Project acronym 9 SALT
Project Reassessing Ninth Century Philosophy. A Synchronic Approach to the Logical Traditions
Researcher (PI) Christophe Florian Erismann
Host Institution (HI) UNIVERSITAT WIEN
Country Austria
Call Details Consolidator Grant (CoG), SH5, ERC-2014-CoG
Summary This project aims at a better understanding of the philosophical richness of ninth century thought using the unprecedented and highly innovative method of the synchronic approach. The hypothesis directing this synchronic approach is that studying together in parallel the four main philosophical traditions of the century – i.e. Latin, Greek, Syriac and Arabic – will bring results that the traditional enquiry limited to one tradition alone can never reach. This implies pioneering a new methodology to overcome the compartmentalization of research which prevails nowadays. Using this method is only possible because the four conditions of applicability – comparable intellectual environment, common text corpus, similar methodological perspective, commensurable problems – are fulfilled. The ninth century, a time of cultural renewal in the Carolingian, Byzantine and Abbasid empires, possesses the remarkable characteristic – which ensures commensurability – that the same texts, namely the writings of Aristotelian logic (mainly Porphyry’s Isagoge and Aristotle’s Categories) were read and commented upon in Latin, Greek, Syriac and Arabic alike.
Logic is fundamental to philosophical enquiry. The contested question is the human capacity to rationalise, analyse and describe the sensible reality, to understand the ontological structure of the world, and to define the types of entities which exist. The use of this unprecedented synchronic approach will allow us a deeper understanding of the positions, a clear identification of the a priori postulates of the philosophical debates, and a critical evaluation of the arguments used. It provides a unique opportunity to compare the different traditions and highlight the heritage which is common, to stress the specificities of each tradition when tackling philosophical issues and to discover the doctrinal results triggered by their mutual interactions, be they constructive (scholarly exchanges) or polemic (religious controversies).
Summary
This project aims at a better understanding of the philosophical richness of ninth century thought using the unprecedented and highly innovative method of the synchronic approach. The hypothesis directing this synchronic approach is that studying together in parallel the four main philosophical traditions of the century – i.e. Latin, Greek, Syriac and Arabic – will bring results that the traditional enquiry limited to one tradition alone can never reach. This implies pioneering a new methodology to overcome the compartmentalization of research which prevails nowadays. Using this method is only possible because the four conditions of applicability – comparable intellectual environment, common text corpus, similar methodological perspective, commensurable problems – are fulfilled. The ninth century, a time of cultural renewal in the Carolingian, Byzantine and Abbasid empires, possesses the remarkable characteristic – which ensures commensurability – that the same texts, namely the writings of Aristotelian logic (mainly Porphyry’s Isagoge and Aristotle’s Categories) were read and commented upon in Latin, Greek, Syriac and Arabic alike.
Logic is fundamental to philosophical enquiry. The contested question is the human capacity to rationalise, analyse and describe the sensible reality, to understand the ontological structure of the world, and to define the types of entities which exist. The use of this unprecedented synchronic approach will allow us a deeper understanding of the positions, a clear identification of the a priori postulates of the philosophical debates, and a critical evaluation of the arguments used. It provides a unique opportunity to compare the different traditions and highlight the heritage which is common, to stress the specificities of each tradition when tackling philosophical issues and to discover the doctrinal results triggered by their mutual interactions, be they constructive (scholarly exchanges) or polemic (religious controversies).
