Project acronym 15CBOOKTRADE
Project The 15th-century Book Trade: An Evidence-based Assessment and Visualization of the Distribution, Sale, and Reception of Books in the Renaissance
Researcher (PI) Cristina Dondi
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Consolidator Grant (CoG), SH6, ERC-2013-CoG
Summary The idea that underpins this project is to use the material evidence from thousands of surviving 15th-c. books, as well as unique documentary evidence — the unpublished ledger of a Venetian bookseller in the 1480s which records the sale of 25,000 printed books with their prices — to address four fundamental questions relating to the introduction of printing in the West which have so far eluded scholarship, partly because of lack of evidence, partly because of the lack of effective tools to deal with existing evidence. The book trade differs from other trades operating in the medieval and early modern periods in that the goods traded survive in considerable numbers. Not only do they survive, but many of them bear stratified evidence of their history in the form of marks of ownership, prices, manuscript annotations, binding and decoration styles. A British Academy pilot project conceived by the PI produced a now internationally-used database which gathers together this kind of evidence for thousands of surviving 15th-c. printed books. For the first time, this makes it possible to track the circulation of books, their trade routes and later collecting, across Europe and the USA, and throughout the centuries. The objectives of this project are to examine (1) the distribution and trade-routes, national and international, of 15th-c. printed books, along with the identity of the buyers and users (private, institutional, religious, lay, female, male, and by profession) and their reading practices; (2) the books' contemporary market value; (3) the transmission and dissemination of the texts they contain, their survival and their loss (rebalancing potentially skewed scholarship); and (4) the circulation and re-use of the illustrations they contain. Finally, the project will experiment with the application of scientific visualization techniques to represent, geographically and chronologically, the movement of 15th-c. printed books and of the texts they contain.
Summary
The idea that underpins this project is to use the material evidence from thousands of surviving 15th-c. books, as well as unique documentary evidence — the unpublished ledger of a Venetian bookseller in the 1480s which records the sale of 25,000 printed books with their prices — to address four fundamental questions relating to the introduction of printing in the West which have so far eluded scholarship, partly because of lack of evidence, partly because of the lack of effective tools to deal with existing evidence. The book trade differs from other trades operating in the medieval and early modern periods in that the goods traded survive in considerable numbers. Not only do they survive, but many of them bear stratified evidence of their history in the form of marks of ownership, prices, manuscript annotations, binding and decoration styles. A British Academy pilot project conceived by the PI produced a now internationally-used database which gathers together this kind of evidence for thousands of surviving 15th-c. printed books. For the first time, this makes it possible to track the circulation of books, their trade routes and later collecting, across Europe and the USA, and throughout the centuries. The objectives of this project are to examine (1) the distribution and trade-routes, national and international, of 15th-c. printed books, along with the identity of the buyers and users (private, institutional, religious, lay, female, male, and by profession) and their reading practices; (2) the books' contemporary market value; (3) the transmission and dissemination of the texts they contain, their survival and their loss (rebalancing potentially skewed scholarship); and (4) the circulation and re-use of the illustrations they contain. Finally, the project will experiment with the application of scientific visualization techniques to represent, geographically and chronologically, the movement of 15th-c. printed books and of the texts they contain.
Max ERC Funding
1 999 172 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym 2D4QT
Project 2D Materials for Quantum Technology
Researcher (PI) Christoph STAMPFER
Host Institution (HI) RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Country Germany
Call Details Consolidator Grant (CoG), PE3, ERC-2018-COG
Summary Since its discovery, graphene has been indicated as a promising platform for quantum technologies (QT). The number of theoretical proposal dedicated to this vision has grown steadily, exploring a wide range of directions, ranging from spin and valley qubits, to topologically-protected states. The experimental confirmation of these ideas lagged so far significantly behind, mostly because of material quality problems. The quality of graphene-based devices has however improved dramatically in the past five years, thanks to the advent of the so-called van der Waals (vdW) heteostructures - artificial solids formed by mechanically stacking layers of different two dimensional (2D) materials, such as graphene, hexagonal boron nitride and transition metal dichalcogenides. These new advances open now finally the door to put several of those theoretical proposals to test.
