Project acronym 1D-Engine
Project 1D-electrons coupled to dissipation: a novel approach for understanding and engineering superconducting materials and devices
Researcher (PI) Adrian KANTIAN
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary Correlated electrons are at the forefront of condensed matter theory. Interacting quasi-1D electrons have seen vast progress in analytical and numerical theory, and thus in fundamental understanding and quantitative prediction. Yet, in the 1D limit fluctuations preclude important technological use, particularly of superconductors. In contrast, high-Tc superconductors in 2D/3D are not precluded by fluctuations, but lack a fundamental theory, making prediction and engineering of their properties, a major goal in physics, very difficult. This project aims to combine the advantages of both areas by making major progress in the theory of quasi-1D electrons coupled to an electron bath, in part building on recent breakthroughs (with the PIs extensive involvement) in simulating 1D and 2D electrons with parallelized density matrix renormalization group (pDMRG) numerics. Such theory will fundamentally advance the study of open electron systems, and show how to use 1D materials as elements of new superconducting (SC) devices and materials: 1) It will enable a new state of matter, 1D electrons with true SC order. Fluctuations from the electronic liquid, such as graphene, could also enable nanoscale wires to appear SC at high temperatures. 2) A new approach for the deliberate engineering of a high-Tc superconductor. In 1D, how electrons pair by repulsive interactions is understood and can be predicted. Stabilization by reservoir - formed by a parallel array of many such 1D systems - offers a superconductor for which all factors setting Tc are known and can be optimized. 3) Many existing superconductors with repulsive electron pairing, all presently not understood, can be cast as 1D electrons coupled to a bath. Developing chain-DMFT theory based on pDMRG will allow these materials SC properties to be simulated and understood for the first time. 4) The insights gained will be translated to 2D superconductors to study how they could be enhanced by contact with electronic liquids.
Summary
Correlated electrons are at the forefront of condensed matter theory. Interacting quasi-1D electrons have seen vast progress in analytical and numerical theory, and thus in fundamental understanding and quantitative prediction. Yet, in the 1D limit fluctuations preclude important technological use, particularly of superconductors. In contrast, high-Tc superconductors in 2D/3D are not precluded by fluctuations, but lack a fundamental theory, making prediction and engineering of their properties, a major goal in physics, very difficult. This project aims to combine the advantages of both areas by making major progress in the theory of quasi-1D electrons coupled to an electron bath, in part building on recent breakthroughs (with the PIs extensive involvement) in simulating 1D and 2D electrons with parallelized density matrix renormalization group (pDMRG) numerics. Such theory will fundamentally advance the study of open electron systems, and show how to use 1D materials as elements of new superconducting (SC) devices and materials: 1) It will enable a new state of matter, 1D electrons with true SC order. Fluctuations from the electronic liquid, such as graphene, could also enable nanoscale wires to appear SC at high temperatures. 2) A new approach for the deliberate engineering of a high-Tc superconductor. In 1D, how electrons pair by repulsive interactions is understood and can be predicted. Stabilization by reservoir - formed by a parallel array of many such 1D systems - offers a superconductor for which all factors setting Tc are known and can be optimized. 3) Many existing superconductors with repulsive electron pairing, all presently not understood, can be cast as 1D electrons coupled to a bath. Developing chain-DMFT theory based on pDMRG will allow these materials SC properties to be simulated and understood for the first time. 4) The insights gained will be translated to 2D superconductors to study how they could be enhanced by contact with electronic liquids.
Max ERC Funding
1 491 013 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
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 DEINVESTIGACIONES 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 2MoveMate4Melanoma
Project A treatment for BRAF inhibitor resistant melanoma
Researcher (PI) René BERNARDS
Host Institution (HI) STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Call Details Proof of Concept (PoC), PC1, ERC-2015-PoC
Summary Some 50% of human melanoma tumors have activating mutations in the BRAF gene. BRAF inhibitor drugs given either alone or in combination with MEK inhibitors have improved progression-free and overall survival in patients with BRAF mutant metastatic melanoma. However, drug resistance invariably limits the duration of clinical benefit of such treatments and is almost always associated with re-activation of signaling through the MAP kinase pathway in the presence of drug due to secondary mutations in the pathway. This highlights the urgent need to develop strategies to treat melanomas that have developed resistance to BRAF and/or MEK inhibitors.
As part of an ERC advanced grant, my laboratory has shown that BRAF inhibitor withdrawal in melanomas that have developed resistance to BRAF inhibitors leads to a transient growth arrest that is the consequence of temporary hyperactivation of signaling through the MAP kinase pathway, explaining the so called “drug holiday effect”. We have also found that subsequent treatment of such BRAF inhibitor resistant melanomas with Histone DeACetylase inhibitor drugs (HDACi) leads to persistent hyperactivation of MAP kinase signaling, causing both chronic proliferation arrest and cell death, ultimately leading to complete regression of BRAF-inhibitor resistant melanomas in mice.
We propose here to perform a proof of concept study in at least 10 evaluable melanoma patients that, after proven initial tumor response, have developed resistance to BRAF inhibitors to validate that subsequent treatment of such patients with an HDACi drug will result in durable responses. Translational studies on tumor biopsies taken before, during and after HDACi treatment will be performed to study the cellular effects of HDACi treatment. Our goal is to provide initial proof of concept in patients for use of this sequential BRAFi-HDACi therapy as the treatment of choice for the some 40,000 BRAF mutant melanomas that are diagnosed in the EU annually.
Summary
Some 50% of human melanoma tumors have activating mutations in the BRAF gene. BRAF inhibitor drugs given either alone or in combination with MEK inhibitors have improved progression-free and overall survival in patients with BRAF mutant metastatic melanoma. However, drug resistance invariably limits the duration of clinical benefit of such treatments and is almost always associated with re-activation of signaling through the MAP kinase pathway in the presence of drug due to secondary mutations in the pathway. This highlights the urgent need to develop strategies to treat melanomas that have developed resistance to BRAF and/or MEK inhibitors.
As part of an ERC advanced grant, my laboratory has shown that BRAF inhibitor withdrawal in melanomas that have developed resistance to BRAF inhibitors leads to a transient growth arrest that is the consequence of temporary hyperactivation of signaling through the MAP kinase pathway, explaining the so called “drug holiday effect”. We have also found that subsequent treatment of such BRAF inhibitor resistant melanomas with Histone DeACetylase inhibitor drugs (HDACi) leads to persistent hyperactivation of MAP kinase signaling, causing both chronic proliferation arrest and cell death, ultimately leading to complete regression of BRAF-inhibitor resistant melanomas in mice.
We propose here to perform a proof of concept study in at least 10 evaluable melanoma patients that, after proven initial tumor response, have developed resistance to BRAF inhibitors to validate that subsequent treatment of such patients with an HDACi drug will result in durable responses. Translational studies on tumor biopsies taken before, during and after HDACi treatment will be performed to study the cellular effects of HDACi treatment. Our goal is to provide initial proof of concept in patients for use of this sequential BRAFi-HDACi therapy as the treatment of choice for the some 40,000 BRAF mutant melanomas that are diagnosed in the EU annually.
Max ERC Funding
149 750 €
Duration
Start date: 2016-05-01, End date: 2017-10-31
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-FABRIC
Project 3D Flow Analysis in Bijels Reconfigured for Interfacial Catalysis
Researcher (PI) Martin F. HAASE
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Starting Grant (StG), PE8, ERC-2018-STG
Summary The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Summary
The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Max ERC Funding
1 905 000 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
