Project acronym BTVI
Project First Biodegradable Biocatalytic VascularTherapeutic Implants
Researcher (PI) Alexander Zelikin
Host Institution (HI) AARHUS UNIVERSITET
Call Details Consolidator Grant (CoG), PE8, ERC-2013-CoG
Summary "We aim to perform academic development of a novel biomedical opportunity: localized synthesis of drugs within biocatalytic therapeutic vascular implants (BVI) for site-specific drug delivery to target organs and tissues. Primary envisioned targets for therapeutic intervention using BVI are atherosclerosis, viral hepatitis, and hepatocellular carcinoma: three of the most prevalent and debilitating conditions which affect hundreds of millions worldwide and which continue to increase in their importance in the era of increasingly aging population. For hepatic applications, we aim to develop drug eluting beads which are equipped with tools of enzyme-prodrug therapy (EPT) and are administered to the liver via trans-arterial catheter embolization. Therein, the beads perform localized synthesis of drugs and imaging reagents for anticancer combination therapy and theranostics, antiviral and anti-inflammatory agents for the treatment of hepatitis. Further, we conceive vascular therapeutic inserts (VTI) as a novel type of implantable biomaterials for treatment of atherosclerosis and re-endothelialization of vascular stents and grafts. Using EPT, inserts will tame “the guardian of cardiovascular grafts”, nitric oxide, for which localized, site specific synthesis and delivery spell success of therapeutic intervention and/or aided tissue regeneration. This proposal is positioned on the forefront of biomedical engineering and its success requires excellence in polymer chemistry, materials design, medicinal chemistry, and translational medicine. Each part of this proposal - design of novel types of vascular implants, engineering novel biomaterials, developing innovative fabrication and characterization techniques – is of high value for fundamental biomedical sciences. The project is target-oriented and once successful, will be of highest practical value and contribute to increased quality of life of millions of people worldwide."
Summary
"We aim to perform academic development of a novel biomedical opportunity: localized synthesis of drugs within biocatalytic therapeutic vascular implants (BVI) for site-specific drug delivery to target organs and tissues. Primary envisioned targets for therapeutic intervention using BVI are atherosclerosis, viral hepatitis, and hepatocellular carcinoma: three of the most prevalent and debilitating conditions which affect hundreds of millions worldwide and which continue to increase in their importance in the era of increasingly aging population. For hepatic applications, we aim to develop drug eluting beads which are equipped with tools of enzyme-prodrug therapy (EPT) and are administered to the liver via trans-arterial catheter embolization. Therein, the beads perform localized synthesis of drugs and imaging reagents for anticancer combination therapy and theranostics, antiviral and anti-inflammatory agents for the treatment of hepatitis. Further, we conceive vascular therapeutic inserts (VTI) as a novel type of implantable biomaterials for treatment of atherosclerosis and re-endothelialization of vascular stents and grafts. Using EPT, inserts will tame “the guardian of cardiovascular grafts”, nitric oxide, for which localized, site specific synthesis and delivery spell success of therapeutic intervention and/or aided tissue regeneration. This proposal is positioned on the forefront of biomedical engineering and its success requires excellence in polymer chemistry, materials design, medicinal chemistry, and translational medicine. Each part of this proposal - design of novel types of vascular implants, engineering novel biomaterials, developing innovative fabrication and characterization techniques – is of high value for fundamental biomedical sciences. The project is target-oriented and once successful, will be of highest practical value and contribute to increased quality of life of millions of people worldwide."
Max ERC Funding
1 996 126 €
Duration
Start date: 2014-04-01, End date: 2019-09-30
Project acronym FRECOM
Project Nonlinear-Distortion Free Communication over the Optical Fibre Channel
Researcher (PI) Darko ZIBAR
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Consolidator Grant (CoG), PE7, ERC-2017-COG
Summary Motivation
The enormous growth in the Internet of Things and server farms for cloud services has increased the strain on the optical communication infrastructure. By 2025, our society will require data rates that are physically impossible to implement using current state-of-the-art optical communication technologies. This is because fibre-optic communication systems are rapidly approaching their fundamental capacity limits imposed by the Kerr nonlinearity of the fibre. Nonlinear distortion limits the ability to transport and detect the information stream. This is a very critical problem for increasing the data rates of any optical fibre communication system.
