechanisms driving chemoresistance, and design novel therapeutic to overcome; importantly, such effort should be equally performed on two additional key players: CSCs and CTCs. On the opposite side, it is unquestionable that a selected group of patients does experience long-term survival irrespectively of the depth of response achieved, but we fail to understand the mechanisms driving sustained disease control. Is it because of persistent residual benign clones? Is it because of immune surveillance? Here, we will integrate next-generation flow cytometry and sequencing to define i) the signature of CTCs and ultra-chemoresistant MRD cells, ii) the hierarchical place of putative CSCs, iii) the genomic landscape of benign vs. malignant clones; and iv) the role of immune surveillance to achieve functional cures. Hence, we will characterize for the first-time-ever the highly-professional subclones responsible for malignant transformation, disease dissemination, and dramatic relapses after optimal response to therapy. Noteworthy, the innovative approach of this scientific proposal strongly relies on the use and expertise of highly-sensitive next-generation flow cytometry, coupled with optimized DNA- and RNA-sequencing for low-cell-numbers, and prospective patient samples longitudinally available within the scope of well-controlled clinical trials. Herein, we believe that all requirements are met to conduct this ground-breaking research program.
Max ERC Funding
1 468 606 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym OPTICALBULLET
Project Studies of neurosecretion by remote control of exocytosis and endocytosis with ligt
Researcher (PI) Pau Gorostiza
Host Institution (HI) FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
Call Details Starting Grant (StG), LS7, ERC-2007-StG
Summary Optical switches are photoisomerizable compounds that allow to remotely controlling the activity of proteins, cells and entire organisms with light. These tools are revolutionizing research in biology with their high selectivity and spatiotemporal resolution. Here we propose to develop and apply optical switches to investigate the fundamental processes of secretion, exocytosis and endocytosis, in a way that is non-invasive, acute, and orthogonal to pharmacological and electrophysiological techniques. The optical control of exocytosis will be carried out by means of photoswitchable, Ca2+-permeable channels (LiGluR and Channelrhodopsin-2) which allow triggering vesicle fusion at single synaptic terminals. This procedure will allow studying vesicle release kinetics and the differences between synapses of the same neuron. The photocontrol of endocytosis will be carried out with: (1) inhibitory peptides of the clathrin pathway modified with an azobenzene crosslinker in order to photomodulate their structure and affinity, and (2) photoswitchable synthetic compounds based on chemical inhibitors of dynamin. Photomodulation of endocytosis in chromaffin cells and neurons will allow interfering with the internalisation of membrane receptors with an unprecedented spatial and temporal control. The use of photoswitchable inhibitors of endocytosis would allow for the first time to manipulate reversibly and with subcellular resolution, the vesicular trafficking of the endocytic pathway. In addition, these photoswitches could reveal how endocytosis regulates spatially receptor activation, controlling cell patterning and cell fate.
Summary
Optical switches are photoisomerizable compounds that allow to remotely controlling the activity of proteins, cells and entire organisms with light. These tools are revolutionizing research in biology with their high selectivity and spatiotemporal resolution. Here we propose to develop and apply optical switches to investigate the fundamental processes of secretion, exocytosis and endocytosis, in a way that is non-invasive, acute, and orthogonal to pharmacological and electrophysiological techniques. The optical control of exocytosis will be carried out by means of photoswitchable, Ca2+-permeable channels (LiGluR and Channelrhodopsin-2) which allow triggering vesicle fusion at single synaptic terminals. This procedure will allow studying vesicle release kinetics and the differences between synapses of the same neuron. The photocontrol of endocytosis will be carried out with: (1) inhibitory peptides of the clathrin pathway modified with an azobenzene crosslinker in order to photomodulate their structure and affinity, and (2) photoswitchable synthetic compounds based on chemical inhibitors of dynamin. Photomodulation of endocytosis in chromaffin cells and neurons will allow interfering with the internalisation of membrane receptors with an unprecedented spatial and temporal control. The use of photoswitchable inhibitors of endocytosis would allow for the first time to manipulate reversibly and with subcellular resolution, the vesicular trafficking of the endocytic pathway. In addition, these photoswitches could reveal how endocytosis regulates spatially receptor activation, controlling cell patterning and cell fate.
