Project acronym 4DRepLy
Project Closing the 4D Real World Reconstruction Loop
Researcher (PI) Christian THEOBALT
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Consolidator Grant (CoG), PE6, ERC-2017-COG
Summary 4D reconstruction, the camera-based dense dynamic scene reconstruction, is a grand challenge in computer graphics and computer vision. Despite great progress, 4D capturing the complex, diverse real world outside a studio is still far from feasible. 4DRepLy builds a new generation of high-fidelity 4D reconstruction (4DRecon) methods. They will be the first to efficiently capture all types of deformable objects (humans and other types) in crowded real world scenes with a single color or depth camera. They capture space-time coherent deforming geometry, motion, high-frequency reflectance and illumination at unprecedented detail, and will be the first to handle difficult occlusions, topology changes and large groups of interacting objects. They automatically adapt to new scene types, yet deliver models with meaningful, interpretable parameters. This requires far reaching contributions: First, we develop groundbreaking new plasticity-enhanced model-based 4D reconstruction methods that automatically adapt to new scenes. Second, we develop radically new machine learning-based dense 4D reconstruction methods. Third, these model- and learning-based methods are combined in two revolutionary new classes of 4DRecon methods: 1) advanced fusion-based methods and 2) methods with deep architectural integration. Both, 1) and 2), are automatically designed in the 4D Real World Reconstruction Loop, a revolutionary new design paradigm in which 4DRecon methods refine and adapt themselves while continuously processing unlabeled real world input. This overcomes the previously unbreakable scalability barrier to real world scene diversity, complexity and generality. This paradigm shift opens up a new research direction in graphics and vision and has far reaching relevance across many scientific fields. It enables new applications of profound social pervasion and significant economic impact, e.g., for visual media and virtual/augmented reality, and for future autonomous and robotic systems.
Summary
4D reconstruction, the camera-based dense dynamic scene reconstruction, is a grand challenge in computer graphics and computer vision. Despite great progress, 4D capturing the complex, diverse real world outside a studio is still far from feasible. 4DRepLy builds a new generation of high-fidelity 4D reconstruction (4DRecon) methods. They will be the first to efficiently capture all types of deformable objects (humans and other types) in crowded real world scenes with a single color or depth camera. They capture space-time coherent deforming geometry, motion, high-frequency reflectance and illumination at unprecedented detail, and will be the first to handle difficult occlusions, topology changes and large groups of interacting objects. They automatically adapt to new scene types, yet deliver models with meaningful, interpretable parameters. This requires far reaching contributions: First, we develop groundbreaking new plasticity-enhanced model-based 4D reconstruction methods that automatically adapt to new scenes. Second, we develop radically new machine learning-based dense 4D reconstruction methods. Third, these model- and learning-based methods are combined in two revolutionary new classes of 4DRecon methods: 1) advanced fusion-based methods and 2) methods with deep architectural integration. Both, 1) and 2), are automatically designed in the 4D Real World Reconstruction Loop, a revolutionary new design paradigm in which 4DRecon methods refine and adapt themselves while continuously processing unlabeled real world input. This overcomes the previously unbreakable scalability barrier to real world scene diversity, complexity and generality. This paradigm shift opens up a new research direction in graphics and vision and has far reaching relevance across many scientific fields. It enables new applications of profound social pervasion and significant economic impact, e.g., for visual media and virtual/augmented reality, and for future autonomous and robotic systems.