Proposed research
The only physical quantities not affected by the nonlinearity are eigenvalues, associated with the optical fibre propagation equation. Eigenvalues are thereby ideal candidates for information transport. The concept of eigenvalues is derived under the assumption that the fibre is lossless and that there is no noise in the system which is not strictly correct. Therefore, novel methodologies and concepts for the design of a noise mitigating receiver and a noise robust transmitter are needed to reap the full benefits of optical communication systems employing eigenvalues. This proposal will develop such strategies. This will be achieved by combining, for the first time, the fields of nonlinear optics, optical communication and nonlinear digital signal processing. The results from the project will be verified experimentally, and will form the basis for a new generation of commercial optical communication systems.
Preliminary results
Our proof-of-concept results demonstrate, for the first time, that noise can be handled by employing novel receiver concepts. An order of magnitude improvement compared to the state-of-the-art is demonstrated.
Environment
The research will be carried out in close cooperation with leading groups at Stanford University and Technical University of Munich.
Summary
Motivation
The enormous growth in the Internet of Things and server farms for cloud services has increased the strain on the optical communication infrastructure. By 2025, our society will require data rates that are physically impossible to implement using current state-of-the-art optical communication technologies. This is because fibre-optic communication systems are rapidly approaching their fundamental capacity limits imposed by the Kerr nonlinearity of the fibre. Nonlinear distortion limits the ability to transport and detect the information stream. This is a very critical problem for increasing the data rates of any optical fibre communication system.
Proposed research
The only physical quantities not affected by the nonlinearity are eigenvalues, associated with the optical fibre propagation equation. Eigenvalues are thereby ideal candidates for information transport. The concept of eigenvalues is derived under the assumption that the fibre is lossless and that there is no noise in the system which is not strictly correct. Therefore, novel methodologies and concepts for the design of a noise mitigating receiver and a noise robust transmitter are needed to reap the full benefits of optical communication systems employing eigenvalues. This proposal will develop such strategies. This will be achieved by combining, for the first time, the fields of nonlinear optics, optical communication and nonlinear digital signal processing. The results from the project will be verified experimentally, and will form the basis for a new generation of commercial optical communication systems.
Preliminary results
Our proof-of-concept results demonstrate, for the first time, that noise can be handled by employing novel receiver concepts. An order of magnitude improvement compared to the state-of-the-art is demonstrated.
Environment
The research will be carried out in close cooperation with leading groups at Stanford University and Technical University of Munich.
Max ERC Funding
2 000 000 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym M4D
Project Metal Microstructures in Four Dimensions
Researcher (PI) Dorte JUUL JENSEN
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Advanced Grant (AdG), PE8, ERC-2017-ADG
Summary The goals are:
1) to develop a universal laboratory-based 4D X-ray microscope with potentials in the broad field of materials science and beyond;
2) to advance metal research by quantifying local microstructural variations using the new 4D tool and by including the effects hereof in the understanding and modelling of industrially relevant metals.
Today, high resolution 4D (x,y,z,time) crystallographic characterization of materials is possible only at large international facilities. This is a serious limitation preventing the common use. The new technique will allow such 4D characterization to be carried out at home laboratories, thereby wide spreading this powerful tool.
Whereas current metal research mainly focuses on average properties, local microstructural variations are present in all metals on several length scales, and are often of critical importance for the properties and performance of the metal. In this project, the new technique will be the cornerstone in studies of such variations in three types of metallic materials: 3D printed, multilayered and micrometre-scale metals. Effects of local variations on the subsequent microstructural evolution will be followed during deformation and annealing, i.e. during processes typical for manufacturing, and occurring during in-service operation.
Current models largely ignore the presence of local microstructural variations and lack predictive power. Based on the new experimental data, three models operating on different length scales will be improved and combined, namely crystal plasticity finite element, phase field and molecular dynamics models. The main novelty here relates to the full 4D validation of the models, which has not been possible hitherto because of lack of sufficient experimental data.
The resulting fundamental understanding of the inherent microstructural variations and the new models are foreseen to be an integral part of the future design of metallic materials for high performance applications.
Summary
The goals are:
1) to develop a universal laboratory-based 4D X-ray microscope with potentials in the broad field of materials science and beyond;
2) to advance metal research by quantifying local microstructural variations using the new 4D tool and by including the effects hereof in the understanding and modelling of industrially relevant metals.