Max ERC Funding
1 338 000 €
Duration
Start date: 2008-09-01, End date: 2013-08-31
Project acronym POSTDATA
Project Poetry Standardization and Linked Open Data
Researcher (PI) Elena Gonzalez-Blanco Garcia
Host Institution (HI) INDRA SISTEMAS SA
Call Details Starting Grant (StG), SH5, ERC-2015-STG
Summary This project aims at bridging the digital gap among traditional cultural assets and the growing world of data. It is focused on poetry analysis, classification and publication, applying Digital Humanities methods of academic analysis -such as XML-TEI encoding- in order to look for standardization. Interoperability problems between the different poetry collections are solved by using semantic web technologies to link and publish literary datasets in a structured way in the linked data cloud. The advantages of making poetry available online as machine-readable linked data are threefold: first, the academic community will have an accessible digital platform to work with poetic corpora and to contribute to its enrichment with their own texts; second, this way of encoding and standardizing poetic information will be a guarantee of preservation for poems published only in old books or even transmitted orally, as texts will be digitized and stored as XML files; third: datasets and corpora will be available and open access to be used by the community for other purposes, such as education, cultural diffusion or entertainment. To accomplish such a ground-breaking approach, I have a hybrid profile, combining a strong philological background, specialized in poetry and metrics, with a deep knowledge of Digital Humanities proven by my leadership and experience in interdisciplinary projects. Since 2011, I am the Principal Investigator of the first Digital Repertoire of Medieval Spanish Poetry (ReMetCa), an innovative project that combines traditional metrical analysis with digital text encoding, and since 2014 I am the Academic Director of LINHD, The Digital Humanities Innovation Lab created at UNED as a research interdisciplinary centre.
Summary
This project aims at bridging the digital gap among traditional cultural assets and the growing world of data. It is focused on poetry analysis, classification and publication, applying Digital Humanities methods of academic analysis -such as XML-TEI encoding- in order to look for standardization. Interoperability problems between the different poetry collections are solved by using semantic web technologies to link and publish literary datasets in a structured way in the linked data cloud. The advantages of making poetry available online as machine-readable linked data are threefold: first, the academic community will have an accessible digital platform to work with poetic corpora and to contribute to its enrichment with their own texts; second, this way of encoding and standardizing poetic information will be a guarantee of preservation for poems published only in old books or even transmitted orally, as texts will be digitized and stored as XML files; third: datasets and corpora will be available and open access to be used by the community for other purposes, such as education, cultural diffusion or entertainment. To accomplish such a ground-breaking approach, I have a hybrid profile, combining a strong philological background, specialized in poetry and metrics, with a deep knowledge of Digital Humanities proven by my leadership and experience in interdisciplinary projects. Since 2011, I am the Principal Investigator of the first Digital Repertoire of Medieval Spanish Poetry (ReMetCa), an innovative project that combines traditional metrical analysis with digital text encoding, and since 2014 I am the Academic Director of LINHD, The Digital Humanities Innovation Lab created at UNED as a research interdisciplinary centre.
Max ERC Funding
1 131 413 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym SUMO
Project Study of the role of protein posttranslational modification by SUMO (Small Ubiquitin-like MOdifier) in abscisic acid signaling and stress responses in plants
Researcher (PI) Luisa Maria Lois
Host Institution (HI) CENTRE DE RECERCA EN AGRIGENOMICA CSIC-IRTA-UAB-UB
Call Details Starting Grant (StG), LS7, ERC-2007-StG
Summary Eukaryotic protein function is regulated in vivo by diverse mechanisms such as protein turnover, regulation of protein activity, localization and protein-protein interactions. These mechanisms involve constitutive or reversible post-translational modifications of specific amino-acid residues in the target protein by molecules of different nature. Ubiquitin and ubiquitin-like modifiers are polypeptides that are covalently attached to a lysine residue in the target protein. SUMO is a member of the ubiquitin family, but it differs from ubiquitin in its cellular function. Whereas protein ubiquitination results in degradation by the 26S proteasome, sumoylation is involved in regulation of protein activity, cellular localization, or protection from ubiquitination. In plants, SUMO plays an important role in biotic and abiotic stress responses, and regulates abscisic acid (ABA) signaling, plant hormone that mediates environmental stress responses, and flowering. In addition, we have found that a functional sumoylation system is essential during seed development, process that is also regulated by ABA at different stages. Our general goal is to investigate the biological role of SUMO in the context of ABA signaling and stress responses in Arabidopsis. For this purpose we will study different aspects of this novel posttranslational regulatory system involving the analysis of the SUMO biological role during seed development and germination, identification of new SUMO targets and dissection of the biological role of the catalase AtCAT3 sumoylation, and the study of molecular factors that could be responsible for recognition of SUMO conjugates. The data generated will contribute to better understanding of this biological process and, eventually, to a thoughtful design of plants with improved agronomical traits. Also, as sumoylation is an evolutionary conserved regulatory system, our work will greatly contribute to understand its mechanism of action in mammals.
