Project acronym 2LIVEr
Project IL-2 gene therapy for chronic hepatitis B virus infection
Researcher (PI) Matteo IANNACONE
Host Institution (HI) OSPEDALE SAN RAFFAELE SRL
Country Italy
Call Details Proof of Concept (PoC), ERC-2020-PoC
Summary Hepatitis B virus (HBV) infections remain a major public health issue worldwide. Over 350 -400 million people are chronically infected by HBV, and about 1 million people die each year from the complications of this infection (cirrhosis and hepatocellular carcinoma) with a consequent hefty economic impact on national health systems. This led the World Health Organization to recognise HBV infection as a key priority and adopt the global health sector strategy to eliminate viral hepatitis, with a target of reducing new infections by 90% and mortality by 65% by 2030.
The risk of developing a chronic infection in healthy adults is due to a weaker, dysfunctional and narrowly focused CD8+ T cell response. Since the mechanisms underlying HBV persistence are not fully elucidated, current treatments (antiviral drugs and Interferon) aim to reduce the development of liver disease, while a definitive treatment for curing this infection is not yet available on the market.
Within the ERC Consolidator Grant 725038 “FATE”, we recently characterized the mechanisms behind the ineffective CD8+ T cell response towards HBV, demonstrating the potential efficacy of interleukin-2 (IL-2) – a cytokine – to reactivate it, thus achieving antiviral activity. This discovery, jointly with our proprietary third-generation, self-inactivating lentiviral vectors (LVs) that allow selective hepatocellular expression of IL-2, pave the way to single-dose gene therapy-based approach, a potential functional cure against chronic hepatitis B.
2LIVEr project intends to optimize and further validate our novel therapeutic approach from both a technical and commercial standpoint, moving from TRL3 to TRL4, thus fastening the roadmap towards the market.
Summary
Hepatitis B virus (HBV) infections remain a major public health issue worldwide. Over 350 -400 million people are chronically infected by HBV, and about 1 million people die each year from the complications of this infection (cirrhosis and hepatocellular carcinoma) with a consequent hefty economic impact on national health systems. This led the World Health Organization to recognise HBV infection as a key priority and adopt the global health sector strategy to eliminate viral hepatitis, with a target of reducing new infections by 90% and mortality by 65% by 2030.
The risk of developing a chronic infection in healthy adults is due to a weaker, dysfunctional and narrowly focused CD8+ T cell response. Since the mechanisms underlying HBV persistence are not fully elucidated, current treatments (antiviral drugs and Interferon) aim to reduce the development of liver disease, while a definitive treatment for curing this infection is not yet available on the market.
Within the ERC Consolidator Grant 725038 “FATE”, we recently characterized the mechanisms behind the ineffective CD8+ T cell response towards HBV, demonstrating the potential efficacy of interleukin-2 (IL-2) – a cytokine – to reactivate it, thus achieving antiviral activity. This discovery, jointly with our proprietary third-generation, self-inactivating lentiviral vectors (LVs) that allow selective hepatocellular expression of IL-2, pave the way to single-dose gene therapy-based approach, a potential functional cure against chronic hepatitis B.
2LIVEr project intends to optimize and further validate our novel therapeutic approach from both a technical and commercial standpoint, moving from TRL3 to TRL4, thus fastening the roadmap towards the market.
