Project acronym 4DPHOTON
Project Beyond Light Imaging: High-Rate Single-Photon Detection in Four Dimensions
Researcher (PI) Massimiliano FIORINI
Host Institution (HI) ISTITUTO NAZIONALE DI FISICA NUCLEARE
Country Italy
Call Details Consolidator Grant (CoG), PE2, ERC-2018-COG
Summary Goal of the 4DPHOTON project is the development and construction of a photon imaging detector with unprecedented performance. The proposed device will be capable of detecting fluxes of single-photons up to one billion photons per second, over areas of several square centimetres, and will measure - for each photon - position and time simultaneously with resolutions better than ten microns and few tens of picoseconds, respectively. These figures of merit will open many important applications allowing significant advances in particle physics, life sciences or other emerging fields where excellent timing and position resolutions are simultaneously required.
Our goal will be achieved thanks to the use of an application-specific integrated circuit in 65 nm complementary metal-oxide-semiconductor (CMOS) technology, that will deliver a timing resolution of few tens of picoseconds at the pixel level, over few hundred thousand individually-active pixel channels, allowing very high rates of photons to be detected, and the corresponding information digitized and transferred to a processing unit.
As a result of the 4DPHOTON project we will remove the constraints that many light imaging applications have due to the lack of precise single-photon information on four dimensions (4D): the three spatial coordinates and time simultaneously. In particular, we will prove the performance of this detector in the field of particle physics, performing the reconstruction of Cherenkov photon rings with a timing resolution of ten picoseconds. With its excellent granularity, timing resolution, rate capability and compactness, this detector will represent a new paradigm for the realisation of future Ring Imaging Cherenkov detectors, capable of achieving high efficiency particle identification in environments with very high particle multiplicities, exploiting time-association of the photon hits.
Summary
Goal of the 4DPHOTON project is the development and construction of a photon imaging detector with unprecedented performance. The proposed device will be capable of detecting fluxes of single-photons up to one billion photons per second, over areas of several square centimetres, and will measure - for each photon - position and time simultaneously with resolutions better than ten microns and few tens of picoseconds, respectively. These figures of merit will open many important applications allowing significant advances in particle physics, life sciences or other emerging fields where excellent timing and position resolutions are simultaneously required.
Our goal will be achieved thanks to the use of an application-specific integrated circuit in 65 nm complementary metal-oxide-semiconductor (CMOS) technology, that will deliver a timing resolution of few tens of picoseconds at the pixel level, over few hundred thousand individually-active pixel channels, allowing very high rates of photons to be detected, and the corresponding information digitized and transferred to a processing unit.
As a result of the 4DPHOTON project we will remove the constraints that many light imaging applications have due to the lack of precise single-photon information on four dimensions (4D): the three spatial coordinates and time simultaneously. In particular, we will prove the performance of this detector in the field of particle physics, performing the reconstruction of Cherenkov photon rings with a timing resolution of ten picoseconds. With its excellent granularity, timing resolution, rate capability and compactness, this detector will represent a new paradigm for the realisation of future Ring Imaging Cherenkov detectors, capable of achieving high efficiency particle identification in environments with very high particle multiplicities, exploiting time-association of the photon hits.
Max ERC Funding
1 975 000 €
Duration
Start date: 2019-12-01, End date: 2024-11-30
Project acronym ACOPS
Project Advanced Coherent Ultrafast Laser Pulse Stacking
Researcher (PI) Jens Limpert
Host Institution (HI) FRIEDRICH-SCHILLER-UNIVERSITAT JENA
Country Germany
Call Details Consolidator Grant (CoG), PE2, ERC-2013-CoG
Summary "An important driver of scientific progress has always been the envisioning of applications far beyond existing technological capabilities. Such thinking creates new challenges for physicists, driven by the groundbreaking nature of the anticipated application. In the case of laser physics, one of these applications is laser wake-field particle acceleration and possible future uses thereof, such as in collider experiments, or for medical applications such as cancer treatment. To accelerate electrons and positrons to TeV-energies, a laser architecture is required that allows for the combination of high efficiency, Petawatt peak powers, and Megawatt average powers. Developing such a laser system would be a challenging task that might take decades of aggressive research, development, and, most important, revolutionary approaches and innovative ideas.
