Project acronym A-FRO
Project Actively Frozen - contextual modulation of freezing and its neuronal basis
Researcher (PI) Marta de Aragão Pacheco Moita
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Summary
When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Max ERC Funding
1 969 750 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym DNA Funs
Project DNA-based functional lattices
Researcher (PI) Tim LIEDL
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary Nature has evolved astonishingly diverse structures where the nanoscale assembly of components is key to their functionality. Such nanostructures self-assemble at massive scales and at spatial resolutions surpassing top-down production techniques. The leaves of a single tree, e.g., can cover the area of 10.000 m^2 while every mm^2 contains more than 10^8 highly efficient light-harvesting complexes. For future photovoltaic devices, light-managing surfaces and photonic devices it will thus be beneficial to adopt principles of self-assembly. Advances in design and low-cost production of DNA nanostructures allow us to challenge nature. By combining the assembly power of bottom-up DNA origami with top-down lithography it will be possible to fabricate functional nanostructured materials designed on the molecular level while reaching macroscopic dimensions.
With the goal to boost energy conversion rates, I will design DNA structures that grow from pre-patterned surfaces and assemble into interpenetrating 3D networks that exhibit the highest possible contact area for electron donor and acceptor molecules in organic photovoltaic devices. Spectral tuning through carefully designed dye arrangements will complement these efforts.
Custom-tailored photonic crystals built from lattices of DNA origami structures will control the flow of light. By incorporating dynamic DNA reconfigurability and colloidal nanoparticles at freely chosen positions, intelligent materials that respond to external cues such as light or heat are projected.
Positioning accuracy of 1 nm renders possible the emergence of so-called “Dirac plasmons” in DNA-assembled particle lattices. Such topologically protected states are sought after for the coherent and loss-less propagation of energy and information in next-generation all-optical circuits.
These approaches have the potential to reduce production costs and increase efficiencies of light-harvesting devices, intelligent surfaces and future computing devices.
Summary
Nature has evolved astonishingly diverse structures where the nanoscale assembly of components is key to their functionality. Such nanostructures self-assemble at massive scales and at spatial resolutions surpassing top-down production techniques. The leaves of a single tree, e.g., can cover the area of 10.000 m^2 while every mm^2 contains more than 10^8 highly efficient light-harvesting complexes. For future photovoltaic devices, light-managing surfaces and photonic devices it will thus be beneficial to adopt principles of self-assembly. Advances in design and low-cost production of DNA nanostructures allow us to challenge nature. By combining the assembly power of bottom-up DNA origami with top-down lithography it will be possible to fabricate functional nanostructured materials designed on the molecular level while reaching macroscopic dimensions.
With the goal to boost energy conversion rates, I will design DNA structures that grow from pre-patterned surfaces and assemble into interpenetrating 3D networks that exhibit the highest possible contact area for electron donor and acceptor molecules in organic photovoltaic devices. Spectral tuning through carefully designed dye arrangements will complement these efforts.
Custom-tailored photonic crystals built from lattices of DNA origami structures will control the flow of light. By incorporating dynamic DNA reconfigurability and colloidal nanoparticles at freely chosen positions, intelligent materials that respond to external cues such as light or heat are projected.
Positioning accuracy of 1 nm renders possible the emergence of so-called “Dirac plasmons” in DNA-assembled particle lattices. Such topologically protected states are sought after for the coherent and loss-less propagation of energy and information in next-generation all-optical circuits.
These approaches have the potential to reduce production costs and increase efficiencies of light-harvesting devices, intelligent surfaces and future computing devices.
Max ERC Funding
1 997 500 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym F-ELEMENT_ARCHITECT
Project Building Precise Molecular Architectures to Unlock Remarkable f-Element Properties
Researcher (PI) David MILLS
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary The astonishing properties of the f-elements have been exploited in numerous consumer technologies, despite their fundamental chemistry being poorly developed. It is now crucial to address this issue to provide the necessary insights to develop future applications. Design criteria exist to build f-element complexes with maximised physical attributes. This adventurous proposal targets the synthesis and thorough analysis of two complementary molecular f-element architectures that 1) optimise magnetic properties and 2) stabilise unusual oxidation states.
In Part 1, we target highly axial f-element complexes that lack equatorial ligand interactions. These molecules can exhibit maximised single-molecule magnet properties, including magnetic hysteresis, a memory effect and as a prerequisite of data storage, at liquid nitrogen temperatures. This is the necessary first step towards achieving high-density molecular data storage without expensive liquid helium cooling and future commercial applications.
In Part 2, we target trigonal f-element complexes that lack axial ligand interactions. These are optimal ligand fields for the stabilisation of low oxidation states, thus we aim for rare lanthanide/actinide(II) and unprecedented lanthanide/actinide(I) complexes. These compounds are ideal candidates for unique measurements of covalency by pulsed electron paramagnetic resonance spectroscopy, which will provide textbook data that can be transferable to nuclear fuel cycles.
An ERC CoG will provide the necessary resources to build a world-leading research team that will deliver landmark synthetic results and fresh insights into f-element electronic structure, whilst opening up new chemical space for future exploitation. These findings will underpin current technologies and will facilitate the discovery of future applications, supporting key Horizon 2020 priority areas including the Flagship on Quantum Technologies, and enhancing the scientific reputation and economy of the EU.
Summary
The astonishing properties of the f-elements have been exploited in numerous consumer technologies, despite their fundamental chemistry being poorly developed. It is now crucial to address this issue to provide the necessary insights to develop future applications. Design criteria exist to build f-element complexes with maximised physical attributes. This adventurous proposal targets the synthesis and thorough analysis of two complementary molecular f-element architectures that 1) optimise magnetic properties and 2) stabilise unusual oxidation states.
In Part 1, we target highly axial f-element complexes that lack equatorial ligand interactions. These molecules can exhibit maximised single-molecule magnet properties, including magnetic hysteresis, a memory effect and as a prerequisite of data storage, at liquid nitrogen temperatures. This is the necessary first step towards achieving high-density molecular data storage without expensive liquid helium cooling and future commercial applications.
In Part 2, we target trigonal f-element complexes that lack axial ligand interactions. These are optimal ligand fields for the stabilisation of low oxidation states, thus we aim for rare lanthanide/actinide(II) and unprecedented lanthanide/actinide(I) complexes. These compounds are ideal candidates for unique measurements of covalency by pulsed electron paramagnetic resonance spectroscopy, which will provide textbook data that can be transferable to nuclear fuel cycles.
An ERC CoG will provide the necessary resources to build a world-leading research team that will deliver landmark synthetic results and fresh insights into f-element electronic structure, whilst opening up new chemical space for future exploitation. These findings will underpin current technologies and will facilitate the discovery of future applications, supporting key Horizon 2020 priority areas including the Flagship on Quantum Technologies, and enhancing the scientific reputation and economy of the EU.
