Project acronym 2-HIT
Project Genetic interaction networks: From C. elegans to human disease
Researcher (PI) Ben Lehner
Host Institution (HI) FUNDACIO CENTRE DE REGULACIO GENOMICA
Call Details Starting Grant (StG), LS2, ERC-2007-StG
Summary Most hereditary diseases in humans are genetically complex, resulting from combinations of mutations in multiple genes. However synthetic interactions between genes are very difficult to identify in population studies because of a lack of statistical power and we fundamentally do not understand how mutations interact to produce phenotypes. C. elegans is a unique animal in which genetic interactions can be rapidly identified in vivo using RNA interference, and we recently used this system to construct the first genetic interaction network for any animal, focused on signal transduction genes. The first objective of this proposal is to extend this work and map a comprehensive genetic interaction network for this model metazoan. This project will provide the first insights into the global properties of animal genetic interaction networks, and a comprehensive view of the functional relationships between genes in an animal. The second objective of the proposal is to use C. elegans to develop and validate experimentally integrated gene networks that connect genes to phenotypes and predict genetic interactions on a genome-wide scale. The methods that we develop and validate in C. elegans will then be applied to predict phenotypes and interactions for human genes. The final objective is to dissect the molecular mechanisms underlying genetic interactions, and to understand how these interactions evolve. The combined aim of these three objectives is to generate a framework for understanding and predicting how mutations interact to produce phenotypes, including in human disease.
Summary
Most hereditary diseases in humans are genetically complex, resulting from combinations of mutations in multiple genes. However synthetic interactions between genes are very difficult to identify in population studies because of a lack of statistical power and we fundamentally do not understand how mutations interact to produce phenotypes. C. elegans is a unique animal in which genetic interactions can be rapidly identified in vivo using RNA interference, and we recently used this system to construct the first genetic interaction network for any animal, focused on signal transduction genes. The first objective of this proposal is to extend this work and map a comprehensive genetic interaction network for this model metazoan. This project will provide the first insights into the global properties of animal genetic interaction networks, and a comprehensive view of the functional relationships between genes in an animal. The second objective of the proposal is to use C. elegans to develop and validate experimentally integrated gene networks that connect genes to phenotypes and predict genetic interactions on a genome-wide scale. The methods that we develop and validate in C. elegans will then be applied to predict phenotypes and interactions for human genes. The final objective is to dissect the molecular mechanisms underlying genetic interactions, and to understand how these interactions evolve. The combined aim of these three objectives is to generate a framework for understanding and predicting how mutations interact to produce phenotypes, including in human disease.
Max ERC Funding
1 100 000 €
Duration
Start date: 2008-09-01, End date: 2014-04-30
Project acronym 2-NanoSi
Project Ratiometric FRET Based Nanosensors for Trypsin Related Human Recessive Diseases
Researcher (PI) Emilio Jose Palomares Gil
Host Institution (HI) FUNDACIO PRIVADA INSTITUT CATALA D'INVESTIGACIO QUIMICA
Call Details Proof of Concept (PoC), PC1, ERC-2014-PoC
Summary The project aims to create a demo system for cost effective, non-invasive device for rapid detection of cystic fibrosis in humans. The detection of human recessive diseases has been dominated by the use of fluorescent biomarkers, based on organic dyes, helping researchers to study and analyse gene expression, cell cycle, and enzymatic activity. Among several proteolytic enzymes, trypsin has attracted much attention, as it is a target in the study of various important human recessive diseases including, for example, cystic fibrosis (CF).
We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of cystic in humans. Current detection technologies for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a fast (minutes), a single-step and with two times higher sensitivity than the state-of-the-art biomarkers based sensors for cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range (25-350 μg/L). Moreover, our approach can be used from the 4th day of life when the trypsin concentration is already the same as in adults. Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human phenotypes, i.e. normal (160-340 μg/L), CF homozygotic (0-90 μg/L), and CF heterozygotic (91-349 μg/L), respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescence biomarker for recessive genetic diseases alike human cystic fibrosis.