Max ERC Funding
150 000 €
Duration
Start date: 2020-07-01, End date: 2021-12-31
Project acronym 3DALIGN
Project Enhancing the performance of 3D-printed organic thermoelectrics by electric field-assisted molecular alignment
Researcher (PI) Francisco Molina-Lopez
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Country Belgium
Call Details Starting Grant (StG), PE7, ERC-2020-STG
Summary Thermoelectrics (TEs) are important because they can convert heat directly into electrical energy and enable efficient heating/cooling. However, their popularization has been hindered by 1) their low efficiency (especially at room temperature), 2) the use of rare/toxic materials, and 3) the difficulty to process those materials. In 3DALIGN, I target a 3-in-1 solution to these challenges by using for the first time electric-field-assisted molecular alignment of 3D-printed TE polymers. High electrical/low thermal conductivity is required for efficient TEs, but both conductivities go hand in hand in traditional inorganic TE materials. This paradigm can shift for polymers, which possess complicated molecular structure. Despite their relatively low electrical conductivity, conducting polymers are appealing for TEs due to their much lower thermal conductivity than inorganic TE materials. Existing studies of organic TEs have focused on finding new materials, but no attention has been paid to molecular ordering, a known strategy to improve performance in organic transistors. I have recently developed a versatile method to induce molecular alignment in solution-processed polymers by using externally applied electric fields. In 3DALIGN, I propose to use this new method to boost the electrical conductivity of polymer TEs while inducing minimal alteration in their thermal conductivity. The high-risk of this goal is mitigated by other advantages of using polymer TEs: polymers are less toxic and more abundant than inorganic TE materials; and they are easy to 3D print, enabling a simple fabrication route for large-area through-plane TE structures that will lead to novel applications. In conclusion, this project will shed light in the relationship between molecular ordering and transport properties of organic electronic materials. If successful, it will also introduce a breakthrough in the performance and feasibility of TEs.
Summary
Thermoelectrics (TEs) are important because they can convert heat directly into electrical energy and enable efficient heating/cooling. However, their popularization has been hindered by 1) their low efficiency (especially at room temperature), 2) the use of rare/toxic materials, and 3) the difficulty to process those materials. In 3DALIGN, I target a 3-in-1 solution to these challenges by using for the first time electric-field-assisted molecular alignment of 3D-printed TE polymers. High electrical/low thermal conductivity is required for efficient TEs, but both conductivities go hand in hand in traditional inorganic TE materials. This paradigm can shift for polymers, which possess complicated molecular structure. Despite their relatively low electrical conductivity, conducting polymers are appealing for TEs due to their much lower thermal conductivity than inorganic TE materials. Existing studies of organic TEs have focused on finding new materials, but no attention has been paid to molecular ordering, a known strategy to improve performance in organic transistors. I have recently developed a versatile method to induce molecular alignment in solution-processed polymers by using externally applied electric fields. In 3DALIGN, I propose to use this new method to boost the electrical conductivity of polymer TEs while inducing minimal alteration in their thermal conductivity. The high-risk of this goal is mitigated by other advantages of using polymer TEs: polymers are less toxic and more abundant than inorganic TE materials; and they are easy to 3D print, enabling a simple fabrication route for large-area through-plane TE structures that will lead to novel applications. In conclusion, this project will shed light in the relationship between molecular ordering and transport properties of organic electronic materials. If successful, it will also introduce a breakthrough in the performance and feasibility of TEs.
Max ERC Funding
1 710 853 €
Duration
Start date: 2021-02-01, End date: 2026-01-31
Project acronym 3DX-FLASH
Project Probing MHz processes in 3D with X-ray microscopy
Researcher (PI) Pablo Villanueva Perez
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE4, ERC-2020-STG
Summary I aim to develop an X-ray imaging technique capable of filming processes in 3D, with a temporal resolution several orders of magnitude faster than up-to-date 3D X-ray imaging techniques.
The unique penetration power of X-rays allows us to study systems in their native environment. This property has led to the development of X-ray microtomography (µCT). µCT acquires 3D information, which determines the functionality and mechanical properties of nature, by rotating a sample with respect to the X-ray source. µCT is a crucial tool for several scientific disciplines such as physics, biology, and chemistry.
Over the last decade, µCT has become a technique capable of not only recording 3D information but also filming dynamical processes. Several breakthroughs have made this possible: i) intense X-ray sources (synchrotron light sources), ii) efficient and fast X-ray detectors, and iii) fast 3D reconstruction algorithms. Despite all of these developments, the acquisition protocols remain unchanged, i.e., the sample is only rotated faster. This fast rotation introduces forces which may alter the studied dynamics and ultimately limit the achievable temporal resolution.