The goal of the ACOPS project is to develop a compact, efficient, scalable, and cost-effective high-average and high-peak power ultra-short pulse laser concept.
The proposed approach to this goal relies on the spatially and temporally separated amplification of ultrashort laser pulses in waveguide structures, followed by coherent combination into a single train of pulses with increased average power and pulse energy. This combination can be realized through the coherent addition of the output beams of spatially separated amplifiers, combined with the pulse stacking of temporally separated pulses in passive enhancement cavities, employing a fast-switching element as cavity dumper.
Therefore, the three main tasks are the development of kW-class high-repetition-rate driving lasers, the investigation of non-steady state pulse enhancement in passive cavities, and the development of a suitable dumping element.
If successful, the proposed concept would undoubtedly provide a tool that would allow researchers to surpass the current limits in high-field physics and accelerator science."
Summary
"An important driver of scientific progress has always been the envisioning of applications far beyond existing technological capabilities. Such thinking creates new challenges for physicists, driven by the groundbreaking nature of the anticipated application. In the case of laser physics, one of these applications is laser wake-field particle acceleration and possible future uses thereof, such as in collider experiments, or for medical applications such as cancer treatment. To accelerate electrons and positrons to TeV-energies, a laser architecture is required that allows for the combination of high efficiency, Petawatt peak powers, and Megawatt average powers. Developing such a laser system would be a challenging task that might take decades of aggressive research, development, and, most important, revolutionary approaches and innovative ideas.
The goal of the ACOPS project is to develop a compact, efficient, scalable, and cost-effective high-average and high-peak power ultra-short pulse laser concept.
The proposed approach to this goal relies on the spatially and temporally separated amplification of ultrashort laser pulses in waveguide structures, followed by coherent combination into a single train of pulses with increased average power and pulse energy. This combination can be realized through the coherent addition of the output beams of spatially separated amplifiers, combined with the pulse stacking of temporally separated pulses in passive enhancement cavities, employing a fast-switching element as cavity dumper.
Therefore, the three main tasks are the development of kW-class high-repetition-rate driving lasers, the investigation of non-steady state pulse enhancement in passive cavities, and the development of a suitable dumping element.
If successful, the proposed concept would undoubtedly provide a tool that would allow researchers to surpass the current limits in high-field physics and accelerator science."
Max ERC Funding
1 881 040 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym ACQDIV
Project Acquisition processes in maximally diverse languages: Min(d)ing the ambient language
Researcher (PI) Sabine Erika Stoll
Host Institution (HI) University of Zurich
Country Switzerland
Call Details Consolidator Grant (CoG), SH4, ERC-2013-CoG
Summary "Children learn any language that they grow up with, adapting to any of the ca. 7000 languages of the world, no matter how divergent or complex their structures are. What cognitive processes make this extreme flexibility possible? This is one of the most burning questions in cognitive science and the ACQDIV project aims at answering it by testing and refining the following leading hypothesis: Language acquisition is flexible and adaptive to any kind of language because it relies on a small set of universal cognitive processes that variably target different structures at different times during acquisition in every language. The project aims at establishing the precise set of processes and at determining the conditions of variation across maximally diverse languages. This project focuses on three processes: (i) distributional learning, (ii) generalization-based learning and (iii) interaction-based learning. To investigate these processes I will work with a sample of five clusters of languages including longitudinal data of two languages each. The clusters were determined by a clustering algorithm seeking the structurally most divergent languages in a typological database. The languages are: Cluster 1: Slavey and Cree, Cluster 2: Indonesian and Yucatec, Cluster 3: Inuktitut and Chintang, Cluster 4: Sesotho and Russian, Cluster 5: Japanese and Turkish. For all languages, corpora are available, except for Slavey where fieldwork is planned. The leading hypothesis will be tested against the acquisition of aspect and negation in each language of the sample and also against the two structures in each language that are most salient and challenging in them (e. g. complex morphology in Chintang). The acquisition processes also depend on statistical patterns in the input children receive. I will examine these patterns across the sample with respect to repetitiveness effects, applying data-mining methods and systematically comparing child-directed and child-surrounding speech."