Max ERC Funding
1 998 566 €
Duration
Start date: 2015-09-01, End date: 2021-02-28
Project acronym AdriArchCult
Project Architectural Culture of the Early Modern Eastern Adriatic
Researcher (PI) Jasenka Gudelj
Host Institution (HI) UNIVERSITA CA' FOSCARI VENEZIA
Country Italy
Call Details Consolidator Grant (CoG), SH5, ERC-2019-COG
Summary During the 15th century, the political process of reducing the Eastern Adriatic, here considered as encompassing what is now littoral of Slovenia, Croatia and Montenegro, to a thin strip of border territories substantially separated from the continental massive to which they belong, reached its conclusion. The insularity of its large natural archipelago, i.e. almost exclusive dependence on the maritime communications, became characteristic even of mainland coastal towns, with lasting consequences. The project explores the impact of this change in the area between 15th and 18th c., focusing on architecture as the most evident materialization of a culture and its transformations. The goal is to examine the architectural culture in question in terms of both consumption and production. Factors such as political and economic consolidation of Venetian and Dubrovnik Republics as well as Habsburg Empire in the area, war and commerce with the Ottomans, but also the quick spread of revival of antiquity and the Catholic Revival, all fuelled the need for architectural creation with certain functional and symbolic characteristics, setting the cultural standards. On the other hand, the economics of production of architecture consisted of interrelated systems of the provision of materials (esp. Istrian stone) and organisation of construction sites, which, given the ease of the sea transport, resulted in an active market for architectural goods. This approach will provide an original contribution to the understanding of cultural practices that not only produced specific buildings, the most significant among which are now listed as World Heritage sites but also put into circulation ancient and modern models, techniques and materials for a European-wide audience. Moreover, it will investigate the trans-border and trans-confessional character of the architectural market, thus providing an innovative model for a study of such phenomena across Europe.
Summary
During the 15th century, the political process of reducing the Eastern Adriatic, here considered as encompassing what is now littoral of Slovenia, Croatia and Montenegro, to a thin strip of border territories substantially separated from the continental massive to which they belong, reached its conclusion. The insularity of its large natural archipelago, i.e. almost exclusive dependence on the maritime communications, became characteristic even of mainland coastal towns, with lasting consequences. The project explores the impact of this change in the area between 15th and 18th c., focusing on architecture as the most evident materialization of a culture and its transformations. The goal is to examine the architectural culture in question in terms of both consumption and production. Factors such as political and economic consolidation of Venetian and Dubrovnik Republics as well as Habsburg Empire in the area, war and commerce with the Ottomans, but also the quick spread of revival of antiquity and the Catholic Revival, all fuelled the need for architectural creation with certain functional and symbolic characteristics, setting the cultural standards. On the other hand, the economics of production of architecture consisted of interrelated systems of the provision of materials (esp. Istrian stone) and organisation of construction sites, which, given the ease of the sea transport, resulted in an active market for architectural goods. This approach will provide an original contribution to the understanding of cultural practices that not only produced specific buildings, the most significant among which are now listed as World Heritage sites but also put into circulation ancient and modern models, techniques and materials for a European-wide audience. Moreover, it will investigate the trans-border and trans-confessional character of the architectural market, thus providing an innovative model for a study of such phenomena across Europe.
Max ERC Funding
1 999 750 €
Duration
Start date: 2020-09-01, End date: 2025-08-31
Project acronym AlchemEast
Project Alchemy in the Making: From ancient Babylonia via Graeco-Roman Egypt into the Byzantine, Syriac and Arabic traditions (1500 BCE - 1000 AD)
Researcher (PI) Matteo MARTELLI
Host Institution (HI) ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA
Country Italy
Call Details Consolidator Grant (CoG), SH5, ERC-2016-COG
Summary "The AlchemEast project is devoted to the study of alchemical theory and practice as it appeared and developed in distinct, albeit contiguous (both chronologically and geographically) areas: Graeco-Roman Egypt, Byzantium, and the Near East, from Ancient Babylonian times to the early Islamic Period. This project combines innovative textual investigations with experimental replications of ancient alchemical procedures. It uses sets of historically and philologically informed laboratory replications in order to reconstruct the actual practice of ancient alchemists, and it studies the texts and literary forms in which this practice was conceptualized and transmitted. It proposes new models for textual criticism in order to capture the fluidity of the transmission of ancient alchemical writings. AlchemEast is designed to carry out a comparative investigation of cuneiform tablets as well as a vast corpus of Greek, Syriac and Arabic writings. It will overcome the old, pejorative paradigm that dismissed ancient alchemy as a ""pseudo-science"", by proposing a new theoretical framework for comprehending the entirety of ancient alchemical practices and theories. Alongside established forms of scholarly output, such as critical editions of key texts, AlchemEast will provide an integrative, longue durée perspective on the many different phases of ancient alchemy. It will thus offer a radically new vision of this discipline as a dynamic and diversified art that developed across different technical and scholastic traditions. This new representation will allow us to connect ancient alchemy with medieval and early modern alchemy and thus fully reintegrate ancient alchemy in the history of pre-modern alchemy as well as in the history of ancient science more broadly."