My project is to establish an X-ray microscope that avoids the sample rotation, obtaining 3D information from a single X-ray flash by splitting it into nine-angularly resolved beams which illuminate the sample simultaneously. This approach, when implemented at intense X-ray sources such as synchrotron light sources and X-ray free-electron lasers, will allow the filming of natural processes with micrometer to nanometer resolution and resolve dynamics from microseconds to femtoseconds. To demonstrate its capabilities, I will study fundamental processes in cellulose fibers, a renewable biomaterial, which can replace fossil-based materials, such as plastics. This technique will open up the possibility to film dynamics in 3D to answer questions coming from industry and natural sciences at rates not accessible today.
Summary
I aim to develop an X-ray imaging technique capable of filming processes in 3D, with a temporal resolution several orders of magnitude faster than up-to-date 3D X-ray imaging techniques.
The unique penetration power of X-rays allows us to study systems in their native environment. This property has led to the development of X-ray microtomography (µCT). µCT acquires 3D information, which determines the functionality and mechanical properties of nature, by rotating a sample with respect to the X-ray source. µCT is a crucial tool for several scientific disciplines such as physics, biology, and chemistry.
Over the last decade, µCT has become a technique capable of not only recording 3D information but also filming dynamical processes. Several breakthroughs have made this possible: i) intense X-ray sources (synchrotron light sources), ii) efficient and fast X-ray detectors, and iii) fast 3D reconstruction algorithms. Despite all of these developments, the acquisition protocols remain unchanged, i.e., the sample is only rotated faster. This fast rotation introduces forces which may alter the studied dynamics and ultimately limit the achievable temporal resolution.
My project is to establish an X-ray microscope that avoids the sample rotation, obtaining 3D information from a single X-ray flash by splitting it into nine-angularly resolved beams which illuminate the sample simultaneously. This approach, when implemented at intense X-ray sources such as synchrotron light sources and X-ray free-electron lasers, will allow the filming of natural processes with micrometer to nanometer resolution and resolve dynamics from microseconds to femtoseconds. To demonstrate its capabilities, I will study fundamental processes in cellulose fibers, a renewable biomaterial, which can replace fossil-based materials, such as plastics. This technique will open up the possibility to film dynamics in 3D to answer questions coming from industry and natural sciences at rates not accessible today.
Max ERC Funding
1 999 213 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
Project acronym 4D-BIOMAP
Project Biomechanical Stimulation based on 4D Printed Magneto-Active Polymers
Researcher (PI) DANIEL GARCIA GONZALEZ
Host Institution (HI) UNIVERSIDAD CARLOS III DE MADRID
Country Spain
Call Details Starting Grant (StG), PE8, ERC-2020-STG
Summary MAPs are polymer-based composites that respond to magnetic fields with large deformation or tuneable mechanical properties. I aim to apply heterogeneous 3D printed MAPs as modifiable substrates to support biological structures which can have their deformation state and stiffness controlled by the external application of magnetic stimuli. Such mechanical stimulation has an important role on biological structures leading to alterations in functional responses, morphological changes and activation of growth or healing processes. Current bottlenecks preventing progress in this field are a lack of: a) appropriate experimental methodologies to enable characterisation of the behaviour of these materials; b) fundamental theoretical underpinnings to support the design and application of these new materials. The first step is to undertake in depth characterisation and assessment of 4D printed MAPs to create a detailed understanding of the underlying physics controlling the interactions between the polymeric matrices and embedded magnetic particles during application of mechanical and/or magnetic loadings. I will then culture biological structures on the novel 4D printed MAPs to create a ‘designed’ biostructure with specified and controllable responses to a given magnetic stimulus. These novel biostructures will be assessed using three applications: a) astrocyte cellular networks, b) neuronal circuits and c) astrocyte-neuronal networks. The evaluation of cellular damage, morphological and physiological alterations will validate the performance of the new biostructures and also contribute new understanding to the effects of deformation and stiffness gradients during glial scarring on physiological functions of central nervous system cells. The resulting deep understanding of magneto-mechanics of MAPs and their further development for controllable stimulation devices, will enable the international consolidation of my research group within the mechanics and bioengineering fields.