Summary
"Children learn any language that they grow up with, adapting to any of the ca. 7000 languages of the world, no matter how divergent or complex their structures are. What cognitive processes make this extreme flexibility possible? This is one of the most burning questions in cognitive science and the ACQDIV project aims at answering it by testing and refining the following leading hypothesis: Language acquisition is flexible and adaptive to any kind of language because it relies on a small set of universal cognitive processes that variably target different structures at different times during acquisition in every language. The project aims at establishing the precise set of processes and at determining the conditions of variation across maximally diverse languages. This project focuses on three processes: (i) distributional learning, (ii) generalization-based learning and (iii) interaction-based learning. To investigate these processes I will work with a sample of five clusters of languages including longitudinal data of two languages each. The clusters were determined by a clustering algorithm seeking the structurally most divergent languages in a typological database. The languages are: Cluster 1: Slavey and Cree, Cluster 2: Indonesian and Yucatec, Cluster 3: Inuktitut and Chintang, Cluster 4: Sesotho and Russian, Cluster 5: Japanese and Turkish. For all languages, corpora are available, except for Slavey where fieldwork is planned. The leading hypothesis will be tested against the acquisition of aspect and negation in each language of the sample and also against the two structures in each language that are most salient and challenging in them (e. g. complex morphology in Chintang). The acquisition processes also depend on statistical patterns in the input children receive. I will examine these patterns across the sample with respect to repetitiveness effects, applying data-mining methods and systematically comparing child-directed and child-surrounding speech."
Max ERC Funding
1 998 438 €
Duration
Start date: 2014-09-01, End date: 2019-08-31
Project acronym ActionContraThreat
Project Action selection under threat: the complex control of human defense
Researcher (PI) Dominik BACH
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Country United Kingdom
Call Details Consolidator Grant (CoG), SH4, ERC-2018-COG
Summary Run away, sidestep, duck-and-cover, watch: when under threat, humans immediately choreograph a large repertoire of defensive actions. Understanding action-selection under threat is important for anybody wanting to explain why anxiety disorders imply some of these behaviours in harmless situations. Current concepts of human defensive behaviour are largely derived from rodent research and focus on a small number of broad, cross-species, action tendencies. This is likely to underestimate the complexity of the underlying action-selection mechanisms. This research programme will take decisive steps to understand these psychological mechanisms and elucidate their neural implementation.
To elicit threat-related action in the laboratory, I will use virtual reality computer games with full body motion, and track actions with motion-capture technology. Based on a cognitive-computational framework, I will systematically characterise the space of actions under threat, investigate the psychological mechanisms by which actions are selected in different scenarios, and describe them with computational algorithms that allow quantitative predictions. To independently verify their neural implementation, I will use wearable magnetoencephalography (MEG) in freely moving subjects.
This proposal fills a lacuna between defence system concepts based on rodent research, emotion psychology, and clinical accounts of anxiety disorders. By combining a stringent experimental approach with the formalism of cognitive-computational psychology, it furnishes a unique opportunity to understand the mechanisms of action-selection under threat, and how these are distinct from more general-purpose action-selection systems. Beyond its immediate scope, the proposal has a potential to lead to a better understanding of anxiety disorders, and to pave the way towards improved diagnostics and therapies.
Summary
Run away, sidestep, duck-and-cover, watch: when under threat, humans immediately choreograph a large repertoire of defensive actions. Understanding action-selection under threat is important for anybody wanting to explain why anxiety disorders imply some of these behaviours in harmless situations. Current concepts of human defensive behaviour are largely derived from rodent research and focus on a small number of broad, cross-species, action tendencies. This is likely to underestimate the complexity of the underlying action-selection mechanisms. This research programme will take decisive steps to understand these psychological mechanisms and elucidate their neural implementation.
