Project acronym 1toStopVax
Project RNA virus attenuation by altering mutational robustness
Researcher (PI) Marco VIGNUZZI
Host Institution (HI) INSTITUT PASTEUR
Call Details Proof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC
Summary RNA viruses have extreme mutation frequencies. When a RNA virus replicates, nucleotide mutations are generated resulting in a population of variants. This genetic diversity creates a cloud of mutations that are potentially beneficial to viral survival, but the majority of mutations are detrimental to the virus. By increasing the mutation rate of a RNA virus, viral fitness is reduced because it generates more errors, and attenuates the virus during in vivo infection. Another feature that affects RNA virus fitness is mutational robustness. Mutational robustness is the ability to buffer the negative effects of mutation.
The attenuation of RNA viruses for vaccine production faces problems of genetic instability and reversion to a pathogenic phenotype. The conventional method for attenuation is mostly empirical and specific to the particular RNA virus species.
Hence, it cannot be universally applied to a variety of virus types. We've developed a non-empirical, rational means of attenuating RNA viruses, targeting mutational robustness as modifiable trait.
We demonstrate that mutational robustness of RNA viruses can be modified without changing a virus' physical and biological properties for vaccine production; yet the virus is attenuated as it becomes victim of its naturally high mutation rate. Specifically, the genome of RNA viruses are modified so that a larger proportion of mutations become lethal Stop mutations. Our technology places the virus one step away from these Stop mutations (1-to-Stop). We succeeded in attenuating two RNA viruses from very different viral families, confirming the broad applicability of this approach. These viruses were attenuated in vivo, generated high levels of neutralizing antibody and protected mice from lethal challenge infection.
The proposal now seeks to complete proof of concept studies and develop commercialization strategies to scale up this new technology to preclinical testing with industrial partners.
Summary
RNA viruses have extreme mutation frequencies. When a RNA virus replicates, nucleotide mutations are generated resulting in a population of variants. This genetic diversity creates a cloud of mutations that are potentially beneficial to viral survival, but the majority of mutations are detrimental to the virus. By increasing the mutation rate of a RNA virus, viral fitness is reduced because it generates more errors, and attenuates the virus during in vivo infection. Another feature that affects RNA virus fitness is mutational robustness. Mutational robustness is the ability to buffer the negative effects of mutation.
The attenuation of RNA viruses for vaccine production faces problems of genetic instability and reversion to a pathogenic phenotype. The conventional method for attenuation is mostly empirical and specific to the particular RNA virus species.
Hence, it cannot be universally applied to a variety of virus types. We've developed a non-empirical, rational means of attenuating RNA viruses, targeting mutational robustness as modifiable trait.
We demonstrate that mutational robustness of RNA viruses can be modified without changing a virus' physical and biological properties for vaccine production; yet the virus is attenuated as it becomes victim of its naturally high mutation rate. Specifically, the genome of RNA viruses are modified so that a larger proportion of mutations become lethal Stop mutations. Our technology places the virus one step away from these Stop mutations (1-to-Stop). We succeeded in attenuating two RNA viruses from very different viral families, confirming the broad applicability of this approach. These viruses were attenuated in vivo, generated high levels of neutralizing antibody and protected mice from lethal challenge infection.
The proposal now seeks to complete proof of concept studies and develop commercialization strategies to scale up this new technology to preclinical testing with industrial partners.
Max ERC Funding
150 000 €
Duration
Start date: 2016-09-01, End date: 2018-02-28
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 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-Ink
Project Ink-Jet printed supercapacitors based on 2D nanomaterials.
Researcher (PI) Valeria Nicolosi
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Proof of Concept (PoC), PC1, ERC-2014-PoC
Summary This proposal will determine the technical-economic viability of scaling-up ultra-thin, ink-jet printed films based on liquid-phase exfoliated single atomic layers of a range of nanomaterials. The PI has developed methods to produce in liquid nanosheets of a range of layered materials such as graphene, transition metal oxides, etc. These 2D-materials have immediate and far-reaching potential in several high-impact technological applications such as microelectronics, composites and energy harvesting and storage. 2DNanoCaps (ERC ref: 278516) has demonstrated that lab-scale ultra-thin graphene-based supercapacitor electrodes result in unusually high-power and extremely long device life-time (100% capacitance retention for 5000 charge-discharge cycles at the high power scan rate of 10,000 mV/s). This performance is an order of magnitude better than similar systems produced with conventional methods which cause materials restacking and aggregation. A following ERC PoC grant (2D-USD, Project-Number 620189) is currently focussed on up-scaling the production of thin-films deposition methods based on ultrasonic spray for the production of large-area electrodes for supercapacitors applications. In this proposal we want to explore the new concept of manufacturing conductive, robust, thin, easily assembled electrode and solid electrolytes to realize highly-flexible and all-solid-state supercapacitors by ink-jet printing. This opportunity is particularly relevant to the electronics and portable-device industry and offers the possibility to solve flammability issues, maintaining light weight, flexibility, transparency and portability. In order to do so it will be imperative to develop ink-jet printing methods and techniques. We believe our combination of unique materials and cost-effective, robust and production-scalable process of ultra- thin ink-jet printing will enable us to compete for significant global market opportunities in the energy-storage space.