The goal of this project is to assess experimentally the potential of graphene-based heterostructures for QT applications. Specifically, I will push the development of an advanced technological platform for vdW heterostructures, which will allow to give quantitative answers to the following open questions: i) what are the relaxation and coherence times of spin and valley qubits in isotopically purified bilayer graphene (BLG); ii) what is the efficiency of a Cooper-pair splitter based on BLG; and iii) what are the characteristic energy scales of topologically protected quantum states engineered in graphene-based heterostructures.
At the end of this project, I aim at being in the position of saying whether graphene is the horse-worth-betting-on predicted by theory, or whether it still hides surprises in terms of fundamental physics. The technological advancements developed in this project for integrating nanostructured layers into vdW heterostructures will reach even beyond this goal, opening the door to new research directions and possible applications.
Summary
Since its discovery, graphene has been indicated as a promising platform for quantum technologies (QT). The number of theoretical proposal dedicated to this vision has grown steadily, exploring a wide range of directions, ranging from spin and valley qubits, to topologically-protected states. The experimental confirmation of these ideas lagged so far significantly behind, mostly because of material quality problems. The quality of graphene-based devices has however improved dramatically in the past five years, thanks to the advent of the so-called van der Waals (vdW) heteostructures - artificial solids formed by mechanically stacking layers of different two dimensional (2D) materials, such as graphene, hexagonal boron nitride and transition metal dichalcogenides. These new advances open now finally the door to put several of those theoretical proposals to test.
The goal of this project is to assess experimentally the potential of graphene-based heterostructures for QT applications. Specifically, I will push the development of an advanced technological platform for vdW heterostructures, which will allow to give quantitative answers to the following open questions: i) what are the relaxation and coherence times of spin and valley qubits in isotopically purified bilayer graphene (BLG); ii) what is the efficiency of a Cooper-pair splitter based on BLG; and iii) what are the characteristic energy scales of topologically protected quantum states engineered in graphene-based heterostructures.
At the end of this project, I aim at being in the position of saying whether graphene is the horse-worth-betting-on predicted by theory, or whether it still hides surprises in terms of fundamental physics. The technological advancements developed in this project for integrating nanostructured layers into vdW heterostructures will reach even beyond this goal, opening the door to new research directions and possible applications.
Max ERC Funding
1 806 250 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
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 ADaPt
Project Adaptation, Dispersals and Phenotype: understanding the roles of climate,
natural selection and energetics in shaping global hunter-gatherer adaptability
Researcher (PI) Jay Stock
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Consolidator Grant (CoG), SH6, ERC-2013-CoG
Summary Relative to other species, humans are characterised by considerable biological diversity despite genetic homogeneity. This diversity is reflected in skeletal variation, but we lack sufficient understanding of the underlying mechanisms to adequately interpret the archaeological record. The proposed research will address problems in our current understanding of the origins of human variation in the past by: 1) documenting and interpreting the pattern of global hunter-gatherer variation relative to genetic phylogenies and climatic variation; 2) testing the relationship between environmental and skeletal variation among genetically related hunter-gatherers from different environments; 3) examining the adaptability of living humans to different environments, through the study of energetic expenditure and life history trade-offs associated with locomotion; and 4) investigating the relationship between muscle and skeletal variation associated with locomotion in diverse environments. This will be achieved by linking: a) detailed study of the global pattern of hunter-gatherer variation in the Late Pleistocene and Holocene with; b) ground-breaking experimental research which tests the relationship between energetic stress, muscle function, and bone variation in living humans. The first component tests the correspondence between skeletal variation and both genetic and climatic history, to infer mechanisms driving variation. The second component integrates this skeletal variation with experimental studies of living humans to, for the first time, directly test adaptive implications of skeletal variation observed in the past. ADaPt will provide the first links between prehistoric hunter-gatherer variation and the evolutionary parameters of life history and energetics that may have shaped our success as a species. It will lead to breakthroughs necessary to interpret variation in the archaeological record, relative to human dispersals and adaptation in the past.