To elicit threat-related action in the laboratory, I will use virtual reality computer games with full body motion, and track actions with motion-capture technology. Based on a cognitive-computational framework, I will systematically characterise the space of actions under threat, investigate the psychological mechanisms by which actions are selected in different scenarios, and describe them with computational algorithms that allow quantitative predictions. To independently verify their neural implementation, I will use wearable magnetoencephalography (MEG) in freely moving subjects.
This proposal fills a lacuna between defence system concepts based on rodent research, emotion psychology, and clinical accounts of anxiety disorders. By combining a stringent experimental approach with the formalism of cognitive-computational psychology, it furnishes a unique opportunity to understand the mechanisms of action-selection under threat, and how these are distinct from more general-purpose action-selection systems. Beyond its immediate scope, the proposal has a potential to lead to a better understanding of anxiety disorders, and to pave the way towards improved diagnostics and therapies.
Max ERC Funding
1 998 750 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym AdOC
Project Advance Optical Clocks
Researcher (PI) Sebastien Andre Marcel Bize
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Consolidator Grant (CoG), PE2, ERC-2013-CoG
Summary "The proposed research program has three main objectives. The first and second objectives are to seek extreme precisions in optical atomic spectroscopy and optical clocks, and to use this quest as a mean of exploration in atomic physics. The third objective is to explore new possibilities that stem from extreme precision. These goals will be pursued via three complementary activities: #1: Search for extreme precisions with an Hg optical lattice clock. #2: Explore and exploit the rich Hg system, which is essentially unexplored in the cold and ultra-cold regime. #3: Identify new applications of clocks with extreme precision to Earth science. Clocks can measure directly the gravitational potential via Einstein’s gravitational redshift, leading to the idea of “clock-based geodesy”.
The 2 first activities are experimental and build on an existing setup, where we demonstrated the feasibility of an Hg optical lattice clock. Hg is chosen for its potential to surpass competing systems. We will investigate the unexplored physics of the Hg clock. This includes interactions between Hg atoms, lattice-induced light shifts, and sensitivity to external fields which are specific to the atomic species. Beyond, we will explore the fundamental limits of the optical lattice scheme. We will exploit other remarkable features of Hg associated to the high atomic number and the diversity of stable isotopes. These features enable tests of fundamental physical laws, ultra-precise measurements of isotope shifts, measurement of collisional properties toward evaporative cooling and quantum gases of Hg, investigation of forbidden transitions promising for measuring the nuclear anapole moment of Hg.
The third activity is theoretical and is aimed at initiating collaborations with experts in modelling Earth gravity. With this expertise, we will identify the most promising and realistic approaches for clocks and emerging remote comparison methods to contribute to geodesy, hydrology, oceanography, etc."
Summary
"The proposed research program has three main objectives. The first and second objectives are to seek extreme precisions in optical atomic spectroscopy and optical clocks, and to use this quest as a mean of exploration in atomic physics. The third objective is to explore new possibilities that stem from extreme precision. These goals will be pursued via three complementary activities: #1: Search for extreme precisions with an Hg optical lattice clock. #2: Explore and exploit the rich Hg system, which is essentially unexplored in the cold and ultra-cold regime. #3: Identify new applications of clocks with extreme precision to Earth science. Clocks can measure directly the gravitational potential via Einstein’s gravitational redshift, leading to the idea of “clock-based geodesy”.
The 2 first activities are experimental and build on an existing setup, where we demonstrated the feasibility of an Hg optical lattice clock. Hg is chosen for its potential to surpass competing systems. We will investigate the unexplored physics of the Hg clock. This includes interactions between Hg atoms, lattice-induced light shifts, and sensitivity to external fields which are specific to the atomic species. Beyond, we will explore the fundamental limits of the optical lattice scheme. We will exploit other remarkable features of Hg associated to the high atomic number and the diversity of stable isotopes. These features enable tests of fundamental physical laws, ultra-precise measurements of isotope shifts, measurement of collisional properties toward evaporative cooling and quantum gases of Hg, investigation of forbidden transitions promising for measuring the nuclear anapole moment of Hg.
