Project acronym Active-DNA
Project Computationally Active DNA Nanostructures
Researcher (PI) Damien WOODS
Host Institution (HI) NATIONAL UNIVERSITY OF IRELAND MAYNOOTH
Call Details Consolidator Grant (CoG), PE6, ERC-2017-COG
Summary During the 20th century computer technology evolved from bulky, slow, special purpose mechanical engines to the now ubiquitous silicon chips and software that are one of the pinnacles of human ingenuity. The goal of the field of molecular programming is to take the next leap and build a new generation of matter-based computers using DNA, RNA and proteins. This will be accomplished by computer scientists, physicists and chemists designing molecules to execute ``wet'' nanoscale programs in test tubes. The workflow includes proposing theoretical models, mathematically proving their computational properties, physical modelling and implementation in the wet-lab.
The past decade has seen remarkable progress at building static 2D and 3D DNA nanostructures. However, unlike biological macromolecules and complexes that are built via specified self-assembly pathways, that execute robotic-like movements, and that undergo evolution, the activity of human-engineered nanostructures is severely limited. We will need sophisticated algorithmic ideas to build structures that rival active living systems. Active-DNA, aims to address this challenge by achieving a number of objectives on computation, DNA-based self-assembly and molecular robotics. Active-DNA research work will range from defining models and proving theorems that characterise the computational and expressive capabilities of such active programmable materials to experimental work implementing active DNA nanostructures in the wet-lab.
Summary
During the 20th century computer technology evolved from bulky, slow, special purpose mechanical engines to the now ubiquitous silicon chips and software that are one of the pinnacles of human ingenuity. The goal of the field of molecular programming is to take the next leap and build a new generation of matter-based computers using DNA, RNA and proteins. This will be accomplished by computer scientists, physicists and chemists designing molecules to execute ``wet'' nanoscale programs in test tubes. The workflow includes proposing theoretical models, mathematically proving their computational properties, physical modelling and implementation in the wet-lab.
The past decade has seen remarkable progress at building static 2D and 3D DNA nanostructures. However, unlike biological macromolecules and complexes that are built via specified self-assembly pathways, that execute robotic-like movements, and that undergo evolution, the activity of human-engineered nanostructures is severely limited. We will need sophisticated algorithmic ideas to build structures that rival active living systems. Active-DNA, aims to address this challenge by achieving a number of objectives on computation, DNA-based self-assembly and molecular robotics. Active-DNA research work will range from defining models and proving theorems that characterise the computational and expressive capabilities of such active programmable materials to experimental work implementing active DNA nanostructures in the wet-lab.
Max ERC Funding
2 349 603 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym AFRICA-GHG
Project AFRICA-GHG: The role of African tropical forests on the Greenhouse Gases balance of the atmosphere
Researcher (PI) Riccardo Valentini
Host Institution (HI) FONDAZIONE CENTRO EURO-MEDITERRANEOSUI CAMBIAMENTI CLIMATICI
Call Details Advanced Grant (AdG), PE10, ERC-2009-AdG
Summary The role of the African continent in the global carbon cycle, and therefore in climate change, is increasingly recognised. Despite the increasingly acknowledged importance of Africa in the global carbon cycle and its high vulnerability to climate change there is still a lack of studies on the carbon cycle in representative African ecosystems (in particular tropical forests), and on the effects of climate on ecosystem-atmosphere exchange. In the present proposal we want to focus on these spoecifc objectives : 1. Understand the role of African tropical rainforest on the GHG balance of the atmosphere and revise their role on the global methane and N2O emissions. 2. Determine the carbon source/sink strength of African tropical rainforest in the pre-industrial versus the XXth century by temporal reconstruction of biomass growth with biogeochemical markers 3. Understand and quantify carbon and GHG fluxes variability across African tropical forests (west east equatorial belt) 4.Analyse the impact of forest degradation and deforestation on carbon and other GHG emissions
Summary