Summary
MAPs are polymer-based composites that respond to magnetic fields with large deformation or tuneable mechanical properties. I aim to apply heterogeneous 3D printed MAPs as modifiable substrates to support biological structures which can have their deformation state and stiffness controlled by the external application of magnetic stimuli. Such mechanical stimulation has an important role on biological structures leading to alterations in functional responses, morphological changes and activation of growth or healing processes. Current bottlenecks preventing progress in this field are a lack of: a) appropriate experimental methodologies to enable characterisation of the behaviour of these materials; b) fundamental theoretical underpinnings to support the design and application of these new materials. The first step is to undertake in depth characterisation and assessment of 4D printed MAPs to create a detailed understanding of the underlying physics controlling the interactions between the polymeric matrices and embedded magnetic particles during application of mechanical and/or magnetic loadings. I will then culture biological structures on the novel 4D printed MAPs to create a ‘designed’ biostructure with specified and controllable responses to a given magnetic stimulus. These novel biostructures will be assessed using three applications: a) astrocyte cellular networks, b) neuronal circuits and c) astrocyte-neuronal networks. The evaluation of cellular damage, morphological and physiological alterations will validate the performance of the new biostructures and also contribute new understanding to the effects of deformation and stiffness gradients during glial scarring on physiological functions of central nervous system cells. The resulting deep understanding of magneto-mechanics of MAPs and their further development for controllable stimulation devices, will enable the international consolidation of my research group within the mechanics and bioengineering fields.
Max ERC Funding
1 499 625 €
Duration
Start date: 2021-01-01, End date: 2025-12-31
Project acronym AAV-FACTORY
Project Synthetic Viral Nanosystem for Highly Efficient AAV Manufacturing for Gene Therapy
Researcher (PI) Imre Berger
Host Institution (HI) UNIVERSITY OF BRISTOL
Country United Kingdom
Call Details Proof of Concept (PoC), ERC-2020-PoC
Summary Gene therapy is one of the most innovative and fastest growing fields in the pharmaceutical industry. The first approved gene therapy utilized a recombinant AAV vector (rAAV), and dozens of additional rAAVs for gene therapy are presently in clinical trials. rAAV gene therapy drugs have been priced in the region of € 500’000 and above, which is partially a result of them being manufactured by highly complex processes combining multiple components, requiring 5-7 separate GMP production runs. We intend to introduce the first scalable, single-virus rAAV production platform to resolve this bottleneck. The resulting significant reduction of manufacturing complexity will both lower the price of future rAAV gene therapies, and also deliver additional, currently unaddressed or unaffordable rAAV treatments for genetic diseases into the clinic by providing scientists operating at the laboratory R&D stage with more user friendly and productive tools. The proposed project also develops for PoC purposes an rAAV gene therapy candidate to treat the devastating childhood congenital disease known as steroid resistant nephrotic syndrome SRNS.
Summary
Gene therapy is one of the most innovative and fastest growing fields in the pharmaceutical industry. The first approved gene therapy utilized a recombinant AAV vector (rAAV), and dozens of additional rAAVs for gene therapy are presently in clinical trials. rAAV gene therapy drugs have been priced in the region of € 500’000 and above, which is partially a result of them being manufactured by highly complex processes combining multiple components, requiring 5-7 separate GMP production runs. We intend to introduce the first scalable, single-virus rAAV production platform to resolve this bottleneck. The resulting significant reduction of manufacturing complexity will both lower the price of future rAAV gene therapies, and also deliver additional, currently unaddressed or unaffordable rAAV treatments for genetic diseases into the clinic by providing scientists operating at the laboratory R&D stage with more user friendly and productive tools. The proposed project also develops for PoC purposes an rAAV gene therapy candidate to treat the devastating childhood congenital disease known as steroid resistant nephrotic syndrome SRNS.