Summary
This proposal will determine the technical-economic viability of scaling-up ultra-thin, ink-jet printed films based on liquid-phase exfoliated single atomic layers of a range of nanomaterials. The PI has developed methods to produce in liquid nanosheets of a range of layered materials such as graphene, transition metal oxides, etc. These 2D-materials have immediate and far-reaching potential in several high-impact technological applications such as microelectronics, composites and energy harvesting and storage. 2DNanoCaps (ERC ref: 278516) has demonstrated that lab-scale ultra-thin graphene-based supercapacitor electrodes result in unusually high-power and extremely long device life-time (100% capacitance retention for 5000 charge-discharge cycles at the high power scan rate of 10,000 mV/s). This performance is an order of magnitude better than similar systems produced with conventional methods which cause materials restacking and aggregation. A following ERC PoC grant (2D-USD, Project-Number 620189) is currently focussed on up-scaling the production of thin-films deposition methods based on ultrasonic spray for the production of large-area electrodes for supercapacitors applications. In this proposal we want to explore the new concept of manufacturing conductive, robust, thin, easily assembled electrode and solid electrolytes to realize highly-flexible and all-solid-state supercapacitors by ink-jet printing. This opportunity is particularly relevant to the electronics and portable-device industry and offers the possibility to solve flammability issues, maintaining light weight, flexibility, transparency and portability. In order to do so it will be imperative to develop ink-jet printing methods and techniques. We believe our combination of unique materials and cost-effective, robust and production-scalable process of ultra- thin ink-jet printing will enable us to compete for significant global market opportunities in the energy-storage space.
Max ERC Funding
149 774 €
Duration
Start date: 2015-04-01, End date: 2016-09-30
Project acronym 2D-USD
Project Ultrasonic Spray Deposition: Enabling new 2D based technologies
Researcher (PI) Valeria NICOLOSI
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary This proposal will determine the technical and economic viability of scaling up ultra-thin film deposition processes for exfoliated single atomic layers.
The PI has developed methods to produce exfoliated nanosheets from a range of layered materials such as graphene, transition metal chalcogenides and transition metal oxides. These 2D materials have immediate and far-reaching potential in several high-impact technological applications such as microelectronics, composites and energy harvesting and storage.
2DNanoCaps (ERC ref: 278516) has already demonstrated that lab-scale ultra-thin graphene-based supercapacitor electrodes for energy storage result in unusually high power performance and extremely long device life-time (100% capacitance retention for 5000 charge-discharge cycles at the high power scan rate of 10,000 mV/s). This performance is remarkable- an order of magnitude better than similar systems produced with more conventional methods, which cause materials restacking and aggregation. 2D nanosheets also offer the chance of exploring the unique possibility of manufacturing conductive, robust, thin, easily assembled electrode and solid electrolytes to realize highly flexible and all-solid-state supercapacitors. This opportunity is particularly relevant from the industrial point of view especially in relation to the flammability issues of the electrolytes used for commercial energy storage devices at present.
In order to develop and exploit any of the applications listed above, it will be imperative to develop deposition methods and techniques capable of obtaining industrial-scale “sheet-like” coverage, where flake re-aggregation is avoided.
We believe our combination of unique material properties and cost effective, robust and production-scalable process of ultra-thin deposition will enable us to compete for significant global market opportunities in the energy-storage space
Summary
This proposal will determine the technical and economic viability of scaling up ultra-thin film deposition processes for exfoliated single atomic layers.
The PI has developed methods to produce exfoliated nanosheets from a range of layered materials such as graphene, transition metal chalcogenides and transition metal oxides. These 2D materials have immediate and far-reaching potential in several high-impact technological applications such as microelectronics, composites and energy harvesting and storage.