Max ERC Funding
1 990 801 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym HighPotOx
Project Exploring the Limits of High Potential OxidizersPrediction, Validation and Preparation of Unusual Molecules at the Edge of Stability
Researcher (PI) Sebastian HASENSTAB-RIEDEL
Host Institution (HI) FREIE UNIVERSITAET BERLIN
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary The very well-known concept of formal oxidation states, used e. g. for redox reactions is one of the most fundamental ones in general chemistry. However, in the area of very strong oxidizers even the familiar oxido(-II) ligand becomes redox-innocent and assigning oxidation states becomes ambiguous. Very strong (super-) oxidizers are compounds whose oxidizing strength exceeds that of elemental F2. Anyhow, not only molecular oxidizer but also their interaction with the environment in different media needs to be considered, as these dramatically affect their intrinsic oxidizing strength. Here we propose novel conjugate oxidizer/Lewis or Brønsted acid systems with extremely high ox. power. These new ox. media make use of the alliance of high ox. strength and Lewis /Brønsted super acidity. The investigation and development of oxidizers is of essential interest in all areas of chemistry and beyond. Unfortunately a detailed understanding of this fundamental chemistry is still lacking. Here we describe based on three work strands PV, MI, and BP, how we aim at a more fundamental understanding of such systems. The undertaken research, which includes qc investigations, molecular characterizations in matrices and synthetic fluorine chemistry as well as oxido complexes is summarized in five work packages describing different prototype areas (organigram). Based on the gained knowledge, the project will rank and specify such oxidizers and the mechanism leading to ox. media. By using the threefold work strand approach, our project will guide us in a systematic discovery of the systems with high application potential in terms of selectivity and disposability, and oxidizing systems with high to ultrahigh oxidation potentials, and into the chemical terra incognita of fragile molecules at the edge of stability. We envision to highlight that the outcome of the project will be extremely useful for scientists from almost all fields of chemistry and related disciplines.
Summary
The very well-known concept of formal oxidation states, used e. g. for redox reactions is one of the most fundamental ones in general chemistry. However, in the area of very strong oxidizers even the familiar oxido(-II) ligand becomes redox-innocent and assigning oxidation states becomes ambiguous. Very strong (super-) oxidizers are compounds whose oxidizing strength exceeds that of elemental F2. Anyhow, not only molecular oxidizer but also their interaction with the environment in different media needs to be considered, as these dramatically affect their intrinsic oxidizing strength. Here we propose novel conjugate oxidizer/Lewis or Brønsted acid systems with extremely high ox. power. These new ox. media make use of the alliance of high ox. strength and Lewis /Brønsted super acidity. The investigation and development of oxidizers is of essential interest in all areas of chemistry and beyond. Unfortunately a detailed understanding of this fundamental chemistry is still lacking. Here we describe based on three work strands PV, MI, and BP, how we aim at a more fundamental understanding of such systems. The undertaken research, which includes qc investigations, molecular characterizations in matrices and synthetic fluorine chemistry as well as oxido complexes is summarized in five work packages describing different prototype areas (organigram). Based on the gained knowledge, the project will rank and specify such oxidizers and the mechanism leading to ox. media. By using the threefold work strand approach, our project will guide us in a systematic discovery of the systems with high application potential in terms of selectivity and disposability, and oxidizing systems with high to ultrahigh oxidation potentials, and into the chemical terra incognita of fragile molecules at the edge of stability. We envision to highlight that the outcome of the project will be extremely useful for scientists from almost all fields of chemistry and related disciplines.
Max ERC Funding
1 988 280 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym InOutBioLight
Project Advanced biohybrid lighting and photovoltaic devices
Researcher (PI) Rubén Darío COSTA
Host Institution (HI) FUNDACION IMDEA MATERIALES
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary InOutBioLight aims to design multifunctional rubbers with enhanced mechanical, thermal, color-converting, and light-guiding features towards advanced biohybrid lighting and photovoltaic technologies. The latter are placed at the forefront of the EU efforts for low-cost production and efficient consumption of electricity, a critical issue for a sustainable development.
In this context, the use of biomolecules as functional components in lighting and photovoltaic devices is still a challenge, as they quickly denature under storage and device operation conditions. This paradigm has changed using an innovative rubber-like material, in which the biofunctionality is long preserved. As a proof-of-concept, color down-converting rubbers based on fluorescent proteins were used to design the first biohybrid white light-emitting diode (bio-HWLED). To develop a new generation of biohybrid devices, InOutBioLight will address the following critical issues, namely i) the nature of the protein-matrix stabilization, ii) how to enhance the thermal/mechanical features, iii) how to design multifunctional rubbers, iv) how to mimic natural patterns for light-guiding, and v) how to expand the technological use of the rubber approach.
To achieve these goals, InOutBioLight involves comprehensive spectroscopic, microscopic, and mechanical studies to investigate the protein-matrix interaction using new polymer matrices, additives, and protein-based nanoparticles. In addition, the mechanical, thermal, and light-coupling features will be enhanced using structural biocompounds and reproducing biomorphic patterns. As such, InOutBioLight offers three major advances: i) a thorough scientific basis for the rubber approach, ii) a significant thrust of the emerging bio-HWLEDs, and iii) innovative breakthroughs beyond state-of-the-art biohybrid solar cells.
Summary
InOutBioLight aims to design multifunctional rubbers with enhanced mechanical, thermal, color-converting, and light-guiding features towards advanced biohybrid lighting and photovoltaic technologies. The latter are placed at the forefront of the EU efforts for low-cost production and efficient consumption of electricity, a critical issue for a sustainable development.
In this context, the use of biomolecules as functional components in lighting and photovoltaic devices is still a challenge, as they quickly denature under storage and device operation conditions. This paradigm has changed using an innovative rubber-like material, in which the biofunctionality is long preserved. As a proof-of-concept, color down-converting rubbers based on fluorescent proteins were used to design the first biohybrid white light-emitting diode (bio-HWLED). To develop a new generation of biohybrid devices, InOutBioLight will address the following critical issues, namely i) the nature of the protein-matrix stabilization, ii) how to enhance the thermal/mechanical features, iii) how to design multifunctional rubbers, iv) how to mimic natural patterns for light-guiding, and v) how to expand the technological use of the rubber approach.
To achieve these goals, InOutBioLight involves comprehensive spectroscopic, microscopic, and mechanical studies to investigate the protein-matrix interaction using new polymer matrices, additives, and protein-based nanoparticles. In addition, the mechanical, thermal, and light-coupling features will be enhanced using structural biocompounds and reproducing biomorphic patterns. As such, InOutBioLight offers three major advances: i) a thorough scientific basis for the rubber approach, ii) a significant thrust of the emerging bio-HWLEDs, and iii) innovative breakthroughs beyond state-of-the-art biohybrid solar cells.
Max ERC Funding
1 999 188 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym LeaRNN
Project Principles of Learning in a Recurrent Neural Network
Researcher (PI) Marta Zlatic
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary Forming memories, generating predictions based on memories, and updating memories when predictions no longer match actual experience are fundamental brain functions. Dopaminergic neurons provide a so-called “teaching signal” that drives the formation and updates of associative memories across the animal kingdom. Many theoretical models propose how neural circuits could compute the teaching signals, but the actual implementation of this computation in real nervous systems is unknown.
