Project acronym AZIDRUGS
Project Molecular tattooing: azidated compounds pave the path towards light-activated covalent inhibitors for drug development
Researcher (PI) András MÁLNÁSI-CSIZMADIA
Host Institution (HI) DRUGMOTIF KORLATOLT FELELOSSEGU TARSASAG
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary Until now the greatest limitation in the application of bioactive compounds has been the inability of confining them specifically to single cells or subcellular components within the organism. Our recently synthesized photoactive forms of bioactive compounds solve this problem. We have developed effective chemical synthesis methods to attach an azide group to small drug-like molecules, which makes them photoactive. As a result, light irradiation can induce the covalent attachment of these molecules to their target enzymes. By controlling the timing and position of light irradiation it is possible to confine the effect of these molecules in time and space. It is important to emphasize that azidation is the smallest possible modification (adding 3 nitrogen atoms) that makes a compound photoactive and based on our experience it does not alter biological activities of most of the original compounds.
Azidated inhibitors give unprecedented freedom to researchers because the covalent compound-target formations allow them to address questions which could not have been addressed before. Three major advantages are obtained by using azidated compounds 1: determination of small molecule interactome becomes highly effective, especially, the weak interactions can be determined, which was not possible before 2: it improves the pharmacodynamic and pharmacokinetic properties of biological compounds as the covalent attachment prolongs their effect. 3: Recently, we showed that photoactivation can be initiated by two-photon excitation, thereby confining the effect to femtoliter volumes and well-controlled spatial locations. This feature provides unprecedented spatial and temporal control in localizing the effect of biological compounds in cellular and subcelluler level in in vivo experiments. By realizing the need for photoactive compounds, the PI has established Drugmotif Ltd., a spin-off company, which provides the customers with special azidated chemicals for high-tech research.
Summary
Until now the greatest limitation in the application of bioactive compounds has been the inability of confining them specifically to single cells or subcellular components within the organism. Our recently synthesized photoactive forms of bioactive compounds solve this problem. We have developed effective chemical synthesis methods to attach an azide group to small drug-like molecules, which makes them photoactive. As a result, light irradiation can induce the covalent attachment of these molecules to their target enzymes. By controlling the timing and position of light irradiation it is possible to confine the effect of these molecules in time and space. It is important to emphasize that azidation is the smallest possible modification (adding 3 nitrogen atoms) that makes a compound photoactive and based on our experience it does not alter biological activities of most of the original compounds.
Azidated inhibitors give unprecedented freedom to researchers because the covalent compound-target formations allow them to address questions which could not have been addressed before. Three major advantages are obtained by using azidated compounds 1: determination of small molecule interactome becomes highly effective, especially, the weak interactions can be determined, which was not possible before 2: it improves the pharmacodynamic and pharmacokinetic properties of biological compounds as the covalent attachment prolongs their effect. 3: Recently, we showed that photoactivation can be initiated by two-photon excitation, thereby confining the effect to femtoliter volumes and well-controlled spatial locations. This feature provides unprecedented spatial and temporal control in localizing the effect of biological compounds in cellular and subcelluler level in in vivo experiments. By realizing the need for photoactive compounds, the PI has established Drugmotif Ltd., a spin-off company, which provides the customers with special azidated chemicals for high-tech research.
Max ERC Funding
150 000 €
Duration
Start date: 2013-12-01, End date: 2014-11-30
Project acronym COLIBRI
Project Novel platform for combinatorial genetic libraries by recombination
Researcher (PI) Michael LISBY
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary Assembly of combinatorial genetic libraries for identification of biomolecules with novel or improved properties requires high fidelity and efficiency to produce the greatest spectrum of genetically diverse clones. We have been developing homologous recombination (HR) as a platform for the production of combinatorial genetic libraries for affinity maturation and diversification of human therapeutic antibodies. Therapeutic antibodies have a great clinical potential in various therapeutic settings including the treatment of a number of oncology, autoimmune and infectious diseases, organ transplantation, and others. In brief, we describe a method, where CDR-encoding DNA oligos and a gapped vector containing the heavy and light chain genes are cotransformed into budding yeast Saccharomyces cerevisiae for in vivo assembly by HR. Importantly, the affinity of resulting antibody clones in the generated library can be directly assayed by yeast surface display without subcloning and retransformation. Furthermore, mating two haploid yeast strain libraries each encoding a variation of heavy chain or light chain genes enables fast screening of the heavy/light chain combinations displayed by the resulting diploids. Finally, this method can be generalized to generate combinatorial genetic libraries for other applications.