Summary
Relative to other species, humans are characterised by considerable biological diversity despite genetic homogeneity. This diversity is reflected in skeletal variation, but we lack sufficient understanding of the underlying mechanisms to adequately interpret the archaeological record. The proposed research will address problems in our current understanding of the origins of human variation in the past by: 1) documenting and interpreting the pattern of global hunter-gatherer variation relative to genetic phylogenies and climatic variation; 2) testing the relationship between environmental and skeletal variation among genetically related hunter-gatherers from different environments; 3) examining the adaptability of living humans to different environments, through the study of energetic expenditure and life history trade-offs associated with locomotion; and 4) investigating the relationship between muscle and skeletal variation associated with locomotion in diverse environments. This will be achieved by linking: a) detailed study of the global pattern of hunter-gatherer variation in the Late Pleistocene and Holocene with; b) ground-breaking experimental research which tests the relationship between energetic stress, muscle function, and bone variation in living humans. The first component tests the correspondence between skeletal variation and both genetic and climatic history, to infer mechanisms driving variation. The second component integrates this skeletal variation with experimental studies of living humans to, for the first time, directly test adaptive implications of skeletal variation observed in the past. ADaPt will provide the first links between prehistoric hunter-gatherer variation and the evolutionary parameters of life history and energetics that may have shaped our success as a species. It will lead to breakthroughs necessary to interpret variation in the archaeological record, relative to human dispersals and adaptation in the past.
Max ERC Funding
1 911 485 €
Duration
Start date: 2014-07-01, End date: 2019-06-30
Project acronym CANCEREVO
Project Deciphering and predicting the evolution of cancer cell populations
Researcher (PI) Marco Helmut GERLINGER
Host Institution (HI) THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL
Country United Kingdom
Call Details Consolidator Grant (CoG), LS7, ERC-2018-COG
Summary The fundamental evolutionary nature of cancer is well recognized but an understanding of the dynamic evolutionary changes occurring throughout a tumour’s lifetime and their clinical implications is in its infancy. Current approaches to reveal cancer evolution by sequencing of multiple biopsies remain of limited use in the clinic due to sample access problems in multi-metastatic disease. Circulating tumour DNA (ctDNA) is thought to comprehensively sample subclones across metastatic sites. However, available technologies either have high sensitivity but are restricted to the analysis of small gene panels or they allow sequencing of large target regions such as exomes but with too limited sensitivity to detect rare subclones. We developed a novel error corrected sequencing technology that will be applied to perform deep exome sequencing on longitudinal ctDNA samples from highly heterogeneous metastatic gastro-oesophageal carcinomas. This will track the evolution of the entire cancer population over the lifetime of these tumours, from metastatic disease over drug therapy to end-stage disease and enable ground breaking insights into cancer population evolution rules and mechanisms. Specifically, we will: 1. Define the genomic landscape and drivers of metastatic and end stage disease. 2. Understand the rules of cancer evolutionary dynamics of entire cancer cell populations. 3. Predict cancer evolution and define the limits of predictability. 4. Rapidly identify drug resistance mechanisms to chemo- and immunotherapy based on signals of Darwinian selection such as parallel and convergent evolution. Our sequencing technology and analysis framework will also transform the way cancer evolution metrics can be accessed and interpreted in the clinic which will have major impacts, ranging from better biomarkers to predict cancer evolution to the identification of drug targets that drive disease progression and therapy resistance.
Summary
The fundamental evolutionary nature of cancer is well recognized but an understanding of the dynamic evolutionary changes occurring throughout a tumour’s lifetime and their clinical implications is in its infancy. Current approaches to reveal cancer evolution by sequencing of multiple biopsies remain of limited use in the clinic due to sample access problems in multi-metastatic disease. Circulating tumour DNA (ctDNA) is thought to comprehensively sample subclones across metastatic sites. However, available technologies either have high sensitivity but are restricted to the analysis of small gene panels or they allow sequencing of large target regions such as exomes but with too limited sensitivity to detect rare subclones. We developed a novel error corrected sequencing technology that will be applied to perform deep exome sequencing on longitudinal ctDNA samples from highly heterogeneous metastatic gastro-oesophageal carcinomas. This will track the evolution of the entire cancer population over the lifetime of these tumours, from metastatic disease over drug therapy to end-stage disease and enable ground breaking insights into cancer population evolution rules and mechanisms. Specifically, we will: 1. Define the genomic landscape and drivers of metastatic and end stage disease. 2. Understand the rules of cancer evolutionary dynamics of entire cancer cell populations. 3. Predict cancer evolution and define the limits of predictability. 4. Rapidly identify drug resistance mechanisms to chemo- and immunotherapy based on signals of Darwinian selection such as parallel and convergent evolution. Our sequencing technology and analysis framework will also transform the way cancer evolution metrics can be accessed and interpreted in the clinic which will have major impacts, ranging from better biomarkers to predict cancer evolution to the identification of drug targets that drive disease progression and therapy resistance.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym EXQUISITE