Summary
The project aims to create a demo system for cost effective, non-invasive device for rapid detection of cystic fibrosis in humans. The detection of human recessive diseases has been dominated by the use of fluorescent biomarkers, based on organic dyes, helping researchers to study and analyse gene expression, cell cycle, and enzymatic activity. Among several proteolytic enzymes, trypsin has attracted much attention, as it is a target in the study of various important human recessive diseases including, for example, cystic fibrosis (CF).
We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of cystic in humans. Current detection technologies for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a fast (minutes), a single-step and with two times higher sensitivity than the state-of-the-art biomarkers based sensors for cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range (25-350 μg/L). Moreover, our approach can be used from the 4th day of life when the trypsin concentration is already the same as in adults. Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human phenotypes, i.e. normal (160-340 μg/L), CF homozygotic (0-90 μg/L), and CF heterozygotic (91-349 μg/L), respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescence biomarker for recessive genetic diseases alike human cystic fibrosis.
Max ERC Funding
150 000 €
Duration
Start date: 2015-04-01, End date: 2016-09-30
Project acronym 2D-PnictoChem
Project Chemistry and Interface Control of Novel 2D-Pnictogen Nanomaterials
Researcher (PI) Gonzalo ABELLAN SAEZ
Host Institution (HI) UNIVERSITAT DE VALENCIA
Call Details Starting Grant (StG), PE5, ERC-2018-STG
Summary 2D-PnictoChem aims at exploring the Chemistry of a novel class of graphene-like 2D layered
elemental materials of group 15, the pnictogens: P, As, Sb, and Bi. In the last few years, these materials
have taken the field of Materials Science by storm since they can outperform and/or complement graphene
properties. Their strongly layer-dependent unique properties range from semiconducting to metallic,
including high carrier mobilities, tunable bandgaps, strong spin-orbit coupling or transparency. However,
the Chemistry of pnictogens is still in its infancy, remaining largely unexplored. This is the niche that
2D-PnictoChem aims to fill. By mastering the interface chemistry, we will develop the assembly of 2Dpnictogens
in complex hybrid heterostructures for the first time. Success will rely on a cross-disciplinary
approach combining both Inorganic- and Organic Chemistry with Solid-state Physics, including: 1)
Synthetizing and exfoliating high quality ultra-thin layer pnictogens, providing reliable access down to
the monolayer limit. 2) Achieving their chemical functionalization via both non-covalent and covalent
approaches in order to tailor at will their properties, decipher reactivity patterns and enable controlled
doping avenues. 3) Developing hybrid architectures through a precise chemical control of the interface,
in order to promote unprecedented access to novel heterostructures. 4) Exploring novel applications
concepts achieving outstanding performances. These are all priorities in the European Union agenda
aimed at securing an affordable, clean energy future by developing more efficient hybrid systems for
batteries, electronic devices or applications in catalysis. The opportunity is unique to reduce Europe’s
dependence on external technology and the PI’s background is ideally suited to tackle these objectives,
counting as well on a multidisciplinary team of international collaborators.
Summary
2D-PnictoChem aims at exploring the Chemistry of a novel class of graphene-like 2D layered
elemental materials of group 15, the pnictogens: P, As, Sb, and Bi. In the last few years, these materials
have taken the field of Materials Science by storm since they can outperform and/or complement graphene
properties. Their strongly layer-dependent unique properties range from semiconducting to metallic,
including high carrier mobilities, tunable bandgaps, strong spin-orbit coupling or transparency. However,
the Chemistry of pnictogens is still in its infancy, remaining largely unexplored. This is the niche that
2D-PnictoChem aims to fill. By mastering the interface chemistry, we will develop the assembly of 2Dpnictogens
in complex hybrid heterostructures for the first time. Success will rely on a cross-disciplinary
approach combining both Inorganic- and Organic Chemistry with Solid-state Physics, including: 1)
Synthetizing and exfoliating high quality ultra-thin layer pnictogens, providing reliable access down to
the monolayer limit. 2) Achieving their chemical functionalization via both non-covalent and covalent
approaches in order to tailor at will their properties, decipher reactivity patterns and enable controlled
doping avenues. 3) Developing hybrid architectures through a precise chemical control of the interface,
in order to promote unprecedented access to novel heterostructures. 4) Exploring novel applications
concepts achieving outstanding performances. These are all priorities in the European Union agenda
aimed at securing an affordable, clean energy future by developing more efficient hybrid systems for
batteries, electronic devices or applications in catalysis. The opportunity is unique to reduce Europe’s
dependence on external technology and the PI’s background is ideally suited to tackle these objectives,
counting as well on a multidisciplinary team of international collaborators.