The role of the African continent in the global carbon cycle, and therefore in climate change, is increasingly recognised. Despite the increasingly acknowledged importance of Africa in the global carbon cycle and its high vulnerability to climate change there is still a lack of studies on the carbon cycle in representative African ecosystems (in particular tropical forests), and on the effects of climate on ecosystem-atmosphere exchange. In the present proposal we want to focus on these spoecifc objectives : 1. Understand the role of African tropical rainforest on the GHG balance of the atmosphere and revise their role on the global methane and N2O emissions. 2. Determine the carbon source/sink strength of African tropical rainforest in the pre-industrial versus the XXth century by temporal reconstruction of biomass growth with biogeochemical markers 3. Understand and quantify carbon and GHG fluxes variability across African tropical forests (west east equatorial belt) 4.Analyse the impact of forest degradation and deforestation on carbon and other GHG emissions
Max ERC Funding
2 406 950 €
Duration
Start date: 2010-04-01, End date: 2014-12-31
Project acronym AMDROMA
Project Algorithmic and Mechanism Design Research in Online MArkets
Researcher (PI) Stefano LEONARDI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Call Details Advanced Grant (AdG), PE6, ERC-2017-ADG
Summary Online markets currently form an important share of the global economy. The Internet hosts classical markets (real-estate, stocks, e-commerce) as well allowing new markets with previously unknown features (web-based advertisement, viral marketing, digital goods, crowdsourcing, sharing economy). Algorithms play a central role in many decision processes involved in online markets. For example, algorithms run electronic auctions, trade stocks, adjusts prices dynamically, and harvest big data to provide economic information. Thus, it is of paramount importance to understand the algorithmic and mechanism design foundations of online markets.
The algorithmic research issues that we consider involve algorithmic mechanism design, online and approximation algorithms, modelling uncertainty in online market design, and large-scale data analysisonline and approximation algorithms, large-scale optimization and data mining. The aim of this research project is to combine these fields to consider research questions that are central for today's Internet economy. We plan to apply these techniques so as to solve fundamental algorithmic problems motivated by web-basedInternet advertisement, Internet market designsharing economy, and crowdsourcingonline labour marketplaces. While my planned research is focussedcentered on foundational work with rigorous design and analysis of in algorithms and mechanismsic design and analysis, it will also include as an important component empirical validation on large-scale real-life datasets.
Summary
Online markets currently form an important share of the global economy. The Internet hosts classical markets (real-estate, stocks, e-commerce) as well allowing new markets with previously unknown features (web-based advertisement, viral marketing, digital goods, crowdsourcing, sharing economy). Algorithms play a central role in many decision processes involved in online markets. For example, algorithms run electronic auctions, trade stocks, adjusts prices dynamically, and harvest big data to provide economic information. Thus, it is of paramount importance to understand the algorithmic and mechanism design foundations of online markets.
The algorithmic research issues that we consider involve algorithmic mechanism design, online and approximation algorithms, modelling uncertainty in online market design, and large-scale data analysisonline and approximation algorithms, large-scale optimization and data mining. The aim of this research project is to combine these fields to consider research questions that are central for today's Internet economy. We plan to apply these techniques so as to solve fundamental algorithmic problems motivated by web-basedInternet advertisement, Internet market designsharing economy, and crowdsourcingonline labour marketplaces. While my planned research is focussedcentered on foundational work with rigorous design and analysis of in algorithms and mechanismsic design and analysis, it will also include as an important component empirical validation on large-scale real-life datasets.
Max ERC Funding
1 780 150 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym ATOMICAR
Project ATOMic Insight Cavity Array Reactor
Researcher (PI) Peter Christian Kjærgaard VESBORG
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Starting Grant (StG), PE4, ERC-2017-STG
Summary The goal of ATOMICAR is to achieve the ultimate sensitivity limit in heterogeneous catalysis:
Quantitative measurement of chemical turnover on a single catalytic nanoparticle.
