Project acronym bECOMiNG
Project spontaneous Evolution and Clonal heterOgeneity in MoNoclonal Gammopathies: from mechanisms of progression to clinical management
Researcher (PI) Niccolo Bolli
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Country Italy
Call Details Consolidator Grant (CoG), LS7, ERC-2018-COG
Summary As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
Summary
As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
Max ERC Funding
1 998 781 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
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 BIFLOW
Project Bilingualism in Florentine and Tuscan Works (ca. 1260 - ca. 1416)
Researcher (PI) Antonio Montefusco
Host Institution (HI) UNIVERSITA CA' FOSCARI VENEZIA
Country Italy
Call Details Starting Grant (StG), SH5, ERC-2014-STG
Summary This project will undertake the first systematic investigation of the various literary documents that circulated simultaneously in more than one language in Tuscany, and especially Florence, between the mid-13th Century and the beginning of 15th Century.
During that period, Florence was both a prominent literary centre in the vernacular, and home to a renewal of classical Latin eloquence. While both fields are well studied, their interaction remains largely unexplored. This research, at the convergence of several disciplines (literature, philology, linguistics and medieval history), has a strong pioneering character. It aims at changing the perception of medieval Italian culture and interpretation of the break between medieval Culture and Humanism.
For this reason, the project will develop research in varying degrees of depth. First, it will provide the first catalogue of bilingual texts and manuscripts of medieval Tuscany. Organized as a database, this tool of analysis will stir innovative research in this field, some of which will be immediately promoted during the project.
Secondly, two case studies, considered as important and methodologically exemplary, will be researched in detail, through the publication of two important set of texts, of secular and religious nature : 1. The vernacular translation of the Latin Epistles of Dante Alighieri; 2. A collection of polemical, historiographical, devotional and prophetical documents produced by the Tuscan dissident Franciscans in last decades of the 14th Century.
Finally, the entire team, led by the PI, will be involved in the preparation of a synthesis volume on Tuscan culture in the fourteenth century viewed through bilingualism, entitled Cartography of bilingual culture in Fourteenth-Century Tuscany. From this general map of the Italian culture of the time, no literary genre nor field (be it religious or lay) shall be excluded.
Summary
This project will undertake the first systematic investigation of the various literary documents that circulated simultaneously in more than one language in Tuscany, and especially Florence, between the mid-13th Century and the beginning of 15th Century.
During that period, Florence was both a prominent literary centre in the vernacular, and home to a renewal of classical Latin eloquence. While both fields are well studied, their interaction remains largely unexplored. This research, at the convergence of several disciplines (literature, philology, linguistics and medieval history), has a strong pioneering character. It aims at changing the perception of medieval Italian culture and interpretation of the break between medieval Culture and Humanism.
For this reason, the project will develop research in varying degrees of depth. First, it will provide the first catalogue of bilingual texts and manuscripts of medieval Tuscany. Organized as a database, this tool of analysis will stir innovative research in this field, some of which will be immediately promoted during the project.
Secondly, two case studies, considered as important and methodologically exemplary, will be researched in detail, through the publication of two important set of texts, of secular and religious nature : 1. The vernacular translation of the Latin Epistles of Dante Alighieri; 2. A collection of polemical, historiographical, devotional and prophetical documents produced by the Tuscan dissident Franciscans in last decades of the 14th Century.
Finally, the entire team, led by the PI, will be involved in the preparation of a synthesis volume on Tuscan culture in the fourteenth century viewed through bilingualism, entitled Cartography of bilingual culture in Fourteenth-Century Tuscany. From this general map of the Italian culture of the time, no literary genre nor field (be it religious or lay) shall be excluded.
Max ERC Funding
1 480 625 €
Duration
Start date: 2015-10-01, End date: 2021-06-30
Project acronym BIHSNAM
Project Bio-inspired Hierarchical Super Nanomaterials
Researcher (PI) Nicola Pugno
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TRENTO
Country Italy
Call Details Starting Grant (StG), PE8, ERC-2011-StG_20101014
Summary "Nanomaterials such as carbon nanotubes or graphene sheets represent the future of material science, due to their potentially exceptional mechanical properties. One great drawback of all artificial materials, however, is the decrease of strength with increasing toughness, and viceversa. This problem is not encountered in many biological nanomaterials (e.g. spider silk, bone, nacre). Other biological materials display exceptional adhesion or damping properties, and can be self-cleaning or self-healing. The “secret” of biomaterials seems to lie in “hierarchy”: several levels can often be identified (2 in nacre, up to 7 in bone and dentine), from nano- to micro-scale.