Max ERC Funding
1 977 000 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym A-HERO
Project Anthelmintic Research and Optimization
Researcher (PI) Jennifer Irene Keiser
Host Institution (HI) SCHWEIZERISCHES TROPEN- UND PUBLIC HEALTH-INSTITUT
Call Details Consolidator Grant (CoG), LS7, ERC-2013-CoG
Summary "I propose an ambitious, yet feasible 5-year research project that will fill an important gap in global health. Specifically, I will develop and validate novel approaches for anthelmintic drug discovery and development. My proposal pursues the following five research questions: (i) Is a chip calorimeter suitable for high-throughput screening in anthelmintic drug discovery? (ii) Is combination chemotherapy safe and more efficacious than monotherapy against strongyloidiasis and trichuriasis? (iii) What are the key pharmacokinetic parameters of praziquantel in preschool-aged children and school-aged children infected with Schistosoma mansoni and S. haematobium using a novel and validated technology based on dried blood spotting? (iv) What are the metabolic consequences and clearance of praziquantel treatment in S. mansoni-infected mice and S. mansoni- and S. haematobium-infected children? (v) Which is the ideal compartment to study pharmacokinetic parameters for intestinal nematode infections and does age, nutrition, co-infection and infection intensity influence the efficacy of anthelmintic drugs?
My proposed research is of considerable public health relevance since it will ultimately result in improved treatments for soil-transmitted helminthiasis and pediatric schistosomiasis. Additionally, at the end of this project, I have generated comprehensive information on drug disposition of anthelmintics. A comprehensive database of metabolite profiles following praziquantel treatment will be available. Finally, the proof-of-concept of chip calorimetry in anthelmintic drug discovery has been established and broadly validated."
Summary
"I propose an ambitious, yet feasible 5-year research project that will fill an important gap in global health. Specifically, I will develop and validate novel approaches for anthelmintic drug discovery and development. My proposal pursues the following five research questions: (i) Is a chip calorimeter suitable for high-throughput screening in anthelmintic drug discovery? (ii) Is combination chemotherapy safe and more efficacious than monotherapy against strongyloidiasis and trichuriasis? (iii) What are the key pharmacokinetic parameters of praziquantel in preschool-aged children and school-aged children infected with Schistosoma mansoni and S. haematobium using a novel and validated technology based on dried blood spotting? (iv) What are the metabolic consequences and clearance of praziquantel treatment in S. mansoni-infected mice and S. mansoni- and S. haematobium-infected children? (v) Which is the ideal compartment to study pharmacokinetic parameters for intestinal nematode infections and does age, nutrition, co-infection and infection intensity influence the efficacy of anthelmintic drugs?
My proposed research is of considerable public health relevance since it will ultimately result in improved treatments for soil-transmitted helminthiasis and pediatric schistosomiasis. Additionally, at the end of this project, I have generated comprehensive information on drug disposition of anthelmintics. A comprehensive database of metabolite profiles following praziquantel treatment will be available. Finally, the proof-of-concept of chip calorimetry in anthelmintic drug discovery has been established and broadly validated."
Max ERC Funding
1 927 350 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym Acclimatize
Project Hypothalamic mechanisms of thermal homeostasis and adaptation
Researcher (PI) Jan SIEMENS
Host Institution (HI) UNIVERSITATSKLINIKUM HEIDELBERG
Call Details Consolidator Grant (CoG), LS5, ERC-2017-COG
Summary Mammalian organisms possess the remarkable ability to maintain internal body temperature (Tcore) within a narrow range close to 37°C despite wide environmental temperature variations. The brain’s neural “thermostat” is made up by central circuits in the hypothalamic preoptic area (POA), which orchestrate peripheral thermoregulatory responses to maintain Tcore. Thermogenesis requires metabolic fuel, suggesting intricate connections between the thermoregulatory centre and hypothalamic circuits controlling energy balance. How the POA detects and integrates temperature and metabolic information to achieve thermal balance is largely unknown. A major question is whether this circuitry could be harnessed therapeutically to treat obesity.
We have recently identified the first known molecular temperature sensor in thermoregulatory neurons of the POA, transient receptor potential melastatin 2 (TRPM2), a thermo-sensitive ion channel. I aim to use TRPM2 as a molecular marker to gain access to and probe the function of thermoregulatory neurons in vivo. I propose a multidisciplinary approach, combining local, in vivo POA temperature stimulation with optogenetic circuit-mapping to uncover the molecular and cellular logic of the hypothalamic thermoregulatory centre and to assess its medical potential to counteract metabolic syndrome.