Project External Quantum Control of Photonic Semiconductor Nanostructures
Researcher (PI) Stephan Erich Reitzenstein
Host Institution (HI) TECHNISCHE UNIVERSITAT BERLIN
Country Germany
Call Details Consolidator Grant (CoG), PE3, ERC-2013-CoG
Summary In this project, we will control photonic nanostructures by external feedback, optical injection and synchronization. This will allow us to study nonlinear dynamics in quantum systems and to externally manipulate and stabilize light-matter interaction in the regime of quantum electrodynamics (cQED). We will experimentally and theoretically address a) optical injection and feedback control of quantum dot (QD)–microlasers, b) quantum control cQED systems via delayed single photon feedback, and c) mutually coupled and synchronized chaotic microcavity systems. In a) we will advance the concepts of time-delayed coupling in standard semiconductor laser diodes to few photon states, where quantum fluctuations contribute to or even dominate over the usual classical dynamics. Feedback-coupling in microlasers will allow us to explore the limits of a classical description of chaotic laser dynamics via the Lang-Kobayashi rate equations and to develop an advanced model taking cQED- and QD-specific effects into account. This subject will be complemented by the study of optical injection of coherent light and non-classical light into microlasers to influence and study mode-locking, chaos and stimulated emission down to the quantum level. Single photon feedback in b) will be applied to stabilize coherent coupling of light and matter and to act against decoherence which constitutes a major bottleneck for application of semiconductor nanostructures in quantum information technology. In c) the mutual coupling of microlasers will be used to study synchronization of chaotic quantum devices at the single photon limit and to explore the underlying physics of isochronal synchronization. Our work will have important impact at an interdisciplinary level on the development of nonlinear dynamical systems towards the quantum limit and the understanding of fundamental light-matter interaction in the presence of time delayed single photon feedback.
Summary
In this project, we will control photonic nanostructures by external feedback, optical injection and synchronization. This will allow us to study nonlinear dynamics in quantum systems and to externally manipulate and stabilize light-matter interaction in the regime of quantum electrodynamics (cQED). We will experimentally and theoretically address a) optical injection and feedback control of quantum dot (QD)–microlasers, b) quantum control cQED systems via delayed single photon feedback, and c) mutually coupled and synchronized chaotic microcavity systems. In a) we will advance the concepts of time-delayed coupling in standard semiconductor laser diodes to few photon states, where quantum fluctuations contribute to or even dominate over the usual classical dynamics. Feedback-coupling in microlasers will allow us to explore the limits of a classical description of chaotic laser dynamics via the Lang-Kobayashi rate equations and to develop an advanced model taking cQED- and QD-specific effects into account. This subject will be complemented by the study of optical injection of coherent light and non-classical light into microlasers to influence and study mode-locking, chaos and stimulated emission down to the quantum level. Single photon feedback in b) will be applied to stabilize coherent coupling of light and matter and to act against decoherence which constitutes a major bottleneck for application of semiconductor nanostructures in quantum information technology. In c) the mutual coupling of microlasers will be used to study synchronization of chaotic quantum devices at the single photon limit and to explore the underlying physics of isochronal synchronization. Our work will have important impact at an interdisciplinary level on the development of nonlinear dynamical systems towards the quantum limit and the understanding of fundamental light-matter interaction in the presence of time delayed single photon feedback.
Max ERC Funding
1 999 800 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym HydroSync
Project Hydrodynamic Synchronisation in Model and Biological Systems
Researcher (PI) Pietro Cicuta
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Consolidator Grant (CoG), PE3, ERC-2013-CoG
Summary Cilia and flagella beating in synchronised patterns give rise to metachronal waves, beautiful examples of emergent behaviour in biology. These collective dynamical states are essential in life, transporting nutrients and clearing pathogens; they arise from the mechanical interaction of individual cilia mediated by the viscous fluid.
Severe pathologies are associated with cilia malfunction in humans. The current analysis of ciliated tissues in the clinic is focused purely on the frequency of beating: this is insufficient to discriminate between different pathologies. Much more information is present in the cilia dynamics video data that is recorded from patients; it is not being extracted because the correct theoretical framework for analysis is not in place.