Summary
"The AlchemEast project is devoted to the study of alchemical theory and practice as it appeared and developed in distinct, albeit contiguous (both chronologically and geographically) areas: Graeco-Roman Egypt, Byzantium, and the Near East, from Ancient Babylonian times to the early Islamic Period. This project combines innovative textual investigations with experimental replications of ancient alchemical procedures. It uses sets of historically and philologically informed laboratory replications in order to reconstruct the actual practice of ancient alchemists, and it studies the texts and literary forms in which this practice was conceptualized and transmitted. It proposes new models for textual criticism in order to capture the fluidity of the transmission of ancient alchemical writings. AlchemEast is designed to carry out a comparative investigation of cuneiform tablets as well as a vast corpus of Greek, Syriac and Arabic writings. It will overcome the old, pejorative paradigm that dismissed ancient alchemy as a ""pseudo-science"", by proposing a new theoretical framework for comprehending the entirety of ancient alchemical practices and theories. Alongside established forms of scholarly output, such as critical editions of key texts, AlchemEast will provide an integrative, longue durée perspective on the many different phases of ancient alchemy. It will thus offer a radically new vision of this discipline as a dynamic and diversified art that developed across different technical and scholastic traditions. This new representation will allow us to connect ancient alchemy with medieval and early modern alchemy and thus fully reintegrate ancient alchemy in the history of pre-modern alchemy as well as in the history of ancient science more broadly."
Max ERC Funding
1 997 000 €
Duration
Start date: 2017-12-01, End date: 2022-11-30
Project acronym BioDisOrder
Project Order and Disorder at the Surface of Biological Membranes.
Researcher (PI) Alfonso DE SIMONE
Host Institution (HI) UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Country Italy
Call Details Consolidator Grant (CoG), PE4, ERC-2018-COG
Summary Heterogeneous biomolecular mechanisms at the surface of cellular membranes are often fundamental to generate function and dysfunction in living systems. These processes are governed by transient and dynamical macromolecular interactions that pose tremendous challenges to current analytical tools, as the majority of these methods perform best in the study of well-defined and poorly dynamical systems. This proposal aims at a radical innovation in the characterisation of complex processes that are dominated by structural order and disorder, including those occurring at the surface of biological membranes such as cellular signalling, the assembly of molecular machinery, or the regulation vesicular trafficking.
I outline a programme to realise a vision where the combination of experiments and theory can delineate a new analytical platform to study complex biochemical mechanisms at a multiscale level, and to elucidate their role in physiological and pathological contexts. To achieve this ambitious goal, my research team will develop tools based on the combination of nuclear magnetic resonance (NMR) spectroscopy and molecular simulations, which will enable probing the structure, dynamics, thermodynamics and kinetics of complex protein-protein and protein-membrane interactions occurring at the surface of cellular membranes. The ability to advance both the experimental and theoretical sides, and their combination, is fundamental to define the next generation of methods to achieve our transformative aims. We will provide evidence of the innovative nature of the proposed multiscale approach by addressing some of the great questions in neuroscience and elucidate the details of how functional and aberrant biological complexity is achieved via the fine tuning between structural order and disorder at the neuronal synapse.
Summary
Heterogeneous biomolecular mechanisms at the surface of cellular membranes are often fundamental to generate function and dysfunction in living systems. These processes are governed by transient and dynamical macromolecular interactions that pose tremendous challenges to current analytical tools, as the majority of these methods perform best in the study of well-defined and poorly dynamical systems. This proposal aims at a radical innovation in the characterisation of complex processes that are dominated by structural order and disorder, including those occurring at the surface of biological membranes such as cellular signalling, the assembly of molecular machinery, or the regulation vesicular trafficking.