The third activity is theoretical and is aimed at initiating collaborations with experts in modelling Earth gravity. With this expertise, we will identify the most promising and realistic approaches for clocks and emerging remote comparison methods to contribute to geodesy, hydrology, oceanography, etc."
Max ERC Funding
1 946 432 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym ArtHep
Project Hepatocytes-Like Microreactors for Liver Tissue Engineering
Researcher (PI) Brigitte STADLER
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Consolidator Grant (CoG), LS9, ERC-2018-COG
Summary The global epidemics of obesity and diabetes type 2 lead to higher abundancy of medical conditions like non-alcoholic fatty liver disease causing an increase in liver failure and demand for liver transplants. The shortage of donor organs and the insufficient success in tissue engineering to ex vivo grow complex organs like the liver is a global medical challenge.
ArtHep targets the assembly of hepatic-like tissue, consisting of biological and synthetic entities, mimicking the core structure elements and key functions of the liver. ArtHep comprises an entirely new concept in liver regeneration with multi-angled core impact: i) cell mimics are expected to reduce the pressure to obtain donor cells, ii) the integrated biocatalytic subunits are destined to take over tasks of the damaged liver slowing down the progress of liver damage, and iii) the matching micro-environment in the bioprinted tissue is anticipated to facilitate the connection between the transplant and the liver.
Success criteria of ArtHep include engineering enzyme-mimics, which can perform core biocatalytic conversions similar to the liver, the assembly of biocatalytic active subunits and their encapsulation in cell-like carriers (microreactors), which have mechanical properties that match the liver tissue and that have a camouflaging coating to mimic the surface cues of liver tissue-relevant cells. Finally, matured bioprinted liver-lobules consisting of microreactors and live cells need to connect to liver tissue when transplanted into rats.
I am convinced that the ground-breaking research in ArtHep will contribute to the excellence of science in Europe while providing the game-changing foundation to counteract the ever increasing donor liver shortage. Further, consolidating my scientific efforts and moving them forward into unexplored dimensions in biomimicry for medical purposes, is a unique opportunity to advance my career.
Summary
The global epidemics of obesity and diabetes type 2 lead to higher abundancy of medical conditions like non-alcoholic fatty liver disease causing an increase in liver failure and demand for liver transplants. The shortage of donor organs and the insufficient success in tissue engineering to ex vivo grow complex organs like the liver is a global medical challenge.
ArtHep targets the assembly of hepatic-like tissue, consisting of biological and synthetic entities, mimicking the core structure elements and key functions of the liver. ArtHep comprises an entirely new concept in liver regeneration with multi-angled core impact: i) cell mimics are expected to reduce the pressure to obtain donor cells, ii) the integrated biocatalytic subunits are destined to take over tasks of the damaged liver slowing down the progress of liver damage, and iii) the matching micro-environment in the bioprinted tissue is anticipated to facilitate the connection between the transplant and the liver.
Success criteria of ArtHep include engineering enzyme-mimics, which can perform core biocatalytic conversions similar to the liver, the assembly of biocatalytic active subunits and their encapsulation in cell-like carriers (microreactors), which have mechanical properties that match the liver tissue and that have a camouflaging coating to mimic the surface cues of liver tissue-relevant cells. Finally, matured bioprinted liver-lobules consisting of microreactors and live cells need to connect to liver tissue when transplanted into rats.
I am convinced that the ground-breaking research in ArtHep will contribute to the excellence of science in Europe while providing the game-changing foundation to counteract the ever increasing donor liver shortage. Further, consolidating my scientific efforts and moving them forward into unexplored dimensions in biomimicry for medical purposes, is a unique opportunity to advance my career.
Max ERC Funding
1 992 289 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym ARTSILK
Project Novel approaches to the generation of artificial spider silk superfibers
Researcher (PI) Anna RISING
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Consolidator Grant (CoG), LS9, ERC-2018-COG
Summary Spider silk is Nature’s high performance material that has the potential to revolutionize the materials industry. However, production and spinning of artificial spider silk fibers are challenging, and current methods to produce silk fibers include denaturing conditions which prevent the silk proteins from assembling into fibers in the same complex way as native silk proteins do. In order to fulfill the potential of spider silk we need to increase our understanding of the silk formation process and decipher how protein folding and interactions relate to mechanical properties of the resulting silk fiber. Recent insights into the physiology and molecular mechanisms of the spinning process has made it possible to develop a biomimetic artificial spider silk spinning device (see our publications Andersson et al. Nat Chem Biol. 2017; Otikovs et al. Angew Chemie Int Engl Ed. 2017). We are, for the first time, able to spin artificial silk fibers in which the proteins adopt correct secondary, tertiary and quaternary structures.