Most heterogeneous catalysis occurs on metal nanoparticle in the size range of 3 nm - 10 nm. Model studies have established that there is often a strong coupling between nanoparticle size & shape - and catalytic activity. The strong structure-activity coupling renders it probable that “super-active” nanoparticles exist. However, since there is no way to measure catalytic activity of less than ca 1 million nanoparticles at a time, any super-activity will always be hidden by “ensemble smearing” since one million nanoparticles of exactly identical size and shape cannot be made. The state-of-the-art in catalysis benchmarking is microfabricated flow reactors with mass-spectrometric detection, but the sensitivity of this approach cannot be incrementally improved by six orders of magnitude. This calls for a new measurement paradigm where the activity of a single nanoparticle can be benchmarked – the ultimate limit for catalytic measurement.
A tiny batch reactor is the solution, but there are three key problems: How to seal it; how to track catalytic turnover inside it; and how to see the nanoparticle inside it? Graphene solves all three problems: A microfabricated cavity with a thin SixNy bottom window, a single catalytic nanoparticle inside, and a graphene seal forms a gas tight batch reactor since graphene has zero gas permeability. Catalysis is then tracked as an internal pressure change via the stress & deflection of the graphene seal. Crucially, the electron-transparency of graphene and SixNy enables subsequent transmission electron microscope access with atomic resolution so that active nanoparticles can be studied in full detail.
ATOMICAR will re-define the experimental limits of catalyst benchmarking and lift the field of basic catalysis research into the single-nanoparticle age.
Summary
The goal of ATOMICAR is to achieve the ultimate sensitivity limit in heterogeneous catalysis:
Quantitative measurement of chemical turnover on a single catalytic nanoparticle.
Most heterogeneous catalysis occurs on metal nanoparticle in the size range of 3 nm - 10 nm. Model studies have established that there is often a strong coupling between nanoparticle size & shape - and catalytic activity. The strong structure-activity coupling renders it probable that “super-active” nanoparticles exist. However, since there is no way to measure catalytic activity of less than ca 1 million nanoparticles at a time, any super-activity will always be hidden by “ensemble smearing” since one million nanoparticles of exactly identical size and shape cannot be made. The state-of-the-art in catalysis benchmarking is microfabricated flow reactors with mass-spectrometric detection, but the sensitivity of this approach cannot be incrementally improved by six orders of magnitude. This calls for a new measurement paradigm where the activity of a single nanoparticle can be benchmarked – the ultimate limit for catalytic measurement.
A tiny batch reactor is the solution, but there are three key problems: How to seal it; how to track catalytic turnover inside it; and how to see the nanoparticle inside it? Graphene solves all three problems: A microfabricated cavity with a thin SixNy bottom window, a single catalytic nanoparticle inside, and a graphene seal forms a gas tight batch reactor since graphene has zero gas permeability. Catalysis is then tracked as an internal pressure change via the stress & deflection of the graphene seal. Crucially, the electron-transparency of graphene and SixNy enables subsequent transmission electron microscope access with atomic resolution so that active nanoparticles can be studied in full detail.
ATOMICAR will re-define the experimental limits of catalyst benchmarking and lift the field of basic catalysis research into the single-nanoparticle age.
Max ERC Funding
1 496 000 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym BIOINOHYB
Project Smart Bioinorganic Hybrids for Nanomedicine
Researcher (PI) Cristiana Di Valentin
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Call Details Consolidator Grant (CoG), PE5, ERC-2014-CoG
Summary The use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine.
More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.
Summary
The use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine.
More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.
Max ERC Funding
1 748 125 €
Duration
Start date: 2016-02-01, End date: 2021-01-31
Project acronym BODY-UI
Project Using Embodied Cognition to Create the Next Generations of Body-based User Interfaces
Researcher (PI) Kasper Anders Soren Hornbæk
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Consolidator Grant (CoG), PE6, ERC-2014-CoG
Summary Recent advances in user interfaces (UIs) allow users to interact with computers using only their body, so-called body-based UIs. Instead of moving a mouse or tapping a touch surface, people can use whole-body movements to navigate in games, gesture in mid-air to interact with large displays, or scratch their forearm to control a mobile phone. Body-based UIs are attractive because they free users from having to hold or touch a device and because they allow always-on, eyes-free interaction. Currently, however, research on body-based UIs proceeds in an ad hoc fashion and when body-based UIs are compared to device-based alternatives, they perform poorly. This is likely because little is known about the body as a user interface and because it is unclear whether theory and design principles from human-computer interaction (HCI) can be applied to body-based UIs. While body-based UIs may well be the next interaction paradigm for HCI, results so far are mixed.