This project will discover the basic principles by which neural circuits compute the teaching signals that drive memory formation and updates using a tractable insect model system, the Drosophila larva. We will generate, for the first time in any animal, the following essential datasets for a distributed, multilayered, recurrent learning circuit, the mushroom body-related circuitry in the larval brain. First, building on our preliminary work that provides the synaptic-resolution connectome of the circuit, including all feedforward and feedback pathways upstream of all dopaminergic neurons, we will generate a map of functional monosynaptic connections. Second, we will obtain cellular-resolution whole-nervous system activity maps in intact living animals, as they form, extinguish, or consolidate memories to discover the features represented in each layer of the circuit (e.g. predictions, actual reinforcement, and prediction errors), the learning algorithms, and the candidate circuit motifs that implement them. Finally, we will develop a model of the circuit constrained by these datasets and test the predictions about the necessity and sufficiency of uniquely identified circuit elements for implementing learning algorithms by selectively manipulating their activity.
Understanding the basic functional principles of an entire multilayered recurrent learning circuit in an animal has the potential to revolutionize, not only neuroscience and medicine, but also machine-learning and robotics.
Summary
Forming memories, generating predictions based on memories, and updating memories when predictions no longer match actual experience are fundamental brain functions. Dopaminergic neurons provide a so-called “teaching signal” that drives the formation and updates of associative memories across the animal kingdom. Many theoretical models propose how neural circuits could compute the teaching signals, but the actual implementation of this computation in real nervous systems is unknown.
This project will discover the basic principles by which neural circuits compute the teaching signals that drive memory formation and updates using a tractable insect model system, the Drosophila larva. We will generate, for the first time in any animal, the following essential datasets for a distributed, multilayered, recurrent learning circuit, the mushroom body-related circuitry in the larval brain. First, building on our preliminary work that provides the synaptic-resolution connectome of the circuit, including all feedforward and feedback pathways upstream of all dopaminergic neurons, we will generate a map of functional monosynaptic connections. Second, we will obtain cellular-resolution whole-nervous system activity maps in intact living animals, as they form, extinguish, or consolidate memories to discover the features represented in each layer of the circuit (e.g. predictions, actual reinforcement, and prediction errors), the learning algorithms, and the candidate circuit motifs that implement them. Finally, we will develop a model of the circuit constrained by these datasets and test the predictions about the necessity and sufficiency of uniquely identified circuit elements for implementing learning algorithms by selectively manipulating their activity.
Understanding the basic functional principles of an entire multilayered recurrent learning circuit in an animal has the potential to revolutionize, not only neuroscience and medicine, but also machine-learning and robotics.
Max ERC Funding
2 350 000 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym LifeLikeMat
Project Dissipative self-assembly in synthetic systems: Towards life-like materials
Researcher (PI) Rafal KLAJN
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary "Living organisms are sophisticated self-assembled structures that exist and operate far from thermodynamic equilibrium and, as such, represent the ultimate example of dissipative self-assembly. They remain stable at highly organized (low-entropy) states owing to the continuous consumption of energy stored in ""chemical fuels"", which they convert into low-energy waste. Dissipative self-assembly is ubiquitous in nature, where it gives rise to complex structures and properties such as self-healing, homeostasis, and camouflage. In sharp contrast, nearly all man-made materials are static: they are designed to serve a given purpose rather than to exhibit different properties dependent on external conditions. Developing the means to rationally design dissipative self-assembly constructs will greatly impact a range of industries, including the pharmaceutical and energy sectors.
The goal of the proposed research program is to develop novel principles for designing dissipative self-assembly systems and to fabricate a range of dissipative materials based on these principles. To achieve this goal, we will employ novel, unconventional approaches based predominantly on integrating organic and colloidal-inorganic building blocks.
Specifically, we will (WP1) drive dissipative self-assembly using chemical reactions such as polymerization, oxidation of sugars, and CO2-to-methanol conversion, (WP2) develop new modes of intrinsically dissipative self-assembly, whereby the activated building blocks are inherently unstable, and (WP3&4) conceive systems whereby self-assembly is spontaneously followed by disassembly.
The proposed studies will lead to new classes of ""driven"" materials with features such as tunable lifetimes, time-dependent electrical conductivity, and dynamic exchange of building blocks. Overall, this project will lay the foundations for developing new synthetic dissipative materials, bringing us closer to the rich and varied functionality of materials found in nature."
Summary
"Living organisms are sophisticated self-assembled structures that exist and operate far from thermodynamic equilibrium and, as such, represent the ultimate example of dissipative self-assembly. They remain stable at highly organized (low-entropy) states owing to the continuous consumption of energy stored in ""chemical fuels"", which they convert into low-energy waste. Dissipative self-assembly is ubiquitous in nature, where it gives rise to complex structures and properties such as self-healing, homeostasis, and camouflage. In sharp contrast, nearly all man-made materials are static: they are designed to serve a given purpose rather than to exhibit different properties dependent on external conditions. Developing the means to rationally design dissipative self-assembly constructs will greatly impact a range of industries, including the pharmaceutical and energy sectors.
The goal of the proposed research program is to develop novel principles for designing dissipative self-assembly systems and to fabricate a range of dissipative materials based on these principles. To achieve this goal, we will employ novel, unconventional approaches based predominantly on integrating organic and colloidal-inorganic building blocks.
Specifically, we will (WP1) drive dissipative self-assembly using chemical reactions such as polymerization, oxidation of sugars, and CO2-to-methanol conversion, (WP2) develop new modes of intrinsically dissipative self-assembly, whereby the activated building blocks are inherently unstable, and (WP3&4) conceive systems whereby self-assembly is spontaneously followed by disassembly.
The proposed studies will lead to new classes of ""driven"" materials with features such as tunable lifetimes, time-dependent electrical conductivity, and dynamic exchange of building blocks. Overall, this project will lay the foundations for developing new synthetic dissipative materials, bringing us closer to the rich and varied functionality of materials found in nature."
Max ERC Funding
1 999 572 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym makingtheretina
Project Principles of retinal neuronal lamination from zebrafish to humans
Researcher (PI) Caren NORDEN
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary Neuronal lamination is a hallmark of many diverse brain areas where it is important for efficient circuit formation and neuronal wiring. Despite this significance, the cellular and tissue scale principles that ensure successful and robust lamination are not fully understood. In particular, how cell-tissue interactions and biomechanics influence neuronal lamination is only scarcely explored. To fill this gap, we will use the vertebrate retina with its five neuronal cell types arranged in a highly ordered pattern to investigate the emergence of neuronal lamination.
We will initially use the zebrafish system and employ long term light sheet imaging to reveal the migration behaviour of the different retinal neurons. Based on this, transcriptomics approaches will enable the dissection of cellular pathways and extracellular cues involved in neuronal migration and overall lamination. To dissect how biomechanics influence lamination, we will use Brillouin microscopy to explore the influence of changing tissue stiffness on lamination and test the role of differential adhesion. These combined results will be the basis to expand studies to the human system and ex vivo human organoids to generate insights into human retinal development.