The overall objective of ARTSILK is to build on these recent technical leaps and use state-of-the-art technologies to generate artificial silk fibers that are equal or superior to native spider silk in terms of toughness and tensile strength.
To reach the overall objective we will use the recently mapped spider genome, protein engineering and single cell RNA (ScRNA) sequencing to design novel silk proteins for fiber production. We will also study the relationship between protein secondary structure formation and fiber mechanical properties in order to decipher the ques that determine mechanical properties of the fiber. This knowledge will be important also for the basic understanding of how soluble proteins covert into b-sheet rich fibrils in, e.g., Alzheimer’s disease. Finally, we will use microfluidic chips to engineer the next generation spinning device and 3D-printing techniques to make reproducible three-dimensional structures of spider silk.
Summary
Spider silk is Nature’s high performance material that has the potential to revolutionize the materials industry. However, production and spinning of artificial spider silk fibers are challenging, and current methods to produce silk fibers include denaturing conditions which prevent the silk proteins from assembling into fibers in the same complex way as native silk proteins do. In order to fulfill the potential of spider silk we need to increase our understanding of the silk formation process and decipher how protein folding and interactions relate to mechanical properties of the resulting silk fiber. Recent insights into the physiology and molecular mechanisms of the spinning process has made it possible to develop a biomimetic artificial spider silk spinning device (see our publications Andersson et al. Nat Chem Biol. 2017; Otikovs et al. Angew Chemie Int Engl Ed. 2017). We are, for the first time, able to spin artificial silk fibers in which the proteins adopt correct secondary, tertiary and quaternary structures.
The overall objective of ARTSILK is to build on these recent technical leaps and use state-of-the-art technologies to generate artificial silk fibers that are equal or superior to native spider silk in terms of toughness and tensile strength.
To reach the overall objective we will use the recently mapped spider genome, protein engineering and single cell RNA (ScRNA) sequencing to design novel silk proteins for fiber production. We will also study the relationship between protein secondary structure formation and fiber mechanical properties in order to decipher the ques that determine mechanical properties of the fiber. This knowledge will be important also for the basic understanding of how soluble proteins covert into b-sheet rich fibrils in, e.g., Alzheimer’s disease. Finally, we will use microfluidic chips to engineer the next generation spinning device and 3D-printing techniques to make reproducible three-dimensional structures of spider silk.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym Atto-Zepto
Project Ultrasensitive Nano-Optomechanical Sensors
Researcher (PI) Olivier ARCIZET
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Consolidator Grant (CoG), PE2, ERC-2018-COG
Summary By enabling the conversion of forces into measurable displacements, mechanical oscillators have always played a central role in experimental physics. Recent developments in the PI group demonstrated the possibility to realize ultrasensitive and vectorial force field sensing by using suspended SiC nanowires and optical readout of their transverse vibrations. Astonishing sensitivities were obtained at room and dilution temperatures, at the Atto- Zepto-newton level, for which the electron-electron interaction becomes detectable at 100µm.
The goal of the project is to push forward those ultrasensitive nano-optomechanical force sensors, to realize even more challenging explorations of novel fundamental interactions at the quantum-classical interface.
