Project acronym ATLAS
Project Bioengineered autonomous cell-biomaterials devices for generating humanised micro-tissues for regenerative medicine
Researcher (PI) Joao Felipe Colardelle da Luz Mano
Host Institution (HI) UNIVERSIDADE DE AVEIRO
Country Portugal
Call Details Advanced Grant (AdG), PE8, ERC-2014-ADG
Summary New generations of devices for tissue engineering (TE) should rationalize better the physical and biochemical cues operating in tandem during native regeneration, in particular at the scale/organizational-level of the stem cell niche. The understanding and the deconstruction of these factors (e.g. multiple cell types exchanging both paracrine and direct signals, structural and chemical arrangement of the extra-cellular matrix, mechanical signals…) should be then incorporated into the design of truly biomimetic biomaterials. ATLAS proposes rather unique toolboxes combining smart biomaterials and cells for the ground-breaking advances of engineering fully time-self-regulated complex 2D and 3D devices, able to adjust the cascade of processes leading to faster high-quality new tissue formation with minimum pre-processing of cells. Versatile biomaterials based on marine-origin macromolecules will be used, namely in the supramolecular assembly of instructive multilayers as nanostratified building-blocks for engineer such structures. The backbone of these biopolymers will be equipped with a variety of (bio)chemical elements permitting: post-processing chemistry and micro-patterning, specific/non-specific cell attachment, and cell-controlled degradation. Aiming at being applied in bone TE, ATLAS will integrate cells from different units of tissue physiology, namely bone and hematopoietic basic elements and consider the interactions between the immune and skeletal systems. These ingredients will permit to architect innovative films with high-level dialogue control with cells, but in particular sophisticated quasi-closed 3D capsules able to compartmentalise such components in a “globe-like” organization, providing local and long-range order for in vitro microtissue development and function. Such hybrid devices could be used in more generalised front-edge applications, including as disease models for drug discovery or test new therapies in vitro.
Summary
New generations of devices for tissue engineering (TE) should rationalize better the physical and biochemical cues operating in tandem during native regeneration, in particular at the scale/organizational-level of the stem cell niche. The understanding and the deconstruction of these factors (e.g. multiple cell types exchanging both paracrine and direct signals, structural and chemical arrangement of the extra-cellular matrix, mechanical signals…) should be then incorporated into the design of truly biomimetic biomaterials. ATLAS proposes rather unique toolboxes combining smart biomaterials and cells for the ground-breaking advances of engineering fully time-self-regulated complex 2D and 3D devices, able to adjust the cascade of processes leading to faster high-quality new tissue formation with minimum pre-processing of cells. Versatile biomaterials based on marine-origin macromolecules will be used, namely in the supramolecular assembly of instructive multilayers as nanostratified building-blocks for engineer such structures. The backbone of these biopolymers will be equipped with a variety of (bio)chemical elements permitting: post-processing chemistry and micro-patterning, specific/non-specific cell attachment, and cell-controlled degradation. Aiming at being applied in bone TE, ATLAS will integrate cells from different units of tissue physiology, namely bone and hematopoietic basic elements and consider the interactions between the immune and skeletal systems. These ingredients will permit to architect innovative films with high-level dialogue control with cells, but in particular sophisticated quasi-closed 3D capsules able to compartmentalise such components in a “globe-like” organization, providing local and long-range order for in vitro microtissue development and function. Such hybrid devices could be used in more generalised front-edge applications, including as disease models for drug discovery or test new therapies in vitro.
