Project acronym AbioEvo
Project Conditions for the emergence of evolution during abiogenesis
Researcher (PI) Philippe Nghe
Host Institution (HI) ECOLE SUPERIEURE DE PHYSIQUE ET DECHIMIE INDUSTRIELLES DE LA VILLE DEPARIS
Country France
Call Details Consolidator Grant (CoG), LS1, ERC-2020-COG
Summary Abiogenesis, the transition from non-living to living matter, is at the core of the origin of life question. However, the dynamical processes underlying abiogenesis remain unknown.
The AbioEvo project aims to test the hypothesis that RNA-catalysed RNA recombination, if coupled with template-based mechanisms, provides a gradual route for the emergence of evolution by natural selection, starting from collective autocatalysis, toward template-based replication. Indeed, recombination allows both self-reproduction and shuffling of other sequences, thus, once combined with templating, provides the basic ingredients of reproduction, heredity and variation required for Darwinian evolution.
The project decomposes the problem into five steps: (WP1) the study of molecular-level mechanisms to generate and stabilize novel sequences by recombination and templating; (WP2) collective dynamics integrating these mechanisms into the properties of reproduction with heredity, variation, and selection, in order to establish proof-of-concepts of evolutionary modes; (WP3) viability thresholds of recombination-based replicators from increasingly random substrates; (WP4) conditions for open-ended evolution toward template-based replication; (WP5) experimentally informed theoretical estimates of the probability of the proposed evolutionary transitions.
The project would provide first demonstrations of evolution by natural selection in a purely chemical system, gradual and experimentally accessible paths from oligomers to template-based replication, and a method to evaluate prebiotic plausibility from sequence-to-function relationships, kinetics and evolutionary dynamics.
Summary
Abiogenesis, the transition from non-living to living matter, is at the core of the origin of life question. However, the dynamical processes underlying abiogenesis remain unknown.
The AbioEvo project aims to test the hypothesis that RNA-catalysed RNA recombination, if coupled with template-based mechanisms, provides a gradual route for the emergence of evolution by natural selection, starting from collective autocatalysis, toward template-based replication. Indeed, recombination allows both self-reproduction and shuffling of other sequences, thus, once combined with templating, provides the basic ingredients of reproduction, heredity and variation required for Darwinian evolution.
The project decomposes the problem into five steps: (WP1) the study of molecular-level mechanisms to generate and stabilize novel sequences by recombination and templating; (WP2) collective dynamics integrating these mechanisms into the properties of reproduction with heredity, variation, and selection, in order to establish proof-of-concepts of evolutionary modes; (WP3) viability thresholds of recombination-based replicators from increasingly random substrates; (WP4) conditions for open-ended evolution toward template-based replication; (WP5) experimentally informed theoretical estimates of the probability of the proposed evolutionary transitions.
The project would provide first demonstrations of evolution by natural selection in a purely chemical system, gradual and experimentally accessible paths from oligomers to template-based replication, and a method to evaluate prebiotic plausibility from sequence-to-function relationships, kinetics and evolutionary dynamics.
Max ERC Funding
2 000 000 €
Duration
Start date: 2021-06-01, End date: 2026-05-31
Project acronym ACCENT
Project How antibodies and complement orchestrate protective immune responses against bacteria
Researcher (PI) suzan ROOIJAKKERS
Host Institution (HI) UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Country Netherlands
Call Details Consolidator Grant (CoG), LS6, ERC-2020-COG
Summary Due to antibiotic resistance, there is now great interest in the development of antibody-based therapies against bacterial infections, for instance via antibodies that boost the host immune system. In order to kill bacteria, antibodies should trigger activation of the complement cascade, which forms bactericidal Membrane Attack Complex (MAC) pores and strongly enhances phagocytosis. Although the power of complement could be exploited for antibody therapies, such developments are hampered by our limited insights into the mechanisms underlying antibody-dependent complement activation on bacteria. My team has developed unique assays to study complement activation on bacteria. In this proposal, we will combine our function-driven approaches with novel B cell sequencing methods to identify anti-bacterial antibodies with strong complement-activating potential. We will develop novel approaches to identify the variable (VH:VL) sequences of human antibodies that recognize whole bacterial cells. After FACS sorting of memory B cells or yeast Fab display, we will use multi-well functional assays to select monoclonal antibodies driving potent complement activation and subsequent killing of E. coli (via neutrophils or MAC). Thanks to our unique tools and unprecedented insights, we are in an unique position to decipher basic mechanisms by which antibodies induce bacterial killing via neutrophils or MAC. We will combine live-cell imaging and structural approaches to determine how bactericidal antibodies assemble lethal MAC pores in the bacterial cell envelope. Finally, we will explore the design of potent antibody combinations and study the mechanisms by which antibodies steer different effector functions, both in the context of clinical and non-pathogenic E. coli strains. Altogether, this grant will lead to fundamental knowledge about the functioning of the immune system and provide a biological basis for the development of antibody-based therapies against bacteria.