The idea of this project is to combine Nature and Nanotechnology to design hierarchical composites with tailor made characteristics, optimized with respect to both strength and toughness, as well as materials with strong adhesion/easy detachment, smart damping, self-healing/-cleaning properties or controlled energy dissipation. For example, one possible objective is to design the “world’s toughest composite material”. The potential impact and importance of these goals on materials science, the high-tech industry and ultimately the quality of human life could be considerable.
In order to tackle such a challenging design process, the PI proposes to adopt ultimate nanomechanics theoretical tools corroborated by continuum or atomistic simulations, multi-scale numerical parametric simulations and Finite Element optimization procedures, starting from characterization experiments on biological- or nano-materials, from the macroscale to the nanoscale. Results from theoretical, numerical and experimental work packages will be applied to a specific case study in an engineering field of particular interest to demonstrate importance and feasibility, e.g. an airplane wing with a considerably enhanced fatigue resistance and reduced ice-layer adhesion, leading to a 10 fold reduction in wasted fuel."
Summary
"Nanomaterials such as carbon nanotubes or graphene sheets represent the future of material science, due to their potentially exceptional mechanical properties. One great drawback of all artificial materials, however, is the decrease of strength with increasing toughness, and viceversa. This problem is not encountered in many biological nanomaterials (e.g. spider silk, bone, nacre). Other biological materials display exceptional adhesion or damping properties, and can be self-cleaning or self-healing. The “secret” of biomaterials seems to lie in “hierarchy”: several levels can often be identified (2 in nacre, up to 7 in bone and dentine), from nano- to micro-scale.
The idea of this project is to combine Nature and Nanotechnology to design hierarchical composites with tailor made characteristics, optimized with respect to both strength and toughness, as well as materials with strong adhesion/easy detachment, smart damping, self-healing/-cleaning properties or controlled energy dissipation. For example, one possible objective is to design the “world’s toughest composite material”. The potential impact and importance of these goals on materials science, the high-tech industry and ultimately the quality of human life could be considerable.
In order to tackle such a challenging design process, the PI proposes to adopt ultimate nanomechanics theoretical tools corroborated by continuum or atomistic simulations, multi-scale numerical parametric simulations and Finite Element optimization procedures, starting from characterization experiments on biological- or nano-materials, from the macroscale to the nanoscale. Results from theoretical, numerical and experimental work packages will be applied to a specific case study in an engineering field of particular interest to demonstrate importance and feasibility, e.g. an airplane wing with a considerably enhanced fatigue resistance and reduced ice-layer adhesion, leading to a 10 fold reduction in wasted fuel."
Max ERC Funding
1 004 400 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
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: 2024-11-30
Project acronym BIOINOHYB
Project Smart Bioinorganic Hybrids for Nanomedicine
Researcher (PI) Cristiana Di Valentin
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Country Italy
Call Details Consolidator Grant (CoG), PE5, ERC-2014-CoG
Summary The use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine.
More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.
Summary
The use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine.
More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.
Max ERC Funding
1 748 125 €
Duration
Start date: 2016-02-01, End date: 2022-07-31
Project acronym BioLEAP
Project Biotechnological optimization of light use efficiency in algae photobioreactors
Researcher (PI) Tomas Morosinotto
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Country Italy
Call Details Starting Grant (StG), LS9, ERC-2012-StG_20111109
Summary New renewable energy source are highly needed to compensate exhausting fossil fuels reserves and reduce greenhouse gases emissions. Some species of algae have an interesting potential as feedstock for the production of biodiesel thanks to their ability to accumulate large amount of lipids. Strong research efforts are however needed to fulfil this potential and address many issues involving optimization of cultivation systems, biomass harvesting and algae genetic improvement. This proposal aims to address one of these issues, the optimization of algae light use efficiency. Light, in fact, provides the energy supporting algae growth and must be exploited with the highest possible efficiency to achieve sufficient productivity.