Acclimation is a beneficial adaptive process that fortifies thermal responses upon environmental temperature challenges. Thermoregulatory neuron plasticity is thought to mediate acclimation. Conversely, maladaptive thermoregulatory changes affect obesity. The cell-type-specific neuronal plasticity mechanisms underlying these changes within the POA, however, are unknown.
Using ex-vivo slice electrophysiology and in vivo imaging, I propose to characterize acclimation- and obesity-induced plasticity of thermoregulatory neurons. Ultimately, I aim to manipulate thermoregulatory neuron plasticity to test its potential counter-balancing effect on obesity.
Summary
Mammalian organisms possess the remarkable ability to maintain internal body temperature (Tcore) within a narrow range close to 37°C despite wide environmental temperature variations. The brain’s neural “thermostat” is made up by central circuits in the hypothalamic preoptic area (POA), which orchestrate peripheral thermoregulatory responses to maintain Tcore. Thermogenesis requires metabolic fuel, suggesting intricate connections between the thermoregulatory centre and hypothalamic circuits controlling energy balance. How the POA detects and integrates temperature and metabolic information to achieve thermal balance is largely unknown. A major question is whether this circuitry could be harnessed therapeutically to treat obesity.
We have recently identified the first known molecular temperature sensor in thermoregulatory neurons of the POA, transient receptor potential melastatin 2 (TRPM2), a thermo-sensitive ion channel. I aim to use TRPM2 as a molecular marker to gain access to and probe the function of thermoregulatory neurons in vivo. I propose a multidisciplinary approach, combining local, in vivo POA temperature stimulation with optogenetic circuit-mapping to uncover the molecular and cellular logic of the hypothalamic thermoregulatory centre and to assess its medical potential to counteract metabolic syndrome.
Acclimation is a beneficial adaptive process that fortifies thermal responses upon environmental temperature challenges. Thermoregulatory neuron plasticity is thought to mediate acclimation. Conversely, maladaptive thermoregulatory changes affect obesity. The cell-type-specific neuronal plasticity mechanisms underlying these changes within the POA, however, are unknown.
Using ex-vivo slice electrophysiology and in vivo imaging, I propose to characterize acclimation- and obesity-induced plasticity of thermoregulatory neurons. Ultimately, I aim to manipulate thermoregulatory neuron plasticity to test its potential counter-balancing effect on obesity.
Max ERC Funding
1 902 500 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym ACOPS
Project Advanced Coherent Ultrafast Laser Pulse Stacking
Researcher (PI) Jens Limpert
Host Institution (HI) FRIEDRICH-SCHILLER-UNIVERSITAT JENA
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) UNIVERSITAT ZURICH
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 ADHESWITCHES
Project Adhesion switches in cancer and development: from in vivo to synthetic biology
Researcher (PI) Mari Johanna Ivaska
Host Institution (HI) TURUN YLIOPISTO
Call Details Consolidator Grant (CoG), LS3, ERC-2013-CoG
Summary Integrins are transmembrane cell adhesion receptors controlling cell proliferation and migration. Our objective is to gain fundamentally novel mechanistic insight into the emerging new roles of integrins in cancer and to generate a road map of integrin dependent pathways critical in mammary gland development and integrin signalling thus opening new targets for therapeutic interventions. We will combine an in vivo based translational approach with cell and molecular biological studies aiming to identify entirely novel concepts in integrin function using cutting edge techniques and synthetic-biology tools.
The specific objectives are:
1) Integrin inactivation in branching morphogenesis and cancer invasion. Integrins regulate mammary gland development and cancer invasion but the role of integrin inactivating proteins in these processes is currently completely unknown. We will investigate this using genetically modified mice, ex-vivo organoid models and human tissues with the aim to identify beneficial combinational treatments against cancer invasion.