Max ERC Funding
2 498 988 €
Duration
Start date: 2015-12-01, End date: 2021-10-31
Project acronym BI-DSC
Project Building Integrated Dye Sensitized Solar Cells
Researcher (PI) Adelio Miguel Magalhaes Mendes
Host Institution (HI) UNIVERSIDADE DO PORTO
Country Portugal
Call Details Advanced Grant (AdG), PE8, ERC-2012-ADG_20120216
Summary In the last decade, solar and photovoltaic (PV) technologies have emerged as a potentially major technology for power generation in the world. So far the PV field has been dominated by silicon devices, even though this technology is still expensive.Dye-sensitized solar cells (DSC) are an important type of thin-film photovoltaics due to their potential for low-cost fabrication and versatile applications, and because their aesthetic appearance, semi-transparency and different color possibilities.This advantageous characteristic makes DSC the first choice for building integrated photovoltaics.Despite their great potential, DSCs for building applications are still not available at commercial level. However, to bring DSCs to a marketable product several developments are still needed and the present project targets to give relevant answers to three key limitations: encapsulation, glass substrate enhanced electrical conductivity and more efficient and low-cost raw-materials. Recently, the proponent successfully addressed the hermetic devices sealing by developing a laser-assisted glass sealing procedure.Thus, BI-DSC proposal envisages the development of DSC modules 30x30cm2, containing four individual cells, and their incorporation in a 1m2 double glass sheet arrangement for BIPV with an energy efficiency of at least 9% and a lifetime of 20 years. Additionally, aiming at enhanced efficiency of the final device and decreased total costs of DSCs manufacturing, new materials will be also pursued. The following inner-components were identified as critical: carbon-based counter-electrode; carbon quantum-dots and hierarchically TiO2 photoelectrode. It is then clear that this project is divided into two research though parallel directions: a fundamental research line, contributing to the development of the new generation DSC technology; while a more applied research line targets the development of a DSC functional module that can be used to pave the way for its industrialization.
Summary
In the last decade, solar and photovoltaic (PV) technologies have emerged as a potentially major technology for power generation in the world. So far the PV field has been dominated by silicon devices, even though this technology is still expensive.Dye-sensitized solar cells (DSC) are an important type of thin-film photovoltaics due to their potential for low-cost fabrication and versatile applications, and because their aesthetic appearance, semi-transparency and different color possibilities.This advantageous characteristic makes DSC the first choice for building integrated photovoltaics.Despite their great potential, DSCs for building applications are still not available at commercial level. However, to bring DSCs to a marketable product several developments are still needed and the present project targets to give relevant answers to three key limitations: encapsulation, glass substrate enhanced electrical conductivity and more efficient and low-cost raw-materials. Recently, the proponent successfully addressed the hermetic devices sealing by developing a laser-assisted glass sealing procedure.Thus, BI-DSC proposal envisages the development of DSC modules 30x30cm2, containing four individual cells, and their incorporation in a 1m2 double glass sheet arrangement for BIPV with an energy efficiency of at least 9% and a lifetime of 20 years. Additionally, aiming at enhanced efficiency of the final device and decreased total costs of DSCs manufacturing, new materials will be also pursued. The following inner-components were identified as critical: carbon-based counter-electrode; carbon quantum-dots and hierarchically TiO2 photoelectrode. It is then clear that this project is divided into two research though parallel directions: a fundamental research line, contributing to the development of the new generation DSC technology; while a more applied research line targets the development of a DSC functional module that can be used to pave the way for its industrialization.
Max ERC Funding
1 989 300 €
Duration
Start date: 2013-03-01, End date: 2018-08-31
Project acronym BIC
Project Cavitation across scales: following Bubbles from Inception to Collapse
Researcher (PI) Carlo Massimo Casciola
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Country Italy
Call Details Advanced Grant (AdG), PE8, ERC-2013-ADG
Summary Cavitation is the formation of vapor cavities inside a liquid due to low pressure. Cavitation is an ubiquitous and destructive phenomenon common to most engineering applications that deal with flowing water. At the same time, the extreme conditions realized in cavitation are increasingly exploited in medicine, chemistry, and biology. What makes cavitation unpredictable is its multiscale nature: nucleation of vapor bubbles heavily depends on micro- and nanoscale details; mesoscale phenomena, as bubble collapse, determine relevant macroscopic effects, e.g., cavitation damage. In addition, macroscopic flow conditions, such as turbulence, have a major impact on it.
The objective of the BIC project is to develop the lacking multiscale description of cavitation, by proposing new integrated numerical methods capable to perform quantitative predictions. The detailed and physically sound understanding of the multifaceted phenomena involved in cavitation (nucleation, bubble growth, transport, and collapse in turbulent flows) fostered by BIC project will result in new methods for designing fluid machinery, but also therapies in ultrasound medicine and chemical reactors. The BIC project builds upon the exceptionally broad experience of the PI and of his research group in numerical simulations of flows at different scales that include advanced atomistic simulations of nanoscale wetting phenomena, mesoscale models for multiphase flows, and particle-laden turbulent flows. The envisaged numerical methodologies (free-energy atomistic simulations, phase-field models, and Direct Numerical Simulation of bubble-laden flows) will be supported by targeted experimental activities, designed to validate models and characterize realistic conditions.