Summary
Due to antibiotic resistance, there is now great interest in the development of antibody-based therapies against bacterial infections, for instance via antibodies that boost the host immune system. In order to kill bacteria, antibodies should trigger activation of the complement cascade, which forms bactericidal Membrane Attack Complex (MAC) pores and strongly enhances phagocytosis. Although the power of complement could be exploited for antibody therapies, such developments are hampered by our limited insights into the mechanisms underlying antibody-dependent complement activation on bacteria. My team has developed unique assays to study complement activation on bacteria. In this proposal, we will combine our function-driven approaches with novel B cell sequencing methods to identify anti-bacterial antibodies with strong complement-activating potential. We will develop novel approaches to identify the variable (VH:VL) sequences of human antibodies that recognize whole bacterial cells. After FACS sorting of memory B cells or yeast Fab display, we will use multi-well functional assays to select monoclonal antibodies driving potent complement activation and subsequent killing of E. coli (via neutrophils or MAC). Thanks to our unique tools and unprecedented insights, we are in an unique position to decipher basic mechanisms by which antibodies induce bacterial killing via neutrophils or MAC. We will combine live-cell imaging and structural approaches to determine how bactericidal antibodies assemble lethal MAC pores in the bacterial cell envelope. Finally, we will explore the design of potent antibody combinations and study the mechanisms by which antibodies steer different effector functions, both in the context of clinical and non-pathogenic E. coli strains. Altogether, this grant will lead to fundamental knowledge about the functioning of the immune system and provide a biological basis for the development of antibody-based therapies against bacteria.
Max ERC Funding
2 000 000 €
Duration
Start date: 2021-06-01, End date: 2026-05-31
Project acronym ACTIVE_ADAPTIVE
Project Active and Adaptive: Reconfigurable Active Colloids with Internal Feedback and Communication Schemes
Researcher (PI) Lucio ISA
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Consolidator Grant (CoG), PE3, ERC-2020-COG
Summary The vision of creating autonomous materials constituted of microscale motile units promises to disrupt a broad range of technologies but is still far beyond our reach. Inspired by nature, these materials are active, i.e. they convert available energy into functions, and adaptive, i.e. they respond to stimuli by reconfiguring via internal feedback and signalling schemes. In order to progress, we need to rethink the way in which we design, fabricate and control synthetic active units, aka active colloids or artificial microswimmers.
I propose an innovative approach that combines colloidal synthesis, assembly and actuation with nanofabrication and the implementation of feedback to realize a new class of active colloids. Borrowing ideas from soft-robotic systems, we aim to realize and study “cyber-free” artificial microswimmers, which, in addition to on-board energy conversion, present internal degrees of freedom allowing for sensing, feedback and communication pathways ultimately to be regulated without external intervention. In particular, we will: 1) Numerically and experimentally implement feedback schemes to regulate single-particle motility and collective behaviour based on control theory. 2) Use a unique combination of capillary assembly and two-photon nanolithography to create shape-shifting active colloids that autonomously regulate their motility based on stimuli orthogonal to their propulsion schemes. 3) Create “transmitting” and “receiving” active colloids, sending and sensing chemical signals (pH changes), to regulate their motility.
By introducing strong coupling between particles, and with stimuli beyond classical colloidal interactions, this proposal will enable a forward leap in the study of the emergent physics of active systems, as required to realize the vision of autonomous materials and microscale devices.