Summary
Assembly of combinatorial genetic libraries for identification of biomolecules with novel or improved properties requires high fidelity and efficiency to produce the greatest spectrum of genetically diverse clones. We have been developing homologous recombination (HR) as a platform for the production of combinatorial genetic libraries for affinity maturation and diversification of human therapeutic antibodies. Therapeutic antibodies have a great clinical potential in various therapeutic settings including the treatment of a number of oncology, autoimmune and infectious diseases, organ transplantation, and others. In brief, we describe a method, where CDR-encoding DNA oligos and a gapped vector containing the heavy and light chain genes are cotransformed into budding yeast Saccharomyces cerevisiae for in vivo assembly by HR. Importantly, the affinity of resulting antibody clones in the generated library can be directly assayed by yeast surface display without subcloning and retransformation. Furthermore, mating two haploid yeast strain libraries each encoding a variation of heavy chain or light chain genes enables fast screening of the heavy/light chain combinations displayed by the resulting diploids. Finally, this method can be generalized to generate combinatorial genetic libraries for other applications.
Max ERC Funding
150 000 €
Duration
Start date: 2014-05-01, End date: 2015-04-30
Project acronym LIPBA
Project Laser Identification of Pollen and Bacteria in Air
Researcher (PI) Jean-Pierre WOLF
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary "This project aims at marketing a new laser based detector for identifying pollens in air, and further develop it for extending its application to the detection and identification of bacteria in air. Key markets are meteorological institutes for pollens and hospitals for bacteria identification, in order to address the problem of nosocomial infections. Business plans have been elaborated and even highlighted within the Mc Kinsey contest ""Venture 2012"", as one of the 20 finalists over 191 projects. Our bioaerosol detector also participated to the transatlantic campaign ""Planet Solar"" (www.planetsolar.org/deepwater) over the ocean for 6 months, and demonstrated its exceptional reliability and measurement quality. It also provided an extremely broad media coverage and thus worldwide visibility to our project."
Summary
"This project aims at marketing a new laser based detector for identifying pollens in air, and further develop it for extending its application to the detection and identification of bacteria in air. Key markets are meteorological institutes for pollens and hospitals for bacteria identification, in order to address the problem of nosocomial infections. Business plans have been elaborated and even highlighted within the Mc Kinsey contest ""Venture 2012"", as one of the 20 finalists over 191 projects. Our bioaerosol detector also participated to the transatlantic campaign ""Planet Solar"" (www.planetsolar.org/deepwater) over the ocean for 6 months, and demonstrated its exceptional reliability and measurement quality. It also provided an extremely broad media coverage and thus worldwide visibility to our project."
Max ERC Funding
148 901 €
Duration
Start date: 2014-06-01, End date: 2015-05-31
Project acronym MOBILE2DG
Project Mobile Two Dimensional Gas
Researcher (PI) Nava SETTER
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary "In certain physical interfaces between two different materials, or in physical surfaces, electrons or holes behave as if they were confined to two dimensions, forming a 2-dimensional gas, [2DG] and showing exceptional properties, such as very high mobility. 2DG is a common phenomenon widely used, e.g. in Metal-oxide-semiconductor field effect transistors (MOSFETs), currently used in nearly all microprocessors. 2DG is usually confined to physical interfaces between two different materials and its physical location is fixed.