This project aims at establishing the scientific foundation for the next generations of body-based UIs. The main novelty in my approach is to use results and methods from research on embodied cognition. Embodied cognition suggest that thinking (including reasoning, memory, and emotion) is shaped by our bodies, and conversely, that our bodies reflect thinking. We use embodied cognition to study how body-based UIs affect users, and to increase our understanding of similarities and differences to device-based input. From those studies we develop new body-based UIs, both for input (e.g., gestures in mid-air) and output (e.g., stimulating users’ muscles to move their fingers), and evaluate users’ experience of interacting through their bodies. We also show how models, evaluation criteria, and design principles in HCI need to be adapted for embodied cognition and body-based UIs. If successful, the project will show how to create body-based UIs that are usable and orders of magnitude better than current UIs.
Summary
Recent advances in user interfaces (UIs) allow users to interact with computers using only their body, so-called body-based UIs. Instead of moving a mouse or tapping a touch surface, people can use whole-body movements to navigate in games, gesture in mid-air to interact with large displays, or scratch their forearm to control a mobile phone. Body-based UIs are attractive because they free users from having to hold or touch a device and because they allow always-on, eyes-free interaction. Currently, however, research on body-based UIs proceeds in an ad hoc fashion and when body-based UIs are compared to device-based alternatives, they perform poorly. This is likely because little is known about the body as a user interface and because it is unclear whether theory and design principles from human-computer interaction (HCI) can be applied to body-based UIs. While body-based UIs may well be the next interaction paradigm for HCI, results so far are mixed.
This project aims at establishing the scientific foundation for the next generations of body-based UIs. The main novelty in my approach is to use results and methods from research on embodied cognition. Embodied cognition suggest that thinking (including reasoning, memory, and emotion) is shaped by our bodies, and conversely, that our bodies reflect thinking. We use embodied cognition to study how body-based UIs affect users, and to increase our understanding of similarities and differences to device-based input. From those studies we develop new body-based UIs, both for input (e.g., gestures in mid-air) and output (e.g., stimulating users’ muscles to move their fingers), and evaluate users’ experience of interacting through their bodies. We also show how models, evaluation criteria, and design principles in HCI need to be adapted for embodied cognition and body-based UIs. If successful, the project will show how to create body-based UIs that are usable and orders of magnitude better than current UIs.
Max ERC Funding
1 853 158 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym BRiCPT
Project Basic Research in Cryptographic Protocol Theory
Researcher (PI) Jesper Buus Nielsen
Host Institution (HI) AARHUS UNIVERSITET
Call Details Starting Grant (StG), PE6, ERC-2011-StG_20101014
Summary In cryptographic protocol theory, we consider a situation where a number of entities want to solve some problem over a computer network. Each entity has some secret data it does not want the other entities to learn, yet, they all want to learn something about the common set of data. In an electronic election, they want to know the number of yes-votes without revealing who voted what. For instance, in an electronic auction, they want to find the winner without leaking the bids of the losers.
A main focus of the project is to develop new techniques for solving such protocol problems. We are in particular interested in techniques which can automatically construct a protocol solving a problem given only a description of what the problem is. My focus will be theoretical basic research, but I believe that advancing the theory of secure protocol compilers will have an immense impact on the practice of developing secure protocols for practice.
When one develops complex protocols, it is important to be able to verify their correctness before they are deployed, in particular so, when the purpose of the protocols is to protect information. If and when an error is found and corrected, the sensitive data will possibly already be compromised. Therefore, cryptographic protocol theory develops models of what it means for a protocol to be secure, and techniques for analyzing whether a given protocol is secure or not.
A main focuses of the project is to develop better security models, as existing security models either suffer from the problem that it is possible to prove some protocols secure which are not secure in practice, or they suffer from the problem that it is impossible to prove security of some protocol which are believed to be secure in practice. My focus will again be on theoretical basic research, but I believe that better security models are important for advancing a practice where protocols are verified as secure before deployed.