In a photobioreactor algae are highly concentrated and this cause a inhomogeneous light distribution with a large fraction of the cells exposed to very low light or even in the dark. Algae are also actively mixed and they can abruptly move from dark to full illumination and vice versa. This proposal aims to assess how alternation of dark/light cycles affect algae growth and functionality of photosynthetic apparatus both in batch and continuous cultures. In collaboration with the Chemical Engineering department, experimental data will be exploited to build a model describing the photobioreactor, a fundamental tool to improve its design.
The other main scope of this proposal is the isolation of genetically improved strains more suitable to the artificial environment of a photobioreactor. A first part of the work of setting up protocols for transformation will be followed by a second phase for generation and selection of mutants with altered photosynthetic performances. Transcriptome analyses in different light conditions will also be instrumental to identify genes to be targeted by genetic engineering.
Summary
New renewable energy source are highly needed to compensate exhausting fossil fuels reserves and reduce greenhouse gases emissions. Some species of algae have an interesting potential as feedstock for the production of biodiesel thanks to their ability to accumulate large amount of lipids. Strong research efforts are however needed to fulfil this potential and address many issues involving optimization of cultivation systems, biomass harvesting and algae genetic improvement. This proposal aims to address one of these issues, the optimization of algae light use efficiency. Light, in fact, provides the energy supporting algae growth and must be exploited with the highest possible efficiency to achieve sufficient productivity.
In a photobioreactor algae are highly concentrated and this cause a inhomogeneous light distribution with a large fraction of the cells exposed to very low light or even in the dark. Algae are also actively mixed and they can abruptly move from dark to full illumination and vice versa. This proposal aims to assess how alternation of dark/light cycles affect algae growth and functionality of photosynthetic apparatus both in batch and continuous cultures. In collaboration with the Chemical Engineering department, experimental data will be exploited to build a model describing the photobioreactor, a fundamental tool to improve its design.
The other main scope of this proposal is the isolation of genetically improved strains more suitable to the artificial environment of a photobioreactor. A first part of the work of setting up protocols for transformation will be followed by a second phase for generation and selection of mutants with altered photosynthetic performances. Transcriptome analyses in different light conditions will also be instrumental to identify genes to be targeted by genetic engineering.
Max ERC Funding
1 257 600 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym BioMNP
Project Understanding the interaction between metal nanoparticles and biological membranes
Researcher (PI) Giulia Rossi
Host Institution (HI) UNIVERSITA DEGLI STUDI DI GENOVA
Country Italy
Call Details Starting Grant (StG), PE3, ERC-2015-STG
Summary The BioMNP objective is the molecular-level understanding of the interactions between surface functionalized metal nanoparticles and biological membranes, by means of cutting-edge computational techniques and new molecular models.
Metal nanoparticles (NP) play more and more important roles in pharmaceutical and medical technology as diagnostic or therapeutic devices. Metal NPs can nowadays be engineered in a multitude of shapes, sizes and compositions, and they can be decorated with an almost infinite variety of functionalities. Despite such technological advances, there is still poor understanding of the molecular processes that drive the interactions of metal NPs with cells. Cell membranes are the first barrier encountered by NPs entering living organisms. The understanding and control of the interaction of nanoparticles with biological membranes is therefore of paramount importance to understand the molecular basis of the NP biological effects.
BioMNP will go beyond the state of the art by rationalizing the complex interplay of NP size, composition, functionalization and aggregation state during the interaction with model biomembranes. Membranes, in turn, will be modelled at an increasing level of complexity in terms of lipid composition and phase. BioMNP will rely on cutting-edge simulation techniques and facilities, and develop new coarse-grained models grounded on finer-level atomistic simulations, to study the NP-membrane interactions on an extremely large range of length and time scales.
BioMNP will benefit from important and complementary experimental collaborations, will propose interpretations of the available experimental data and make predictions to guide the design of functional, non-toxic metal nanoparticles for biomedical applications. BioMNP aims at answering fundamental questions at the crossroads of physics, biology and chemistry. Its results will have an impact on nanomedicine, toxicology, nanotechnology and material sciences.