Imagine now a new type of 2DG, which is not confined to a physical interface but can be created electrically inside a pure single material; it could be electrically ‘written’ into a working device at will, and could be displaced inside the material by a small voltage pulse. In our ERC project we predicted this theoretically and demonstrated it experimentally inside a single crystal of the ubiquitous insulator BaTiO3. In contrast to conventional 2DG, our 2DG isn't bound to an interface. The free carrier concentration at our 2DG reaches giant 10power19 cm-3 and its metallic conductivity exceeds 10power9 times the bulk conductivity. We have also elaborated and filed a patent application on a way to produce this 2DG inside the insulator. In principle this effect can work in all ferroelectric materials. In the PoC project we plan to demonstrate the phenomenon inside thin films, which are more industrially viable than the bulk crystal used for our first demonstration, to demonstrate the function of our field-controlled 2DG in an industrially exploitable structure, approach industry, and explore together applicability of devices based on this new phenomenon in electronics and related areas, such as MEMS. At the end of the PoC project, we will have confirmed the potential of the new 2DG in a set of devices, secured our new patents, developed IPR strategy and we or partners will have strategic plan towards device development and commercialization."
Summary
"In certain physical interfaces between two different materials, or in physical surfaces, electrons or holes behave as if they were confined to two dimensions, forming a 2-dimensional gas, [2DG] and showing exceptional properties, such as very high mobility. 2DG is a common phenomenon widely used, e.g. in Metal-oxide-semiconductor field effect transistors (MOSFETs), currently used in nearly all microprocessors. 2DG is usually confined to physical interfaces between two different materials and its physical location is fixed.
Imagine now a new type of 2DG, which is not confined to a physical interface but can be created electrically inside a pure single material; it could be electrically ‘written’ into a working device at will, and could be displaced inside the material by a small voltage pulse. In our ERC project we predicted this theoretically and demonstrated it experimentally inside a single crystal of the ubiquitous insulator BaTiO3. In contrast to conventional 2DG, our 2DG isn't bound to an interface. The free carrier concentration at our 2DG reaches giant 10power19 cm-3 and its metallic conductivity exceeds 10power9 times the bulk conductivity. We have also elaborated and filed a patent application on a way to produce this 2DG inside the insulator. In principle this effect can work in all ferroelectric materials. In the PoC project we plan to demonstrate the phenomenon inside thin films, which are more industrially viable than the bulk crystal used for our first demonstration, to demonstrate the function of our field-controlled 2DG in an industrially exploitable structure, approach industry, and explore together applicability of devices based on this new phenomenon in electronics and related areas, such as MEMS. At the end of the PoC project, we will have confirmed the potential of the new 2DG in a set of devices, secured our new patents, developed IPR strategy and we or partners will have strategic plan towards device development and commercialization."
Max ERC Funding
149 869 €
Duration
Start date: 2013-11-01, End date: 2014-10-31
Project acronym NANOTHERAPY
Project A Novel Nanocontainer drug carrier for targeted treatment of cancer
Researcher (PI) George KORDAS
Host Institution (HI) "NATIONAL CENTER FOR SCIENTIFIC RESEARCH ""DEMOKRITOS"""
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary The clinical use and effect of most conventional therapies (e.g. for cancer) are limited, either due to insufficient accumulation of the drug in the target tissue or its severe toxic effects on healthy tissues. Consequently, many treatments are not achieving their full effect and many other highly promising compounds never make it to the market. A promising approach to address this issue of bioavailability is the design and development of nanocarriers. These nanocarriers need to provide stable protection of the compound in the blood stream while they should release the compound at the targeted tissue. Currently, there are no nanocarriers available that effectively address this challenging trade-off.