To date, systematic studies investigating molecular pathways in combination with biophysical parameters to understand brain formation across model systems are rare. Due to our previous expertise, we are in an excellent position to perform such interdisciplinary, integrative and interspecies approach. This will unveil common denominators of retinal neuronal lamination in zebrafish, humans and human organoids and thereby reveal the similarities of retinal development in different species and how developmental programs compare in vivo versus ex vivo.
In addition, while this proposal focuses on neural lamination in the retina, findings will also inspire future cross-disciplinary studies investigating neuronal lamination in other parts of the brain.
Summary
Neuronal lamination is a hallmark of many diverse brain areas where it is important for efficient circuit formation and neuronal wiring. Despite this significance, the cellular and tissue scale principles that ensure successful and robust lamination are not fully understood. In particular, how cell-tissue interactions and biomechanics influence neuronal lamination is only scarcely explored. To fill this gap, we will use the vertebrate retina with its five neuronal cell types arranged in a highly ordered pattern to investigate the emergence of neuronal lamination.
We will initially use the zebrafish system and employ long term light sheet imaging to reveal the migration behaviour of the different retinal neurons. Based on this, transcriptomics approaches will enable the dissection of cellular pathways and extracellular cues involved in neuronal migration and overall lamination. To dissect how biomechanics influence lamination, we will use Brillouin microscopy to explore the influence of changing tissue stiffness on lamination and test the role of differential adhesion. These combined results will be the basis to expand studies to the human system and ex vivo human organoids to generate insights into human retinal development.
To date, systematic studies investigating molecular pathways in combination with biophysical parameters to understand brain formation across model systems are rare. Due to our previous expertise, we are in an excellent position to perform such interdisciplinary, integrative and interspecies approach. This will unveil common denominators of retinal neuronal lamination in zebrafish, humans and human organoids and thereby reveal the similarities of retinal development in different species and how developmental programs compare in vivo versus ex vivo.
In addition, while this proposal focuses on neural lamination in the retina, findings will also inspire future cross-disciplinary studies investigating neuronal lamination in other parts of the brain.
Max ERC Funding
1 923 750 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym MechanoTubes
Project Supramolecular machineries with life-like mechanical functions
Researcher (PI) Tibor Kudernac
Host Institution (HI) UNIVERSITEIT TWENTE
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary Artificial molecular motors and switches have the potential to become a core part of nanotechnology. However, a wide gap in length scales still remains unaccounted for, between the operation of these molecules in solution, where their individual mechanical action is randomly dispersed in the Brownian storm, and on the other hand their action at the macroscopic level, e.g. in polymer networks and crystals.
This proposal is about bridging this gap, by developing chemo-mechanical transduction strategies that will allow dynamic molecules to perform a range of unprecedented tasks, e.g. by generating strong directional forces at the nanoscale, and through shape-shifting microscopic formations.
This project aims to harness the mechanically-purposeful motion of dynamic molecules as to generate measurable forces from the nanoscale, and ultimately establish operational principles for chemo-mechanical transduction in supramolecular systems.
In my wholly synthetic approach, I draw inspiration from the operational principles of microtubules. I will incorporate molecular photo-switches into supramolecular tubes, and enable the controlled growth and disassembly of the tubes by using light as the energy input. Thus, I will: (i) Synthesize stiff supramolecular tubes that grow actively under continuous illumination, and disassemble with a power stroke as soon as illumination stops; (ii) Measure, and harvest the forces generated by the tubes to manipulate individual nanoparticles with a sense of directionality; and (iii) Encapsulate the tubes into water droplets and vesicles, to yield shape-shifting, and eventually rudimentary splitting models for cells.
This project reaches beyond the state of the art in adaptive molecular nano-systems, by pioneering strategies to engineer and harness strain in supramolecular assemblies. It thus lays the foundations for machineries that are capable of manipulating matter at length scales that are also those at which the cytoskeleton operates.
Summary
Artificial molecular motors and switches have the potential to become a core part of nanotechnology. However, a wide gap in length scales still remains unaccounted for, between the operation of these molecules in solution, where their individual mechanical action is randomly dispersed in the Brownian storm, and on the other hand their action at the macroscopic level, e.g. in polymer networks and crystals.
This proposal is about bridging this gap, by developing chemo-mechanical transduction strategies that will allow dynamic molecules to perform a range of unprecedented tasks, e.g. by generating strong directional forces at the nanoscale, and through shape-shifting microscopic formations.
This project aims to harness the mechanically-purposeful motion of dynamic molecules as to generate measurable forces from the nanoscale, and ultimately establish operational principles for chemo-mechanical transduction in supramolecular systems.
In my wholly synthetic approach, I draw inspiration from the operational principles of microtubules. I will incorporate molecular photo-switches into supramolecular tubes, and enable the controlled growth and disassembly of the tubes by using light as the energy input. Thus, I will: (i) Synthesize stiff supramolecular tubes that grow actively under continuous illumination, and disassemble with a power stroke as soon as illumination stops; (ii) Measure, and harvest the forces generated by the tubes to manipulate individual nanoparticles with a sense of directionality; and (iii) Encapsulate the tubes into water droplets and vesicles, to yield shape-shifting, and eventually rudimentary splitting models for cells.
This project reaches beyond the state of the art in adaptive molecular nano-systems, by pioneering strategies to engineer and harness strain in supramolecular assemblies. It thus lays the foundations for machineries that are capable of manipulating matter at length scales that are also those at which the cytoskeleton operates.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym MOF-reactors
Project Metal-Organic Frameworks as Chemical Reactors for the Synthesis of Well-Defined Sub-Nanometer Metal Clusters
Researcher (PI) Emilio PARDO
Host Institution (HI) UNIVERSITAT DE VALENCIA
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary Humankind advancement is connected to the use and development of metal forms. Recent works have unveiled exceptional properties –such as luminescence, biocompatibility, antitumoral activity or a superlative catalytic activity– for small aggregations of metal atoms, so–called sub–nanometer metal clusters (SNMCs). Despite this importance, the gram-scale synthesis of structurally and electronically well–defined SNMCs is still far from being a reality.
The present proposal situates at the centre of such weakness and aims at making a breakthrough step-change on the use of metal-organic frameworks (MOFs) as chemical reactors for the in–situ synthesis of stable ligand-free SNMCs with such unique properties. This challenging synthetic strategy, which is assisted by striking published and inedited preliminary results, has solid foundations. Firstly, the design and large-scale preparation of cheap and novel families of highly robust and crystalline MOFs with tailor-made functional channels to be used as chemical reactors. Secondly, the application of solid-state post-synthetic methods to drive the multigram-scale preparation of unique ligand-free homo- and heterometallic SNMCs, which are, in the best-case scenario, very difficult to be obtained and stabilised outside the channels. Last but not least, single-crystal X-Ray diffraction will be used as the definitive tool for the characterisation, at the atomic level, of such ultrasmall species offering unprecedented snapshots about their real structures and formation mechanisms.