Summary
The vision of creating autonomous materials constituted of microscale motile units promises to disrupt a broad range of technologies but is still far beyond our reach. Inspired by nature, these materials are active, i.e. they convert available energy into functions, and adaptive, i.e. they respond to stimuli by reconfiguring via internal feedback and signalling schemes. In order to progress, we need to rethink the way in which we design, fabricate and control synthetic active units, aka active colloids or artificial microswimmers.
I propose an innovative approach that combines colloidal synthesis, assembly and actuation with nanofabrication and the implementation of feedback to realize a new class of active colloids. Borrowing ideas from soft-robotic systems, we aim to realize and study “cyber-free” artificial microswimmers, which, in addition to on-board energy conversion, present internal degrees of freedom allowing for sensing, feedback and communication pathways ultimately to be regulated without external intervention. In particular, we will: 1) Numerically and experimentally implement feedback schemes to regulate single-particle motility and collective behaviour based on control theory. 2) Use a unique combination of capillary assembly and two-photon nanolithography to create shape-shifting active colloids that autonomously regulate their motility based on stimuli orthogonal to their propulsion schemes. 3) Create “transmitting” and “receiving” active colloids, sending and sensing chemical signals (pH changes), to regulate their motility.
By introducing strong coupling between particles, and with stimuli beyond classical colloidal interactions, this proposal will enable a forward leap in the study of the emergent physics of active systems, as required to realize the vision of autonomous materials and microscale devices.
Max ERC Funding
1 997 718 €
Duration
Start date: 2021-05-01, End date: 2026-04-30
Project acronym ADAPT
Project Autoxidation of Anthropogenic Volatile Organic Compounds (AVOC) as a Source of Urban Air Pollution
Researcher (PI) Matti Rissanen
Host Institution (HI) TAMPEREEN KORKEAKOULUSAATIO SR
Country Finland
Call Details Consolidator Grant (CoG), PE10, ERC-2020-COG
Summary Previous efforts to raise living standards have been based on relentlessly increasing combustion, causing environmental destruction at all scales. In addition to climate-warming CO2, fossil fuel combustion also produces a large number of organic compounds and particulate matter, which deteriorate air quality.
The atmosphere is cleansed from such pollutants by gas-phase oxidation reactions, which are invariably mediated by peroxy radicals (RO2). Oxidation transforms initially volatile and water-insoluble hydrocarbons into water-soluble forms (ultimately CO2), enabling scavenging by liquid droplets. A minor but crucially important alternative oxidation pathway leads to oxidative molecular growth, and formation of atmospheric aerosols. Aerosols impart a huge influence on the atmosphere, from local air quality issues to global climate forcing, yet their formation mechanisms and structures of organic aerosol precursors remains elusive.
In a paradigm change, RO2 was recently found to undergo autoxidation, enabling rapid aerosol precursor formation even at sub-second time-scales – in stark contrast to the long processing times (days - weeks) previously assumed to be necessary. We have shown how abundant biogenic hydrocarbons (BVOC) autoxidize, but due to key structural differences, the same pathways are not available for anthropogenic hydrocarbons (AVOC), and thus they were not expected to autoxidize. My preliminary experiments reveal that AVOCs do autoxidize, but the mechanism enabling this remain unknown. Crucially, the co-reactants shown to inhibit BVOC seem to enforce AVOC autoxidation – potentially explaining the recent mysterious discovery of new-particle formation in polluted megacities. In ADAPT, I will use a combination of novel mass spectrometric detection methods fortified by theoretical calculations, to solve the mechanism of AVOC autoxidation. This will directly assist both air quality management, and the design of cleaner fuels and engines.
Summary
Previous efforts to raise living standards have been based on relentlessly increasing combustion, causing environmental destruction at all scales. In addition to climate-warming CO2, fossil fuel combustion also produces a large number of organic compounds and particulate matter, which deteriorate air quality.
The atmosphere is cleansed from such pollutants by gas-phase oxidation reactions, which are invariably mediated by peroxy radicals (RO2). Oxidation transforms initially volatile and water-insoluble hydrocarbons into water-soluble forms (ultimately CO2), enabling scavenging by liquid droplets. A minor but crucially important alternative oxidation pathway leads to oxidative molecular growth, and formation of atmospheric aerosols. Aerosols impart a huge influence on the atmosphere, from local air quality issues to global climate forcing, yet their formation mechanisms and structures of organic aerosol precursors remains elusive.