I outline a programme to realise a vision where the combination of experiments and theory can delineate a new analytical platform to study complex biochemical mechanisms at a multiscale level, and to elucidate their role in physiological and pathological contexts. To achieve this ambitious goal, my research team will develop tools based on the combination of nuclear magnetic resonance (NMR) spectroscopy and molecular simulations, which will enable probing the structure, dynamics, thermodynamics and kinetics of complex protein-protein and protein-membrane interactions occurring at the surface of cellular membranes. The ability to advance both the experimental and theoretical sides, and their combination, is fundamental to define the next generation of methods to achieve our transformative aims. We will provide evidence of the innovative nature of the proposed multiscale approach by addressing some of the great questions in neuroscience and elucidate the details of how functional and aberrant biological complexity is achieved via the fine tuning between structural order and disorder at the neuronal synapse.
Max ERC Funding
1 999 945 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym BIORECAR
Project Direct cell reprogramming therapy in myocardial regeneration through an engineered multifunctional platform integrating biochemical instructive cues
Researcher (PI) Valeria CHIONO
Host Institution (HI) POLITECNICO DI TORINO
Country Italy
Call Details Consolidator Grant (CoG), PE8, ERC-2017-COG
Summary In BIORECAR I will develop a new breakthrough multifunctional biomaterial-based platform for myocardial regeneration after myocardial infarction, provided with biochemical cues able to enhance the direct reprogramming of human cardiac fibroblasts into functional cardiomyocytes.
My expertise in bioartificial materials and biomimetic scaffolds and the versatile chemistry of polyurethanes will be the key elements to achieve a significant knowledge and technological advancement in cell reprogramming therapy, opening the way to the future translation of the therapy into the clinics.
I will implement this advanced approach through the design of a novel 3D in vitro tissue-engineered model of human cardiac fibrotic tissue, as a tool for testing and validation, to maximise research efforts and reduce animal tests.
I will adapt novel nanomedicine approaches I have recently developed for drug release to design innovative cell-friendly and efficient polyurethane nanoparticles for targeted reprogramming of cardiac fibroblasts.
I will design an injectable bioartificial hydrogel based on a blend of a thermosensitive polyurethane and a natural component selected among a novel cell-secreted natural polymer mixture (“biomatrix”) recapitulating the complexity of cardiac extracellular matrix or one of its main protein constituents. Such multifunctional hydrogel will deliver in situ agents stimulating recruitment of cardiac fibroblasts together with the nanoparticles loaded with reprogramming therapeutics, and will provide biochemical signalling to stimulate efficient conversion of fibroblasts into mature cardiomyocytes.
First-in-field biomaterials-based innovations introduced by BIORECAR will enable more effective regeneration of functional myocardial tissue respect to state-of-the art approaches. BIORECAR innovation is multidisciplinary in nature and will be accelerated towards future clinical translation through my clinical, scientific and industrial collaborations.
Summary
In BIORECAR I will develop a new breakthrough multifunctional biomaterial-based platform for myocardial regeneration after myocardial infarction, provided with biochemical cues able to enhance the direct reprogramming of human cardiac fibroblasts into functional cardiomyocytes.
My expertise in bioartificial materials and biomimetic scaffolds and the versatile chemistry of polyurethanes will be the key elements to achieve a significant knowledge and technological advancement in cell reprogramming therapy, opening the way to the future translation of the therapy into the clinics.
I will implement this advanced approach through the design of a novel 3D in vitro tissue-engineered model of human cardiac fibrotic tissue, as a tool for testing and validation, to maximise research efforts and reduce animal tests.
I will adapt novel nanomedicine approaches I have recently developed for drug release to design innovative cell-friendly and efficient polyurethane nanoparticles for targeted reprogramming of cardiac fibroblasts.
I will design an injectable bioartificial hydrogel based on a blend of a thermosensitive polyurethane and a natural component selected among a novel cell-secreted natural polymer mixture (“biomatrix”) recapitulating the complexity of cardiac extracellular matrix or one of its main protein constituents. Such multifunctional hydrogel will deliver in situ agents stimulating recruitment of cardiac fibroblasts together with the nanoparticles loaded with reprogramming therapeutics, and will provide biochemical signalling to stimulate efficient conversion of fibroblasts into mature cardiomyocytes.
First-in-field biomaterials-based innovations introduced by BIORECAR will enable more effective regeneration of functional myocardial tissue respect to state-of-the art approaches. BIORECAR innovation is multidisciplinary in nature and will be accelerated towards future clinical translation through my clinical, scientific and industrial collaborations.