The ultimate goal will be upscaling this synthetic strategy aiming at the large-scale fabrication of SNMCs and their industrial application will be then evaluated. A successful achievement of all the aforementioned objectives of this ground-breaking project would open new routes for the use of MOFs as chemical reactors to manufacture, at competitive prices, MOF-driven, structurally and electronically well–defined, ligand–free SNMCs in a multigram-scale.
Summary
Humankind advancement is connected to the use and development of metal forms. Recent works have unveiled exceptional properties –such as luminescence, biocompatibility, antitumoral activity or a superlative catalytic activity– for small aggregations of metal atoms, so–called sub–nanometer metal clusters (SNMCs). Despite this importance, the gram-scale synthesis of structurally and electronically well–defined SNMCs is still far from being a reality.
The present proposal situates at the centre of such weakness and aims at making a breakthrough step-change on the use of metal-organic frameworks (MOFs) as chemical reactors for the in–situ synthesis of stable ligand-free SNMCs with such unique properties. This challenging synthetic strategy, which is assisted by striking published and inedited preliminary results, has solid foundations. Firstly, the design and large-scale preparation of cheap and novel families of highly robust and crystalline MOFs with tailor-made functional channels to be used as chemical reactors. Secondly, the application of solid-state post-synthetic methods to drive the multigram-scale preparation of unique ligand-free homo- and heterometallic SNMCs, which are, in the best-case scenario, very difficult to be obtained and stabilised outside the channels. Last but not least, single-crystal X-Ray diffraction will be used as the definitive tool for the characterisation, at the atomic level, of such ultrasmall species offering unprecedented snapshots about their real structures and formation mechanisms.
The ultimate goal will be upscaling this synthetic strategy aiming at the large-scale fabrication of SNMCs and their industrial application will be then evaluated. A successful achievement of all the aforementioned objectives of this ground-breaking project would open new routes for the use of MOFs as chemical reactors to manufacture, at competitive prices, MOF-driven, structurally and electronically well–defined, ligand–free SNMCs in a multigram-scale.
Max ERC Funding
1 886 000 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym PrefrontalMap
Project Organization and learning-associated dynamics of prefrontal synaptic connectivity
Researcher (PI) Ofer YIZHAR
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary How does experience alter the functional architecture of synaptic connections in neural circuits? This question is particularly pertinent for the complex circuits of the medial prefrontal cortex (mPFC), a high-order associative neocortical area that plays a crucial role in flexible, goal-directed behavior. The mPFC is densely interconnected with cortical and subcortical circuits, and its neurons were shown to undergo substantial experience-dependent structural remodeling that is thought to support learning and memory consolidation. However, little is known regarding the synaptic organization of this complex circuit, and of the functional implications of its experience-dependent structural remodeling. In this proposal, we aim to uncover the organization and learning-associated dynamics of functional connectivity in the mouse mPFC.
To obtain high-resolution maps of cell type-specific synaptic connectivity in the mPFC, we will combine single-cell optogenetic manipulation with calcium imaging and electrophysiology in vitro, and establish the circuit-wide organization of connectivity within and between defined projecting neuron populations. We will test the hypothesis that pyramidal neurons projecting to subcortical targets form tightly interconnected subnetworks, and that inhibitory inputs to these networks, through selective innervation, can modulate information output from the mPFC.
To understand how learning changes the functional synaptic organization of the mPFC, we will establish an all-optical system for interrogation of synaptic connectivity in vivo. We will utilize this powerful platform to test the hypothesis that prefrontal-dependent learning is associated with reorganization of local-circuit functional connectivity among identified subcortically-projecting cell assemblies.
Our innovative technology will be widely applicable for neural circuit analysis in a variety of systems, and allow us to gain new insights into the complex circuitry of the mPFC.
Summary
How does experience alter the functional architecture of synaptic connections in neural circuits? This question is particularly pertinent for the complex circuits of the medial prefrontal cortex (mPFC), a high-order associative neocortical area that plays a crucial role in flexible, goal-directed behavior. The mPFC is densely interconnected with cortical and subcortical circuits, and its neurons were shown to undergo substantial experience-dependent structural remodeling that is thought to support learning and memory consolidation. However, little is known regarding the synaptic organization of this complex circuit, and of the functional implications of its experience-dependent structural remodeling. In this proposal, we aim to uncover the organization and learning-associated dynamics of functional connectivity in the mouse mPFC.
To obtain high-resolution maps of cell type-specific synaptic connectivity in the mPFC, we will combine single-cell optogenetic manipulation with calcium imaging and electrophysiology in vitro, and establish the circuit-wide organization of connectivity within and between defined projecting neuron populations. We will test the hypothesis that pyramidal neurons projecting to subcortical targets form tightly interconnected subnetworks, and that inhibitory inputs to these networks, through selective innervation, can modulate information output from the mPFC.
To understand how learning changes the functional synaptic organization of the mPFC, we will establish an all-optical system for interrogation of synaptic connectivity in vivo. We will utilize this powerful platform to test the hypothesis that prefrontal-dependent learning is associated with reorganization of local-circuit functional connectivity among identified subcortically-projecting cell assemblies.
Our innovative technology will be widely applicable for neural circuit analysis in a variety of systems, and allow us to gain new insights into the complex circuitry of the mPFC.
Max ERC Funding
1 880 003 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym REALNANO
Project 3D Structure of Nanomaterials under Realistic Conditions
Researcher (PI) Sara BALS
Host Institution (HI) UNIVERSITEIT ANTWERPEN
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary The properties of nanomaterials are essentially determined by their 3D structure. Electron tomography enables one to measure the morphology and composition of nanostructures in 3D, even at atomic resolution. Unfortunately, all these measurements are performed at room temperature and in ultra-high vacuum, which are conditions that are completely irrelevant for the use of nanoparticles in real applications! Moreover, nanoparticles often have ligands at their surface, which form the interface to the environment. These ligands are mostly neglected in imaging, although they strongly influence the growth, thermal stability and drive self-assembly.
I will develop innovative and quantitative 3D characterisation tools, compatible with the fast changes of nanomaterials that occur in a realistic thermal and gaseous environment. To visualise surface ligands, I will combine direct electron detection with novel exit wave reconstruction techniques.
Tracking the 3D structure of nanomaterials in a relevant environment is extremely challenging and ambitious. However, our preliminary experiments demonstrate the enormous impact. We will be able to perform a dynamic characterisation of shape changes of nanoparticles. This is important to improve thermal stability during drug delivery, sensing, data storage or hyperthermic cancer treatment. We will provide quantitative 3D measurements of the coordination numbers of the surface atoms of catalytic nanoparticles and follow the motion of individual atoms live during catalysis. By visualising surface ligands, we will understand their fundamental influence on particle shape and during self-assembly.
This program will be the start of a completely new research line in the field of 3D imaging at the atomic scale. The outcome will certainly boost the design and performance of nanomaterials. This is not only of importance at a fundamental level, but is a prerequisite for the incorporation of nanomaterials in our future technology.