2) Endosomal adhesomes – cross-talk between integrin activity and integrin “inside-in signaling”. We hypothesize that endocytosed active integrins engage in specialized endosomal signaling that governs cell survival especially in cancer. RNAi cell arrays, super-resolution STED imaging and endosomal proteomics will be used to investigate integrin signaling in endosomes.
3) Spatio-temporal co-ordination of adhesion and endocytosis. Several cytosolic proteins compete for integrin binding to regulate activation, endocytosis and recycling. Photoactivatable protein-traps and predefined matrix micropatterns will be employed to mechanistically dissect the spatio-temporal dynamics and hierarchy of their recruitment.
We will employ innovative and unconventional techniques to address three major unanswered questions in the field and significantly advance our understanding of integrin function in development and cancer.
Summary
Integrins are transmembrane cell adhesion receptors controlling cell proliferation and migration. Our objective is to gain fundamentally novel mechanistic insight into the emerging new roles of integrins in cancer and to generate a road map of integrin dependent pathways critical in mammary gland development and integrin signalling thus opening new targets for therapeutic interventions. We will combine an in vivo based translational approach with cell and molecular biological studies aiming to identify entirely novel concepts in integrin function using cutting edge techniques and synthetic-biology tools.
The specific objectives are:
1) Integrin inactivation in branching morphogenesis and cancer invasion. Integrins regulate mammary gland development and cancer invasion but the role of integrin inactivating proteins in these processes is currently completely unknown. We will investigate this using genetically modified mice, ex-vivo organoid models and human tissues with the aim to identify beneficial combinational treatments against cancer invasion.
2) Endosomal adhesomes – cross-talk between integrin activity and integrin “inside-in signaling”. We hypothesize that endocytosed active integrins engage in specialized endosomal signaling that governs cell survival especially in cancer. RNAi cell arrays, super-resolution STED imaging and endosomal proteomics will be used to investigate integrin signaling in endosomes.
3) Spatio-temporal co-ordination of adhesion and endocytosis. Several cytosolic proteins compete for integrin binding to regulate activation, endocytosis and recycling. Photoactivatable protein-traps and predefined matrix micropatterns will be employed to mechanistically dissect the spatio-temporal dynamics and hierarchy of their recruitment.
We will employ innovative and unconventional techniques to address three major unanswered questions in the field and significantly advance our understanding of integrin function in development and cancer.
Max ERC Funding
1 887 910 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym ANTILEAK
Project Development of antagonists of vascular leakage
Researcher (PI) Pipsa SAHARINEN
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Consolidator Grant (CoG), LS4, ERC-2017-COG
Summary Dysregulation of capillary permeability is a severe problem in critically ill patients, but the mechanisms involved are poorly understood. Further, there are no targeted therapies to stabilize leaky vessels in various common, potentially fatal diseases, such as systemic inflammation and sepsis, which affect millions of people annually. Although a multitude of signals that stimulate opening of endothelial cell-cell junctions leading to permeability have been characterized using cellular and in vivo models, approaches to reverse the harmful process of capillary leakage in disease conditions are yet to be identified. I propose to explore a novel autocrine endothelial permeability regulatory system as a potentially universal mechanism that antagonizes vascular stabilizing ques and sustains vascular leakage in inflammation. My group has identified inflammation-induced mechanisms that switch vascular stabilizing factors into molecules that destabilize vascular barriers, and identified tools to prevent the barrier disruption. Building on these discoveries, my group will use mouse genetics, structural biology and innovative, systematic antibody development coupled with gene editing and gene silencing technology, in order to elucidate mechanisms of vascular barrier breakdown and repair in systemic inflammation. The expected outcomes include insights into endothelial cell signaling and permeability regulation, and preclinical proof-of-concept antibodies to control endothelial activation and vascular leakage in systemic inflammation and sepsis models. Ultimately, the new knowledge and preclinical tools developed in this project may facilitate future development of targeted approaches against vascular leakage.