Max ERC Funding
1 499 419 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym 2D-TOPSENSE
Project Tunable optoelectronic devices by strain engineering of 2D semiconductors
Researcher (PI) Andres CASTELLANOS
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Call Details Starting Grant (StG), PE7, ERC-2017-STG
Summary The goal of 2D-TOPSENSE is to exploit the remarkable stretchability of two-dimensional semiconductors to fabricate optoelectronic devices where strain is used as an external knob to tune their properties.
While bulk semiconductors tend to break under strains larger than 1.5%, 2D semiconductors (such as MoS2) can withstand deformations of up to 10-20% before rupture. This large breaking strength promises a great potential of 2D semiconductors as ‘straintronic’ materials, whose properties can be adjusted by applying a deformation to their lattice. In fact, recent theoretical works predicted an interesting physical phenomenon: a tensile strain-induced semiconductor-to-metal transition in 2D semiconductors. By tensioning single-layer MoS2 from 0% up to 10%, its electronic band structure is expected to undergo a continuous transition from a wide direct band-gap of 1.8 eV to a metallic behavior. This unprecedented large strain-tunability will undoubtedly have a strong impact in a wide range of optoelectronic applications such as photodetectors whose cut-off wavelength is tuned by varying the applied strain or atomically thin light modulators.
To date, experimental works on strain engineering have been mostly focused on fundamental studies, demonstrating part of the potential of 2D semiconductors in straintronics, but they have failed to exploit strain engineering to add extra functionalities to optoelectronic devices. In 2D-TOPSENSE I will go beyond the state of the art in straintronics by designing and fabricating optoelectronic devices whose properties and performance can be tuned by means of applying strain. 2D-TOPSENSE will focus on photodetectors with a tunable bandwidth and detectivity, light emitting devices whose emission wavelength can be adjusted, light modulators based on 2D semiconductors such as transition metal dichalcogenides or black phosphorus and solar funnels capable of directing the photogenerated charge carriers towards a specific position.
Summary
The goal of 2D-TOPSENSE is to exploit the remarkable stretchability of two-dimensional semiconductors to fabricate optoelectronic devices where strain is used as an external knob to tune their properties.
While bulk semiconductors tend to break under strains larger than 1.5%, 2D semiconductors (such as MoS2) can withstand deformations of up to 10-20% before rupture. This large breaking strength promises a great potential of 2D semiconductors as ‘straintronic’ materials, whose properties can be adjusted by applying a deformation to their lattice. In fact, recent theoretical works predicted an interesting physical phenomenon: a tensile strain-induced semiconductor-to-metal transition in 2D semiconductors. By tensioning single-layer MoS2 from 0% up to 10%, its electronic band structure is expected to undergo a continuous transition from a wide direct band-gap of 1.8 eV to a metallic behavior. This unprecedented large strain-tunability will undoubtedly have a strong impact in a wide range of optoelectronic applications such as photodetectors whose cut-off wavelength is tuned by varying the applied strain or atomically thin light modulators.
To date, experimental works on strain engineering have been mostly focused on fundamental studies, demonstrating part of the potential of 2D semiconductors in straintronics, but they have failed to exploit strain engineering to add extra functionalities to optoelectronic devices. In 2D-TOPSENSE I will go beyond the state of the art in straintronics by designing and fabricating optoelectronic devices whose properties and performance can be tuned by means of applying strain. 2D-TOPSENSE will focus on photodetectors with a tunable bandwidth and detectivity, light emitting devices whose emission wavelength can be adjusted, light modulators based on 2D semiconductors such as transition metal dichalcogenides or black phosphorus and solar funnels capable of directing the photogenerated charge carriers towards a specific position.
