Project acronym ADHESWITCHES
Project Adhesion switches in cancer and development: from in vivo to synthetic biology
Researcher (PI) Mari Johanna Ivaska
Host Institution (HI) TURUN YLIOPISTO
Country Finland
Call Details Consolidator Grant (CoG), LS3, ERC-2013-CoG
Summary Integrins are transmembrane cell adhesion receptors controlling cell proliferation and migration. Our objective is to gain fundamentally novel mechanistic insight into the emerging new roles of integrins in cancer and to generate a road map of integrin dependent pathways critical in mammary gland development and integrin signalling thus opening new targets for therapeutic interventions. We will combine an in vivo based translational approach with cell and molecular biological studies aiming to identify entirely novel concepts in integrin function using cutting edge techniques and synthetic-biology tools.
The specific objectives are:
1) Integrin inactivation in branching morphogenesis and cancer invasion. Integrins regulate mammary gland development and cancer invasion but the role of integrin inactivating proteins in these processes is currently completely unknown. We will investigate this using genetically modified mice, ex-vivo organoid models and human tissues with the aim to identify beneficial combinational treatments against cancer invasion.
2) Endosomal adhesomes – cross-talk between integrin activity and integrin “inside-in signaling”. We hypothesize that endocytosed active integrins engage in specialized endosomal signaling that governs cell survival especially in cancer. RNAi cell arrays, super-resolution STED imaging and endosomal proteomics will be used to investigate integrin signaling in endosomes.
3) Spatio-temporal co-ordination of adhesion and endocytosis. Several cytosolic proteins compete for integrin binding to regulate activation, endocytosis and recycling. Photoactivatable protein-traps and predefined matrix micropatterns will be employed to mechanistically dissect the spatio-temporal dynamics and hierarchy of their recruitment.
We will employ innovative and unconventional techniques to address three major unanswered questions in the field and significantly advance our understanding of integrin function in development and cancer.
Summary
Integrins are transmembrane cell adhesion receptors controlling cell proliferation and migration. Our objective is to gain fundamentally novel mechanistic insight into the emerging new roles of integrins in cancer and to generate a road map of integrin dependent pathways critical in mammary gland development and integrin signalling thus opening new targets for therapeutic interventions. We will combine an in vivo based translational approach with cell and molecular biological studies aiming to identify entirely novel concepts in integrin function using cutting edge techniques and synthetic-biology tools.
The specific objectives are:
1) Integrin inactivation in branching morphogenesis and cancer invasion. Integrins regulate mammary gland development and cancer invasion but the role of integrin inactivating proteins in these processes is currently completely unknown. We will investigate this using genetically modified mice, ex-vivo organoid models and human tissues with the aim to identify beneficial combinational treatments against cancer invasion.
2) Endosomal adhesomes – cross-talk between integrin activity and integrin “inside-in signaling”. We hypothesize that endocytosed active integrins engage in specialized endosomal signaling that governs cell survival especially in cancer. RNAi cell arrays, super-resolution STED imaging and endosomal proteomics will be used to investigate integrin signaling in endosomes.
3) Spatio-temporal co-ordination of adhesion and endocytosis. Several cytosolic proteins compete for integrin binding to regulate activation, endocytosis and recycling. Photoactivatable protein-traps and predefined matrix micropatterns will be employed to mechanistically dissect the spatio-temporal dynamics and hierarchy of their recruitment.
We will employ innovative and unconventional techniques to address three major unanswered questions in the field and significantly advance our understanding of integrin function in development and cancer.
Max ERC Funding
1 887 910 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym AdjustNet
Project Self-Adjusting Networks
Researcher (PI) Stefan SCHMID
Host Institution (HI) UNIVERSITAT WIEN
Country Austria
Call Details Consolidator Grant (CoG), PE6, ERC-2019-COG
Summary Communication networks have become a critical infrastructure of our digital society. However, with the explosive growth of data-centric applications and the resulting increasing workloads headed for the world’s datacenter networks, today’s static and demand-oblivious network architectures are reaching their capacity limits.