In a paradigm change, RO2 was recently found to undergo autoxidation, enabling rapid aerosol precursor formation even at sub-second time-scales – in stark contrast to the long processing times (days - weeks) previously assumed to be necessary. We have shown how abundant biogenic hydrocarbons (BVOC) autoxidize, but due to key structural differences, the same pathways are not available for anthropogenic hydrocarbons (AVOC), and thus they were not expected to autoxidize. My preliminary experiments reveal that AVOCs do autoxidize, but the mechanism enabling this remain unknown. Crucially, the co-reactants shown to inhibit BVOC seem to enforce AVOC autoxidation – potentially explaining the recent mysterious discovery of new-particle formation in polluted megacities. In ADAPT, I will use a combination of novel mass spectrometric detection methods fortified by theoretical calculations, to solve the mechanism of AVOC autoxidation. This will directly assist both air quality management, and the design of cleaner fuels and engines.
Max ERC Funding
2 689 147 €
Duration
Start date: 2021-02-01, End date: 2026-01-31
Project acronym AIM.imaging.CKD
Project AI-augmented, Multiscale Image-based Diagnostics of Chronic Kidney Disease
Researcher (PI) Peter BOOR
Host Institution (HI) UNIVERSITAETSKLINIKUM AACHEN
Country Germany
Call Details Consolidator Grant (CoG), LS7, ERC-2020-COG
Summary Chronic kidney disease (CKD) is a major global health problem, affecting 10% of the world population and projected to be the fifth major cause of death in 2040. CKD patients are one of the most complex and multi-morbid populations in internal medicine while at the same time having the least translational randomized clinical trials and limited treatment options. One of the major reasons for this is the lack of reproducible approaches specifically reflecting intrarenal pathological processes and disease activity. The overall goal of AIM.imaging.CKD is to specifically address this unmet need by developing, validating and integrating image-based diagnostics for CKD. The integration of broad interdisciplinary expertise will enable to develop a multiscale approach from nano- to micro- to macromorphological and molecular diagnostics. Specifically, the project will develop augmented full-spectrum ultrastructural (“nano”) and histological (“micro”) renal biopsy diagnostics, focusing on reproducible, quantitative nephropathological analyses and prediction of clinically relevant outcome parameters. The project will also explore macro-morphological and molecular imaging in CKD, focusing on translatable non-invasive approaches. The central feature will be the development of advanced, scalable and modular image analyses models utilizing artificial intelligence (AI), particularly machine and deep learning. Using preclinical testing and clinical validation, the main emphasis will be on accelerated or, whenever possible, direct implementation into the clinical practice. The integration of the above-mentioned tools and technologies provides a comprehensive multiscale and multiplex approach for improved diagnostics of CKD patients and facilitate future randomized clinical trials. At each level, and even more so when integrated, the results are expected to augment and transform image-based diagnostics of kidney diseases, and thereby lead to improved patient management and outcome.
Summary
Chronic kidney disease (CKD) is a major global health problem, affecting 10% of the world population and projected to be the fifth major cause of death in 2040. CKD patients are one of the most complex and multi-morbid populations in internal medicine while at the same time having the least translational randomized clinical trials and limited treatment options. One of the major reasons for this is the lack of reproducible approaches specifically reflecting intrarenal pathological processes and disease activity. The overall goal of AIM.imaging.CKD is to specifically address this unmet need by developing, validating and integrating image-based diagnostics for CKD. The integration of broad interdisciplinary expertise will enable to develop a multiscale approach from nano- to micro- to macromorphological and molecular diagnostics. Specifically, the project will develop augmented full-spectrum ultrastructural (“nano”) and histological (“micro”) renal biopsy diagnostics, focusing on reproducible, quantitative nephropathological analyses and prediction of clinically relevant outcome parameters. The project will also explore macro-morphological and molecular imaging in CKD, focusing on translatable non-invasive approaches. The central feature will be the development of advanced, scalable and modular image analyses models utilizing artificial intelligence (AI), particularly machine and deep learning. Using preclinical testing and clinical validation, the main emphasis will be on accelerated or, whenever possible, direct implementation into the clinical practice. The integration of the above-mentioned tools and technologies provides a comprehensive multiscale and multiplex approach for improved diagnostics of CKD patients and facilitate future randomized clinical trials. At each level, and even more so when integrated, the results are expected to augment and transform image-based diagnostics of kidney diseases, and thereby lead to improved patient management and outcome.