Max ERC Funding
1 930 437 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym 2DNANOPTICA
Project Nano-optics on flatland: from quantum nanotechnology to nano-bio-photonics
Researcher (PI) Pablo Alonso-González
Host Institution (HI) UNIVERSIDAD DE OVIEDO
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary Ubiquitous in nature, light-matter interactions are of fundamental importance in science and all optical technologies. Understanding and controlling them has been a long-pursued objective in modern physics. However, so far, related experiments have relied on traditional optical schemes where, owing to the classical diffraction limit, control of optical fields to length scales below the wavelength of light is prevented. Importantly, this limitation impedes to exploit the extraordinary fundamental and scaling potentials of nanoscience and nanotechnology. A solution to concentrate optical fields into sub-diffracting volumes is the excitation of surface polaritons –coupled excitations of photons and mobile/bound charges in metals/polar materials (plasmons/phonons)-. However, their initial promises have been hindered by either strong optical losses or lack of electrical control in metals, and difficulties to fabricate high optical quality nanostructures in polar materials.
With the advent of two-dimensional (2D) materials and their extraordinary optical properties, during the last 2-3 years the visualization of both low-loss and electrically tunable (active) plasmons in graphene and high optical quality phonons in monolayer and multilayer h-BN nanostructures have been demonstrated in the mid-infrared spectral range, thus introducing a very encouraging arena for scientifically ground-breaking discoveries in nano-optics. Inspired by these extraordinary prospects, this ERC project aims to make use of our knowledge and unique expertise in 2D nanoplasmonics, and the recent advances in nanophononics, to establish a technological platform that, including coherent sources, waveguides, routers, and efficient detectors, permits an unprecedented active control and manipulation (at room temperature) of light and light-matter interactions on the nanoscale, thus laying experimentally the foundations of a 2D nano-optics field.
Summary
Ubiquitous in nature, light-matter interactions are of fundamental importance in science and all optical technologies. Understanding and controlling them has been a long-pursued objective in modern physics. However, so far, related experiments have relied on traditional optical schemes where, owing to the classical diffraction limit, control of optical fields to length scales below the wavelength of light is prevented. Importantly, this limitation impedes to exploit the extraordinary fundamental and scaling potentials of nanoscience and nanotechnology. A solution to concentrate optical fields into sub-diffracting volumes is the excitation of surface polaritons –coupled excitations of photons and mobile/bound charges in metals/polar materials (plasmons/phonons)-. However, their initial promises have been hindered by either strong optical losses or lack of electrical control in metals, and difficulties to fabricate high optical quality nanostructures in polar materials.
With the advent of two-dimensional (2D) materials and their extraordinary optical properties, during the last 2-3 years the visualization of both low-loss and electrically tunable (active) plasmons in graphene and high optical quality phonons in monolayer and multilayer h-BN nanostructures have been demonstrated in the mid-infrared spectral range, thus introducing a very encouraging arena for scientifically ground-breaking discoveries in nano-optics. Inspired by these extraordinary prospects, this ERC project aims to make use of our knowledge and unique expertise in 2D nanoplasmonics, and the recent advances in nanophononics, to establish a technological platform that, including coherent sources, waveguides, routers, and efficient detectors, permits an unprecedented active control and manipulation (at room temperature) of light and light-matter interactions on the nanoscale, thus laying experimentally the foundations of a 2D nano-optics field.
Max ERC Funding
1 459 219 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym 2DTHERMS
Project Design of new thermoelectric devices based on layered and field modulated nanostructures of strongly correlated electron systems
Researcher (PI) Jose Francisco Rivadulla Fernandez
Host Institution (HI) UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Call Details Starting Grant (StG), PE3, ERC-2010-StG_20091028
Summary Design of new thermoelectric devices based on layered and field modulated nanostructures of strongly correlated electron systems
Summary
Design of new thermoelectric devices based on layered and field modulated nanostructures of strongly correlated electron systems
Max ERC Funding
1 427 190 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym 2shRNA
Project 2shRNA branched nanobinders as promising therapeutic tools for combined cancer therapy
Researcher (PI) Modesto Orozco López
Host Institution (HI) FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary This project aims to optimize and validate a promising therapeutic tool for combined cancer therapy, 2shRNA, in an ex vivo model system.