The AdjustNet project proposes a radically different perspective, envisioning demand-aware networks which can dynamically adapt their topology to the workload they currently serve. Such self-adjusting networks hence allow to exploit structure in the demand, and thereby reach higher levels of efficiency and performance. The vision of AdjustNet is timely and enabled by recent innovations in optical technologies which allow to flexibly reconfigure the physical network topology.
The goal of AdjustNet is to lay the theoretical foundations for self-adjusting networks. We will identify metrics that serve as yardstick of what can and cannot be achieved in a self-adjusting network for a given demand, devise algorithms for online adaption, and validate our framework through case studies. Our novel methodology is motivated by an intriguing connection of self-adjusting networks to known datastructures and to information theory.
AdjustNet comes with significant challenges since, similar to self-driving cars, self-adjusting networks require human network operators to give away control, and since more autonomous network operations may lead to instabilities. AdjustNet will overcome these risks and achieve its objectives by pursuing a rigorous approach, devising a theoretical well-founded framework for self-adjusting networks which come with provable guarantees and incorporate self–protection mechanisms.
The PI is well-equipped for this project and recently obtained first promising results. As the community is currently re-architecting communication networks, there is a unique opportunity to bridge the gap between theory and practice, and have impact.
Summary
Communication networks have become a critical infrastructure of our digital society. However, with the explosive growth of data-centric applications and the resulting increasing workloads headed for the world’s datacenter networks, today’s static and demand-oblivious network architectures are reaching their capacity limits.
The AdjustNet project proposes a radically different perspective, envisioning demand-aware networks which can dynamically adapt their topology to the workload they currently serve. Such self-adjusting networks hence allow to exploit structure in the demand, and thereby reach higher levels of efficiency and performance. The vision of AdjustNet is timely and enabled by recent innovations in optical technologies which allow to flexibly reconfigure the physical network topology.
The goal of AdjustNet is to lay the theoretical foundations for self-adjusting networks. We will identify metrics that serve as yardstick of what can and cannot be achieved in a self-adjusting network for a given demand, devise algorithms for online adaption, and validate our framework through case studies. Our novel methodology is motivated by an intriguing connection of self-adjusting networks to known datastructures and to information theory.
AdjustNet comes with significant challenges since, similar to self-driving cars, self-adjusting networks require human network operators to give away control, and since more autonomous network operations may lead to instabilities. AdjustNet will overcome these risks and achieve its objectives by pursuing a rigorous approach, devising a theoretical well-founded framework for self-adjusting networks which come with provable guarantees and incorporate self–protection mechanisms.
The PI is well-equipped for this project and recently obtained first promising results. As the community is currently re-architecting communication networks, there is a unique opportunity to bridge the gap between theory and practice, and have impact.
Max ERC Funding
1 670 823 €
Duration
Start date: 2020-03-01, End date: 2025-02-28
Project acronym ARTIST
Project Automated Reasoning with Theories and Induction for Software Technology
Researcher (PI) Laura KOVACS
Host Institution (HI) TECHNISCHE UNIVERSITAET WIEN
Country Austria
Call Details Consolidator Grant (CoG), PE6, ERC-2020-COG
Summary The long list of software failures over the past years calls for serious concerns in our digital society, creating bad reputation and adding huge economic burden on organizations, industries and governments. Improving software reliability is no more enough, ensuring software reliability is mandatory. Our project complements other advances in the area and addresses this demand by turning first-order theorem proving into an alternative, yet powerful approach to ensuring software reliability,
Saturation-based proof search is the leading technology for automated first-order theorem proving. The high-gain/high-risk aspect of our project comes from the development and use of saturation-based theorem proving as a unifying framework to reason about software technologies. We use first-order theorem proving methods not only to prove, but also to generate software properties that imply the absence of program errors at intermediate program steps.