Summary
In cryptographic protocol theory, we consider a situation where a number of entities want to solve some problem over a computer network. Each entity has some secret data it does not want the other entities to learn, yet, they all want to learn something about the common set of data. In an electronic election, they want to know the number of yes-votes without revealing who voted what. For instance, in an electronic auction, they want to find the winner without leaking the bids of the losers.
A main focus of the project is to develop new techniques for solving such protocol problems. We are in particular interested in techniques which can automatically construct a protocol solving a problem given only a description of what the problem is. My focus will be theoretical basic research, but I believe that advancing the theory of secure protocol compilers will have an immense impact on the practice of developing secure protocols for practice.
When one develops complex protocols, it is important to be able to verify their correctness before they are deployed, in particular so, when the purpose of the protocols is to protect information. If and when an error is found and corrected, the sensitive data will possibly already be compromised. Therefore, cryptographic protocol theory develops models of what it means for a protocol to be secure, and techniques for analyzing whether a given protocol is secure or not.
A main focuses of the project is to develop better security models, as existing security models either suffer from the problem that it is possible to prove some protocols secure which are not secure in practice, or they suffer from the problem that it is impossible to prove security of some protocol which are believed to be secure in practice. My focus will again be on theoretical basic research, but I believe that better security models are important for advancing a practice where protocols are verified as secure before deployed.
Max ERC Funding
1 171 019 €
Duration
Start date: 2011-12-01, End date: 2016-11-30
Project acronym BRIDGE
Project Bridging the gap between Gas Emissions and geophysical observations at active volcanoes
Researcher (PI) Alessandro Aiuppa
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PALERMO
Call Details Starting Grant (StG), PE10, ERC-2012-StG_20111012
Summary In spite of their significance in a variety of volcanological aspects, gas observations at volcanoes have lagged behind geophysical studies for a long time. This has primarily reflected the inherent technical limitations met by gas geochemists in capturing volcanic gas properties (chemistry and flux) at high-rate (1 Hz), and using permanent instrumental arrays. The poor temporal resolution of volcanic gas observations has, in addition, precluded the real-time analysis of fast-occurring volcanic processes, as those occurring shortly prior to eruptions, therefore generally limiting the use of gas geochemistry in volcanic hazard assessment. However, the recent progresses made by modern multi-component/high frequency measurement techniques now open the way for decisive step ahead in the current state-of-the-art to be finally attempted.
The BRIDGE research proposal has the ambitious goals to bridge the existing technological gap between geochemical and geophysical observations at volcanoes. This will be achieved by designing, setting up, and deploying in the field, innovative instruments for 1 Hz observations of volcanic SO2 and CO2 fluxes. From this, the co-acquired volcanic gas and geophysical information will be then combined within a single interpretative framework, therefore contributing to fill our current gap of knowledge on fast (timescales of seconds/minutes) degassing processes, and to deeper exploration of the role played by gas exsolution from (and migration through) silicate liquids as effective source mechanism of the physical signals (e.g., LP and VLP seismicity, and tremor) measured at volcanoes. Finally, this combined volcanic gas-geophysical approach will be used to yield improved modelling/understanding of a variety of volcanic features, including modes/rates of gas separation from magmas, mechanisms of gas flow in conduits, and trigger mechanisms of explosive volcanic eruptions.
Summary
In spite of their significance in a variety of volcanological aspects, gas observations at volcanoes have lagged behind geophysical studies for a long time. This has primarily reflected the inherent technical limitations met by gas geochemists in capturing volcanic gas properties (chemistry and flux) at high-rate (1 Hz), and using permanent instrumental arrays. The poor temporal resolution of volcanic gas observations has, in addition, precluded the real-time analysis of fast-occurring volcanic processes, as those occurring shortly prior to eruptions, therefore generally limiting the use of gas geochemistry in volcanic hazard assessment. However, the recent progresses made by modern multi-component/high frequency measurement techniques now open the way for decisive step ahead in the current state-of-the-art to be finally attempted.