Summary
Dysregulation of capillary permeability is a severe problem in critically ill patients, but the mechanisms involved are poorly understood. Further, there are no targeted therapies to stabilize leaky vessels in various common, potentially fatal diseases, such as systemic inflammation and sepsis, which affect millions of people annually. Although a multitude of signals that stimulate opening of endothelial cell-cell junctions leading to permeability have been characterized using cellular and in vivo models, approaches to reverse the harmful process of capillary leakage in disease conditions are yet to be identified. I propose to explore a novel autocrine endothelial permeability regulatory system as a potentially universal mechanism that antagonizes vascular stabilizing ques and sustains vascular leakage in inflammation. My group has identified inflammation-induced mechanisms that switch vascular stabilizing factors into molecules that destabilize vascular barriers, and identified tools to prevent the barrier disruption. Building on these discoveries, my group will use mouse genetics, structural biology and innovative, systematic antibody development coupled with gene editing and gene silencing technology, in order to elucidate mechanisms of vascular barrier breakdown and repair in systemic inflammation. The expected outcomes include insights into endothelial cell signaling and permeability regulation, and preclinical proof-of-concept antibodies to control endothelial activation and vascular leakage in systemic inflammation and sepsis models. Ultimately, the new knowledge and preclinical tools developed in this project may facilitate future development of targeted approaches against vascular leakage.
Max ERC Funding
1 999 770 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym ASIAPAST
Project From herds to empire: Biomolecular and zooarchaeological investigations of mobile pastoralism in the ancient Eurasian steppe
Researcher (PI) Cheryl Ann Makarewicz
Host Institution (HI) CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL
Call Details Consolidator Grant (CoG), SH6, ERC-2017-COG
Summary The emergence of mobile pastoralism in the Eurasian steppe five thousand years ago marked a unique transformation in human lifeways where, for the first time, people relied almost exclusively on herd animals of sheep, goat, cattle, and horses for sustenance and as symbols. Mobile pastoralism also generated altogether new forms of socio-political organization exceptional to the steppe that ultimately laid the foundation for nomadic states and empires. However, there remain striking gaps in our knowledge of how the pastoralist niche spread and evolved across Eurasia in the past and influenced cultural trajectories that frame the human-herd systems of today. Little is known about the scale of pastoralist movements connected with the initial translocation of domesticated animals, how mobility became embedded in pastoralist life, or how movement contributed to the formation of sophisticated political networks. There is a poor understanding of the character of herd animal husbandry strategies that were central to pastoralist subsistence and how these co-evolved alongside pastoralist dietary intake and ritual use of herd animals. We have a remarkably poor understanding of what pastoralists ate, especially the dietary contribution of dairy products - the quintessential dietary cornerstone food of pastoralist societies.
ASIAPAST addresses these gaps through a biomolecular approach that recovers the dietary and mobility histories of pastoralists and their animals recorded in bones, teeth, and pottery. This project pairs these methods to detailed analyses of the economic and symbolic use of herd animals preserved in zooarchaeological archives. These investigations draw from materials obtained from key sites that capture the transition to mobile pastoralism, its intensification, and emergence of trans-regional political structures located across the culturally connected regions of Mongolia, Kazakhstan, Russia, Kyrgyzstan, and Uzbekistan.
Summary
The emergence of mobile pastoralism in the Eurasian steppe five thousand years ago marked a unique transformation in human lifeways where, for the first time, people relied almost exclusively on herd animals of sheep, goat, cattle, and horses for sustenance and as symbols. Mobile pastoralism also generated altogether new forms of socio-political organization exceptional to the steppe that ultimately laid the foundation for nomadic states and empires. However, there remain striking gaps in our knowledge of how the pastoralist niche spread and evolved across Eurasia in the past and influenced cultural trajectories that frame the human-herd systems of today. Little is known about the scale of pastoralist movements connected with the initial translocation of domesticated animals, how mobility became embedded in pastoralist life, or how movement contributed to the formation of sophisticated political networks. There is a poor understanding of the character of herd animal husbandry strategies that were central to pastoralist subsistence and how these co-evolved alongside pastoralist dietary intake and ritual use of herd animals. We have a remarkably poor understanding of what pastoralists ate, especially the dietary contribution of dairy products - the quintessential dietary cornerstone food of pastoralist societies.