Max ERC Funding
1 999 375 €
Duration
Start date: 2021-05-01, End date: 2026-04-30
Project acronym ALIENIMPACTS
Project Predicting impacts of alien plant invasions on community diversity
Researcher (PI) Jane Catford
Host Institution (HI) KING'S COLLEGE LONDON
Country United Kingdom
Call Details Consolidator Grant (CoG), LS8, ERC-2020-COG
Summary The Anthropocene, the current geological epoch, is characterised by human-induced ecological changes, which have prompted a global biodiversity crisis. Human-introduced alien plants could help to offset native species loss, augmenting diversity and maintaining the services and capital that humans derive from nature. However, alien species that become invasive are themselves a key threat to biodiversity. Alien species thus presents a huge challenge for biodiversity conservation in the Anthropocene: should their arrival and establishment be inhibited or disregarded as they can potentially both exacerbate and ameliorate biodiversity loss? Coupling empirical and theoretical approaches, ALIENIMPACTS will directly address this challenge by developing an approach for accurately predicting impacts of alien plant invasions on plant community diversity and identifying the circumstances under which negative impacts will occur. Using temperate grasslands as a model system, ALIENIMPACTS will use innovative field experiments and global observations to systematically quantify – for the first time – how often, for how long, to what extent, under what conditions and in what ways alien plants can impact plant community diversity. ALIENIMPACTS will develop mechanistic niche models, validated with empirical data from grasslands in North America, Europe and Australia, that will enable realistic scenarios of invasion biodiversity impacts to be forecast, now and in the future. Developing empirically accurate mechanistic models that predict invasions and their biodiversity impact is a highly ambitious goal. Its achievement will mark a step-change in ecological theory and understanding, will inform environmental policy and management, and address a critical research challenge of the Anthropocene: how to conserve the biodiversity of plants – the dominant life form on earth – under global environmental change.
Summary
The Anthropocene, the current geological epoch, is characterised by human-induced ecological changes, which have prompted a global biodiversity crisis. Human-introduced alien plants could help to offset native species loss, augmenting diversity and maintaining the services and capital that humans derive from nature. However, alien species that become invasive are themselves a key threat to biodiversity. Alien species thus presents a huge challenge for biodiversity conservation in the Anthropocene: should their arrival and establishment be inhibited or disregarded as they can potentially both exacerbate and ameliorate biodiversity loss? Coupling empirical and theoretical approaches, ALIENIMPACTS will directly address this challenge by developing an approach for accurately predicting impacts of alien plant invasions on plant community diversity and identifying the circumstances under which negative impacts will occur. Using temperate grasslands as a model system, ALIENIMPACTS will use innovative field experiments and global observations to systematically quantify – for the first time – how often, for how long, to what extent, under what conditions and in what ways alien plants can impact plant community diversity. ALIENIMPACTS will develop mechanistic niche models, validated with empirical data from grasslands in North America, Europe and Australia, that will enable realistic scenarios of invasion biodiversity impacts to be forecast, now and in the future. Developing empirically accurate mechanistic models that predict invasions and their biodiversity impact is a highly ambitious goal. Its achievement will mark a step-change in ecological theory and understanding, will inform environmental policy and management, and address a critical research challenge of the Anthropocene: how to conserve the biodiversity of plants – the dominant life form on earth – under global environmental change.
Max ERC Funding
1 999 997 €
Duration
Start date: 2021-04-01, End date: 2026-03-31
Project acronym ALLOWE
Project Highly Reactive Low-valent Aluminium Complexes and their Application in Synthesis and Catalysis
Researcher (PI) Shigeyoshi INOUE
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Consolidator Grant (CoG), PE5, ERC-2020-COG
Summary This ERC-CoG 2020 proposal, ALLOWE outlines a strategy for the development of low-valent aluminium systems through their synthesis, isolation, and reactivity investigation of neutral, ambiphilic, low-valent aluminium compounds, denoted “alumylenes”. Their dimeric form “dialumenes” featuring an aluminium-aluminium double bond will also be within the scope of the project. These low-valent aluminium species are expected to provide, along with greater understanding of the fundamental behaviour of low-valent aluminium, a varied and deep reactivity profile. These highly reactive compounds will offer a cheap, sustainable and non-toxic alternative to the current transition metal-based industrial chemical processes.