Max ERC Funding
2 000 000 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym BOOST
Project Biomimetic trick to re-balance Osteblast-Osteoclast loop in osteoporoSis treatment: a Topological and materials driven approach
Researcher (PI) Chiara Silvia Vitale Brovarone
Host Institution (HI) POLITECNICO DI TORINO
Country Italy
Call Details Consolidator Grant (CoG), PE8, ERC-2015-CoG
Summary One out of 5 people in their fifties will experience a bone fracture due to osteoporosis (OP)-induced fragility in their lifetime. The OP socio-economic burden is dramatic and involves tens of millions of people in the EU, with a steadily increasing number due to population ageing. Current treatments entail drug-therapy coupled with a healthy lifestyle but OP fractures need mechanical fixation to rapidly achieve union: the contribution of biomaterial scientists in this field is still far from taking its expected leading role in cutting-edge research. Bone remodelling is a well-coordinated process of bone resorption by osteoclasts followed by the production of new bone by osteoblasts. This process occurs continuously throughout life in a coupling with a positive balance during growth and negative with ageing, which can result in OP. We believe that an architecture driven stimulation of the osteoclast/osteoblast coupling, with an avant-garde focus on osteoclasts activity, is the key to success in treating unbalanced bone remodelling. We aim to manufacture a scaffold that mimics healthy bone features which will establish a new microenvironment favoring a properly stimulated and active population of osteoclasts and osteoblasts, i.e. a well-balanced bone cooperation. After 5 years we will be able to prove the efficacy of this approach. A benchmark will be set up for OP fracture treatment and for the realization of smart bone substitutes that will be able to locally “trick” aged bone cells stimulating them to act as healthy ones. BOOST results will have an unprecedented impact on the scientific research community, opening a new approach to set up smart, biomimetic strategies to treat aged, unbalanced bone tissues and to reduce OP-associated disabilities and financial burdens.
Summary
One out of 5 people in their fifties will experience a bone fracture due to osteoporosis (OP)-induced fragility in their lifetime. The OP socio-economic burden is dramatic and involves tens of millions of people in the EU, with a steadily increasing number due to population ageing. Current treatments entail drug-therapy coupled with a healthy lifestyle but OP fractures need mechanical fixation to rapidly achieve union: the contribution of biomaterial scientists in this field is still far from taking its expected leading role in cutting-edge research. Bone remodelling is a well-coordinated process of bone resorption by osteoclasts followed by the production of new bone by osteoblasts. This process occurs continuously throughout life in a coupling with a positive balance during growth and negative with ageing, which can result in OP. We believe that an architecture driven stimulation of the osteoclast/osteoblast coupling, with an avant-garde focus on osteoclasts activity, is the key to success in treating unbalanced bone remodelling. We aim to manufacture a scaffold that mimics healthy bone features which will establish a new microenvironment favoring a properly stimulated and active population of osteoclasts and osteoblasts, i.e. a well-balanced bone cooperation. After 5 years we will be able to prove the efficacy of this approach. A benchmark will be set up for OP fracture treatment and for the realization of smart bone substitutes that will be able to locally “trick” aged bone cells stimulating them to act as healthy ones. BOOST results will have an unprecedented impact on the scientific research community, opening a new approach to set up smart, biomimetic strategies to treat aged, unbalanced bone tissues and to reduce OP-associated disabilities and financial burdens.