2DNanoCaps (ERC ref: 278516) has already demonstrated that lab-scale ultra-thin graphene-based supercapacitor electrodes for energy storage result in unusually high power performance and extremely long device life-time (100% capacitance retention for 5000 charge-discharge cycles at the high power scan rate of 10,000 mV/s). This performance is remarkable- an order of magnitude better than similar systems produced with more conventional methods, which cause materials restacking and aggregation. 2D nanosheets also offer the chance of exploring the unique possibility of manufacturing conductive, robust, thin, easily assembled electrode and solid electrolytes to realize highly flexible and all-solid-state supercapacitors. This opportunity is particularly relevant from the industrial point of view especially in relation to the flammability issues of the electrolytes used for commercial energy storage devices at present.
In order to develop and exploit any of the applications listed above, it will be imperative to develop deposition methods and techniques capable of obtaining industrial-scale “sheet-like” coverage, where flake re-aggregation is avoided.
We believe our combination of unique material properties and cost effective, robust and production-scalable process of ultra-thin deposition will enable us to compete for significant global market opportunities in the energy-storage space
Max ERC Funding
148 021 €
Duration
Start date: 2014-01-01, End date: 2014-12-31
Project acronym 2DIR SPECTROMETER
Project A step-change in sensitivity for two dimensional laser infrared spectroscopy
Researcher (PI) Jasper VAN THOR
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary "Here, we propose a novel design for a significantly improved detector for the emerging field of coherent two-dimension infrared (2DIR) spectroscopy, which is an optical analog of Nuclear Magnetic Resonance spectroscopy (NMR). 2DIR is a cutting edge technique which is rapidly growing and has applications in subjects as diverse as energy sciences, biophysics, biomedical research and physical chemistry. Currently, the single most important technical problem that is generally agreed to limit applications of the methodology is the sensitivity with which the signals are measured. Having worked on multiple stabilisation techniques during the ERC funded research it was realised that a straightforward design alteration of the infrared detector will improve the sensitivity very significantly, theoretically by more than one order of magnitude. Here, the technical principles are explained, and a plan for commercialising the instrument in collaboration with the current market leader - Infrared System Development Corp. (ISDC) -. We apply for funding to develop the prototype."
Summary
"Here, we propose a novel design for a significantly improved detector for the emerging field of coherent two-dimension infrared (2DIR) spectroscopy, which is an optical analog of Nuclear Magnetic Resonance spectroscopy (NMR). 2DIR is a cutting edge technique which is rapidly growing and has applications in subjects as diverse as energy sciences, biophysics, biomedical research and physical chemistry. Currently, the single most important technical problem that is generally agreed to limit applications of the methodology is the sensitivity with which the signals are measured. Having worked on multiple stabilisation techniques during the ERC funded research it was realised that a straightforward design alteration of the infrared detector will improve the sensitivity very significantly, theoretically by more than one order of magnitude. Here, the technical principles are explained, and a plan for commercialising the instrument in collaboration with the current market leader - Infrared System Development Corp. (ISDC) -. We apply for funding to develop the prototype."
Max ERC Funding
149 999 €
Duration
Start date: 2013-11-01, End date: 2014-10-31
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 Cer-Met
Project 3D Thin-Walled Ceramic and Ceramic-Metal Components using Electrolytic Plasma Processing
Researcher (PI) Allan MATTHEWS
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary This proposal relates to the Proof of Concept stage investigation of exciting new findings in the ERC Advanced Grant ‘IMPUNEP’ project relating to the study and use of plasma-based processes. These findings offer significant advantages for the creation of complex 3D ceramic and ceramic-metal products at relatively low cost in an environmentally friendly manner. The potential applications of this new technology are very wide-ranging, and include the creation of new products as diverse as healthcare devices, MEMS and aero/automotive parts. Before we properly and fully identify the most promising applications, we need to investigate key aspects of the performance of materials created by this new method. This aspect wasn’t envisaged in the original proposal and involves research into the mechanical properties (especially the strength and elastic modulus) of these 3D parts and their response to deformation and dynamic displacements, as well as their physical (including electrical) properties. These components will be highly resistant to attack by aggressive (e.g. acidic) media as well as highly tolerant to both low (cryogenic) and high (combustion) temperatures. The expected applications opened up by this new method to produce ceramic and ceramic-metal components of complex shape are extensive. Hence the need for this Proof of Concept study, which will focus on validating the process for 3D ceramic-metal and ceramic parts and evaluating the mechanical, chemical, electrical and physical attributes of the 3D shapes, and will explore their potential applications in this pre-demonstration phase.