Generating and proving program properties call for new methods supporting reasoning with both theories and quantifiers. Our project extends saturation-based first-order theorem provers with domain-specific inference rules to keep reasoning efficient. This includes commonly used theories in software development, such as the theories of integers, arrays and inductively defined data types, and automation of induction within saturation-based theorem proving, contributing to the ultimate goal of generating and proving inductive software properties, such as invariants.
Thanks to the full automation of our project, our results can be integrated and used in other frameworks, to allow end-users and developers of software technologies to gain from theorem proving without the need of becoming experts of it.
Summary
The long list of software failures over the past years calls for serious concerns in our digital society, creating bad reputation and adding huge economic burden on organizations, industries and governments. Improving software reliability is no more enough, ensuring software reliability is mandatory. Our project complements other advances in the area and addresses this demand by turning first-order theorem proving into an alternative, yet powerful approach to ensuring software reliability,
Saturation-based proof search is the leading technology for automated first-order theorem proving. The high-gain/high-risk aspect of our project comes from the development and use of saturation-based theorem proving as a unifying framework to reason about software technologies. We use first-order theorem proving methods not only to prove, but also to generate software properties that imply the absence of program errors at intermediate program steps.
Generating and proving program properties call for new methods supporting reasoning with both theories and quantifiers. Our project extends saturation-based first-order theorem provers with domain-specific inference rules to keep reasoning efficient. This includes commonly used theories in software development, such as the theories of integers, arrays and inductively defined data types, and automation of induction within saturation-based theorem proving, contributing to the ultimate goal of generating and proving inductive software properties, such as invariants.
Thanks to the full automation of our project, our results can be integrated and used in other frameworks, to allow end-users and developers of software technologies to gain from theorem proving without the need of becoming experts of it.
Max ERC Funding
2 000 000 €
Duration
Start date: 2021-07-01, End date: 2026-06-30
Project acronym AutoRecon
Project Molecular mechanisms of autophagosome formation during selective autophagy
Researcher (PI) Sascha Martens
Host Institution (HI) UNIVERSITAT WIEN
Country Austria
Call Details Consolidator Grant (CoG), LS3, ERC-2014-CoG
Summary I propose to study how eukaryotic cells generate autophagosomes, organelles bounded by a double membrane. These are formed during autophagy and mediate the degradation of cytoplasmic substances within the lysosomal compartment. Autophagy thereby protects the organism from pathological conditions such as neurodegeneration, cancer and infections. Many core factors required for autophagosome formation have been identified but the order in which they act and their mode of action is still unclear. We will use a combination of biochemical and cell biological approaches to elucidate the choreography and mechanism of these core factors. In particular, we will focus on selective autophagy and determine how the autophagic machinery generates an autophagosome that selectively contains the cargo.
To this end we will focus on the cytoplasm-to-vacuole-targeting pathway in S. cerevisiae that mediates the constitutive delivery of the prApe1 enzyme into the vacuole. We will use cargo mimetics or prApe1 complexes in combination with purified autophagy proteins and vesicles to reconstitute the process and so determine which factors are both necessary and sufficient for autophagosome formation, as well as elucidating their mechanism of action.
In parallel we will study selective autophagosome formation in human cells. This will reveal common principles and special adaptations. In particular, we will use cell lysates from genome-edited cells in combination with purified autophagy proteins to reconstitute selective autophagosome formation around ubiquitin-positive cargo material. The insights and hypotheses obtained from these reconstituted systems will be validated using cell biological approaches.
Taken together, our experiments will allow us to delineate the major steps of autophagosome formation during selective autophagy. Our results will yield detailed insights into how cells form and shape organelles in a de novo manner, which is major question in cell- and developmental biology.
Summary
I propose to study how eukaryotic cells generate autophagosomes, organelles bounded by a double membrane. These are formed during autophagy and mediate the degradation of cytoplasmic substances within the lysosomal compartment. Autophagy thereby protects the organism from pathological conditions such as neurodegeneration, cancer and infections. Many core factors required for autophagosome formation have been identified but the order in which they act and their mode of action is still unclear. We will use a combination of biochemical and cell biological approaches to elucidate the choreography and mechanism of these core factors. In particular, we will focus on selective autophagy and determine how the autophagic machinery generates an autophagosome that selectively contains the cargo.