Summary
The properties of nanomaterials are essentially determined by their 3D structure. Electron tomography enables one to measure the morphology and composition of nanostructures in 3D, even at atomic resolution. Unfortunately, all these measurements are performed at room temperature and in ultra-high vacuum, which are conditions that are completely irrelevant for the use of nanoparticles in real applications! Moreover, nanoparticles often have ligands at their surface, which form the interface to the environment. These ligands are mostly neglected in imaging, although they strongly influence the growth, thermal stability and drive self-assembly.
I will develop innovative and quantitative 3D characterisation tools, compatible with the fast changes of nanomaterials that occur in a realistic thermal and gaseous environment. To visualise surface ligands, I will combine direct electron detection with novel exit wave reconstruction techniques.
Tracking the 3D structure of nanomaterials in a relevant environment is extremely challenging and ambitious. However, our preliminary experiments demonstrate the enormous impact. We will be able to perform a dynamic characterisation of shape changes of nanoparticles. This is important to improve thermal stability during drug delivery, sensing, data storage or hyperthermic cancer treatment. We will provide quantitative 3D measurements of the coordination numbers of the surface atoms of catalytic nanoparticles and follow the motion of individual atoms live during catalysis. By visualising surface ligands, we will understand their fundamental influence on particle shape and during self-assembly.
This program will be the start of a completely new research line in the field of 3D imaging at the atomic scale. The outcome will certainly boost the design and performance of nanomaterials. This is not only of importance at a fundamental level, but is a prerequisite for the incorporation of nanomaterials in our future technology.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym RECON
Project Reprogramming Conformation by Fluorination: Exploring New Areas of Chemical Space
Researcher (PI) Ryan GILMOUR
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary Despite the abundance of organic compounds in Nature, only 12 contain fluorine. In contrast, fluorinated organic materials account for over 40% of all pharmaceuticals and agrochemicals. Closer inspection of the fluorination patterns in these functional molecules reveals striking extremes towards perfluorination (in both 2D and 3D scaffolds) or single site fluorination predominantly in aryl substituents. Consequently, most fluorinated moieties in functional materials lack stereochemical information and are thus achiral. This disparity between the paucity of naturally occurring organofluorine compounds and their venerable history in functional molecule design confirms the enormous potential of fluorinated materials in the discovery of novel properties. That progress has largely been confined to 3 dimensional achiral and 2 dimensional achiral architectures reflects the synthetic challenges associated with preparing stereochemical defined multiply fluorinated systems. A major limitation in the construction of C(sp3)-F units remains the need for substrate pre-functionalisation via oxidation and the competing substitution/elimination scenario that compromises efficiency in the deoxyfluorination. This problem is magnified in the synthesis of optically active fluorides where the deoxyfluorination can compromise the enantiopurity of the starting materials. The principle aim of RECON is to facilitate exploration of 3D, chiral space by providing access to multiply fluorinated, stereochemically complex organofluorine materials from simple feedstock using inexpensive, commercially available fluoride sources. In providing a modular platform to rationally place function on a structural basis, exploration of uncharted chemical space will accelerate the discovery of next generation materials for medicinal and agrochemistry, material sciences and bio-medicine.
Summary
Despite the abundance of organic compounds in Nature, only 12 contain fluorine. In contrast, fluorinated organic materials account for over 40% of all pharmaceuticals and agrochemicals. Closer inspection of the fluorination patterns in these functional molecules reveals striking extremes towards perfluorination (in both 2D and 3D scaffolds) or single site fluorination predominantly in aryl substituents. Consequently, most fluorinated moieties in functional materials lack stereochemical information and are thus achiral. This disparity between the paucity of naturally occurring organofluorine compounds and their venerable history in functional molecule design confirms the enormous potential of fluorinated materials in the discovery of novel properties. That progress has largely been confined to 3 dimensional achiral and 2 dimensional achiral architectures reflects the synthetic challenges associated with preparing stereochemical defined multiply fluorinated systems. A major limitation in the construction of C(sp3)-F units remains the need for substrate pre-functionalisation via oxidation and the competing substitution/elimination scenario that compromises efficiency in the deoxyfluorination. This problem is magnified in the synthesis of optically active fluorides where the deoxyfluorination can compromise the enantiopurity of the starting materials. The principle aim of RECON is to facilitate exploration of 3D, chiral space by providing access to multiply fluorinated, stereochemically complex organofluorine materials from simple feedstock using inexpensive, commercially available fluoride sources. In providing a modular platform to rationally place function on a structural basis, exploration of uncharted chemical space will accelerate the discovery of next generation materials for medicinal and agrochemistry, material sciences and bio-medicine.
Max ERC Funding
1 999 375 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym RememberEx
Project Human Subcortical-Cortical Circuit Dynamics for Remembering the Exceptional
Researcher (PI) Bryan STRANGE
Host Institution (HI) UNIVERSIDAD POLITECNICA DE MADRID
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary Our memory system is optimised for remembering the exceptional over the mundane. We remember better those events that violate predictions generated by the prevailing context, particularly because of surprise or emotional impact. Understanding how we form and retrieve long-term memories for important or salient events is critical for combating the rapidly growing incidence of pathologies associated with memory dysfunction with huge socio-econonomic burden. Human lesion and non-invasive functional imaging data, motivated by findings from animal models, have identified subcortical structures that are critical for upregulating hippocampal function during salient event memory. However, mechanistic understanding of these processes in humans remains scarce, and requires better experimental approaches such as direct intracranial recordings from, and focal electrical stimulation of, these subcortical structures.
This project will characterise human subcortico-cortical neuronal circuit dynamics associated with enhanced episodic memory for salient stimuli by studying direct recordings from human hippocampus, amygdala, nucleus accumbens, ventral midbrain and cortex. Within this framework, I will elucidate the electrophysiological mechanisms underlying amygdala-hippocampal-cortical coupling that lead to better memory for emotional stimuli, extend the hippocampal role in detecting unpredicted stimuli to define its role in orchestrating cortical dynamics in unpredictable contexts, and discover the neuronal response profile of the human mesolimbic dopamine system during salient stimulus encoding. The predicted results, based on my own preliminary data, will offer several conceptual breakthroughs, particularly regarding hippocampal function and the role of dopaminergic ventral midbrain in memory. The knowledge gained from this project is a fundamental requirement for designing therapeutic interventions for patients with memory deficits and other neuropsychiatric disorders.
Summary
Our memory system is optimised for remembering the exceptional over the mundane. We remember better those events that violate predictions generated by the prevailing context, particularly because of surprise or emotional impact. Understanding how we form and retrieve long-term memories for important or salient events is critical for combating the rapidly growing incidence of pathologies associated with memory dysfunction with huge socio-econonomic burden. Human lesion and non-invasive functional imaging data, motivated by findings from animal models, have identified subcortical structures that are critical for upregulating hippocampal function during salient event memory. However, mechanistic understanding of these processes in humans remains scarce, and requires better experimental approaches such as direct intracranial recordings from, and focal electrical stimulation of, these subcortical structures.