Max ERC Funding
1 977 500 €
Duration
Start date: 2016-05-01, End date: 2022-06-30
Project acronym CapTherPV
Project Integration of Capacitor, Thermoelectric and PhotoVoltaic thin films for efficient energy conversion and storage
Researcher (PI) Isabel Maria Das Merces Ferreira
Host Institution (HI) NOVA ID FCT - ASSOCIACAO PARA A INOVACAO E DESENVOLVIMENTO DA FCT
Country Portugal
Call Details Consolidator Grant (CoG), PE8, ERC-2014-CoG
Summary The possibility of having a unique device that converts thermal and photonics energy into electrical energy and simultaneously stores it, is something dreamed by the PI since the beginning of her research career. To achieve that goal, this project aims to gather, in a single substrate, solar cells with up-conversion nanoparticles, thermoelectrics and graphene super-capacitor, all made of thin films. These three main components will be developed separately and integrated sequentially. The innovation proposed is not limited to the integration of components, but rely in ground-breaking concepts: 1) thermoelectric elements based on thin film (TE-TF) oxides; 2) plasmonic nanoparticles for up conversion of near infrared radiation to visible emission in solar cells; 3) graphene super-capacitors; 4) integration and optimization of all components in a single CapTherPV device. This ambitious project will bring new insights at large area, low cost and flexible energy harvesting and comes from an old idea of combining energy conversion and storage that has been pursued by the PI. She started her career in amorphous silicon thin film solar cells, later she started the development of thin film batteries and more recently started a research line in thermoelectric films. If approved, this project will give financial support to consolidate the research being carried out and will give independence to the PI in terms of resources and creative think. More importantly, will facilitate the concretization of the dream that has been pursued with hard work.
Summary
The possibility of having a unique device that converts thermal and photonics energy into electrical energy and simultaneously stores it, is something dreamed by the PI since the beginning of her research career. To achieve that goal, this project aims to gather, in a single substrate, solar cells with up-conversion nanoparticles, thermoelectrics and graphene super-capacitor, all made of thin films. These three main components will be developed separately and integrated sequentially. The innovation proposed is not limited to the integration of components, but rely in ground-breaking concepts: 1) thermoelectric elements based on thin film (TE-TF) oxides; 2) plasmonic nanoparticles for up conversion of near infrared radiation to visible emission in solar cells; 3) graphene super-capacitors; 4) integration and optimization of all components in a single CapTherPV device. This ambitious project will bring new insights at large area, low cost and flexible energy harvesting and comes from an old idea of combining energy conversion and storage that has been pursued by the PI. She started her career in amorphous silicon thin film solar cells, later she started the development of thin film batteries and more recently started a research line in thermoelectric films. If approved, this project will give financial support to consolidate the research being carried out and will give independence to the PI in terms of resources and creative think. More importantly, will facilitate the concretization of the dream that has been pursued with hard work.
Max ERC Funding
1 999 375 €
Duration
Start date: 2015-07-01, End date: 2021-09-30
Project acronym CAPTUR3D
Project CAPTURING THE PHYSICS OF LIFE ON 3D-TRAFFICKING SUBCELLULAR NANOSYSTEMS
Researcher (PI) Francesco CARDARELLI
Host Institution (HI) SCUOLA NORMALE SUPERIORE
Country Italy
Call Details Consolidator Grant (CoG), PE3, ERC-2019-COG
Summary Which physical principles govern life regulation at the level of subcellular, membrane-enclosed nanosystems, such as transport vesicles and organelles? How do they achieve controlled movements across the crowded intracellular world? Which is the structural and functional organization of their surface and their lumen? This is only a small subset of key open questions that the biophysical approach envisaged here will allow to answer directly within living matter, for the first time.
Thus far, state-of-the-art optical microscopy tools for delivering quantitative information in living matter failed to subtract the natural 3D movement of subcellular nanosystems while preserving the spatial and temporal resolution required to probe their structure and function at the molecular level.
CAPTUR3D will tackle this bottleneck. An excitation light-beam will be focused in a periodic orbit around the nanosystem of interest and used to localize its position with unprecedented spatial (~10 nm) and temporal (~1000 Hz frequency response) resolution. Such privileged observation point will push biophysical investigations to a new level. For the first time, state-of-the-art imaging technologies and analytical tools (e.g. fluorescence correlation spectroscopy), will be used to perform molecular investigations on a moving, nanoscopic reference system.
The insulin secretory granule (ISG) is selected as a paradigmatic case study. Key open issues at the ISG level are selected, namely: (i) ISG-environment interactions and their role in directing ISG trafficking, (ii) ISG-membrane spatiotemporal organization, (iii) ISG-lumen structural and functional organization, (iv) ISG alterations in type-2 diabetes (T2D). These issues will be tackled directly within human-derived Langherans islets.
CAPTUR3D is envisioned not only to foster our knowledge on T2D physiopathology but also to concomitantly drive an unprecedented revolution in the way we address living matter at the subcellular scale.