We have constructed nanocontainers (NCs) that show high promise to address this issue. Our NCs are engineered from biocompatible and biodegradable polymers and are unique in their stability and resistance to drug leakage in the circulation, while they exert conformational changes under specific conditions targeting at the pathological tissue, inducing localised drug release. This technology leverages the fact that tumours (as well as other types of diseased tissue) are known to have specific extracellular environments with lower pH, higher temperature and enhanced glutathione levels compared to healthy tissues. Our NCs integrate four stimuli, namely pH, temperature (T), reducing environments (glutathione) and alternating magnetic fields. With the PoC grant we aim at obtaining in vivo evidence of the functional added value of our proprietary NCs for the delivery of anti-tumour and antibacterial drugs. Furthermore, we aim to strengthen our IP position and develop a business plan thatdescribes theoptimal route-to-market for our technology.
Summary
The clinical use and effect of most conventional therapies (e.g. for cancer) are limited, either due to insufficient accumulation of the drug in the target tissue or its severe toxic effects on healthy tissues. Consequently, many treatments are not achieving their full effect and many other highly promising compounds never make it to the market. A promising approach to address this issue of bioavailability is the design and development of nanocarriers. These nanocarriers need to provide stable protection of the compound in the blood stream while they should release the compound at the targeted tissue. Currently, there are no nanocarriers available that effectively address this challenging trade-off.
We have constructed nanocontainers (NCs) that show high promise to address this issue. Our NCs are engineered from biocompatible and biodegradable polymers and are unique in their stability and resistance to drug leakage in the circulation, while they exert conformational changes under specific conditions targeting at the pathological tissue, inducing localised drug release. This technology leverages the fact that tumours (as well as other types of diseased tissue) are known to have specific extracellular environments with lower pH, higher temperature and enhanced glutathione levels compared to healthy tissues. Our NCs integrate four stimuli, namely pH, temperature (T), reducing environments (glutathione) and alternating magnetic fields. With the PoC grant we aim at obtaining in vivo evidence of the functional added value of our proprietary NCs for the delivery of anti-tumour and antibacterial drugs. Furthermore, we aim to strengthen our IP position and develop a business plan thatdescribes theoptimal route-to-market for our technology.
Max ERC Funding
150 000 €
Duration
Start date: 2014-01-01, End date: 2015-05-31
Project acronym PARQUERY
Project Video-Based Smart Parking System
Researcher (PI) Luc VAN GOOL
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary In the central business districts of many cities, a large fraction of the traffic comes from cars cruising for parking. One study estimates that as much as 30% of the traffic in downtown areas of major cities. Cruising wastes time and fuel for drivers and is also detrimental to the municipality, as it pollutes, congests traffic and degrades pedestrian environments. Parking search assistance is one of the major unsolved problems in urban mobility. Occupancy information is currently only available in parking garages and off-street parking, where parked cars are easily counted. For on-street parking, which is more preferable to drivers since it is usually cheaper and more convenient, occupancy is not so easily obtained.
We are developing a vision-based smart parking system for monitoring on-street parking occupancy. A camera network monitors parking spots throughout the city and sends images to centralized servers, where the images are then processed with computer vision algorithms to determine parking availability. Real-time occupancy information can be broadcast to drivers through a website or phone app, while aggregate statistics can be provided to parking administrators. One can further integrate navigation to nearby parking, payment and enforcement functions directly into the system. Such a smart parking system can greatly reduce frustrations of finding parking and also the noise and pollution from traffic congestion.
Summary
In the central business districts of many cities, a large fraction of the traffic comes from cars cruising for parking. One study estimates that as much as 30% of the traffic in downtown areas of major cities. Cruising wastes time and fuel for drivers and is also detrimental to the municipality, as it pollutes, congests traffic and degrades pedestrian environments. Parking search assistance is one of the major unsolved problems in urban mobility. Occupancy information is currently only available in parking garages and off-street parking, where parked cars are easily counted. For on-street parking, which is more preferable to drivers since it is usually cheaper and more convenient, occupancy is not so easily obtained.