The proposed scheme of work begins with the synthesis of neutral alumylenes and dialumenes, respectively. This will be achieved through the use of donor ligands (i.e. N-heterocyclic carbenes) and substituents with differing electronic and steric properties. With these compounds in hand, the reactivity towards small molecules will be investigated along with development of low-valent aluminium based catalysts. Furthermore, incorporation of transition metals into these aluminium systems will be targeted as these may possess unique and interesting properties.
Established methodologies such as reductive dehalogenation or reductive dehydrohalogenation will provide access to novel low-valent aluminium compounds bearing bulky substituents and donor ligands. The synthetic portion of the work will also be supported by theoretical calculations.
The outcome of ALLOWE will provide (i) in-depth insight and understanding into low-valent aluminium’s bonding nature, particularly emphasis laid on ambiphilic aluminium center (ii) plethora of striking reactivity towards transition metal free stoichiometric and catalytic activation of small molecules, and (iii) various potential applications in aluminium-based material chemistry.
Summary
This ERC-CoG 2020 proposal, ALLOWE outlines a strategy for the development of low-valent aluminium systems through their synthesis, isolation, and reactivity investigation of neutral, ambiphilic, low-valent aluminium compounds, denoted “alumylenes”. Their dimeric form “dialumenes” featuring an aluminium-aluminium double bond will also be within the scope of the project. These low-valent aluminium species are expected to provide, along with greater understanding of the fundamental behaviour of low-valent aluminium, a varied and deep reactivity profile. These highly reactive compounds will offer a cheap, sustainable and non-toxic alternative to the current transition metal-based industrial chemical processes.
The proposed scheme of work begins with the synthesis of neutral alumylenes and dialumenes, respectively. This will be achieved through the use of donor ligands (i.e. N-heterocyclic carbenes) and substituents with differing electronic and steric properties. With these compounds in hand, the reactivity towards small molecules will be investigated along with development of low-valent aluminium based catalysts. Furthermore, incorporation of transition metals into these aluminium systems will be targeted as these may possess unique and interesting properties.
Established methodologies such as reductive dehalogenation or reductive dehydrohalogenation will provide access to novel low-valent aluminium compounds bearing bulky substituents and donor ligands. The synthetic portion of the work will also be supported by theoretical calculations.
The outcome of ALLOWE will provide (i) in-depth insight and understanding into low-valent aluminium’s bonding nature, particularly emphasis laid on ambiphilic aluminium center (ii) plethora of striking reactivity towards transition metal free stoichiometric and catalytic activation of small molecules, and (iii) various potential applications in aluminium-based material chemistry.
Max ERC Funding
1 997 750 €
Duration
Start date: 2021-06-01, End date: 2026-05-31
Project acronym AMIGA
Project Autonomous Computing Artificial Cells
Researcher (PI) Tom DE GREEF
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Country Netherlands
Call Details Consolidator Grant (CoG), PE4, ERC-2020-COG
Summary We propose an ambitious 5-year multidisciplinary program that seeks to pioneer and establish a fundamentally new paradigm in molecular information systems that is based on novel conceptual and experimental advances on the integration of DNA-based chemical reaction networks (CRNs) and semipermeable microcapsules, i.e. protocells. In AutonoMous computInG Artificial cells (AMIGA), we will establish a platform technology, based on molecular communication between interacting protocells, capable of revolutionary new modes of molecular sensing, computation and data storage/retrieval.