Summary
Which physical principles govern life regulation at the level of subcellular, membrane-enclosed nanosystems, such as transport vesicles and organelles? How do they achieve controlled movements across the crowded intracellular world? Which is the structural and functional organization of their surface and their lumen? This is only a small subset of key open questions that the biophysical approach envisaged here will allow to answer directly within living matter, for the first time.
Thus far, state-of-the-art optical microscopy tools for delivering quantitative information in living matter failed to subtract the natural 3D movement of subcellular nanosystems while preserving the spatial and temporal resolution required to probe their structure and function at the molecular level.
CAPTUR3D will tackle this bottleneck. An excitation light-beam will be focused in a periodic orbit around the nanosystem of interest and used to localize its position with unprecedented spatial (~10 nm) and temporal (~1000 Hz frequency response) resolution. Such privileged observation point will push biophysical investigations to a new level. For the first time, state-of-the-art imaging technologies and analytical tools (e.g. fluorescence correlation spectroscopy), will be used to perform molecular investigations on a moving, nanoscopic reference system.
The insulin secretory granule (ISG) is selected as a paradigmatic case study. Key open issues at the ISG level are selected, namely: (i) ISG-environment interactions and their role in directing ISG trafficking, (ii) ISG-membrane spatiotemporal organization, (iii) ISG-lumen structural and functional organization, (iv) ISG alterations in type-2 diabetes (T2D). These issues will be tackled directly within human-derived Langherans islets.
CAPTUR3D is envisioned not only to foster our knowledge on T2D physiopathology but also to concomitantly drive an unprecedented revolution in the way we address living matter at the subcellular scale.
Max ERC Funding
1 985 750 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
Project acronym CeraText
Project Tailoring Microstructure and Architecture to Build Ceramic Components with Unprecedented Damage Tolerance
Researcher (PI) Raul BERMEJO
Host Institution (HI) MONTANUNIVERSITAET LEOBEN
Country Austria
Call Details Consolidator Grant (CoG), PE8, ERC-2018-COG
Summary Advanced ceramics are often combined with metals, polymers or other ceramics to produce structural and functional systems with exceptional properties. Examples are resistors and capacitors in microelectronics, piezo-ceramic actuators in car injection devices, and bio-implants for hip joint replacements. However, a critical issue affecting the functionality, lifetime and reliability of such systems is the initiation and uncontrolled propagation of cracks in the brittle ceramic parts, yielding in some cases rejection rates up to 70% of components production.
The remarkable “damage tolerance” found in natural materials such as wood, bone or mollusc, has yet to be achieved in technical ceramics, where incipient damage is synonymous with catastrophic failure. Novel “multilayer designs” combining microstructure and architecture could change this situation. Recent work of the PI has shown that tuning the location of “protective” layers within a 3D multilayer ceramic can increase its fracture resistance by five times (from ~3.5 to ~17 MPa∙m1/2) relative to constituent bulk ceramic layers, while retaining high strength (~500 MPa). By orienting the grain structure, similar to the textured and organized microstructure found in natural systems such as nacre, the PI has shown that crack propagation can be controlled within the textured ceramic layer. Thus, I believe tailored microstructures with controlled grain boundaries engineered in a layer-by-layer 3D architectural design hold the key to a new generation of “damage tolerant” ceramics.
This proposal outlines a research program to establish new scientific principles for the fabrication of innovative ceramic components that exhibit unprecedented damage tolerance. The successful implementation of microstructural features (e.g. texture degree, tailored internal stresses, second phases, interfaces) in a layer-by-layer architecture will provide outstanding lifetime and reliability in both structural and functional ceramic devices.
Summary
Advanced ceramics are often combined with metals, polymers or other ceramics to produce structural and functional systems with exceptional properties. Examples are resistors and capacitors in microelectronics, piezo-ceramic actuators in car injection devices, and bio-implants for hip joint replacements. However, a critical issue affecting the functionality, lifetime and reliability of such systems is the initiation and uncontrolled propagation of cracks in the brittle ceramic parts, yielding in some cases rejection rates up to 70% of components production.