Combined therapies are of great significance nowadays, due to their key role in fighting, for instances, resistance processes during cancer treatment. Nonetheless, the drug combinations approved to date face several problems, such as cooperative toxicity effects, lack of efficiency and poor bioavailability. We have designed and synthesized 2shRNA, a new bifunctional RNA tool that can simultaneously attack two therapeutic targets involved in drug resistance pathways, and that can additionally bind other molecules such as peptide carriers or fluorophores, to improve delivery and efficacy. The 2shRNA nanostructure displayed low toxicity and excellent anti-proliferative properties in resistant HER2+ breast cancer cell lines. The present proposal is aimed at optimizing and validating this novel and promising RNA tool by combining state-of-the-art bioinformatics design and cycles of chemical refinement with biological evaluation in PDx-derived primary cell cultures and biodistribution studies in PDx mouse models. The proposed strategy presents a novel therapeutic approach with great potential to circumvent drug resistance in breast cancer, which is a major health challenge for our society. The ability of our biostable RNA tool to administer two drugs in a single dose could improve the quality of life of the patients, as fewer doses might be needed to stall disease progression.
Summary
This project aims to optimize and validate a promising therapeutic tool for combined cancer therapy, 2shRNA, in an ex vivo model system.
Combined therapies are of great significance nowadays, due to their key role in fighting, for instances, resistance processes during cancer treatment. Nonetheless, the drug combinations approved to date face several problems, such as cooperative toxicity effects, lack of efficiency and poor bioavailability. We have designed and synthesized 2shRNA, a new bifunctional RNA tool that can simultaneously attack two therapeutic targets involved in drug resistance pathways, and that can additionally bind other molecules such as peptide carriers or fluorophores, to improve delivery and efficacy. The 2shRNA nanostructure displayed low toxicity and excellent anti-proliferative properties in resistant HER2+ breast cancer cell lines. The present proposal is aimed at optimizing and validating this novel and promising RNA tool by combining state-of-the-art bioinformatics design and cycles of chemical refinement with biological evaluation in PDx-derived primary cell cultures and biodistribution studies in PDx mouse models. The proposed strategy presents a novel therapeutic approach with great potential to circumvent drug resistance in breast cancer, which is a major health challenge for our society. The ability of our biostable RNA tool to administer two drugs in a single dose could improve the quality of life of the patients, as fewer doses might be needed to stall disease progression.
Max ERC Funding
150 000 €
Duration
Start date: 2019-01-01, End date: 2020-06-30
Project acronym 3D-FIREFLUC
Project Taming the particle transport in magnetized plasmas via perturbative fields
Researcher (PI) Eleonora VIEZZER
Host Institution (HI) UNIVERSIDAD DE SEVILLA
Call Details Starting Grant (StG), PE2, ERC-2018-STG
Summary Wave-particle interactions are ubiquitous in nature and play a fundamental role in astrophysical and fusion plasmas. In solar plasmas, magnetohydrodynamic (MHD) fluctuations are thought to be responsible for the heating of the solar corona and the generation of the solar wind. In magnetically confined fusion (MCF) devices, enhanced particle transport induced by MHD fluctuations can deteriorate the plasma confinement, and also endanger the device integrity. MCF devices are an ideal testbed to verify current models and develop mitigation / protection techniques.
The proposed project paves the way for providing active control techniques to tame the MHD induced particle transport in a fusion plasma. A solid understanding of the interaction between energetic particles and MHD instabilities in the presence of electric fields and plasma currents is required to develop such techniques. I will pursue this goal through innovative diagnosis techniques with unprecedented spatio-temporal resolution. Combined with state-of-the-art hybrid MHD codes, a deep insight into the underlying physics mechanism will be gained. The outcome of this research project will have a major impact for next-step MCF devices as I will provide ground-breaking control techniques for mitigating MHD induced particle transport in magnetized plasmas.