This project will characterise human subcortico-cortical neuronal circuit dynamics associated with enhanced episodic memory for salient stimuli by studying direct recordings from human hippocampus, amygdala, nucleus accumbens, ventral midbrain and cortex. Within this framework, I will elucidate the electrophysiological mechanisms underlying amygdala-hippocampal-cortical coupling that lead to better memory for emotional stimuli, extend the hippocampal role in detecting unpredicted stimuli to define its role in orchestrating cortical dynamics in unpredictable contexts, and discover the neuronal response profile of the human mesolimbic dopamine system during salient stimulus encoding. The predicted results, based on my own preliminary data, will offer several conceptual breakthroughs, particularly regarding hippocampal function and the role of dopaminergic ventral midbrain in memory. The knowledge gained from this project is a fundamental requirement for designing therapeutic interventions for patients with memory deficits and other neuropsychiatric disorders.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym ReNewHydrides
Project Renewable Hydride Donors and Their Utilization in Catalytic Reduction and Deoxygenation Reactions
Researcher (PI) Thibault CANTAT
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary The production of chemicals, plastics, solvents, etc., contributes to 20 % of the Gross Value Added in the EU, where sales have doubled over the last 20 years. Despite this dynamism, the chemical industry is energy intensive and 95 % of organic chemicals derive from fossil oil and natural gas. To sustain the growth of this industry, the replacement of fossil feedstocks with renewable carbon, phosphorus and silicon sources should be encouraged. Nonetheless, such a sourcing shift represents a paradigm shift: while the development of petrochemistry has relied on the selective oxidation of hydrocarbons, the conversion of renewable feedstocks (e.g. CO2, phosphates, silicates or biomass) requires efficient reduction methods and catalysts to overcome their oxidized nature.
Today, no reduction method meets the criteria for a versatile and energy efficient reduction of oxidized feedstocks and the aim of the ReNewHydrides project is to design novel reductants and catalytic reactions to achieve this important aim. At the crossroads of main group element chemistry, organometallic chemistry, electrochemistry and homogenous catalysis, I propose to develop innovative and recyclable reductants based on silicon and boron compounds, and to utilize them to tackle catalytic challenges in the reduction of C–O, P–O and Si–O bonds. The overarching principle is to build a balanced synthetic cycle, where the electrochemical reduction of functionalized and oxidized substrates is ensured by silicon and boron based hydride donors, with a high energy efficiency and selectivity.
This project will foster innovative routes in the utilization of renewable carbon, phosphorus and silicon feedstocks. It is therefore of high risk, but ultimately extremely rewarding. The results will also also open-up new horizons in silicon and boron chemistry and they will finally serve the scientific community involved in the fields of organic and inorganic chemistry, sustainable chemistry and energy storage.
Summary
The production of chemicals, plastics, solvents, etc., contributes to 20 % of the Gross Value Added in the EU, where sales have doubled over the last 20 years. Despite this dynamism, the chemical industry is energy intensive and 95 % of organic chemicals derive from fossil oil and natural gas. To sustain the growth of this industry, the replacement of fossil feedstocks with renewable carbon, phosphorus and silicon sources should be encouraged. Nonetheless, such a sourcing shift represents a paradigm shift: while the development of petrochemistry has relied on the selective oxidation of hydrocarbons, the conversion of renewable feedstocks (e.g. CO2, phosphates, silicates or biomass) requires efficient reduction methods and catalysts to overcome their oxidized nature.
Today, no reduction method meets the criteria for a versatile and energy efficient reduction of oxidized feedstocks and the aim of the ReNewHydrides project is to design novel reductants and catalytic reactions to achieve this important aim. At the crossroads of main group element chemistry, organometallic chemistry, electrochemistry and homogenous catalysis, I propose to develop innovative and recyclable reductants based on silicon and boron compounds, and to utilize them to tackle catalytic challenges in the reduction of C–O, P–O and Si–O bonds. The overarching principle is to build a balanced synthetic cycle, where the electrochemical reduction of functionalized and oxidized substrates is ensured by silicon and boron based hydride donors, with a high energy efficiency and selectivity.
This project will foster innovative routes in the utilization of renewable carbon, phosphorus and silicon feedstocks. It is therefore of high risk, but ultimately extremely rewarding. The results will also also open-up new horizons in silicon and boron chemistry and they will finally serve the scientific community involved in the fields of organic and inorganic chemistry, sustainable chemistry and energy storage.
Max ERC Funding
1 999 838 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym SUPRAVACC
Project Supramolecular engineering of glycan-decorated peptides as synthetic vaccines
Researcher (PI) Pol BESENIUS
Host Institution (HI) JOHANNES GUTENBERG-UNIVERSITAT MAINZ
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary The main and most important feature of vaccines is the induction of an immunological memory response, which is key to providing long-term protection against pathogens. The current strategies for potent antibacterial and antiviral vaccines employ conjugation of pathogen specific entities onto carrier proteins, and are limited to formulations that suffer from low stability and short shelf-lives, and are thus not viable in developing countries. Strategies for the development of new vaccinations against endogenous diseases like cancer further remain an unmet challenge, since current methodologies suffer from a lack of a modular and tailored vaccine-specific functionalisation. I therefore propose a radically new design approach in the development of fully synthetic molecular vaccines. My team will synthesise carbohydrate and glycopeptide appended epitopes that are grafted onto supramolecular building blocks. These units can be individually designed to attach disease specific antigens and immunostimulants. Due to their self-assembling properties into nanoscaled pathogen mimetic particles, they serve as a supramolecular subunit vaccine toolbox. By developing a universal supramolecular polymer platform, we will construct multipotent vaccines from glycan-decorated peptides, that combine the activity of protein conjugates with the facile handling, precise composition and increased stability of traditional small molecule pharmaceutical compounds.
SUPRAVACC will pioneer the design of minimalistic and broadly applicable vaccines, and will evaluate the supramolecular engineering approach for immunisations against antibacterial diseases, as well as for applications as antitumour vaccine candidates. The fundamental insights gained will drive a paradigm shift in the design and preparation of vaccine candidates in academic and industrial research laboratories.
Summary
The main and most important feature of vaccines is the induction of an immunological memory response, which is key to providing long-term protection against pathogens. The current strategies for potent antibacterial and antiviral vaccines employ conjugation of pathogen specific entities onto carrier proteins, and are limited to formulations that suffer from low stability and short shelf-lives, and are thus not viable in developing countries. Strategies for the development of new vaccinations against endogenous diseases like cancer further remain an unmet challenge, since current methodologies suffer from a lack of a modular and tailored vaccine-specific functionalisation. I therefore propose a radically new design approach in the development of fully synthetic molecular vaccines. My team will synthesise carbohydrate and glycopeptide appended epitopes that are grafted onto supramolecular building blocks. These units can be individually designed to attach disease specific antigens and immunostimulants. Due to their self-assembling properties into nanoscaled pathogen mimetic particles, they serve as a supramolecular subunit vaccine toolbox. By developing a universal supramolecular polymer platform, we will construct multipotent vaccines from glycan-decorated peptides, that combine the activity of protein conjugates with the facile handling, precise composition and increased stability of traditional small molecule pharmaceutical compounds.