The remarkable “damage tolerance” found in natural materials such as wood, bone or mollusc, has yet to be achieved in technical ceramics, where incipient damage is synonymous with catastrophic failure. Novel “multilayer designs” combining microstructure and architecture could change this situation. Recent work of the PI has shown that tuning the location of “protective” layers within a 3D multilayer ceramic can increase its fracture resistance by five times (from ~3.5 to ~17 MPa∙m1/2) relative to constituent bulk ceramic layers, while retaining high strength (~500 MPa). By orienting the grain structure, similar to the textured and organized microstructure found in natural systems such as nacre, the PI has shown that crack propagation can be controlled within the textured ceramic layer. Thus, I believe tailored microstructures with controlled grain boundaries engineered in a layer-by-layer 3D architectural design hold the key to a new generation of “damage tolerant” ceramics.
This proposal outlines a research program to establish new scientific principles for the fabrication of innovative ceramic components that exhibit unprecedented damage tolerance. The successful implementation of microstructural features (e.g. texture degree, tailored internal stresses, second phases, interfaces) in a layer-by-layer architecture will provide outstanding lifetime and reliability in both structural and functional ceramic devices.
Max ERC Funding
1 985 000 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym CharFL
Project Characterizing the fitness landscape on population and global scales
Researcher (PI) Fyodor Kondrashov
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Country Austria
Call Details Consolidator Grant (CoG), LS2, ERC-2017-COG
Summary The fitness landscape, the representation of how the genotype manifests at the phenotypic (fitness) levels, may be among the most useful concepts in biology with impact on diverse fields, including quantitative genetics, emergence of pathogen resistance, synthetic biology and protein engineering. While progress in characterizing fitness landscapes has been made, three directions of research in the field remain virtually unexplored: the nature of the genotype to phenotype of standing variation (variation found in a natural population), the shape of the fitness landscape encompassing many genotypes and the modelling of complex genetic interactions in protein sequences.
The current proposal is designed to advance the study of fitness landscapes in these three directions using large-scale genomic experiments and experimental data from a model protein and theoretical work. The study of the fitness landscape of standing variation is aimed at the resolution of an outstanding question in quantitative genetics: the extent to which epistasis, non-additive genetic interactions, is shaping the phenotype. The second aim of characterizing the global fitness landscape will give us an understanding of how evolution proceeds along long evolutionary timescales, which can be directly applied to protein engineering and synthetic biology for the design of novel phenotypes. Finally, the third aim of modelling complex interactions will improve our ability to predict phenotypes from genotypes, such as the prediction of human disease mutations. In summary, the proposed study presents an opportunity to provide a unifying understanding of how phenotypes are shaped through genetic interactions. The consolidation of our empirical and theoretical work on different scales of the genotype to phenotype relationship will provide empirical data and novel context for several fields of biology.
Summary
The fitness landscape, the representation of how the genotype manifests at the phenotypic (fitness) levels, may be among the most useful concepts in biology with impact on diverse fields, including quantitative genetics, emergence of pathogen resistance, synthetic biology and protein engineering. While progress in characterizing fitness landscapes has been made, three directions of research in the field remain virtually unexplored: the nature of the genotype to phenotype of standing variation (variation found in a natural population), the shape of the fitness landscape encompassing many genotypes and the modelling of complex genetic interactions in protein sequences.
The current proposal is designed to advance the study of fitness landscapes in these three directions using large-scale genomic experiments and experimental data from a model protein and theoretical work. The study of the fitness landscape of standing variation is aimed at the resolution of an outstanding question in quantitative genetics: the extent to which epistasis, non-additive genetic interactions, is shaping the phenotype. The second aim of characterizing the global fitness landscape will give us an understanding of how evolution proceeds along long evolutionary timescales, which can be directly applied to protein engineering and synthetic biology for the design of novel phenotypes. Finally, the third aim of modelling complex interactions will improve our ability to predict phenotypes from genotypes, such as the prediction of human disease mutations. In summary, the proposed study presents an opportunity to provide a unifying understanding of how phenotypes are shaped through genetic interactions. The consolidation of our empirical and theoretical work on different scales of the genotype to phenotype relationship will provide empirical data and novel context for several fields of biology.
Max ERC Funding
1 998 280 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