The project consists of 3 research lines which follow a bottom-up approach:
(1) Cutting-edge instrumentation, aiming at the new generation of energetic particle and edge current diagnostics.
(2) Unravel the dynamics of energetic particles, electric fields, edge currents and MHD fluctuations.
(3) From lab to space weather: The developed models will revolutionize our understanding of the observed particle acceleration and transport in the solar corona.
Based on this approach, the project represents a gateway between the fusion, astrophysics and space communities opening new avenues for a common basic understanding.
Summary
Wave-particle interactions are ubiquitous in nature and play a fundamental role in astrophysical and fusion plasmas. In solar plasmas, magnetohydrodynamic (MHD) fluctuations are thought to be responsible for the heating of the solar corona and the generation of the solar wind. In magnetically confined fusion (MCF) devices, enhanced particle transport induced by MHD fluctuations can deteriorate the plasma confinement, and also endanger the device integrity. MCF devices are an ideal testbed to verify current models and develop mitigation / protection techniques.
The proposed project paves the way for providing active control techniques to tame the MHD induced particle transport in a fusion plasma. A solid understanding of the interaction between energetic particles and MHD instabilities in the presence of electric fields and plasma currents is required to develop such techniques. I will pursue this goal through innovative diagnosis techniques with unprecedented spatio-temporal resolution. Combined with state-of-the-art hybrid MHD codes, a deep insight into the underlying physics mechanism will be gained. The outcome of this research project will have a major impact for next-step MCF devices as I will provide ground-breaking control techniques for mitigating MHD induced particle transport in magnetized plasmas.
The project consists of 3 research lines which follow a bottom-up approach:
(1) Cutting-edge instrumentation, aiming at the new generation of energetic particle and edge current diagnostics.
(2) Unravel the dynamics of energetic particles, electric fields, edge currents and MHD fluctuations.
(3) From lab to space weather: The developed models will revolutionize our understanding of the observed particle acceleration and transport in the solar corona.
Based on this approach, the project represents a gateway between the fusion, astrophysics and space communities opening new avenues for a common basic understanding.
Max ERC Funding
1 512 250 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym 3DNANOMECH
Project Three-dimensional molecular resolution mapping of soft matter-liquid interfaces
Researcher (PI) Ricardo Garcia
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), PE4, ERC-2013-ADG
Summary Optical, electron and probe microscopes are enabling tools for discoveries and knowledge generation in nanoscale sicence and technology. High resolution –nanoscale or molecular-, noninvasive and label-free imaging of three-dimensional soft matter-liquid interfaces has not been achieved by any microscopy method.
Force microscopy (AFM) is considered the second most relevant advance in materials science since 1960. Despite its impressive range of applications, the technique has some key limitations. Force microscopy has not three dimensional depth. What lies above or in the subsurface is not readily characterized.
3DNanoMech proposes to design, build and operate a high speed force-based method for the three-dimensional characterization soft matter-liquid interfaces (3D AFM). The microscope will combine a detection method based on force perturbations, adaptive algorithms, high speed piezo actuators and quantitative-oriented multifrequency approaches. The development of the microscope cannot be separated from its applications: imaging the error-free DNA repair and to understand the relationship existing between the nanomechanical properties and the malignancy of cancer cells. Those problems encompass the different spatial –molecular-nano-mesoscopic- and time –milli to seconds- scales of the instrument.
In short, 3DNanoMech aims to image, map and measure with picoNewton, millisecond and angstrom resolution soft matter surfaces and interfaces in liquid. The long-term vision of 3DNanoMech is to replace models or computer animations of bimolecular-liquid interfaces by real time, molecular resolution maps of properties and processes.
Summary
Optical, electron and probe microscopes are enabling tools for discoveries and knowledge generation in nanoscale sicence and technology. High resolution –nanoscale or molecular-, noninvasive and label-free imaging of three-dimensional soft matter-liquid interfaces has not been achieved by any microscopy method.
Force microscopy (AFM) is considered the second most relevant advance in materials science since 1960. Despite its impressive range of applications, the technique has some key limitations. Force microscopy has not three dimensional depth. What lies above or in the subsurface is not readily characterized.