We will develop our current work on actively driven colloidal systems to selectively test aspects of the biological scenarios, and start a new line of investigation in our lab, with cell culture experiments to validate these findings; we will understand the onset of collective dynamics (new physics), and how cilia waves are robust against fluctuations in cilia beat frequency, spatial arrangement and fluid rheology. New video analysis tools will be developed based on this full understanding of mechanical synchronisation, enabling the collective dynamics to be related back to the behaviour of individual cilia and to the physical properties of the fluid.
The team will be of two Post-docs, responsible for the two parts of the project: model and biological systems. A PhD student will contribute to the biological experiments, which present multiple lines of investigation, and will develop the video-analysis code to obtain the full degree of information from biological experiments.
The new analysis tool that results from this project will be deployed in the clinical setting through an established collaboration; enabling diagnosis of airway disorders represents a broad impact on physiology and clinical practice.
Summary
Cilia and flagella beating in synchronised patterns give rise to metachronal waves, beautiful examples of emergent behaviour in biology. These collective dynamical states are essential in life, transporting nutrients and clearing pathogens; they arise from the mechanical interaction of individual cilia mediated by the viscous fluid.
Severe pathologies are associated with cilia malfunction in humans. The current analysis of ciliated tissues in the clinic is focused purely on the frequency of beating: this is insufficient to discriminate between different pathologies. Much more information is present in the cilia dynamics video data that is recorded from patients; it is not being extracted because the correct theoretical framework for analysis is not in place.
We will develop our current work on actively driven colloidal systems to selectively test aspects of the biological scenarios, and start a new line of investigation in our lab, with cell culture experiments to validate these findings; we will understand the onset of collective dynamics (new physics), and how cilia waves are robust against fluctuations in cilia beat frequency, spatial arrangement and fluid rheology. New video analysis tools will be developed based on this full understanding of mechanical synchronisation, enabling the collective dynamics to be related back to the behaviour of individual cilia and to the physical properties of the fluid.
The team will be of two Post-docs, responsible for the two parts of the project: model and biological systems. A PhD student will contribute to the biological experiments, which present multiple lines of investigation, and will develop the video-analysis code to obtain the full degree of information from biological experiments.
The new analysis tool that results from this project will be deployed in the clinical setting through an established collaboration; enabling diagnosis of airway disorders represents a broad impact on physiology and clinical practice.
Max ERC Funding
1 261 572 €
Duration
Start date: 2014-05-01, End date: 2018-04-30
Project acronym iHEAR
Project Gene therapy of inherited and acquired hearing loss
Researcher (PI) Axel Rainer Schambach
Host Institution (HI) MEDIZINISCHE HOCHSCHULE HANNOVER
Country Germany
Call Details Consolidator Grant (CoG), LS7, ERC-2018-COG
Summary To address the substantial financial and social burden caused by hearing loss in 360 million people world-wide, I aim to improve hearing via gene therapy to correct inherited and protect from acquired hearing loss. In vitro experiments will establish the best vector configurations for transfer of therapeutic genes and miRNAs into inner ear hair cells (HC) and spiral ganglion neurons (SGN). The efficiency of the best-performing vector designs will then be explored in vivo using fluorescent marker proteins. Cell-type specific and inducible promoters as well as receptor-targeted vectors will be employed as a safety measure and to ensure transgene expression in HC and SGN target cells. Once efficient transduction of appropriate target cells and proper expression of therapeutic proteins are demonstrated, I will perform proof-of-concept studies in hearing loss models, incl. established mouse models, to correct (WP1) or protect (WP2) from impaired hearing. To ensure translatability of these findings, I will generate human induced pluripotent stem cells (iPSC) from patients with hearing loss (WP3), so that I can test optimized constructs in human otic cells. Moreover, I have access to a collection of well-characterized samples from over 600 hearing loss patients, including children with congenital hearing loss in whom many novel monogenetic alterations were identified. These resources provide the unique opportunity to generate a novel toolbox for the treatment of hearing loss. In addition to lentiviral and adeno-associated viral (AAV) vector delivery of corrective or protective genes to treat hearing loss, I will apply state-of-the-art genome editing tools to model and correct mutations causative for hearing loss in cell lines, primary cells from murine models, human patients and patient-derived iPSC. This work will contribute to development of clinically translatable approaches for precision medicine strategies to improve hearing loss treatment.