ASIAPAST addresses these gaps through a biomolecular approach that recovers the dietary and mobility histories of pastoralists and their animals recorded in bones, teeth, and pottery. This project pairs these methods to detailed analyses of the economic and symbolic use of herd animals preserved in zooarchaeological archives. These investigations draw from materials obtained from key sites that capture the transition to mobile pastoralism, its intensification, and emergence of trans-regional political structures located across the culturally connected regions of Mongolia, Kazakhstan, Russia, Kyrgyzstan, and Uzbekistan.
Max ERC Funding
1 999 145 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym ATTOLIQ
Project Attosecond X-ray spectroscopy of liquids
Researcher (PI) Hans Jakob WÖRNER
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Consolidator Grant (CoG), PE4, ERC-2017-COG
Summary Charge and energy transfer are the key steps underlying most chemical reactions and biological transformations. The purely electronic dynamics that control such processes take place on attosecond time scales. A complete understanding of these dynamics on the electronic level therefore calls for new experimental methods with attosecond resolution that are applicable to aqueous environments. We propose to combine the element sensitivity of X-ray spectroscopy with attosecond temporal resolution and ultrathin liquid microjets to study electronic dynamics of relevance to chemical, biological and photovoltaic processes. We will build on our recent achievements in demonstrating femtosecond time-resolved measurements in the water, attosecond pho-toelectron spectroscopy on a liquid microjet and measuring and controlling attosecond charge migration in isolated molecules. We will first concentrate on liquid water to study its electronic dynamics following outer-valence ionization, the formation pathway of the solvated electron and the time scales and intermolecular Coulombic decay following inner-valence or core-level ionization. Second, we will turn to solvated species and measure electronic dynamics and charge migration in solvated molecules, transition-metal complexes and pho-toexcited nanoparticles. These goals will be achieved by developing several innovative experimental tech-niques. We will develop a source of isolated attosecond pulses covering the water window (285-538 eV) and combine it with a flat liquid microjet to realize attosecond transient absorption in liquids. We will complement these measurements with attosecond X-ray emission spectroscopy, Auger spectroscopy and a novel hetero-dyne-detected variant of resonant inelastic Raman scattering, exploiting the large bandwidth that is naturally available from attosecond X-ray sources.
Summary
Charge and energy transfer are the key steps underlying most chemical reactions and biological transformations. The purely electronic dynamics that control such processes take place on attosecond time scales. A complete understanding of these dynamics on the electronic level therefore calls for new experimental methods with attosecond resolution that are applicable to aqueous environments. We propose to combine the element sensitivity of X-ray spectroscopy with attosecond temporal resolution and ultrathin liquid microjets to study electronic dynamics of relevance to chemical, biological and photovoltaic processes. We will build on our recent achievements in demonstrating femtosecond time-resolved measurements in the water, attosecond pho-toelectron spectroscopy on a liquid microjet and measuring and controlling attosecond charge migration in isolated molecules. We will first concentrate on liquid water to study its electronic dynamics following outer-valence ionization, the formation pathway of the solvated electron and the time scales and intermolecular Coulombic decay following inner-valence or core-level ionization. Second, we will turn to solvated species and measure electronic dynamics and charge migration in solvated molecules, transition-metal complexes and pho-toexcited nanoparticles. These goals will be achieved by developing several innovative experimental tech-niques. We will develop a source of isolated attosecond pulses covering the water window (285-538 eV) and combine it with a flat liquid microjet to realize attosecond transient absorption in liquids. We will complement these measurements with attosecond X-ray emission spectroscopy, Auger spectroscopy and a novel hetero-dyne-detected variant of resonant inelastic Raman scattering, exploiting the large bandwidth that is naturally available from attosecond X-ray sources.