3DNanoMech proposes to design, build and operate a high speed force-based method for the three-dimensional characterization soft matter-liquid interfaces (3D AFM). The microscope will combine a detection method based on force perturbations, adaptive algorithms, high speed piezo actuators and quantitative-oriented multifrequency approaches. The development of the microscope cannot be separated from its applications: imaging the error-free DNA repair and to understand the relationship existing between the nanomechanical properties and the malignancy of cancer cells. Those problems encompass the different spatial –molecular-nano-mesoscopic- and time –milli to seconds- scales of the instrument.
In short, 3DNanoMech aims to image, map and measure with picoNewton, millisecond and angstrom resolution soft matter surfaces and interfaces in liquid. The long-term vision of 3DNanoMech is to replace models or computer animations of bimolecular-liquid interfaces by real time, molecular resolution maps of properties and processes.
Max ERC Funding
2 499 928 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym 4D-GENOME
Project Dynamics of human genome architecture in stable and transient gene expression changes
Researcher (PI) Thomas Graf
Host Institution (HI) FUNDACIO CENTRE DE REGULACIO GENOMICA
Call Details Synergy Grants (SyG), SYG6, ERC-2013-SyG
Summary The classical view of genomes as linear sequences has been replaced by a vision of nuclear organization that is both dynamic and complex, with chromosomes and genes non-randomly positioned in the nucleus. Process compartmentalization and spatial location of genes modulate the transcriptional output of the genomes. However, how the interplay between genome structure and gene regulation is established and maintained is still unclear. The aim of this project is to explore whether the genome 3D structure acts as an information source for modulating transcription in response to external stimuli. With a genuine interdisciplinary team effort, we will study the conformation of the genome at various integrated levels, from the nucleosome fiber to the distribution of chromosomes territories in the nuclear space. We will generate high-resolution 3D models of the spatial organization of the genomes of distinct eukaryotic cell types in interphase to identify differences in the chromatin landscape. We will follow the time course of structural changes in response to cues that affect gene expression either permanently or transiently. We will analyze the changes in genome structure during the stable trans-differentiation of immortalized B cells to macrophages and during the transient hormonal responses of differentiated cells. We plan to establish novel functional strategies, based on targeted and high-throughput reporter assays, to assess the relevance of the spatial environment on gene regulation. Using sophisticated modeling and computational approaches, we will combine high-resolution data from chromosome interactions, super-resolution images and omics information. Our long-term plan is to implement a 3D browser for the comprehensive mapping of chromatin properties and genomic features, to better understand how external signals are integrated at the genomic, epigenetic and structural level to orchestrate changes in gene expression that are cell specific and dynamic.
Summary
The classical view of genomes as linear sequences has been replaced by a vision of nuclear organization that is both dynamic and complex, with chromosomes and genes non-randomly positioned in the nucleus. Process compartmentalization and spatial location of genes modulate the transcriptional output of the genomes. However, how the interplay between genome structure and gene regulation is established and maintained is still unclear. The aim of this project is to explore whether the genome 3D structure acts as an information source for modulating transcription in response to external stimuli. With a genuine interdisciplinary team effort, we will study the conformation of the genome at various integrated levels, from the nucleosome fiber to the distribution of chromosomes territories in the nuclear space. We will generate high-resolution 3D models of the spatial organization of the genomes of distinct eukaryotic cell types in interphase to identify differences in the chromatin landscape. We will follow the time course of structural changes in response to cues that affect gene expression either permanently or transiently. We will analyze the changes in genome structure during the stable trans-differentiation of immortalized B cells to macrophages and during the transient hormonal responses of differentiated cells. We plan to establish novel functional strategies, based on targeted and high-throughput reporter assays, to assess the relevance of the spatial environment on gene regulation. Using sophisticated modeling and computational approaches, we will combine high-resolution data from chromosome interactions, super-resolution images and omics information. Our long-term plan is to implement a 3D browser for the comprehensive mapping of chromatin properties and genomic features, to better understand how external signals are integrated at the genomic, epigenetic and structural level to orchestrate changes in gene expression that are cell specific and dynamic.
Max ERC Funding
12 272 645 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