Summary
To address the substantial financial and social burden caused by hearing loss in 360 million people world-wide, I aim to improve hearing via gene therapy to correct inherited and protect from acquired hearing loss. In vitro experiments will establish the best vector configurations for transfer of therapeutic genes and miRNAs into inner ear hair cells (HC) and spiral ganglion neurons (SGN). The efficiency of the best-performing vector designs will then be explored in vivo using fluorescent marker proteins. Cell-type specific and inducible promoters as well as receptor-targeted vectors will be employed as a safety measure and to ensure transgene expression in HC and SGN target cells. Once efficient transduction of appropriate target cells and proper expression of therapeutic proteins are demonstrated, I will perform proof-of-concept studies in hearing loss models, incl. established mouse models, to correct (WP1) or protect (WP2) from impaired hearing. To ensure translatability of these findings, I will generate human induced pluripotent stem cells (iPSC) from patients with hearing loss (WP3), so that I can test optimized constructs in human otic cells. Moreover, I have access to a collection of well-characterized samples from over 600 hearing loss patients, including children with congenital hearing loss in whom many novel monogenetic alterations were identified. These resources provide the unique opportunity to generate a novel toolbox for the treatment of hearing loss. In addition to lentiviral and adeno-associated viral (AAV) vector delivery of corrective or protective genes to treat hearing loss, I will apply state-of-the-art genome editing tools to model and correct mutations causative for hearing loss in cell lines, primary cells from murine models, human patients and patient-derived iPSC. This work will contribute to development of clinically translatable approaches for precision medicine strategies to improve hearing loss treatment.
Max ERC Funding
1 999 500 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym LawWithoutMercy
Project Law without Mercy: Japanese Courts-Martial and Military Courts During the Asia-Pacific War, 1937-45
Researcher (PI) Urs Matthias Zachmann
Host Institution (HI) FREIE UNIVERSITAET BERLIN
Country Germany
Call Details Consolidator Grant (CoG), SH6, ERC-2018-COG
Summary Japan fought the war over East and Southeast Asia between 1937 and 1945 not only in the theatres of war, but with equal harshness in the courtrooms of military justice. Wherever Japanese soldiers went, judge-advocates followed, meeting out stern justice to soldiers, civilians and enemy soldiers alike. The system of courts-martial and military courts throughout East and Southeast Asia served three purposes: regulate violence and channel it efficiently to serve Japan's war goals; deter the civilian population and coerce it into following Japan's 'New Order' in East Asia; and finally, convince domestic and international audiences that Japan's war was not only legitimate, but also 'legal'. Yet, despite formal pretences, verdicts routinely ended in execution or harsh imprisonment. As such, the violence of the justice system mirrored the brutality of the war in general.
Despite the highly contentious nature of the war even today, a systematic study of mass violence during the Asia-Pacific War has been sorely lacking. 'Law without Mercy' undertakes this daunting task by using military justice as focal point and as a highly precise lens for studying the various figurations of violence during the war. It is pioneering in analysing legal practice as an integral part of this violence and facilitator for its routinisation and escalation on the battlefield and in the occupied territories. And finally, it opens up a wholly new and large body of sources through original archival work that helps to overcome the notorious direness of documentation on Japan's conduct during the war.
Situated at the intersection of several historical fields, 'Law without Mercy' capitalises on the double expertise of the PI in modern Japanese history and international law. With the complex and precarious relation between law, war and violence still at the heart of humanitarian issues, the historical insights of this project have very practical implications for our conflict-laden world today.
Summary
Japan fought the war over East and Southeast Asia between 1937 and 1945 not only in the theatres of war, but with equal harshness in the courtrooms of military justice. Wherever Japanese soldiers went, judge-advocates followed, meeting out stern justice to soldiers, civilians and enemy soldiers alike. The system of courts-martial and military courts throughout East and Southeast Asia served three purposes: regulate violence and channel it efficiently to serve Japan's war goals; deter the civilian population and coerce it into following Japan's 'New Order' in East Asia; and finally, convince domestic and international audiences that Japan's war was not only legitimate, but also 'legal'. Yet, despite formal pretences, verdicts routinely ended in execution or harsh imprisonment. As such, the violence of the justice system mirrored the brutality of the war in general.