Summary
The BioMNP objective is the molecular-level understanding of the interactions between surface functionalized metal nanoparticles and biological membranes, by means of cutting-edge computational techniques and new molecular models.
Metal nanoparticles (NP) play more and more important roles in pharmaceutical and medical technology as diagnostic or therapeutic devices. Metal NPs can nowadays be engineered in a multitude of shapes, sizes and compositions, and they can be decorated with an almost infinite variety of functionalities. Despite such technological advances, there is still poor understanding of the molecular processes that drive the interactions of metal NPs with cells. Cell membranes are the first barrier encountered by NPs entering living organisms. The understanding and control of the interaction of nanoparticles with biological membranes is therefore of paramount importance to understand the molecular basis of the NP biological effects.
BioMNP will go beyond the state of the art by rationalizing the complex interplay of NP size, composition, functionalization and aggregation state during the interaction with model biomembranes. Membranes, in turn, will be modelled at an increasing level of complexity in terms of lipid composition and phase. BioMNP will rely on cutting-edge simulation techniques and facilities, and develop new coarse-grained models grounded on finer-level atomistic simulations, to study the NP-membrane interactions on an extremely large range of length and time scales.
BioMNP will benefit from important and complementary experimental collaborations, will propose interpretations of the available experimental data and make predictions to guide the design of functional, non-toxic metal nanoparticles for biomedical applications. BioMNP aims at answering fundamental questions at the crossroads of physics, biology and chemistry. Its results will have an impact on nanomedicine, toxicology, nanotechnology and material sciences.
Max ERC Funding
1 131 250 €
Duration
Start date: 2016-04-01, End date: 2021-11-30
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 BIOSMA
Project Mathematics for Shape Memory Technologies in Biomechanics
Researcher (PI) Ulisse Stefanelli
Host Institution (HI) CONSIGLIO NAZIONALE DELLE RICERCHE
Country Italy
Call Details Starting Grant (StG), PE1, ERC-2007-StG
Summary Shape Memory Alloys (SMAs) are nowadays widely exploited for the realization of innovative devices and have a great impact on the development of a variety of biomedical applications ranging from orthodontic archwires to vascular stents. The design, realization, and optimization of such devices are quite demanding tasks. Mathematics is involved in this process as a major tool in order to let the modeling more accurate, the numerical simulations more reliable, and the design more effective. Many material properties of SMAs such as martensitic reorientation, training, and ferromagnetic behavior, are still to be properly and efficiently addressed. Therefore, new modeling ideas, along with original analytical and numerical techniques, are required. This project is aimed at addressing novel mathematical issues in order to move from experimental materials results toward the solution of real-scale biomechanical Engineering problems. The research focus will be multidisciplinary and include modeling, analytic, numerical, and computational issues. A progress in the macroscopic description of SMAs, the computational simulation of real-scale SMA devices, and the optimization of the production processes will contribute to advance in the direction of innovative applications.
Summary
Shape Memory Alloys (SMAs) are nowadays widely exploited for the realization of innovative devices and have a great impact on the development of a variety of biomedical applications ranging from orthodontic archwires to vascular stents. The design, realization, and optimization of such devices are quite demanding tasks. Mathematics is involved in this process as a major tool in order to let the modeling more accurate, the numerical simulations more reliable, and the design more effective. Many material properties of SMAs such as martensitic reorientation, training, and ferromagnetic behavior, are still to be properly and efficiently addressed. Therefore, new modeling ideas, along with original analytical and numerical techniques, are required. This project is aimed at addressing novel mathematical issues in order to move from experimental materials results toward the solution of real-scale biomechanical Engineering problems. The research focus will be multidisciplinary and include modeling, analytic, numerical, and computational issues. A progress in the macroscopic description of SMAs, the computational simulation of real-scale SMA devices, and the optimization of the production processes will contribute to advance in the direction of innovative applications.
Max ERC Funding
700 000 €
Duration
Start date: 2008-09-01, End date: 2013-08-31