Today, high resolution 4D (x,y,z,time) crystallographic characterization of materials is possible only at large international facilities. This is a serious limitation preventing the common use. The new technique will allow such 4D characterization to be carried out at home laboratories, thereby wide spreading this powerful tool.
Whereas current metal research mainly focuses on average properties, local microstructural variations are present in all metals on several length scales, and are often of critical importance for the properties and performance of the metal. In this project, the new technique will be the cornerstone in studies of such variations in three types of metallic materials: 3D printed, multilayered and micrometre-scale metals. Effects of local variations on the subsequent microstructural evolution will be followed during deformation and annealing, i.e. during processes typical for manufacturing, and occurring during in-service operation.
Current models largely ignore the presence of local microstructural variations and lack predictive power. Based on the new experimental data, three models operating on different length scales will be improved and combined, namely crystal plasticity finite element, phase field and molecular dynamics models. The main novelty here relates to the full 4D validation of the models, which has not been possible hitherto because of lack of sufficient experimental data.
The resulting fundamental understanding of the inherent microstructural variations and the new models are foreseen to be an integral part of the future design of metallic materials for high performance applications.
Max ERC Funding
2 496 519 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym miPDesign
Project Designing microProteins to alter growth processes in crop plants
Researcher (PI) Stephan Wenkel
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), LS9, ERC-2013-StG
Summary The directed control of protein activity plays a crucial role in the regulation of growth and development of multicellular organisms. Different post-translational control mechanisms are known to influence the activity of proteins. Here, I am proposing a novel way to control the activity of proteins that function as multimeric complexes. MicroProteins, are small single-domain protein species that can influence target proteins by sequestering them into non-productive protein complexes. I have developed the concept of microProtein function and subsequently started to identify novel microProtein regulators in the model plant Arabidopsis. The aim of this proposal is to use the microProtein concept and build synthetic microProtein modules in economical import crop plants. By combining synthetic biology approaches with modern plant breeding, we intent to re-wire plant development and alter the flowering behaviour of rice. In addition, we will use a combination of artificial microProteins and microProtein-resistant transcription factors to modify the inclination angle of leaves in rice and the bioenergy model species Brachypodium distachion. Modification of the leaf angle will allow us to grow crops at higher densities, thus having the potential to increase both biomass and seed production per acreage. Finally, we aim to identify novel, evolutionary conserved microProtein-modules and unravel the mechanism of microProtein function, to study their role in plant development and adaptation.
Summary
The directed control of protein activity plays a crucial role in the regulation of growth and development of multicellular organisms. Different post-translational control mechanisms are known to influence the activity of proteins. Here, I am proposing a novel way to control the activity of proteins that function as multimeric complexes. MicroProteins, are small single-domain protein species that can influence target proteins by sequestering them into non-productive protein complexes. I have developed the concept of microProtein function and subsequently started to identify novel microProtein regulators in the model plant Arabidopsis. The aim of this proposal is to use the microProtein concept and build synthetic microProtein modules in economical import crop plants. By combining synthetic biology approaches with modern plant breeding, we intent to re-wire plant development and alter the flowering behaviour of rice. In addition, we will use a combination of artificial microProteins and microProtein-resistant transcription factors to modify the inclination angle of leaves in rice and the bioenergy model species Brachypodium distachion. Modification of the leaf angle will allow us to grow crops at higher densities, thus having the potential to increase both biomass and seed production per acreage. Finally, we aim to identify novel, evolutionary conserved microProtein-modules and unravel the mechanism of microProtein function, to study their role in plant development and adaptation.
Max ERC Funding
1 443 320 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
Project acronym PHOENEEX
Project Pyrolytic Hierarchical Organic Electrodes for sustaiNable Electrochemical Energy Systems
Researcher (PI) Stephan Sylvest Keller
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Consolidator Grant (CoG), PE7, ERC-2017-COG
Summary The demand for compact energy systems for portable devices such as wearable sensors or mobile phones is increasing. Electrochemical systems are promising candidates for sustainable energy conversion and storage on miniaturised platforms. A recent approach to harvest green energy is biophotovoltaic systems (BPVs), where photosynthetic microorganisms are used to transform light into electrical energy. However, BPVs still provide a relatively low efficiency and are yet unable to deliver the high peak power required for sensor operation or wireless signal transmission in portable systems. In PHOENEEX, I will address these limitations by i) improving the efficiency of BPVs and ii) combining the BPVs with microsupercapacitors (µSCs) which can temporarily store the harvested electrical energy and provide a higher peak power output upon request. More specifically, I will develop highly optimised 3D carbon microelectrodes (3DCMEs) to enhance electron harvesting from cyanobacteria in BPVs and for increased energy density in µSCs. Finally, the improved BPVs and the optimised µSCs will be integrated on the BioCapacitor Microchip - a compact sustainable energy platform for portable systems.