To this end we will focus on the cytoplasm-to-vacuole-targeting pathway in S. cerevisiae that mediates the constitutive delivery of the prApe1 enzyme into the vacuole. We will use cargo mimetics or prApe1 complexes in combination with purified autophagy proteins and vesicles to reconstitute the process and so determine which factors are both necessary and sufficient for autophagosome formation, as well as elucidating their mechanism of action.
In parallel we will study selective autophagosome formation in human cells. This will reveal common principles and special adaptations. In particular, we will use cell lysates from genome-edited cells in combination with purified autophagy proteins to reconstitute selective autophagosome formation around ubiquitin-positive cargo material. The insights and hypotheses obtained from these reconstituted systems will be validated using cell biological approaches.
Taken together, our experiments will allow us to delineate the major steps of autophagosome formation during selective autophagy. Our results will yield detailed insights into how cells form and shape organelles in a de novo manner, which is major question in cell- and developmental biology.
Max ERC Funding
1 999 640 €
Duration
Start date: 2016-03-01, End date: 2021-02-28
Project acronym BabyRhythm
Project Tuned to the Rhythm: How Prenatally and Postnatally Heard Speech Prosody Lays the Foundations for Language Learning
Researcher (PI) Judit Gervain
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Country Italy
Call Details Consolidator Grant (CoG), SH4, ERC-2017-COG
Summary The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved.
The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language.
The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.
Summary
The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved.
The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language.
The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.
Max ERC Funding
1 621 250 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym BHIVE
Project Bio-derived HIgh Value polymers through novel Enzyme function
Researcher (PI) Emma Rusi Master
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Consolidator Grant (CoG), LS9, ERC-2014-CoG
Summary Recent advances in systems-level study of cells and organisms have revealed the enormous potential to live more sustainably through better use of biological processes. Plants sustainably synthesize the most abundant and diverse materials on Earth. By applying recent advances in life science technology, we can better harness renewable plant resources and bioconversion processes, to develop environmentally and politically sustainable human enterprise and lifestyles. At the same time, the global market for high-value biochemicals and bioplastics from forest and agricultural sources is rapidly increasing, which presents new opportunities for forest and agricultural sectors.
The overall aim of BHIVE is to illuminate uncharted regions of genome and metagenome sequences to discover entirely new protein families that can be used to sustainably synthesize novel, high-value biomaterials from renewable plant resources. The approach will include three parallel research thrusts: 1) strategic analysis of transcriptome and metagenome sequences to identify proteins with entirely unknown function relevant to biomass (lignocellulose) transformation, 2) mapping of uncharted regions within phylogenetic trees of poorly characterized enzyme families with recognized potential to modify the chemistry and biophysical properties of plant polysaccharides, and 3) the design and development of novel enzyme screens to directly address the increasing limitations of existing assays to uncover entirely new protein functions. BHIVE will be unique in its undivided focus on characterizing lignocellulose-active proteins encoded by the 30-40% of un-annotated sequence, or genomic “dark matter”, typical of nearly all genome sequences. In this way, BHIVE tackles a key constraint to fully realizing the societal and environmental benefits of the genomics era.
Summary
Recent advances in systems-level study of cells and organisms have revealed the enormous potential to live more sustainably through better use of biological processes. Plants sustainably synthesize the most abundant and diverse materials on Earth. By applying recent advances in life science technology, we can better harness renewable plant resources and bioconversion processes, to develop environmentally and politically sustainable human enterprise and lifestyles. At the same time, the global market for high-value biochemicals and bioplastics from forest and agricultural sources is rapidly increasing, which presents new opportunities for forest and agricultural sectors.