Despite the highly contentious nature of the war even today, a systematic study of mass violence during the Asia-Pacific War has been sorely lacking. 'Law without Mercy' undertakes this daunting task by using military justice as focal point and as a highly precise lens for studying the various figurations of violence during the war. It is pioneering in analysing legal practice as an integral part of this violence and facilitator for its routinisation and escalation on the battlefield and in the occupied territories. And finally, it opens up a wholly new and large body of sources through original archival work that helps to overcome the notorious direness of documentation on Japan's conduct during the war.
Situated at the intersection of several historical fields, 'Law without Mercy' capitalises on the double expertise of the PI in modern Japanese history and international law. With the complex and precarious relation between law, war and violence still at the heart of humanitarian issues, the historical insights of this project have very practical implications for our conflict-laden world today.
Max ERC Funding
1 697 776 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym LHCtoLISA
Project Precision Gravity: From the LHC to LISA
Researcher (PI) Rafael Alejandro PORTO PEREIRA
Host Institution (HI) STIFTUNG DEUTSCHES ELEKTRONEN-SYNCHROTRON DESY
Country Germany
Call Details Consolidator Grant (CoG), PE2, ERC-2018-COG
Summary The nascent field of gravitational wave (GW) science will be an interdisciplinary subject, enriching different branches of physics, yet the associated computational challenges are enormous. Faithful theoretical templates are a compulsory ingredient for successful data analysis and reliable physical interpretation of the signals. This is critical, for instance, to study the equation of state of neutron stars, the nature of black holes, and binary formation channels. However, while current templates for compact binary sources may be sufficient for detection and crude parameter estimation, they are too coarse for precision physics with GW data. We then find ourselves in a situation in which, for key processes within empirical reach, theoretical uncertainties may dominate. To move forward, profiting the most from GW observations, more accurate waveforms will be needed.
I have played a pioneering role in the development and implementation of a new formalism, known as the ‘effective field theory approach’, which has been instrumental for the construction of the state-of-the-art GW template bank. The goal of my proposal is thus to redefine the frontiers of analytic understanding in gravity through the effective field theory framework. Even more ambitiously, to go beyond the current computational paradigm with powerful tools which have been crucial for `new-physics' searches at the Large Hadron Collider.
The impact of the high-accuracy calculations I propose to undertake will be immense: from probes of dynamical spacetime and strongly interacting matter, to the potential to discover exotic compact objects and ultra-light particles in nature. Furthermore, GW observations scan gravity in a regime which is otherwise unexplored. Consequently, the coming decade will tell whether Einstein's theory withstands precision scrutiny. In summary, my program will provide novel techniques and key results that will enable foundational investigations in physics through GW precision data.
Summary
The nascent field of gravitational wave (GW) science will be an interdisciplinary subject, enriching different branches of physics, yet the associated computational challenges are enormous. Faithful theoretical templates are a compulsory ingredient for successful data analysis and reliable physical interpretation of the signals. This is critical, for instance, to study the equation of state of neutron stars, the nature of black holes, and binary formation channels. However, while current templates for compact binary sources may be sufficient for detection and crude parameter estimation, they are too coarse for precision physics with GW data. We then find ourselves in a situation in which, for key processes within empirical reach, theoretical uncertainties may dominate. To move forward, profiting the most from GW observations, more accurate waveforms will be needed.
I have played a pioneering role in the development and implementation of a new formalism, known as the ‘effective field theory approach’, which has been instrumental for the construction of the state-of-the-art GW template bank. The goal of my proposal is thus to redefine the frontiers of analytic understanding in gravity through the effective field theory framework. Even more ambitiously, to go beyond the current computational paradigm with powerful tools which have been crucial for `new-physics' searches at the Large Hadron Collider.
The impact of the high-accuracy calculations I propose to undertake will be immense: from probes of dynamical spacetime and strongly interacting matter, to the potential to discover exotic compact objects and ultra-light particles in nature. Furthermore, GW observations scan gravity in a regime which is otherwise unexplored. Consequently, the coming decade will tell whether Einstein's theory withstands precision scrutiny. In summary, my program will provide novel techniques and key results that will enable foundational investigations in physics through GW precision data.
Max ERC Funding
1 975 000 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