Summary
Cavitation is the formation of vapor cavities inside a liquid due to low pressure. Cavitation is an ubiquitous and destructive phenomenon common to most engineering applications that deal with flowing water. At the same time, the extreme conditions realized in cavitation are increasingly exploited in medicine, chemistry, and biology. What makes cavitation unpredictable is its multiscale nature: nucleation of vapor bubbles heavily depends on micro- and nanoscale details; mesoscale phenomena, as bubble collapse, determine relevant macroscopic effects, e.g., cavitation damage. In addition, macroscopic flow conditions, such as turbulence, have a major impact on it.
The objective of the BIC project is to develop the lacking multiscale description of cavitation, by proposing new integrated numerical methods capable to perform quantitative predictions. The detailed and physically sound understanding of the multifaceted phenomena involved in cavitation (nucleation, bubble growth, transport, and collapse in turbulent flows) fostered by BIC project will result in new methods for designing fluid machinery, but also therapies in ultrasound medicine and chemical reactors. The BIC project builds upon the exceptionally broad experience of the PI and of his research group in numerical simulations of flows at different scales that include advanced atomistic simulations of nanoscale wetting phenomena, mesoscale models for multiphase flows, and particle-laden turbulent flows. The envisaged numerical methodologies (free-energy atomistic simulations, phase-field models, and Direct Numerical Simulation of bubble-laden flows) will be supported by targeted experimental activities, designed to validate models and characterize realistic conditions.
Max ERC Funding
2 491 200 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym CARBONANOBRIDGE
Project Neuron Networking with Nano Bridges via the Synthesis and Integration of Functionalized Carbon Nanotubes
Researcher (PI) Maurizio Prato
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TRIESTE
Country Italy
Call Details Advanced Grant (AdG), PE5, ERC-2008-AdG
Summary We propose the development of novel nanodevices, such as nanoscale bridges and nanovectors, based on functionalized carbon nanotubes (CNT) for manipulating neurons and neuronal network activity in vitro. The main aim is to put forward innovative solutions that have the potential to circumvent the problems currently faced by spinal cord lesions or by neurodegenerative diseases. The unifying theme is to use recent advances in chemistry and nanotechnology to gain insight into the functioning of hybrid neuronal/CNT networks, relevant for the development of novel implantable devices to control neuronal signaling and improve synapse formation in a controlled fashion. The proposal s core strategy is to exploit the expertise of the PI in the chemical control of CNT properties to develop devices reaching various degrees of functional integration with the physiological electrical activity of cells and their networks, and to understand how such global dynamics are orchestrated when integrated by different substrates. An unconventional strategy will be represented by the electrical characterization of micro and nano patterned substrates by AFM and conductive tip AFM, both before and after neurons have grown on the substrates. We will also use the capability of AFM to identify critical positions in the neuronal network, while delivering time-dependent chemical stimulations. We will apply nanotechnology to contemporary neuroscience in the perspective of novel neuro-implantable devices and drug nanovectors, engineered to treat neurological and neurodegenerative lesions. The scientific strategy at the core of the proposal is the convergence between nanotechnology, chemistry and neurobiology. Such convergence, beyond helping understand the functioning and malfunctioning of the brain, can stimulate further research in this area and may ultimately lead to a new generation of nanomedicine applications in neurology and to new opportunities for the health care industry.
Summary
We propose the development of novel nanodevices, such as nanoscale bridges and nanovectors, based on functionalized carbon nanotubes (CNT) for manipulating neurons and neuronal network activity in vitro. The main aim is to put forward innovative solutions that have the potential to circumvent the problems currently faced by spinal cord lesions or by neurodegenerative diseases. The unifying theme is to use recent advances in chemistry and nanotechnology to gain insight into the functioning of hybrid neuronal/CNT networks, relevant for the development of novel implantable devices to control neuronal signaling and improve synapse formation in a controlled fashion. The proposal s core strategy is to exploit the expertise of the PI in the chemical control of CNT properties to develop devices reaching various degrees of functional integration with the physiological electrical activity of cells and their networks, and to understand how such global dynamics are orchestrated when integrated by different substrates. An unconventional strategy will be represented by the electrical characterization of micro and nano patterned substrates by AFM and conductive tip AFM, both before and after neurons have grown on the substrates. We will also use the capability of AFM to identify critical positions in the neuronal network, while delivering time-dependent chemical stimulations. We will apply nanotechnology to contemporary neuroscience in the perspective of novel neuro-implantable devices and drug nanovectors, engineered to treat neurological and neurodegenerative lesions. The scientific strategy at the core of the proposal is the convergence between nanotechnology, chemistry and neurobiology. Such convergence, beyond helping understand the functioning and malfunctioning of the brain, can stimulate further research in this area and may ultimately lead to a new generation of nanomedicine applications in neurology and to new opportunities for the health care industry.