Progress in this emerging field requires i) the development of computer-aided design (CAD) strategies to implement large-scale CRNs consisting of hundreds of components, ii) formulating suitable micro-substrates, such as droplets or vesicles, to spatially localize CRNs and ways to manipulate their interconnection and iii) strategies that allow direct recording of molecular operations onto a chemical storage medium such as DNA. We address these challenges via a comprehensive research program in which we implement large-scale, DNA-based CRNs by localization of components in interacting protocells resulting in distributed molecular circuits programmed to display advanced computational functions such as (i) asynchronous logic, (ii) integral feedback control and (iii) molecular pattern recognition. Combining protocell localization with recent advances in CRISPR base editors, we will construct an integrated system where molecular operations can write instructions on permanent memory storage elements. The developed methodology finds applications in emerging technologies aimed at using molecular circuits for in-vitro diagnostics and the use of synthetic DNA as a storage medium for digital data.
Summary
We propose an ambitious 5-year multidisciplinary program that seeks to pioneer and establish a fundamentally new paradigm in molecular information systems that is based on novel conceptual and experimental advances on the integration of DNA-based chemical reaction networks (CRNs) and semipermeable microcapsules, i.e. protocells. In AutonoMous computInG Artificial cells (AMIGA), we will establish a platform technology, based on molecular communication between interacting protocells, capable of revolutionary new modes of molecular sensing, computation and data storage/retrieval.
Progress in this emerging field requires i) the development of computer-aided design (CAD) strategies to implement large-scale CRNs consisting of hundreds of components, ii) formulating suitable micro-substrates, such as droplets or vesicles, to spatially localize CRNs and ways to manipulate their interconnection and iii) strategies that allow direct recording of molecular operations onto a chemical storage medium such as DNA. We address these challenges via a comprehensive research program in which we implement large-scale, DNA-based CRNs by localization of components in interacting protocells resulting in distributed molecular circuits programmed to display advanced computational functions such as (i) asynchronous logic, (ii) integral feedback control and (iii) molecular pattern recognition. Combining protocell localization with recent advances in CRISPR base editors, we will construct an integrated system where molecular operations can write instructions on permanent memory storage elements. The developed methodology finds applications in emerging technologies aimed at using molecular circuits for in-vitro diagnostics and the use of synthetic DNA as a storage medium for digital data.
Max ERC Funding
1 999 497 €
Duration
Start date: 2022-02-01, End date: 2027-01-31
Project acronym AMPS
Project Ancient Mesopotamian Priestly Scholasticism in the First Millennium BCE
Researcher (PI) Uri Gabbay
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Country Israel
Call Details Consolidator Grant (CoG), SH5, ERC-2020-COG
Summary The scholarly texts of ancient Mesopotamia in the first millennium BCE, specifically commentaries written in Akkadian on cuneiform tablets, were the work of priests who also performed cultic activities in the temple. The proposed project seeks to demonstrate how these scholarly and cultic activities were interrelated and how they shaped the self-identity of the priestly-scholarly community that was in charge of both. The project thus aims to bridge the gap between the study of intellectual history and the study of priesthood in ancient Mesopotamia, which are treated as two separate fields in Assyriology.
The project innovatively treats Mesopotamian scholarship and Mesopotamian priesthood as complementary aspects of one phenomenon: “scholasticism.” This concept, which originally referred to the scholarly activities of Catholic priests in the Middle Ages, has recently been applied to the study of non-European communities of priestly scholars with great success. Using the scholastic model to study the priestly-scholarly community of ancient Mesopotamia will reveal the intricate connections between the ritual and textual activities of this community and illuminate the holistic and systematic worldview of its members.
Combining traditional philology and the comparative approach, the project investigates how, like other scholastic communities, the scholar-priests of ancient Mesopotamia “internalized” the liturgical texts they studied and performed, how they attributed authority to these texts, and how their study of the liturgical corpus generated new exegetical texts. Key points of comparison between the scholar-priests of ancient Mesopotamia and various ancient and contemporary scholastic communities include their interest in language, textual authority, commentaries, and rituals. By applying the comparative method to the study of cuneiform tablets, the project aims to reconstruct the social, religious, and intellectual reality in which they were written.
Summary
The scholarly texts of ancient Mesopotamia in the first millennium BCE, specifically commentaries written in Akkadian on cuneiform tablets, were the work of priests who also performed cultic activities in the temple. The proposed project seeks to demonstrate how these scholarly and cultic activities were interrelated and how they shaped the self-identity of the priestly-scholarly community that was in charge of both. The project thus aims to bridge the gap between the study of intellectual history and the study of priesthood in ancient Mesopotamia, which are treated as two separate fields in Assyriology.