Summary
Eukaryotic protein function is regulated in vivo by diverse mechanisms such as protein turnover, regulation of protein activity, localization and protein-protein interactions. These mechanisms involve constitutive or reversible post-translational modifications of specific amino-acid residues in the target protein by molecules of different nature. Ubiquitin and ubiquitin-like modifiers are polypeptides that are covalently attached to a lysine residue in the target protein. SUMO is a member of the ubiquitin family, but it differs from ubiquitin in its cellular function. Whereas protein ubiquitination results in degradation by the 26S proteasome, sumoylation is involved in regulation of protein activity, cellular localization, or protection from ubiquitination. In plants, SUMO plays an important role in biotic and abiotic stress responses, and regulates abscisic acid (ABA) signaling, plant hormone that mediates environmental stress responses, and flowering. In addition, we have found that a functional sumoylation system is essential during seed development, process that is also regulated by ABA at different stages. Our general goal is to investigate the biological role of SUMO in the context of ABA signaling and stress responses in Arabidopsis. For this purpose we will study different aspects of this novel posttranslational regulatory system involving the analysis of the SUMO biological role during seed development and germination, identification of new SUMO targets and dissection of the biological role of the catalase AtCAT3 sumoylation, and the study of molecular factors that could be responsible for recognition of SUMO conjugates. The data generated will contribute to better understanding of this biological process and, eventually, to a thoughtful design of plants with improved agronomical traits. Also, as sumoylation is an evolutionary conserved regulatory system, our work will greatly contribute to understand its mechanism of action in mammals.
Max ERC Funding
1 104 000 €
Duration
Start date: 2008-07-01, End date: 2014-06-30
Project acronym TOHPN
Project Towards the optimization of hydrogen production by nitrogenase
Researcher (PI) Luis Manuel Rubio Herrero
Host Institution (HI) UNIVERSIDAD POLITECNICA DE MADRID
Call Details Starting Grant (StG), LS7, ERC-2007-StG
Summary In nature, molecular hydrogen is produced by the hydrogenase and the nitrogenase enzymes. Nitrogenase reduces dinitrogen to ammonia and, in this process, it evolves hydrogen. Nitrogenase and hydrogenase are oxygen-sensitive enzymes. We chose to optimize a hydrogen production system based on nitrogenase for four reasons: some organisms carrying nitrogenase simultaneously perform photosynthesis and hydrogen evolution by nitrogenase (direct biophotolysis), thus harvesting solar energy and autonomously converting it into chemical energy in a continuous process; cellular mechanisms exist to protect nitrogenase from oxygen but do not appear to exist for hydrogenase; because nitrogenase couples ATP hydrolysis to hydrogen evolution, this enzyme is able to generate hydrogen against a substantial gas pressure; finally, the biochemistry of the nitrogenase system is well known. The objective of our proposal is to provide new eco-efficient strategies for the biological production of hydrogen. Energy research is a priority theme under the Seventh Research Framework (FP7) cooperation program. The objective of energy research under FP7 is to adapt the current energy system into a more sustainable, competitive and secure one, with emphasis and support given to hydrogen research and renewable fuel production. Our proposal has three major components: (i) in vitro evolution of nitrogenase, in which we generate new nitrogenase variants by metagenomic gene shuffling and random mutagenesis, and select those with increased hydrogen production activity; (ii) the development of a genetic system to select for hydrogen overproducers; and (iii) a biochemical element designed to understand the biochemical requisites for efficient hydrogen production by the molybdenum nitrogenase as a basis for its re-engineering.
Summary
In nature, molecular hydrogen is produced by the hydrogenase and the nitrogenase enzymes. Nitrogenase reduces dinitrogen to ammonia and, in this process, it evolves hydrogen. Nitrogenase and hydrogenase are oxygen-sensitive enzymes. We chose to optimize a hydrogen production system based on nitrogenase for four reasons: some organisms carrying nitrogenase simultaneously perform photosynthesis and hydrogen evolution by nitrogenase (direct biophotolysis), thus harvesting solar energy and autonomously converting it into chemical energy in a continuous process; cellular mechanisms exist to protect nitrogenase from oxygen but do not appear to exist for hydrogenase; because nitrogenase couples ATP hydrolysis to hydrogen evolution, this enzyme is able to generate hydrogen against a substantial gas pressure; finally, the biochemistry of the nitrogenase system is well known. The objective of our proposal is to provide new eco-efficient strategies for the biological production of hydrogen. Energy research is a priority theme under the Seventh Research Framework (FP7) cooperation program. The objective of energy research under FP7 is to adapt the current energy system into a more sustainable, competitive and secure one, with emphasis and support given to hydrogen research and renewable fuel production. Our proposal has three major components: (i) in vitro evolution of nitrogenase, in which we generate new nitrogenase variants by metagenomic gene shuffling and random mutagenesis, and select those with increased hydrogen production activity; (ii) the development of a genetic system to select for hydrogen overproducers; and (iii) a biochemical element designed to understand the biochemical requisites for efficient hydrogen production by the molybdenum nitrogenase as a basis for its re-engineering.
Max ERC Funding
1 968 000 €
Duration
Start date: 2008-10-01, End date: 2014-09-30