The BRIDGE research proposal has the ambitious goals to bridge the existing technological gap between geochemical and geophysical observations at volcanoes. This will be achieved by designing, setting up, and deploying in the field, innovative instruments for 1 Hz observations of volcanic SO2 and CO2 fluxes. From this, the co-acquired volcanic gas and geophysical information will be then combined within a single interpretative framework, therefore contributing to fill our current gap of knowledge on fast (timescales of seconds/minutes) degassing processes, and to deeper exploration of the role played by gas exsolution from (and migration through) silicate liquids as effective source mechanism of the physical signals (e.g., LP and VLP seismicity, and tremor) measured at volcanoes. Finally, this combined volcanic gas-geophysical approach will be used to yield improved modelling/understanding of a variety of volcanic features, including modes/rates of gas separation from magmas, mechanisms of gas flow in conduits, and trigger mechanisms of explosive volcanic eruptions.
Max ERC Funding
1 496 222 €
Duration
Start date: 2012-10-01, End date: 2016-09-30
Project acronym CARBENZYMES
Project Probing the relevance of carbene binding motifs in enzyme reactivity
Researcher (PI) Martin Albrecht
Host Institution (HI) UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Call Details Starting Grant (StG), PE4, ERC-2007-StG
Summary Histidine (His) is an ubiquitous ligand in the active site of metalloenzymes that is assumed by default to bind the metal center through one of its nitrogen atoms. However, protonation of His, which is likely to occur in locally slightly acidic environment, gives imidazolium sites that can bind a metal in a carbene-type structure as found in N-heterocyclic carbene complexes. Such carbene bonding has a dramatic effect on the properties of the metal center and may provide a rational for the mode of action of metalloenzymes that are still lacking a solid understanding. Up to now, the possibility of carbene bonding has been completely overlooked. Hence, any evidence for such His coordination via carbon will induce a shift of paradigm in classical peptide chemistry and will be directly included in basic textbooks. Moreover, this unprecedented bonding mode will provide access to unique and hitherto unknown reactivity patterns for artificial enzyme mimics. Undoubtedly, such a break-through will set a new stage in modern metalloenzyme research. A multicentered approach is proposed to identify for the first time carbene bonding in enzymes. This approach unconventionally combines the current frontiers of organometallic and biochemical knowledge and hence crosses traditional boarders. Specifically, we aim at probing carbene bonding of His by identifying reactivity patterns that are selective for metal-carbenes but not for metal-imine complexes. This will allow for efficient screening of large classes of metalloenzymes. In parallel, active site models will be constructed in which the His ligand is substituted by a heterocyclic carbene as a rigidly C-bonding His analog. For this purpose chemical synthesis will be considered as well as enzyme mutagenesis and subsequent carbene coordination. While such new bioorganometallic entities will be highly attractive to probe the influence of C-bound His on the metal site, they also provide conceputally new types of versatile catalysts.
Summary
Histidine (His) is an ubiquitous ligand in the active site of metalloenzymes that is assumed by default to bind the metal center through one of its nitrogen atoms. However, protonation of His, which is likely to occur in locally slightly acidic environment, gives imidazolium sites that can bind a metal in a carbene-type structure as found in N-heterocyclic carbene complexes. Such carbene bonding has a dramatic effect on the properties of the metal center and may provide a rational for the mode of action of metalloenzymes that are still lacking a solid understanding. Up to now, the possibility of carbene bonding has been completely overlooked. Hence, any evidence for such His coordination via carbon will induce a shift of paradigm in classical peptide chemistry and will be directly included in basic textbooks. Moreover, this unprecedented bonding mode will provide access to unique and hitherto unknown reactivity patterns for artificial enzyme mimics. Undoubtedly, such a break-through will set a new stage in modern metalloenzyme research. A multicentered approach is proposed to identify for the first time carbene bonding in enzymes. This approach unconventionally combines the current frontiers of organometallic and biochemical knowledge and hence crosses traditional boarders. Specifically, we aim at probing carbene bonding of His by identifying reactivity patterns that are selective for metal-carbenes but not for metal-imine complexes. This will allow for efficient screening of large classes of metalloenzymes. In parallel, active site models will be constructed in which the His ligand is substituted by a heterocyclic carbene as a rigidly C-bonding His analog. For this purpose chemical synthesis will be considered as well as enzyme mutagenesis and subsequent carbene coordination. While such new bioorganometallic entities will be highly attractive to probe the influence of C-bound His on the metal site, they also provide conceputally new types of versatile catalysts.