The overall aim of BHIVE is to illuminate uncharted regions of genome and metagenome sequences to discover entirely new protein families that can be used to sustainably synthesize novel, high-value biomaterials from renewable plant resources. The approach will include three parallel research thrusts: 1) strategic analysis of transcriptome and metagenome sequences to identify proteins with entirely unknown function relevant to biomass (lignocellulose) transformation, 2) mapping of uncharted regions within phylogenetic trees of poorly characterized enzyme families with recognized potential to modify the chemistry and biophysical properties of plant polysaccharides, and 3) the design and development of novel enzyme screens to directly address the increasing limitations of existing assays to uncover entirely new protein functions. BHIVE will be unique in its undivided focus on characterizing lignocellulose-active proteins encoded by the 30-40% of un-annotated sequence, or genomic “dark matter”, typical of nearly all genome sequences. In this way, BHIVE tackles a key constraint to fully realizing the societal and environmental benefits of the genomics era.
Max ERC Funding
1 977 781 €
Duration
Start date: 2015-09-01, End date: 2020-12-31
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 BiT
Project How the Human Brain Masters Time
Researcher (PI) Domenica Bueti
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Country Italy
Call Details Consolidator Grant (CoG), SH4, ERC-2015-CoG
Summary If you suddenly hear your song on the radio and spontaneously decide to burst into dance in your living room, you need to precisely time your movements if you do not want to find yourself on your bookshelf. Most of what we do or perceive depends on how accurately we represent the temporal properties of the environment however we cannot see or touch time. As such, time in the millisecond range is both a fundamental and elusive dimension of everyday experiences. Despite the obvious importance of time to information processing and to behavior in general, little is known yet about how the human brain process time. Existing approaches to the study of the neural mechanisms of time mainly focus on the identification of brain regions involved in temporal computations (‘where’ time is processed in the brain), whereas most computational models vary in their biological plausibility and do not always make clear testable predictions. BiT is a groundbreaking research program designed to challenge current models of time perception and to offer a new perspective in the study of the neural basis of time. The groundbreaking nature of BiT derives from the novelty of the questions asked (‘when’ and ‘how’ time is processed in the brain) and from addressing them using complementary but distinct research approaches (from human neuroimaging to brain stimulation techniques, from the investigation of the whole brain to the focus on specific brain regions). By testing a new biologically plausible hypothesis of temporal representation (via duration tuning and ‘chronotopy’) and by scrutinizing the functional properties and, for the first time, the temporal hierarchies of ‘putative’ time regions, BiT will offer a multifaceted knowledge of how the human brain represents time. This new knowledge will challenge our understanding of brain organization and function that typically lacks of a time angle and will impact our understanding of how the brain uses time information for perception and action
Summary
If you suddenly hear your song on the radio and spontaneously decide to burst into dance in your living room, you need to precisely time your movements if you do not want to find yourself on your bookshelf. Most of what we do or perceive depends on how accurately we represent the temporal properties of the environment however we cannot see or touch time. As such, time in the millisecond range is both a fundamental and elusive dimension of everyday experiences. Despite the obvious importance of time to information processing and to behavior in general, little is known yet about how the human brain process time. Existing approaches to the study of the neural mechanisms of time mainly focus on the identification of brain regions involved in temporal computations (‘where’ time is processed in the brain), whereas most computational models vary in their biological plausibility and do not always make clear testable predictions. BiT is a groundbreaking research program designed to challenge current models of time perception and to offer a new perspective in the study of the neural basis of time. The groundbreaking nature of BiT derives from the novelty of the questions asked (‘when’ and ‘how’ time is processed in the brain) and from addressing them using complementary but distinct research approaches (from human neuroimaging to brain stimulation techniques, from the investigation of the whole brain to the focus on specific brain regions). By testing a new biologically plausible hypothesis of temporal representation (via duration tuning and ‘chronotopy’) and by scrutinizing the functional properties and, for the first time, the temporal hierarchies of ‘putative’ time regions, BiT will offer a multifaceted knowledge of how the human brain represents time. This new knowledge will challenge our understanding of brain organization and function that typically lacks of a time angle and will impact our understanding of how the brain uses time information for perception and action
Max ERC Funding
1 670 830 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
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