Max ERC Funding
2 500 000 €
Duration
Start date: 2009-02-01, End date: 2014-01-31
Project acronym CARDIOEPIGEN
Project Epigenetics and microRNAs in Myocardial Function and Disease
Researcher (PI) Gianluigi Condorelli
Host Institution (HI) HUMANITAS MIRASOLE SPA
Country Italy
Call Details Advanced Grant (AdG), LS4, ERC-2011-ADG_20110310
Summary Heart failure (HF) is the ultimate outcome of many cardiovascular diseases. Re-expression of fetal genes in the adult heart contributes to development of HF. Two mechanisms involved in the control of gene expression are epigenetics and microRNAs (miRs). We propose a project on epigenetic and miR-mediated mechanisms leading to HF.
Epigenetics refers to heritable modification of DNA and histones that does not modify the genetic code. Depending on the type of modification and on the site affected, these chemical changes up- or down-regulate transcription of specific genes. Despite it being a major player in gene regulation, epigenetics has been only partly investigated in HF. miRs are regulatory RNAs that target mRNAs for inhibition. Dysregulation of the cardiac miR signature occurs in HF. miR expression may itself be under epigenetic control, constituting a miR-epigenetic regulatory network. To our knowledge, this possibility has not been studied yet.
Our specific hypothesis is that the profile of DNA/histone methylation and the cross-talk between epigenetic enzymes and miRs have fundamental roles in defining the characteristics of cells during cardiac development and that the dysregulation of these processes determines the deleterious nature of the stressed heart’s gene programme. We will test this first through a genome-wide study of DNA/histone methylation to generate maps of the main methylation modifications occurring in the genome of cardiac cells treated with a pro-hypertrophy regulator and of a HF model. We will then investigate the role of epigenetic enzymes deemed important in HF, through the generation and study of knockout mice models. Finally, we will test the possible therapeutic potential of modulating epigenetic genes.
We hope to further understand the pathological mechanisms leading to HF and to generate data instrumental to the development of diagnostic and therapeutic strategies for this disease.
Summary
Heart failure (HF) is the ultimate outcome of many cardiovascular diseases. Re-expression of fetal genes in the adult heart contributes to development of HF. Two mechanisms involved in the control of gene expression are epigenetics and microRNAs (miRs). We propose a project on epigenetic and miR-mediated mechanisms leading to HF.
Epigenetics refers to heritable modification of DNA and histones that does not modify the genetic code. Depending on the type of modification and on the site affected, these chemical changes up- or down-regulate transcription of specific genes. Despite it being a major player in gene regulation, epigenetics has been only partly investigated in HF. miRs are regulatory RNAs that target mRNAs for inhibition. Dysregulation of the cardiac miR signature occurs in HF. miR expression may itself be under epigenetic control, constituting a miR-epigenetic regulatory network. To our knowledge, this possibility has not been studied yet.
Our specific hypothesis is that the profile of DNA/histone methylation and the cross-talk between epigenetic enzymes and miRs have fundamental roles in defining the characteristics of cells during cardiac development and that the dysregulation of these processes determines the deleterious nature of the stressed heart’s gene programme. We will test this first through a genome-wide study of DNA/histone methylation to generate maps of the main methylation modifications occurring in the genome of cardiac cells treated with a pro-hypertrophy regulator and of a HF model. We will then investigate the role of epigenetic enzymes deemed important in HF, through the generation and study of knockout mice models. Finally, we will test the possible therapeutic potential of modulating epigenetic genes.