Max ERC Funding
1 249 808 €
Duration
Start date: 2008-07-01, End date: 2013-06-30
Project acronym CARBONANOBRIDGE
Project Neuron Networking with Nano Bridges via the Synthesis and Integration of Functionalized Carbon Nanotubes
Researcher (PI) Maurizio Prato
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TRIESTE
Call Details Advanced Grant (AdG), PE5, ERC-2008-AdG
Summary We propose the development of novel nanodevices, such as nanoscale bridges and nanovectors, based on functionalized carbon nanotubes (CNT) for manipulating neurons and neuronal network activity in vitro. The main aim is to put forward innovative solutions that have the potential to circumvent the problems currently faced by spinal cord lesions or by neurodegenerative diseases. The unifying theme is to use recent advances in chemistry and nanotechnology to gain insight into the functioning of hybrid neuronal/CNT networks, relevant for the development of novel implantable devices to control neuronal signaling and improve synapse formation in a controlled fashion. The proposal s core strategy is to exploit the expertise of the PI in the chemical control of CNT properties to develop devices reaching various degrees of functional integration with the physiological electrical activity of cells and their networks, and to understand how such global dynamics are orchestrated when integrated by different substrates. An unconventional strategy will be represented by the electrical characterization of micro and nano patterned substrates by AFM and conductive tip AFM, both before and after neurons have grown on the substrates. We will also use the capability of AFM to identify critical positions in the neuronal network, while delivering time-dependent chemical stimulations. We will apply nanotechnology to contemporary neuroscience in the perspective of novel neuro-implantable devices and drug nanovectors, engineered to treat neurological and neurodegenerative lesions. The scientific strategy at the core of the proposal is the convergence between nanotechnology, chemistry and neurobiology. Such convergence, beyond helping understand the functioning and malfunctioning of the brain, can stimulate further research in this area and may ultimately lead to a new generation of nanomedicine applications in neurology and to new opportunities for the health care industry.
Summary
We propose the development of novel nanodevices, such as nanoscale bridges and nanovectors, based on functionalized carbon nanotubes (CNT) for manipulating neurons and neuronal network activity in vitro. The main aim is to put forward innovative solutions that have the potential to circumvent the problems currently faced by spinal cord lesions or by neurodegenerative diseases. The unifying theme is to use recent advances in chemistry and nanotechnology to gain insight into the functioning of hybrid neuronal/CNT networks, relevant for the development of novel implantable devices to control neuronal signaling and improve synapse formation in a controlled fashion. The proposal s core strategy is to exploit the expertise of the PI in the chemical control of CNT properties to develop devices reaching various degrees of functional integration with the physiological electrical activity of cells and their networks, and to understand how such global dynamics are orchestrated when integrated by different substrates. An unconventional strategy will be represented by the electrical characterization of micro and nano patterned substrates by AFM and conductive tip AFM, both before and after neurons have grown on the substrates. We will also use the capability of AFM to identify critical positions in the neuronal network, while delivering time-dependent chemical stimulations. We will apply nanotechnology to contemporary neuroscience in the perspective of novel neuro-implantable devices and drug nanovectors, engineered to treat neurological and neurodegenerative lesions. The scientific strategy at the core of the proposal is the convergence between nanotechnology, chemistry and neurobiology. Such convergence, beyond helping understand the functioning and malfunctioning of the brain, can stimulate further research in this area and may ultimately lead to a new generation of nanomedicine applications in neurology and to new opportunities for the health care industry.
Max ERC Funding
2 500 000 €
Duration
Start date: 2009-02-01, End date: 2014-01-31