We are developing a vision-based smart parking system for monitoring on-street parking occupancy. A camera network monitors parking spots throughout the city and sends images to centralized servers, where the images are then processed with computer vision algorithms to determine parking availability. Real-time occupancy information can be broadcast to drivers through a website or phone app, while aggregate statistics can be provided to parking administrators. One can further integrate navigation to nearby parking, payment and enforcement functions directly into the system. Such a smart parking system can greatly reduce frustrations of finding parking and also the noise and pollution from traffic congestion.
Max ERC Funding
149 490 €
Duration
Start date: 2014-07-01, End date: 2015-06-30
Project acronym ROBOMED
Project Commercialisation of a robotic platform enabling high-precision force control in multi-dimensional applications
Researcher (PI) Grégoire COURTINE
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary Current robotic technologies show severe limitations in multi-dimensional applications requiring force control, both from the accuracy and safety perspective. Although combined hardware and control concepts have been developed that enable accurate force control in a single degree of freedom, the majority of tasks necessitates superior force control capabilities in multiple degrees of freedom.
Within our ERC grant, we have developed a robotic platform that enables high-precision force control in multi-dimensional applications. This system meets the requirements for safe and high-fidelity body-weight supported gait training of rodents. Our system consists of exchangeable and adaptable elastic force sensing modules that can be attached to state-of-the-art macrostructure robots and enable, combined with specific control laws, highly accurate force control along 4 independent degrees of freedom. The interface consists of a compact entity that is relatively light and can be produced at low costs.
Within the ERC PoC ‘Robomed’ the goal is to develop a proposition package for potential investors. On the technical side we will create a novel prototype to validate our robotic technology, which will result in a technical report. In consultation with regulatory specialists a roadmap will be developed to obtain regulatory approval based on the norms and procedures for robotics. A patent protects our robot-assisted training and additional patentability of our findings is currently evaluated. A strategy to overcome any obstacles identified is developed. Market opportunities for our technology include translational research, restoring fine locomotor and manual tasks in humans and industrial applications. These market segments will be extensively analysed and subsequently prioritised within the commercialisation strategy. Results will be assembled in a detailed business plan that is presented to several venture capitalists, existing robotic companies and other relevant stakeholders.
Summary
Current robotic technologies show severe limitations in multi-dimensional applications requiring force control, both from the accuracy and safety perspective. Although combined hardware and control concepts have been developed that enable accurate force control in a single degree of freedom, the majority of tasks necessitates superior force control capabilities in multiple degrees of freedom.
Within our ERC grant, we have developed a robotic platform that enables high-precision force control in multi-dimensional applications. This system meets the requirements for safe and high-fidelity body-weight supported gait training of rodents. Our system consists of exchangeable and adaptable elastic force sensing modules that can be attached to state-of-the-art macrostructure robots and enable, combined with specific control laws, highly accurate force control along 4 independent degrees of freedom. The interface consists of a compact entity that is relatively light and can be produced at low costs.
Within the ERC PoC ‘Robomed’ the goal is to develop a proposition package for potential investors. On the technical side we will create a novel prototype to validate our robotic technology, which will result in a technical report. In consultation with regulatory specialists a roadmap will be developed to obtain regulatory approval based on the norms and procedures for robotics. A patent protects our robot-assisted training and additional patentability of our findings is currently evaluated. A strategy to overcome any obstacles identified is developed. Market opportunities for our technology include translational research, restoring fine locomotor and manual tasks in humans and industrial applications. These market segments will be extensively analysed and subsequently prioritised within the commercialisation strategy. Results will be assembled in a detailed business plan that is presented to several venture capitalists, existing robotic companies and other relevant stakeholders.