Max ERC Funding
2 750 000 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym AutoClean
Project Cell-free reconstitution of autophagy to dissect molecular mechanisms
Researcher (PI) Claudine Simone Kraft
Host Institution (HI) UNIVERSITAETSKLINIKUM FREIBURG
Call Details Consolidator Grant (CoG), LS1, ERC-2017-COG
Summary Autophagy, a lysosomal degradation pathway in which the cell digests its own components, is an essential biological pathway that promotes organismal health and longevity and helps combat cancer and neurodegenerative diseases. Accordingly, the 2016 Nobel Prize in Physiology or Medicine was awarded for research in autophagy. Although autophagy has been extensively studied from yeast to mammals, the molecular events that underlie its induction and progression remain elusive. A highly conserved protein kinase, Atg1, plays a unique and essential role in initiating autophagy, yet despite this pivotal importance it has taken over twenty years for its first downstream target to be discovered. However, whilst our identification of the autophagy related membrane protein Atg9 as the first Atg1 substrate is an important advance, the molecular mechanisms that enable the extensive remodelling of cellular membranes that occurs during autophagy is still completely undefined. A detailed knowledge of the inputs and outputs of the Atg1 kinase will enable us to provide a definitive mechanistic understanding of autophagy. We have devised a novel permeabilized cell assay that reconstitutes the pathway in vitro, allowing us to recapitulate key steps in the autophagic process and thereby determine how the individual steps that lead up to autophagy are controlled. We will use this system to dissect the functional role of Atg1 kinase in autophagosome-vacuole fusion (Objective 1), and to determine the origin of the autophagic membrane and the role of Atg1 in expanding these (Objective 2). To reveal how Atg1/ULK1 kinase is activated in mammalian cells, we will apply the unique and carefully tailored synthetic in vivo approaches that we have recently developed (Objective 3). By focusing on the activation of the Atg1 kinase and the molecular events that it executes, we will be able to explain its central role in regulating the autophagic process and define the mechanistic steps in the pathway.
Summary
Autophagy, a lysosomal degradation pathway in which the cell digests its own components, is an essential biological pathway that promotes organismal health and longevity and helps combat cancer and neurodegenerative diseases. Accordingly, the 2016 Nobel Prize in Physiology or Medicine was awarded for research in autophagy. Although autophagy has been extensively studied from yeast to mammals, the molecular events that underlie its induction and progression remain elusive. A highly conserved protein kinase, Atg1, plays a unique and essential role in initiating autophagy, yet despite this pivotal importance it has taken over twenty years for its first downstream target to be discovered. However, whilst our identification of the autophagy related membrane protein Atg9 as the first Atg1 substrate is an important advance, the molecular mechanisms that enable the extensive remodelling of cellular membranes that occurs during autophagy is still completely undefined. A detailed knowledge of the inputs and outputs of the Atg1 kinase will enable us to provide a definitive mechanistic understanding of autophagy. We have devised a novel permeabilized cell assay that reconstitutes the pathway in vitro, allowing us to recapitulate key steps in the autophagic process and thereby determine how the individual steps that lead up to autophagy are controlled. We will use this system to dissect the functional role of Atg1 kinase in autophagosome-vacuole fusion (Objective 1), and to determine the origin of the autophagic membrane and the role of Atg1 in expanding these (Objective 2). To reveal how Atg1/ULK1 kinase is activated in mammalian cells, we will apply the unique and carefully tailored synthetic in vivo approaches that we have recently developed (Objective 3). By focusing on the activation of the Atg1 kinase and the molecular events that it executes, we will be able to explain its central role in regulating the autophagic process and define the mechanistic steps in the pathway.
Max ERC Funding
1 955 666 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