SUPRAVACC will pioneer the design of minimalistic and broadly applicable vaccines, and will evaluate the supramolecular engineering approach for immunisations against antibacterial diseases, as well as for applications as antitumour vaccine candidates. The fundamental insights gained will drive a paradigm shift in the design and preparation of vaccine candidates in academic and industrial research laboratories.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym SynapSeek
Project Learning the shape of synaptic plasticity rules for neuronal architectures and function through machine learning.
Researcher (PI) Tim VOGELS
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary How do we learn to dance, play an instrument, or a game as complex as chess or go? How do we make a memory? The common answer to these questions is “through synaptic plasticity”, through changing the synaptic connectivity of neural circuits so that representative brain activity can be reliably triggered. Such connectivity changes are governed by rules, i.e., synaptic mechanisms which monitor the activity of their environment and stereotypically strengthen or weaken synapses accordingly. The shape and mode of operation of these rules is still largely unknown: For the more than hundred different connection types in cortical circuits, only a handful of rules has been described at all. Similarly, testing observed rules in simulations of cortical function has only seen limited success. Our slow progress is due to the extraordinary difficulty of measuring and observing synapses without interference.
Here, we propose a new approach. By utilizing the growing power of machine learning methods we can deduce synaptic plasticity rules directly. Newly developed search algorithms and sheer computational power allow us to integrate published data and infer synaptic rules in silico. We aim to (1) develop a new mathematical expression of synaptic plasticity rules, experimentally appropriate and flexible enough to be implemented in a Machine Learning framework, dubbed SYNAPSEEK. Next (2), we will apply SYNAPSEEK to deduce the rules for building various neural structures with increasing complexity. Finally (3), we will incorporate additional constraints to SYNAPSEEK to develop synaptic rules that shape network function as much as its structure. Our work will establish, for the first time, canonical sets of synaptic plasticity rules, based on the circuit structure they must produce, and the function they are meant to support. SYNAPSEEK will have immediate and wide ranging applications, from a basic understanding of cortical development to better protocols for Deep Brain Stimulation.
Summary
How do we learn to dance, play an instrument, or a game as complex as chess or go? How do we make a memory? The common answer to these questions is “through synaptic plasticity”, through changing the synaptic connectivity of neural circuits so that representative brain activity can be reliably triggered. Such connectivity changes are governed by rules, i.e., synaptic mechanisms which monitor the activity of their environment and stereotypically strengthen or weaken synapses accordingly. The shape and mode of operation of these rules is still largely unknown: For the more than hundred different connection types in cortical circuits, only a handful of rules has been described at all. Similarly, testing observed rules in simulations of cortical function has only seen limited success. Our slow progress is due to the extraordinary difficulty of measuring and observing synapses without interference.
Here, we propose a new approach. By utilizing the growing power of machine learning methods we can deduce synaptic plasticity rules directly. Newly developed search algorithms and sheer computational power allow us to integrate published data and infer synaptic rules in silico. We aim to (1) develop a new mathematical expression of synaptic plasticity rules, experimentally appropriate and flexible enough to be implemented in a Machine Learning framework, dubbed SYNAPSEEK. Next (2), we will apply SYNAPSEEK to deduce the rules for building various neural structures with increasing complexity. Finally (3), we will incorporate additional constraints to SYNAPSEEK to develop synaptic rules that shape network function as much as its structure. Our work will establish, for the first time, canonical sets of synaptic plasticity rules, based on the circuit structure they must produce, and the function they are meant to support. SYNAPSEEK will have immediate and wide ranging applications, from a basic understanding of cortical development to better protocols for Deep Brain Stimulation.
Max ERC Funding
1 798 605 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym T2DCP
Project Development of Thiophene Based Conjugated Polymers in Two Dimensions
Researcher (PI) Xinliang FENG
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary The proceeding inexorable digitalisation of modern economics and society creates a steadily increasing demand on smart devices in the context of the industrial internet and the internet of things. To meet future requirements, organic electronics is a disruptive technology featuring low-cost, robust, lightweight, flexible and affordable devices based on organic small molecules and polymers. In contrast to the boosting development of linear conjugated polymers and their applications in organic electronics, the successive increase of dimensionality by connecting multiple strands towards two-dimensional (2D) conjugated polymers remains largely unexplored. In this project, we will develop unprecedented thiophene-based double- and triple-strand conjugated polymers to 2D conjugated polymers (T2DCPs) for organic electronics with tailorable electronic band gap at the molecular level for superior performance in terms of charge carrier mobility, and defect tolerance enabled by the increased dimensionality. In this respect, we aim to establish versatile but also reliable solution-based synthesis strategies (one-pot solvothermal, two-step metal-templating reaction and interfacial soft-templating route) employing thiophene monomers rendering T2DCPs with entirely C=C/Ar-Ar backbone. We will further establish ground-breaking one-pot synthesis of donor-acceptor type T2DCPs featuring lower band gap and unique charge transport behavior. By employing designed thiophene-based monomers and linkage topologies, we will accomplish optical and energy gap engineering, control of the molecular weight (or crystalline domain size), and conjugation channel densities. The consequence is that we will explore the key functions of this intriguing class of semiconducting polymers. As the key achievements, we expect to establish a novel solution-based chemistry, delineation of reliable structure-property relationships and superior device performance of T2DCPs for organic field effect transistors.
Summary
The proceeding inexorable digitalisation of modern economics and society creates a steadily increasing demand on smart devices in the context of the industrial internet and the internet of things. To meet future requirements, organic electronics is a disruptive technology featuring low-cost, robust, lightweight, flexible and affordable devices based on organic small molecules and polymers. In contrast to the boosting development of linear conjugated polymers and their applications in organic electronics, the successive increase of dimensionality by connecting multiple strands towards two-dimensional (2D) conjugated polymers remains largely unexplored. In this project, we will develop unprecedented thiophene-based double- and triple-strand conjugated polymers to 2D conjugated polymers (T2DCPs) for organic electronics with tailorable electronic band gap at the molecular level for superior performance in terms of charge carrier mobility, and defect tolerance enabled by the increased dimensionality. In this respect, we aim to establish versatile but also reliable solution-based synthesis strategies (one-pot solvothermal, two-step metal-templating reaction and interfacial soft-templating route) employing thiophene monomers rendering T2DCPs with entirely C=C/Ar-Ar backbone. We will further establish ground-breaking one-pot synthesis of donor-acceptor type T2DCPs featuring lower band gap and unique charge transport behavior. By employing designed thiophene-based monomers and linkage topologies, we will accomplish optical and energy gap engineering, control of the molecular weight (or crystalline domain size), and conjugation channel densities. The consequence is that we will explore the key functions of this intriguing class of semiconducting polymers. As the key achievements, we expect to establish a novel solution-based chemistry, delineation of reliable structure-property relationships and superior device performance of T2DCPs for organic field effect transistors.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-03-01, End date: 2024-02-29