We will develop universal advanced sensing protocols to explore the vectorial structure of fundamental optical, electrostatic or magnetic interactions, and investigate Casimir force fields above nanostructured surfaces, in geometries where it was recently predicted to become repulsive. The second research axis is the one of cavity nano-optomechanics: inserting the ultrasensitive nanowire in a high finesse optical microcavity should enhance the light-nanowire interaction up to the point where a single cavity photon can displace the nanowire by more than its zero point quantum fluctuations. We will investigate this so-called ultrastrong optomechanical coupling regime, and further explore novel regimes in cavity optomechanics, where optical non-linearities at the single photon level become accessible. The last part is dedicated to the exploration of hybrid qubit-mechanical systems, in which nanowire vibrations are magnetically coupled to the spin of a single Nitrogen Vacancy defect in diamond. We will focus on the exploration of spin-dependent forces, aiming at mechanically detecting qubit excitations, opening a novel road towards the generation of non-classical states of motion, and mechanically enhanced quantum sensors.
Summary
By enabling the conversion of forces into measurable displacements, mechanical oscillators have always played a central role in experimental physics. Recent developments in the PI group demonstrated the possibility to realize ultrasensitive and vectorial force field sensing by using suspended SiC nanowires and optical readout of their transverse vibrations. Astonishing sensitivities were obtained at room and dilution temperatures, at the Atto- Zepto-newton level, for which the electron-electron interaction becomes detectable at 100µm.
The goal of the project is to push forward those ultrasensitive nano-optomechanical force sensors, to realize even more challenging explorations of novel fundamental interactions at the quantum-classical interface.
We will develop universal advanced sensing protocols to explore the vectorial structure of fundamental optical, electrostatic or magnetic interactions, and investigate Casimir force fields above nanostructured surfaces, in geometries where it was recently predicted to become repulsive. The second research axis is the one of cavity nano-optomechanics: inserting the ultrasensitive nanowire in a high finesse optical microcavity should enhance the light-nanowire interaction up to the point where a single cavity photon can displace the nanowire by more than its zero point quantum fluctuations. We will investigate this so-called ultrastrong optomechanical coupling regime, and further explore novel regimes in cavity optomechanics, where optical non-linearities at the single photon level become accessible. The last part is dedicated to the exploration of hybrid qubit-mechanical systems, in which nanowire vibrations are magnetically coupled to the spin of a single Nitrogen Vacancy defect in diamond. We will focus on the exploration of spin-dependent forces, aiming at mechanically detecting qubit excitations, opening a novel road towards the generation of non-classical states of motion, and mechanically enhanced quantum sensors.
Max ERC Funding
2 067 905 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym AutoCAb
Project Automated computational design of site-targeted repertoires of camelid antibodies
Researcher (PI) Sarel-Jacob FLEISHMAN
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Country Israel
Call Details Consolidator Grant (CoG), LS9, ERC-2018-COG
Summary We propose to develop the first high-throughput strategy to design, synthesize, and screen repertoires comprising millions of single-domain camelid antibodies (VHH) that target desired protein surfaces. Each VHH will be individually designed for high stability and target-site affinity. We will leverage recent methods developed by our lab for designing stable, specific, and accurate backbones at interfaces, the advent of massive and affordable custom-DNA oligo synthesis, and machine learning methods to accomplish the following aims:
Aim 1: Establish a completely automated computational pipeline that uses Rosetta to design millions of VHHs targeting desired protein surfaces. The variable regions in each design will be encoded in DNA oligo pools, which will be assembled to generate the entire site-targeted repertoire. We will then use high-throughput binding screens followed by deep sequencing to characterize the designs’ target-site affinity and isolate high-affinity binders.
Aim 2: Develop an epitope-focusing strategy that designs several variants of a target antigen, each of which encodes dozens of radical surface mutations outside the target site to disrupt potential off-target site binding. The designs will be used to isolate site-targeting binders from repertoires of Aim 1.
Each high-throughput screen will provide unprecedented experimental data on target-site affinity in millions of individually designed VHHs.
Aim 3: Use machine learning methods to infer combinations of molecular features that distinguish high-affinity binders from non binders. These will be encoded in subsequent designed repertoires, leading to a continuous “learning loop” of methods for high-affinity, site-targeted binding.
AutoCAb’s interdisciplinary strategy will thus lead to deeper understanding of and new general methods for designing stable, high-affinity, site-targeted antibodies, potentially revolutionizing binder and inhibitor discovery in basic and applied biomedical research.