We hope to further understand the pathological mechanisms leading to HF and to generate data instrumental to the development of diagnostic and therapeutic strategies for this disease.
Max ERC Funding
2 500 000 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym ComplexiTE
Project An integrated multidisciplinary tissue engineering approach combining novel high-throughput screening and advanced methodologies to create complex biomaterials-stem cells constructs
Researcher (PI) Rui Luis Goncalves Dos Reis
Host Institution (HI) UNIVERSIDADE DO MINHO
Country Portugal
Call Details Advanced Grant (AdG), PE8, ERC-2012-ADG_20120216
Summary New developments on tissue engineering strategies should realize the complexity of tissue remodelling and the inter-dependency of many variables associated to stem cells and biomaterials interactions. ComplexiTE proposes an integrated approach to address such multiple factors in which different innovative methodologies are implemented, aiming at developing tissue-like substitutes with enhanced in vivo functionality. Several ground-breaking advances are expected to be achieved, including: i) improved methodologies for isolation and expansion of sub-populations of stem cells derived from not so explored sources such as adipose tissue and amniotic fluid; ii) radically new methods to monitor human stem cells behaviour in vivo; iii) new macromolecules isolated from renewable resources, especially from marine origin; iv) combinations of liquid volumes mingling biomaterials and distinct stem cells, generating hydrogel beads upon adequate cross-linking reactions; v) optimised culture of the produced beads in adequate 3D bioreactors and a novel selection method to sort the beads that show a (pre-defined) positive biological reading; vi) random 3D arrays validated by identifying the natural polymers and cells composing the positive beads; v) 2D arrays of selected hydrogel spots for brand new in vivo tests, in which each spot of the implanted chip may be evaluated within the living animal using adequate imaging methods; vi) new porous scaffolds of the best combinations formed by particles agglomeration or fiber-based rapid-prototyping. The ultimate goal of this proposal is to develop breakthrough research specifically focused on the above mentioned key issues and radically innovative approaches to produce and scale-up new tissue engineering strategies that are both industrially and clinically relevant, by mastering the inherent complexity associated to the correct selection among a great number of combinations of possible biomaterials, stem cells and culturing conditions.
Summary
New developments on tissue engineering strategies should realize the complexity of tissue remodelling and the inter-dependency of many variables associated to stem cells and biomaterials interactions. ComplexiTE proposes an integrated approach to address such multiple factors in which different innovative methodologies are implemented, aiming at developing tissue-like substitutes with enhanced in vivo functionality. Several ground-breaking advances are expected to be achieved, including: i) improved methodologies for isolation and expansion of sub-populations of stem cells derived from not so explored sources such as adipose tissue and amniotic fluid; ii) radically new methods to monitor human stem cells behaviour in vivo; iii) new macromolecules isolated from renewable resources, especially from marine origin; iv) combinations of liquid volumes mingling biomaterials and distinct stem cells, generating hydrogel beads upon adequate cross-linking reactions; v) optimised culture of the produced beads in adequate 3D bioreactors and a novel selection method to sort the beads that show a (pre-defined) positive biological reading; vi) random 3D arrays validated by identifying the natural polymers and cells composing the positive beads; v) 2D arrays of selected hydrogel spots for brand new in vivo tests, in which each spot of the implanted chip may be evaluated within the living animal using adequate imaging methods; vi) new porous scaffolds of the best combinations formed by particles agglomeration or fiber-based rapid-prototyping. The ultimate goal of this proposal is to develop breakthrough research specifically focused on the above mentioned key issues and radically innovative approaches to produce and scale-up new tissue engineering strategies that are both industrially and clinically relevant, by mastering the inherent complexity associated to the correct selection among a great number of combinations of possible biomaterials, stem cells and culturing conditions.