Summary
This proposal relates to the Proof of Concept stage investigation of exciting new findings in the ERC Advanced Grant ‘IMPUNEP’ project relating to the study and use of plasma-based processes. These findings offer significant advantages for the creation of complex 3D ceramic and ceramic-metal products at relatively low cost in an environmentally friendly manner. The potential applications of this new technology are very wide-ranging, and include the creation of new products as diverse as healthcare devices, MEMS and aero/automotive parts. Before we properly and fully identify the most promising applications, we need to investigate key aspects of the performance of materials created by this new method. This aspect wasn’t envisaged in the original proposal and involves research into the mechanical properties (especially the strength and elastic modulus) of these 3D parts and their response to deformation and dynamic displacements, as well as their physical (including electrical) properties. These components will be highly resistant to attack by aggressive (e.g. acidic) media as well as highly tolerant to both low (cryogenic) and high (combustion) temperatures. The expected applications opened up by this new method to produce ceramic and ceramic-metal components of complex shape are extensive. Hence the need for this Proof of Concept study, which will focus on validating the process for 3D ceramic-metal and ceramic parts and evaluating the mechanical, chemical, electrical and physical attributes of the 3D shapes, and will explore their potential applications in this pre-demonstration phase.
Max ERC Funding
149 500 €
Duration
Start date: 2019-01-01, End date: 2020-03-31
Project acronym 3D-COUNT
Project 3D-Integrated single photon detector
Researcher (PI) Fabio SCIARRINO
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Call Details Proof of Concept (PoC), PC1, ERC-2015-PoC
Summary Photonics, in recognition of its strategic significance and pervasiveness throughout many industrial sectors, has been identified as one of the Key Enabling Technologies for Europe. Photonics in combination with quantum information science has great potential to facilitate, transform and innovate future technologies for the better. The Proof of Concept (PoC) project intends to contribute to this by developing and testing a communication platform prototype, comprised of single photon detectors, which are efficiently coupled to single mode fibers using an innovative laser written device. This enables the integration of single photon detectors on innovative glass waveguides. These glass integrated photonic circuits offer excellent specifics for on-chip quantum optics implementations in terms of scattering losses, offering flexibility of the waveguide geometry and ensuring high coupling efficiency with optical fibers.
The device developed and tested in the PoC, directly addresses a market need for an integrated and efficient on-chip communication systems. Current available systems have limitations involving high costs, complex production, and inefficient coupling of detectors to optical fibers. The proposed platform will offer 1.) a simplified production process, 2.) high optical fiber coupling efficiency 3.) improved performance levels, 4.) high cost efficiency, and 5.) compactness. Such systems can be applied in a wide range of communication and non-communication applications, such as free-space optical communication, quantum communication, quantum cryptography, DNA sequencing, single molecule detection and material analysis. Moreover, the future commercialisation of quantum computing is expected to create a vast demand for these communication systems.
In addition to the technology PoC, the project carries out IPR strategy considerations through patenting actions, determines the market potential, seeks market feedback, and plans for post-PoC commercialisation paths.
Summary
Photonics, in recognition of its strategic significance and pervasiveness throughout many industrial sectors, has been identified as one of the Key Enabling Technologies for Europe. Photonics in combination with quantum information science has great potential to facilitate, transform and innovate future technologies for the better. The Proof of Concept (PoC) project intends to contribute to this by developing and testing a communication platform prototype, comprised of single photon detectors, which are efficiently coupled to single mode fibers using an innovative laser written device. This enables the integration of single photon detectors on innovative glass waveguides. These glass integrated photonic circuits offer excellent specifics for on-chip quantum optics implementations in terms of scattering losses, offering flexibility of the waveguide geometry and ensuring high coupling efficiency with optical fibers.
The device developed and tested in the PoC, directly addresses a market need for an integrated and efficient on-chip communication systems. Current available systems have limitations involving high costs, complex production, and inefficient coupling of detectors to optical fibers. The proposed platform will offer 1.) a simplified production process, 2.) high optical fiber coupling efficiency 3.) improved performance levels, 4.) high cost efficiency, and 5.) compactness. Such systems can be applied in a wide range of communication and non-communication applications, such as free-space optical communication, quantum communication, quantum cryptography, DNA sequencing, single molecule detection and material analysis. Moreover, the future commercialisation of quantum computing is expected to create a vast demand for these communication systems.
In addition to the technology PoC, the project carries out IPR strategy considerations through patenting actions, determines the market potential, seeks market feedback, and plans for post-PoC commercialisation paths.
Max ERC Funding
150 000 €
Duration
Start date: 2016-02-01, End date: 2017-07-31