Summary
We propose to develop the first high-throughput strategy to design, synthesize, and screen repertoires comprising millions of single-domain camelid antibodies (VHH) that target desired protein surfaces. Each VHH will be individually designed for high stability and target-site affinity. We will leverage recent methods developed by our lab for designing stable, specific, and accurate backbones at interfaces, the advent of massive and affordable custom-DNA oligo synthesis, and machine learning methods to accomplish the following aims:
Aim 1: Establish a completely automated computational pipeline that uses Rosetta to design millions of VHHs targeting desired protein surfaces. The variable regions in each design will be encoded in DNA oligo pools, which will be assembled to generate the entire site-targeted repertoire. We will then use high-throughput binding screens followed by deep sequencing to characterize the designs’ target-site affinity and isolate high-affinity binders.
Aim 2: Develop an epitope-focusing strategy that designs several variants of a target antigen, each of which encodes dozens of radical surface mutations outside the target site to disrupt potential off-target site binding. The designs will be used to isolate site-targeting binders from repertoires of Aim 1.
Each high-throughput screen will provide unprecedented experimental data on target-site affinity in millions of individually designed VHHs.
Aim 3: Use machine learning methods to infer combinations of molecular features that distinguish high-affinity binders from non binders. These will be encoded in subsequent designed repertoires, leading to a continuous “learning loop” of methods for high-affinity, site-targeted binding.
AutoCAb’s interdisciplinary strategy will thus lead to deeper understanding of and new general methods for designing stable, high-affinity, site-targeted antibodies, potentially revolutionizing binder and inhibitor discovery in basic and applied biomedical research.
Max ERC Funding
2 337 500 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym BACTERIAL SYRINGES
Project Protein Translocation Through Bacterial Syringes
Researcher (PI) Stefan Raunser
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Country Germany
Call Details Consolidator Grant (CoG), LS1, ERC-2013-CoG
Summary "The main objective of this application is to study the molecular basis of cellular infection by bacterial ABC-type toxins (Tc). Tc complexes are important virulence factors of a range of bacteria, including Photorhabdus luminescens and Yersinia pseudotuberculosis that infect insects and humans. Belonging to the class of pore-forming toxins, tripartite Tc complexes perforate the host membrane by forming channels that translocate toxic enzymes into the host.
In our previous cryo-EM work on the P. luminescens Tc complex we discovered that Tcs use a special syringe-like device for cell entry. Building on these results, we now intend to unravel the molecular mechanism through which this unusual and complicated injection system allows membrane permeation and protein translocation. We will use a hybrid approach, including biochemical reconstitution, structural analysis by cryo-EM and X-ray crystallography, fluorescence-based assays and site-directed mutagenesis to provide a comprehensive description of the molecular mechanism of infection at an unprecedented level of molecular detail.
Our results will be paradigmatic for understanding the mechanism of action of ABC-type toxins and will shed new light on the interactions of bacterial pathogens with their hosts."
Summary
"The main objective of this application is to study the molecular basis of cellular infection by bacterial ABC-type toxins (Tc). Tc complexes are important virulence factors of a range of bacteria, including Photorhabdus luminescens and Yersinia pseudotuberculosis that infect insects and humans. Belonging to the class of pore-forming toxins, tripartite Tc complexes perforate the host membrane by forming channels that translocate toxic enzymes into the host.
In our previous cryo-EM work on the P. luminescens Tc complex we discovered that Tcs use a special syringe-like device for cell entry. Building on these results, we now intend to unravel the molecular mechanism through which this unusual and complicated injection system allows membrane permeation and protein translocation. We will use a hybrid approach, including biochemical reconstitution, structural analysis by cryo-EM and X-ray crystallography, fluorescence-based assays and site-directed mutagenesis to provide a comprehensive description of the molecular mechanism of infection at an unprecedented level of molecular detail.
Our results will be paradigmatic for understanding the mechanism of action of ABC-type toxins and will shed new light on the interactions of bacterial pathogens with their hosts."
Max ERC Funding
1 999 992 €
Duration
Start date: 2014-07-01, End date: 2019-06-30