Max ERC Funding
2 320 000 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym COPMAT
Project Full-scale COmputational design of Porous mesoscale MATerials
Researcher (PI) Sauro SUCCI
Host Institution (HI) FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Country Italy
Call Details Advanced Grant (AdG), PE8, ERC-2016-ADG
Summary The last decades have witnessed major progress in our understanding of the basic physics of soft matter materials. At the same time, microfluidics has also undergone spectacular theoretical and experimental progress. The confluence of such major advances spawns unprecedented opportunities for the design and manufacturing of new soft mesoscale materials, with promising applications in tissue engineering, photonics, catalysis and many others. COPMAT is targeted at making the most this opportunity through the pursuit of a single general goal: the full-scale simulation at nanometric resolution of micro-reactors for the design and synthesis of new tunable porous materials. In particular, we shall focus on the microfluidic design of: multi-jel materials, trabecular porous media and soft mesoscale molecules. We shall also explore new designs concepts based on unexplored microscale phenomena, such as the interaction between plasticity and nano-rugosity. The complex interplay between the highly non-linear rheology of soft materials and the major experimental control parameters leads to an engineering design of formidable complexity, characterized by a strong sensitivity of the macroscale material properties on the details of nanoscale interfacial interactions. COPMAT will tackle this formidable multiscale challenge through the deployment of an entirely new family of multiscale techniques, centered upon highly innovative extensions of the Lattice Boltzmann method and its combinations with Immersed Boundary Method, Dissipative Particle Dynamics and Dissipative Voronoi Dynamics. The success of COPMAT will be gauged by its capability of inspiring and realizing the design of microfluidic devices for the synthesis of novel families of porous materials for bio-engineering applications. The new paradigm established by COPMAT for the computational design of soft materials is expected to extend well beyond the time-horizon of the project.
Summary
The last decades have witnessed major progress in our understanding of the basic physics of soft matter materials. At the same time, microfluidics has also undergone spectacular theoretical and experimental progress. The confluence of such major advances spawns unprecedented opportunities for the design and manufacturing of new soft mesoscale materials, with promising applications in tissue engineering, photonics, catalysis and many others. COPMAT is targeted at making the most this opportunity through the pursuit of a single general goal: the full-scale simulation at nanometric resolution of micro-reactors for the design and synthesis of new tunable porous materials. In particular, we shall focus on the microfluidic design of: multi-jel materials, trabecular porous media and soft mesoscale molecules. We shall also explore new designs concepts based on unexplored microscale phenomena, such as the interaction between plasticity and nano-rugosity. The complex interplay between the highly non-linear rheology of soft materials and the major experimental control parameters leads to an engineering design of formidable complexity, characterized by a strong sensitivity of the macroscale material properties on the details of nanoscale interfacial interactions. COPMAT will tackle this formidable multiscale challenge through the deployment of an entirely new family of multiscale techniques, centered upon highly innovative extensions of the Lattice Boltzmann method and its combinations with Immersed Boundary Method, Dissipative Particle Dynamics and Dissipative Voronoi Dynamics. The success of COPMAT will be gauged by its capability of inspiring and realizing the design of microfluidic devices for the synthesis of novel families of porous materials for bio-engineering applications. The new paradigm established by COPMAT for the computational design of soft materials is expected to extend well beyond the time-horizon of the project.
Max ERC Funding
1 880 060 €
Duration
Start date: 2017-10-01, End date: 2023-03-31
Project acronym DENOVOSTEM
Project DE NOVO GENERATION OF SOMATIC STEM CELLS: REGULATION AND MECHANISMS OF CELL PLASTICITY
Researcher (PI) Stefano Piccolo
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Country Italy
Call Details Advanced Grant (AdG), LS4, ERC-2014-ADG
Summary The possibility to artificially induce and expand in vitro tissue-specific stem cells (SCs) is an important goal for regenerative medicine, to understand organ physiology, for in vitro modeling of human diseases and many other applications. Here we found that this goal can be achieved in the culture dish by transiently inducing expression of YAP or TAZ - nuclear effectors of the Hippo and biomechanical pathways - into primary/terminally differentiated cells of distinct tissue origins. Moreover, YAP/TAZ are essential endogenous factors that preserve ex-vivo naturally arising SCs of distinct tissues.
In this grant, we aim to gain insights into YAP/TAZ molecular networks (upstream regulators and downstream targets) involved in somatic SC reprogramming and SC identity. Our studies will entail the identification of the genetic networks and epigenetic changes controlled by YAP/TAZ during cell de-differentiation and the re-acquisition of SC-traits in distinct cell types. We will also investigate upstream inputs establishing YAP/TAZ activity, with particular emphasis on biomechanical and cytoskeletal cues that represent overarching regulators of YAP/TAZ in tissues.