The fabrication of 3DCMEs with highly tailored material properties, large surface area and hierarchical architecture is achieved by pyrolysis of polymer templates in an inert atmosphere. The fundamental hypothesis of PHOENEEX is that the combination of novel precursor materials, new methods for 3D polymer microfabrication and optimised pyrolysis processes will allow for fabrication of 3DCMEs with highly tailored material properties, large surface area and hierarchical architecture impossible to obtain with any other method.
Summary
The demand for compact energy systems for portable devices such as wearable sensors or mobile phones is increasing. Electrochemical systems are promising candidates for sustainable energy conversion and storage on miniaturised platforms. A recent approach to harvest green energy is biophotovoltaic systems (BPVs), where photosynthetic microorganisms are used to transform light into electrical energy. However, BPVs still provide a relatively low efficiency and are yet unable to deliver the high peak power required for sensor operation or wireless signal transmission in portable systems. In PHOENEEX, I will address these limitations by i) improving the efficiency of BPVs and ii) combining the BPVs with microsupercapacitors (µSCs) which can temporarily store the harvested electrical energy and provide a higher peak power output upon request. More specifically, I will develop highly optimised 3D carbon microelectrodes (3DCMEs) to enhance electron harvesting from cyanobacteria in BPVs and for increased energy density in µSCs. Finally, the improved BPVs and the optimised µSCs will be integrated on the BioCapacitor Microchip - a compact sustainable energy platform for portable systems.
The fabrication of 3DCMEs with highly tailored material properties, large surface area and hierarchical architecture is achieved by pyrolysis of polymer templates in an inert atmosphere. The fundamental hypothesis of PHOENEEX is that the combination of novel precursor materials, new methods for 3D polymer microfabrication and optimised pyrolysis processes will allow for fabrication of 3DCMEs with highly tailored material properties, large surface area and hierarchical architecture impossible to obtain with any other method.
Max ERC Funding
2 745 500 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym YEAST-TRANS
Project Deciphering the transport mechanisms of small xenobiotic molecules in synthetic yeast cell factories
Researcher (PI) Irina BORODINA
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Starting Grant (StG), LS9, ERC-2017-STG
Summary Industrial biotechnology employs synthetic cell factories to create bulk and fine chemicals and fuels from renewable resources, laying the basis for the future bio-based economy. The major part of the wanted bio-based chemicals are not native to the host cell, such as yeast, i.e. they are xenobiotic. Some xenobiotic compounds are readily secreted by synthetic cells, some are poorly secreted and some are not secreted at all, but how does this transport occur? Or why does it not occur? These fundamental questions remain to be answered and this will have great implications on industrial biotechnology, because improved secretion would bring down the production costs and enable the emergence of novel bio-based products.
YEAST-TRANS will fill in this knowledge gap by carrying out the first systematic genome-scale transporter study to uncover the transport mechanisms of small xenobiotic molecules by synthetic yeast cells and to apply this knowledge for engineering more efficient cell factories for bio-based production of fuels and chemicals.
Summary
Industrial biotechnology employs synthetic cell factories to create bulk and fine chemicals and fuels from renewable resources, laying the basis for the future bio-based economy. The major part of the wanted bio-based chemicals are not native to the host cell, such as yeast, i.e. they are xenobiotic. Some xenobiotic compounds are readily secreted by synthetic cells, some are poorly secreted and some are not secreted at all, but how does this transport occur? Or why does it not occur? These fundamental questions remain to be answered and this will have great implications on industrial biotechnology, because improved secretion would bring down the production costs and enable the emergence of novel bio-based products.
YEAST-TRANS will fill in this knowledge gap by carrying out the first systematic genome-scale transporter study to uncover the transport mechanisms of small xenobiotic molecules by synthetic yeast cells and to apply this knowledge for engineering more efficient cell factories for bio-based production of fuels and chemicals.
Max ERC Funding
1 423 358 €
Duration
Start date: 2017-12-01, End date: 2022-11-30