Max ERC Funding
149 757 €
Duration
Start date: 2014-06-01, End date: 2015-05-31
Project acronym ROMANS
Project Rotating Opto-Magnetic Analysis System
Researcher (PI) Anja BOISEN
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary The purpose of this PoC project is to develop a prototype of portable, highly sensitive and low cost technology for point-of care detection of inflammatory diseases biomarkers. At DTU Nanotech we have developed a completely new technology which holds a great potential to become, in a short period, an extremely useful tool for small medical facilities, family doctors, and chronically ill patients. The core readout element is represented, as in the HERMES project, by an optical pickup head, as used in CD, DVD-ROM or BLU-RAY, which embeds in a single optical path both a laser source and a high-resolution photodetector. By measuring how the light is scattered by magnetic nano-particles actuated by an external AC field we have demonstrated that it is possible to detect low concentration of analytes present in the sample. The key feature of our invention is that blood preconcentration and analyte readout are integrated into the same magnetic-based operations, leading to a compact, low-cost and user-friendly device. Doctors will benefit from our technology which allows performing multiple analyses without relying on centralized laboratories. A fast technology capable to detect multiple parameters would for example allow patient screening at the family doctors’ offices, or would allow chronic diseases patients to be monitored without the need of regularly going to the hospital. The scope of the project is both to provide a benchmarked prototype and to identify the best approach to commercialize the invention. The PoC grant will provide the instruments for understanding the low-cost point-of-care market more deeply, in order to start addressing as soon as possible the challenges of breaking through a complex market such as human diagnostics. Thanks to the intrinsic low-cost of the machine components, several cycles of production/testing/evaluation are expected to be performed, facilitating a constant and fast improvement of our platform development and testing.
Summary
The purpose of this PoC project is to develop a prototype of portable, highly sensitive and low cost technology for point-of care detection of inflammatory diseases biomarkers. At DTU Nanotech we have developed a completely new technology which holds a great potential to become, in a short period, an extremely useful tool for small medical facilities, family doctors, and chronically ill patients. The core readout element is represented, as in the HERMES project, by an optical pickup head, as used in CD, DVD-ROM or BLU-RAY, which embeds in a single optical path both a laser source and a high-resolution photodetector. By measuring how the light is scattered by magnetic nano-particles actuated by an external AC field we have demonstrated that it is possible to detect low concentration of analytes present in the sample. The key feature of our invention is that blood preconcentration and analyte readout are integrated into the same magnetic-based operations, leading to a compact, low-cost and user-friendly device. Doctors will benefit from our technology which allows performing multiple analyses without relying on centralized laboratories. A fast technology capable to detect multiple parameters would for example allow patient screening at the family doctors’ offices, or would allow chronic diseases patients to be monitored without the need of regularly going to the hospital. The scope of the project is both to provide a benchmarked prototype and to identify the best approach to commercialize the invention. The PoC grant will provide the instruments for understanding the low-cost point-of-care market more deeply, in order to start addressing as soon as possible the challenges of breaking through a complex market such as human diagnostics. Thanks to the intrinsic low-cost of the machine components, several cycles of production/testing/evaluation are expected to be performed, facilitating a constant and fast improvement of our platform development and testing.
Max ERC Funding
149 833 €
Duration
Start date: 2014-01-01, End date: 2015-03-31
Project acronym SNAP
Project SnAP Reagents for Accelerating Drug Discovery
Researcher (PI) Jeffrey William BODE
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary A new class of reagents for directly accessing more drug like molecules at the early stages of drug development will be developed. This technology is based on a new method to easily prepare saturated N-heterocycles, which have proven advantages in drug like molecules but are difficult to prepare at the early stages of lead discovery and optimization. The key reactions and reagent has been validated and partners for distribution and test marketing established. The ERC PoC funding will support a first delivery of the reagents and support the development of new reagent classes in consultation with key industry leaders.
Summary
A new class of reagents for directly accessing more drug like molecules at the early stages of drug development will be developed. This technology is based on a new method to easily prepare saturated N-heterocycles, which have proven advantages in drug like molecules but are difficult to prepare at the early stages of lead discovery and optimization. The key reactions and reagent has been validated and partners for distribution and test marketing established. The ERC PoC funding will support a first delivery of the reagents and support the development of new reagent classes in consultation with key industry leaders.
Max ERC Funding
149 528 €
Duration
Start date: 2014-05-01, End date: 2015-04-30