For many tumors, it appears that acquisition of an immature, stem-like state is a prerequisite for tumor progression and an early step in oncogene-mediated transformation. YAP/TAZ activation is widespread in human tumors. However, a connection between YAP/TAZ and oncogene-induced cell plasticity has never been investigated. We will also pursue some intriguing preliminary results and investigate how oncogenes and chromatin remodelers may link to cell mechanics, and the plasticity of the differentiated and SC states by controlling YAP/TAZ.
In sum, this research should advance our understanding of the cellular and molecular basis underpinning organ growth, tissue regeneration and tumor initiation.
Summary
The possibility to artificially induce and expand in vitro tissue-specific stem cells (SCs) is an important goal for regenerative medicine, to understand organ physiology, for in vitro modeling of human diseases and many other applications. Here we found that this goal can be achieved in the culture dish by transiently inducing expression of YAP or TAZ - nuclear effectors of the Hippo and biomechanical pathways - into primary/terminally differentiated cells of distinct tissue origins. Moreover, YAP/TAZ are essential endogenous factors that preserve ex-vivo naturally arising SCs of distinct tissues.
In this grant, we aim to gain insights into YAP/TAZ molecular networks (upstream regulators and downstream targets) involved in somatic SC reprogramming and SC identity. Our studies will entail the identification of the genetic networks and epigenetic changes controlled by YAP/TAZ during cell de-differentiation and the re-acquisition of SC-traits in distinct cell types. We will also investigate upstream inputs establishing YAP/TAZ activity, with particular emphasis on biomechanical and cytoskeletal cues that represent overarching regulators of YAP/TAZ in tissues.
For many tumors, it appears that acquisition of an immature, stem-like state is a prerequisite for tumor progression and an early step in oncogene-mediated transformation. YAP/TAZ activation is widespread in human tumors. However, a connection between YAP/TAZ and oncogene-induced cell plasticity has never been investigated. We will also pursue some intriguing preliminary results and investigate how oncogenes and chromatin remodelers may link to cell mechanics, and the plasticity of the differentiated and SC states by controlling YAP/TAZ.
In sum, this research should advance our understanding of the cellular and molecular basis underpinning organ growth, tissue regeneration and tumor initiation.
Max ERC Funding
2 498 934 €
Duration
Start date: 2015-09-01, End date: 2021-08-31
Project acronym DIGISMART
Project Multifunctional Digital Materials Platform for Smart Integrated Applications
Researcher (PI) Elvira Fortunato
Host Institution (HI) UNIVERSIDADE NOVA DE LISBOA
Country Portugal
Call Details Advanced Grant (AdG), PE8, ERC-2017-ADG
Summary DIGISMART creates new avenues into two main areas: 1) processing nanomaterials/nanostructures applied to electronic devices by exploring a new digital multifunctional direct laser writing (LDW) method for in situ synthesis of small-sized nanomaterials/nanofilms micro-patterned growth by selective photothermal decomposition of semiconductors, dielectrics and conductors precursors and 2) provide simultaneously multifunction to single based metal oxide devices (like thin film transistors, the workhorses for large area electronics having electron, charge and color modulation), as the basic unit to promote systems’ integration by exploring the use of new advanced materials with unique multi-functionalities using low cost process solutions.
This new fabrication process will be very useful for low-cost, eco-friendly, and efficient fabrication of nanostructures and thin films-integrated microelectronic devices due to its low-power, simple setup as well as excellent reliability. This new and disruptive concept will be achieved with low cost and non-toxic materials (new metal oxides, MO semiconductors, conductors, dielectrics and electrochromics free of In and Ga) associated to a low cost process multifunctional platform technology (ALL-IN-ONE TOOL) well supported by high-resolution nano-characterization techniques. With DIGISMART new and unexplored materials will be produced as well as to boost the original properties of conventional materials in order to contribute to the needs for low cost and flexible electronics. If we succeed to embed some level of intelligence in every object, this would change electronics and it would change society, ranging from embedded window displays to a wide range of biomedical electronics, just to mention a few and this is what the Internet of Things is looking for.
Summary
DIGISMART creates new avenues into two main areas: 1) processing nanomaterials/nanostructures applied to electronic devices by exploring a new digital multifunctional direct laser writing (LDW) method for in situ synthesis of small-sized nanomaterials/nanofilms micro-patterned growth by selective photothermal decomposition of semiconductors, dielectrics and conductors precursors and 2) provide simultaneously multifunction to single based metal oxide devices (like thin film transistors, the workhorses for large area electronics having electron, charge and color modulation), as the basic unit to promote systems’ integration by exploring the use of new advanced materials with unique multi-functionalities using low cost process solutions.
