Project acronym ANFIBIO
Project AmplificatioN Free Identification of cancer and viral biomarkers via plasmonic nanoparticles and liquid BIOpsy
Researcher (PI) Laura Fabris
Host Institution (HI) POLITECNICO DI TORINO
Country Italy
Call Details Consolidator Grant (CoG), PE5, ERC-2019-COG
Summary The detection of circulating disease biomarkers in bodily fluids, also known as liquid biopsy, has taken important strides toward the implementation of personalized medicine. However, it still suffers from low sensitivity and high costs, which render its clinical implementation not practical or affordable. In particular, the identification and quantification of oligonucleotide biomarkers is hampered by the need to employ long- and short-read sequencing tools that are expensive, require highly trained personnel, and are prone to error. Nonetheless, the recent clinical breakthroughs demonstrating the importance of detecting cancerous or viral biomarker to susceptibility, onset, and aggressiveness of the disease, motivate the need for further research that could render their detection simpler, cheaper, and thus more widely available.
By leveraging the intrinsic amplification capability of surface enhanced Raman scattering (SERS), in ANFIBIO I will address the issues of low sensitivity and high costs by combining plasmonic nanoparticles synthesized ad hoc to maximize SERS signal amplification with direct SERS sensing and machine learning tools for the rapid analysis of the complex spectral responses obtained by screening bodily fluids for specific target biomarkers. I will focus in particular on prostate cancer (PCa) DNA and influenza A viral (IAV) RNA in blood, urine, and saliva, to quantify and correlate their amounts to those detected in tissues and cells.
At completion, the proposed work will deliver a breakthrough sensing technology capable of detecting and quantifying cancerous and viral biomarkers in bodily fluids, with minimal sample pretreatment, no target amplification, and that uses SERS as novel and reliable transduction mechanism with distinct advantages over those currently employed. Furthermore, the fundamental insight garnered will likely assess the feasibility of using direct SERS sensing to develop beyond-third generation sequencing technologies.
Summary
The detection of circulating disease biomarkers in bodily fluids, also known as liquid biopsy, has taken important strides toward the implementation of personalized medicine. However, it still suffers from low sensitivity and high costs, which render its clinical implementation not practical or affordable. In particular, the identification and quantification of oligonucleotide biomarkers is hampered by the need to employ long- and short-read sequencing tools that are expensive, require highly trained personnel, and are prone to error. Nonetheless, the recent clinical breakthroughs demonstrating the importance of detecting cancerous or viral biomarker to susceptibility, onset, and aggressiveness of the disease, motivate the need for further research that could render their detection simpler, cheaper, and thus more widely available.
By leveraging the intrinsic amplification capability of surface enhanced Raman scattering (SERS), in ANFIBIO I will address the issues of low sensitivity and high costs by combining plasmonic nanoparticles synthesized ad hoc to maximize SERS signal amplification with direct SERS sensing and machine learning tools for the rapid analysis of the complex spectral responses obtained by screening bodily fluids for specific target biomarkers. I will focus in particular on prostate cancer (PCa) DNA and influenza A viral (IAV) RNA in blood, urine, and saliva, to quantify and correlate their amounts to those detected in tissues and cells.
At completion, the proposed work will deliver a breakthrough sensing technology capable of detecting and quantifying cancerous and viral biomarkers in bodily fluids, with minimal sample pretreatment, no target amplification, and that uses SERS as novel and reliable transduction mechanism with distinct advantages over those currently employed. Furthermore, the fundamental insight garnered will likely assess the feasibility of using direct SERS sensing to develop beyond-third generation sequencing technologies.
Max ERC Funding
2 725 510 €
Duration
Start date: 2021-06-01, End date: 2026-05-31
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 AXIAL.EC
Project PRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
Researcher (PI) Claudio Franco
Host Institution (HI) INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Country Portugal
Call Details Starting Grant (StG), LS4, ERC-2015-STG
Summary The formation of a functional patterned vascular network is essential for development, tissue growth and organ physiology. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms and diabetic retinopathy. Although blood flow is recognised as a stimulus for vascular patterning, very little is known about the molecular mechanisms that regulate endothelial cell behaviour in response to flow and promote vascular patterning.
Recently, we uncovered that endothelial cells migrate extensively in the immature vascular network, and that endothelial cells polarise against the blood flow direction. Here, we put forward the hypothesis that vascular patterning is dependent on the polarisation and migration of endothelial cells against the flow direction, in a continuous flux of cells going from low-shear stress to high-shear stress regions. We will establish new reporter mouse lines to observe and manipulate endothelial polarity in vivo in order to investigate how polarisation and coordination of endothelial cells movements are orchestrated to generate vascular patterning. We will manipulate cell polarity using mouse models to understand the importance of cell polarisation in vascular patterning. Also, using a unique zebrafish line allowing analysis of endothelial cell polarity, we will perform a screen to identify novel regulators of vascular patterning. Finally, we will explore the hypothesis that defective flow-dependent endothelial polarisation underlies arteriovenous malformations using two genetic models.