The project innovatively treats Mesopotamian scholarship and Mesopotamian priesthood as complementary aspects of one phenomenon: “scholasticism.” This concept, which originally referred to the scholarly activities of Catholic priests in the Middle Ages, has recently been applied to the study of non-European communities of priestly scholars with great success. Using the scholastic model to study the priestly-scholarly community of ancient Mesopotamia will reveal the intricate connections between the ritual and textual activities of this community and illuminate the holistic and systematic worldview of its members.
Combining traditional philology and the comparative approach, the project investigates how, like other scholastic communities, the scholar-priests of ancient Mesopotamia “internalized” the liturgical texts they studied and performed, how they attributed authority to these texts, and how their study of the liturgical corpus generated new exegetical texts. Key points of comparison between the scholar-priests of ancient Mesopotamia and various ancient and contemporary scholastic communities include their interest in language, textual authority, commentaries, and rituals. By applying the comparative method to the study of cuneiform tablets, the project aims to reconstruct the social, religious, and intellectual reality in which they were written.
Max ERC Funding
1 959 968 €
Duration
Start date: 2021-10-01, End date: 2026-09-30
Project acronym AngioUnrestUHD
Project Understanding and modulating vascular arrest with ultra-high definition
Researcher (PI) Rui Benedito
Host Institution (HI) CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
Country Spain
Call Details Consolidator Grant (CoG), LS4, ERC-2020-COG
Summary Therapeutic modulation of vascular cell proliferation and migration is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The current view is that an increase in growth factor levels or mitogenic stimulation is beneficial for angiogenesis, since it leads to an increase in both endothelial proliferation and sprouting.
Through the use of innovative genetic and imaging approaches, we have recently elucidated a previously unappreciated, context-dependent mechanism whereby highly mitogenic environments can be detrimental for angiogenesis and lead to the cell-cycle arrest of endothelial cells (ECs), which ultimately impairs vascular growth.
The identified mechanism may explain the failed or inefficient promotion of functional angiogenesis by vascular growth factor delivery therapies, such as those used to treat ischemic cardiovascular disease. We propose that a better understanding and modulation of the identified hypermitogenic arrest process may allow angiogenesis to be induced more effectively.
Taking advantage of recent advances in DNA synthesis, CRISPR gene editing, microscopy and single-cell profiling technologies, we have developed new genetic tools, animal models and methods of broad relevance that enable the study of gene function with higher reliability, throughput and definition.
We propose to use these novel research tools and methods to significantly increase understanding of the biology of blood vessels in distinct physiological and pathological contexts.
We will then use this new knowledge to identify better strategies to promote vascular development in ischemic cardiovascular disease, heal vascular malformations, or inhibit angiogenesis in tumours.
Summary
Therapeutic modulation of vascular cell proliferation and migration is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The current view is that an increase in growth factor levels or mitogenic stimulation is beneficial for angiogenesis, since it leads to an increase in both endothelial proliferation and sprouting.
Through the use of innovative genetic and imaging approaches, we have recently elucidated a previously unappreciated, context-dependent mechanism whereby highly mitogenic environments can be detrimental for angiogenesis and lead to the cell-cycle arrest of endothelial cells (ECs), which ultimately impairs vascular growth.
The identified mechanism may explain the failed or inefficient promotion of functional angiogenesis by vascular growth factor delivery therapies, such as those used to treat ischemic cardiovascular disease. We propose that a better understanding and modulation of the identified hypermitogenic arrest process may allow angiogenesis to be induced more effectively.
Taking advantage of recent advances in DNA synthesis, CRISPR gene editing, microscopy and single-cell profiling technologies, we have developed new genetic tools, animal models and methods of broad relevance that enable the study of gene function with higher reliability, throughput and definition.
We propose to use these novel research tools and methods to significantly increase understanding of the biology of blood vessels in distinct physiological and pathological contexts.
We will then use this new knowledge to identify better strategies to promote vascular development in ischemic cardiovascular disease, heal vascular malformations, or inhibit angiogenesis in tumours.
Max ERC Funding
1 998 500 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
