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 20SComplexity
Project An integrative approach to uncover the multilevel regulation of 20S proteasome degradation
Researcher (PI) Michal Sharon
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Starting Grant (StG), LS1, ERC-2014-STG
Summary For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route.
To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation:
Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome.
Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function.
Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach.
Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.
Summary
For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route.
To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation:
Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome.
Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function.
Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach.
Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym 20SInhibitor
Project Selective 20S proteasome inhibition for multiple myeloma therapy
Researcher (PI) Michal SHARON
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary Multiple myeloma (MM) is a cancer of plasma cells, that is incurable, and the second most common form of blood cancer. Proteasome inhibitors (PIs) are considered a mainstay in the treatment of MM and mantle cell lymphoma (MCL). Current drugs, based on PIs however, target the chymotrypsin-like activity of the 20S proteasome, and inhibit the activities of both the 20S and 26S proteasomes. Thus, it is possible that selective drug intervention specifically inhibiting only the 20S proteasomes will reduce toxicity, and minimize the deleterious side effects of the current therapeutic regimens.
Our preliminary work revealed a family of 20S proteasome inhibitors, which we termed Catalytic Core Regulators (CCRs) that selectively target the 20S proteasome rather than the 26S complex. Based on sequence motif and structural elements of the CCRs we have designed an artificial protein that is capable of inhibiting the 20S proteasome. We anticipate that these findings will lead to the design of synthetic proteins, peptides or peptidomimetic compounds targeting cancer cells more specifically. This specificity will pose the compounds in an attractive light for using them in various therapeutic applications.
What is exciting from the commercialization perspective, is that pharmaceutical research has switched to revisit the use of peptides as therapeutics. Pharmaceutical companies have seen the development of peptides as a promising direction to lower their risk position. Overall, peptide therapeutics have a 20% chance of receiving regulatory approval, a probability that is 50% higher than that for the approval of small molecules, which form the basis of so called traditional drugs.
In the project, we will carry out actions, which will equip us with the sufficient IP protection strategy, business strategy, industry networks and initial contacts for taking the innovation out from the laboratory to next phase in developing therapy first for MM and MCL later on.
Summary
Multiple myeloma (MM) is a cancer of plasma cells, that is incurable, and the second most common form of blood cancer. Proteasome inhibitors (PIs) are considered a mainstay in the treatment of MM and mantle cell lymphoma (MCL). Current drugs, based on PIs however, target the chymotrypsin-like activity of the 20S proteasome, and inhibit the activities of both the 20S and 26S proteasomes. Thus, it is possible that selective drug intervention specifically inhibiting only the 20S proteasomes will reduce toxicity, and minimize the deleterious side effects of the current therapeutic regimens.
Our preliminary work revealed a family of 20S proteasome inhibitors, which we termed Catalytic Core Regulators (CCRs) that selectively target the 20S proteasome rather than the 26S complex. Based on sequence motif and structural elements of the CCRs we have designed an artificial protein that is capable of inhibiting the 20S proteasome. We anticipate that these findings will lead to the design of synthetic proteins, peptides or peptidomimetic compounds targeting cancer cells more specifically. This specificity will pose the compounds in an attractive light for using them in various therapeutic applications.
What is exciting from the commercialization perspective, is that pharmaceutical research has switched to revisit the use of peptides as therapeutics. Pharmaceutical companies have seen the development of peptides as a promising direction to lower their risk position. Overall, peptide therapeutics have a 20% chance of receiving regulatory approval, a probability that is 50% higher than that for the approval of small molecules, which form the basis of so called traditional drugs.
In the project, we will carry out actions, which will equip us with the sufficient IP protection strategy, business strategy, industry networks and initial contacts for taking the innovation out from the laboratory to next phase in developing therapy first for MM and MCL later on.
Max ERC Funding
150 000 €
Duration
Start date: 2019-04-01, End date: 2020-09-30
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 2DNanoSpec
Project Nanoscale Vibrational Spectroscopy of Sensitive 2D Molecular Materials
Researcher (PI) Renato ZENOBI
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE4, ERC-2016-ADG
Summary I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Summary
I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Max ERC Funding
2 311 696 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
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