This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders.
Summary
The formation of a functional patterned vascular network is essential for development, tissue growth and organ physiology. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms and diabetic retinopathy. Although blood flow is recognised as a stimulus for vascular patterning, very little is known about the molecular mechanisms that regulate endothelial cell behaviour in response to flow and promote vascular patterning.
Recently, we uncovered that endothelial cells migrate extensively in the immature vascular network, and that endothelial cells polarise against the blood flow direction. Here, we put forward the hypothesis that vascular patterning is dependent on the polarisation and migration of endothelial cells against the flow direction, in a continuous flux of cells going from low-shear stress to high-shear stress regions. We will establish new reporter mouse lines to observe and manipulate endothelial polarity in vivo in order to investigate how polarisation and coordination of endothelial cells movements are orchestrated to generate vascular patterning. We will manipulate cell polarity using mouse models to understand the importance of cell polarisation in vascular patterning. Also, using a unique zebrafish line allowing analysis of endothelial cell polarity, we will perform a screen to identify novel regulators of vascular patterning. Finally, we will explore the hypothesis that defective flow-dependent endothelial polarisation underlies arteriovenous malformations using two genetic models.
This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders.
Max ERC Funding
1 618 750 €
Duration
Start date: 2016-09-01, End date: 2022-02-28
Project acronym B3YOND
Project Beyond nanofabrication via nanoscale phase engineering of matter
Researcher (PI) Edoardo ALBISETTI
Host Institution (HI) POLITECNICO DI MILANO
Country Italy
Call Details Starting Grant (StG), PE8, ERC-2020-STG
Summary B3YOND proposes a radically new approach to nanofabrication, based on using sub-10 nm confined thermal reactions for patterning and manipulating the physical properties of materials with unprecedented tunability and resolution. Throughout the past decades, the progress in micro- and nano-fabrication techniques has been one of the most powerful and ubiquitous driving forces in science and technology. Nowadays, conventional approaches to nanofabrication reached the fundamental physical limits for the downscaling of devices, so that the search for groundbreaking new paradigms has become vital for enabling significant technological advancement. This project aims to go substantially beyond conventional nanofabrication approaches, through the following ambitious research objectives:
1) Demonstrate a radically new approach to nanofabrication, phase-nanoengineering, based on directly crafting at the nanoscale the physical properties of thin-film materials, by using the recently developed thermally assisted scanning probe lithography (t-SPL) technique for producing highly localized and tunable thermally-induced phase changes.
2) Develop a new class of artificial nanomaterials with unprecedented electronic transport properties, which arise from the proximity and coexistence of different structural and electronic phases, tailored at the nanoscale.
3) Realize novel monolithic three-dimensional nanoelectronic platforms for beyond-CMOS computing, by exploiting the unique capabilities of t-SPL for obtaining sub-10 nm resolution patterning in three-dimensions.
By combining, in a highly multidisciplinary approach, some of the most promising recent advances in materials science, with the tremendous potential of t-SPL, this challenging project will enable disruptive conceptual and technological breakthroughs, beyond the conventional paradigms of nanofabrication.
Summary
B3YOND proposes a radically new approach to nanofabrication, based on using sub-10 nm confined thermal reactions for patterning and manipulating the physical properties of materials with unprecedented tunability and resolution. Throughout the past decades, the progress in micro- and nano-fabrication techniques has been one of the most powerful and ubiquitous driving forces in science and technology. Nowadays, conventional approaches to nanofabrication reached the fundamental physical limits for the downscaling of devices, so that the search for groundbreaking new paradigms has become vital for enabling significant technological advancement. This project aims to go substantially beyond conventional nanofabrication approaches, through the following ambitious research objectives:
1) Demonstrate a radically new approach to nanofabrication, phase-nanoengineering, based on directly crafting at the nanoscale the physical properties of thin-film materials, by using the recently developed thermally assisted scanning probe lithography (t-SPL) technique for producing highly localized and tunable thermally-induced phase changes.
2) Develop a new class of artificial nanomaterials with unprecedented electronic transport properties, which arise from the proximity and coexistence of different structural and electronic phases, tailored at the nanoscale.
3) Realize novel monolithic three-dimensional nanoelectronic platforms for beyond-CMOS computing, by exploiting the unique capabilities of t-SPL for obtaining sub-10 nm resolution patterning in three-dimensions.
By combining, in a highly multidisciplinary approach, some of the most promising recent advances in materials science, with the tremendous potential of t-SPL, this challenging project will enable disruptive conceptual and technological breakthroughs, beyond the conventional paradigms of nanofabrication.
Max ERC Funding
1 498 385 €
Duration
Start date: 2021-02-01, End date: 2026-01-31
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 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 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