Max ERC Funding
150 000 €
Duration
Start date: 2021-02-01, End date: 2022-07-31
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 ACADEMIA
Project Reconstructing Late Medieval Quests for Knowledge: Quodlibetal Debates as Precursors of Modern Academic Practice
Researcher (PI) Ota PavlIcek
Host Institution (HI) FILOSOFICKY USTAV AV CR, v.v.i.
Country Czechia
Call Details Starting Grant (StG), SH6, ERC-2020-STG
Summary ACADEMIA proposes a pioneering study of a neglected corpus of manuscripts stemming from the practice of quodlibetal debates held at Faculties of Arts of European universities, flourishing from the 14th to the early 16th century. As prescribed by the university statutes, dozens of professors participated periodically in these unique collective works of the Middle Ages, which encompassed all the disciplines pursued at the university, from logic to medicine to theology. The PI hypothesises that the professors presented at the hitherto mostly ignored quodlibets their recent scientific innovations, which they then published in the first collective volumes of European academia. The PI thus proposes a novel theoretical framework for understanding the quodlibets: they stand at the origin of the modern concept of science as a collective intellectual enterprise, similar to modern conferences and the subsequent dissemination of results. This makes them and their written form critical for understanding European intellectual and scientific traditions, both past and present. ACADEMIA’s ambition is to establish the corpus of these debates as a new field of study through an extensive examination of manuscripts, thus filling a substantial gap, radically extending the fields of the history of universities and intellectual history, and reconstructing the roots of the modern practice of fostering collective science. A complex analysis of the corpus will bring about a substantial change in our understanding of medieval practices of the production and sharing of knowledge. Aiming to examine the quodlibets as a phenomenon successively interconnecting European intellectual space, ACADEMIA focuses on fourteen universities at which the PI has identified the tradition so far and on their mutual relations and development. ACADEMIA employs an interdisciplinary team and an innovative combination of approaches from history, codicology, palaeography, philology, hermeneutics and Digital Humanities.
Summary
ACADEMIA proposes a pioneering study of a neglected corpus of manuscripts stemming from the practice of quodlibetal debates held at Faculties of Arts of European universities, flourishing from the 14th to the early 16th century. As prescribed by the university statutes, dozens of professors participated periodically in these unique collective works of the Middle Ages, which encompassed all the disciplines pursued at the university, from logic to medicine to theology. The PI hypothesises that the professors presented at the hitherto mostly ignored quodlibets their recent scientific innovations, which they then published in the first collective volumes of European academia. The PI thus proposes a novel theoretical framework for understanding the quodlibets: they stand at the origin of the modern concept of science as a collective intellectual enterprise, similar to modern conferences and the subsequent dissemination of results. This makes them and their written form critical for understanding European intellectual and scientific traditions, both past and present. ACADEMIA’s ambition is to establish the corpus of these debates as a new field of study through an extensive examination of manuscripts, thus filling a substantial gap, radically extending the fields of the history of universities and intellectual history, and reconstructing the roots of the modern practice of fostering collective science. A complex analysis of the corpus will bring about a substantial change in our understanding of medieval practices of the production and sharing of knowledge. Aiming to examine the quodlibets as a phenomenon successively interconnecting European intellectual space, ACADEMIA focuses on fourteen universities at which the PI has identified the tradition so far and on their mutual relations and development. ACADEMIA employs an interdisciplinary team and an innovative combination of approaches from history, codicology, palaeography, philology, hermeneutics and Digital Humanities.
Max ERC Funding
1 260 485 €
Duration
Start date: 2021-07-01, End date: 2026-06-30
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