This new fabrication process will be very useful for low-cost, eco-friendly, and efficient fabrication of nanostructures and thin films-integrated microelectronic devices due to its low-power, simple setup as well as excellent reliability. This new and disruptive concept will be achieved with low cost and non-toxic materials (new metal oxides, MO semiconductors, conductors, dielectrics and electrochromics free of In and Ga) associated to a low cost process multifunctional platform technology (ALL-IN-ONE TOOL) well supported by high-resolution nano-characterization techniques. With DIGISMART new and unexplored materials will be produced as well as to boost the original properties of conventional materials in order to contribute to the needs for low cost and flexible electronics. If we succeed to embed some level of intelligence in every object, this would change electronics and it would change society, ranging from embedded window displays to a wide range of biomedical electronics, just to mention a few and this is what the Internet of Things is looking for.
Max ERC Funding
3 495 250 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym DisCont
Project Discontinuities in Household and Family Formation
Researcher (PI) Francesco Candeloro Billari
Host Institution (HI) UNIVERSITA COMMERCIALE LUIGI BOCCONI
Country Italy
Call Details Advanced Grant (AdG), SH3, ERC-2015-AdG
Summary Household, family and fertility changes are key drivers of population dynamics. Discovering and explaining the velocity of these changes is essential to understand the current situation and to provide scientific evidence on our demographic future. DisCont will provide seminal contributions by studying the impact of macro-level discontinuities on household and family formation (including fertility) in post-industrial contemporary societies. In the past decade, two macro-level discontinuities have radically transformed lives: the Great Recession and the digitalization of life and of the life course. Although their short-term and long-term impacts are likely to be fundamental, they have not yet been systematically analysed. Through a coordinated series of theoretically-founded empirical studies based on linked macro- and micro-level data, and using a comparative perspective, DisCont will argue that macro-level discontinuities are crucial in explaining broad changes in household and family formation, and that their effects can be persistent either for the population as a whole, or for specific cohorts. DisCont will contribute to five areas: 1) it will make theoretical advances by showing the importance of macro-level discontinuities in the explanation of changes in household and family formation in particular, and in population dynamics in general; 2) it will substantially advance our knowledge of household and family formation in post-industrial contemporary societies; 3) it will contribute in a systematic and path-breaking way to research on the broader societal impact of digitalization and of the Great Recession; 4) it will bring a paradigm shift in Age-Period-Cohort modelling; 5) it will make ground-breaking contributions on the demographic use of “big data” and on the use of agent-based models for the population-level implications of household and family change.
Summary
Household, family and fertility changes are key drivers of population dynamics. Discovering and explaining the velocity of these changes is essential to understand the current situation and to provide scientific evidence on our demographic future. DisCont will provide seminal contributions by studying the impact of macro-level discontinuities on household and family formation (including fertility) in post-industrial contemporary societies. In the past decade, two macro-level discontinuities have radically transformed lives: the Great Recession and the digitalization of life and of the life course. Although their short-term and long-term impacts are likely to be fundamental, they have not yet been systematically analysed. Through a coordinated series of theoretically-founded empirical studies based on linked macro- and micro-level data, and using a comparative perspective, DisCont will argue that macro-level discontinuities are crucial in explaining broad changes in household and family formation, and that their effects can be persistent either for the population as a whole, or for specific cohorts. DisCont will contribute to five areas: 1) it will make theoretical advances by showing the importance of macro-level discontinuities in the explanation of changes in household and family formation in particular, and in population dynamics in general; 2) it will substantially advance our knowledge of household and family formation in post-industrial contemporary societies; 3) it will contribute in a systematic and path-breaking way to research on the broader societal impact of digitalization and of the Great Recession; 4) it will bring a paradigm shift in Age-Period-Cohort modelling; 5) it will make ground-breaking contributions on the demographic use of “big data” and on the use of agent-based models for the population-level implications of household and family change.
Max ERC Funding
2 400 555 €
Duration
Start date: 2017-02-01, End date: 2022-07-31