Project acronym 2DNanoSpec
Project Nanoscale Vibrational Spectroscopy of Sensitive 2D Molecular Materials
Researcher (PI) Renato ZENOBI
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE4, ERC-2016-ADG
Summary I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Summary
I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Max ERC Funding
2 311 696 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym 3D-OA-HISTO
Project Development of 3D Histopathological Grading of Osteoarthritis
Researcher (PI) Simo Jaakko Saarakkala
Host Institution (HI) OULUN YLIOPISTO
Call Details Starting Grant (StG), LS7, ERC-2013-StG
Summary "Background: Osteoarthritis (OA) is a common musculoskeletal disease occurring worldwide. Despite extensive research, etiology of OA is still poorly understood. Histopathological grading (HPG) of 2D tissue sections is the gold standard reference method for determination of OA stage. However, traditional 2D-HPG is destructive and based only on subjective visual evaluation. These limitations induce bias to clinical in vitro OA diagnostics and basic research that both rely strongly on HPG.
Objectives: 1) To establish and validate the very first 3D-HPG of OA based on cutting-edge nano/micro-CT (Computed Tomography) technologies in vitro; 2) To use the established method to clarify the beginning phases of OA; and 3) To validate 3D-HPG of OA for in vivo use.
Methods: Several hundreds of human osteochondral samples from patients undergoing total knee arthroplasty will be collected. The samples will be imaged in vitro with nano/micro-CT and clinical high-end extremity CT devices using specific contrast-agents to quantify tissue constituents and structure in 3D in large volume. From this information, a novel 3D-HPG is developed with statistical classification algorithms. Finally, the developed novel 3D-HPG of OA will be applied clinically in vivo.
Significance: This is the very first study to establish 3D-HPG of OA pathology in vitro and in vivo. Furthermore, the developed technique hugely improves the understanding of the beginning phases of OA. Ultimately, the study will contribute for improving OA patients’ quality of life by slowing the disease progression, and for providing powerful tools to develop new OA therapies."
Summary
"Background: Osteoarthritis (OA) is a common musculoskeletal disease occurring worldwide. Despite extensive research, etiology of OA is still poorly understood. Histopathological grading (HPG) of 2D tissue sections is the gold standard reference method for determination of OA stage. However, traditional 2D-HPG is destructive and based only on subjective visual evaluation. These limitations induce bias to clinical in vitro OA diagnostics and basic research that both rely strongly on HPG.
Objectives: 1) To establish and validate the very first 3D-HPG of OA based on cutting-edge nano/micro-CT (Computed Tomography) technologies in vitro; 2) To use the established method to clarify the beginning phases of OA; and 3) To validate 3D-HPG of OA for in vivo use.
Methods: Several hundreds of human osteochondral samples from patients undergoing total knee arthroplasty will be collected. The samples will be imaged in vitro with nano/micro-CT and clinical high-end extremity CT devices using specific contrast-agents to quantify tissue constituents and structure in 3D in large volume. From this information, a novel 3D-HPG is developed with statistical classification algorithms. Finally, the developed novel 3D-HPG of OA will be applied clinically in vivo.
Significance: This is the very first study to establish 3D-HPG of OA pathology in vitro and in vivo. Furthermore, the developed technique hugely improves the understanding of the beginning phases of OA. Ultimately, the study will contribute for improving OA patients’ quality of life by slowing the disease progression, and for providing powerful tools to develop new OA therapies."
Max ERC Funding
1 500 000 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym 4DVIDEO
Project 4DVideo: 4D spatio-temporal modeling of real-world events from video streams
Researcher (PI) Marc Pollefeys
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), PE5, ERC-2007-StG
Summary The focus of this project is the development of algorithms that allow one to capture and analyse dynamic events taking place in the real world. For this, we intend to develop smart camera networks that can perform a multitude of observation tasks, ranging from surveillance and tracking to high-fidelity, immersive reconstructions of important dynamic events (i.e. 4D videos). There are many fundamental questions in computer vision associated with these problems. Can the geometric, topologic and photometric properties of the camera network be obtained from live images? What is changing about the environment in which the network is embedded? How much information can be obtained from dynamic events that are observed by the network? What if the camera network consists of a random collection of sensors that happened to observe a particular event (think hand-held cell phone cameras)? Do we need synchronization? Those questions become even more challenging if one considers active camera networks that can adapt to the vision task at hand. How should resources be prioritized for different tasks? Can we derive optimal strategies to control camera parameters such as pan, tilt and zoom, trade-off resolution, frame-rate and bandwidth? More fundamentally, seeing cameras as points that sample incoming light rays and camera networks as a distributed sensor, how does one decide which rays should be sampled? Many of those issues are particularly interesting when we consider time-varying events. Both spatial and temporal resolution are important and heterogeneous frame-rates and resolution can offer advantages. Prior knowledge or information obtained from earlier samples can be used to restrict the possible range of solutions (e.g. smoothness assumption and motion prediction). My goal is to obtain fundamental answers to many of those question based on thorough theoretical analysis combined with practical algorithms that are proven on real applications.
Summary
The focus of this project is the development of algorithms that allow one to capture and analyse dynamic events taking place in the real world. For this, we intend to develop smart camera networks that can perform a multitude of observation tasks, ranging from surveillance and tracking to high-fidelity, immersive reconstructions of important dynamic events (i.e. 4D videos). There are many fundamental questions in computer vision associated with these problems. Can the geometric, topologic and photometric properties of the camera network be obtained from live images? What is changing about the environment in which the network is embedded? How much information can be obtained from dynamic events that are observed by the network? What if the camera network consists of a random collection of sensors that happened to observe a particular event (think hand-held cell phone cameras)? Do we need synchronization? Those questions become even more challenging if one considers active camera networks that can adapt to the vision task at hand. How should resources be prioritized for different tasks? Can we derive optimal strategies to control camera parameters such as pan, tilt and zoom, trade-off resolution, frame-rate and bandwidth? More fundamentally, seeing cameras as points that sample incoming light rays and camera networks as a distributed sensor, how does one decide which rays should be sampled? Many of those issues are particularly interesting when we consider time-varying events. Both spatial and temporal resolution are important and heterogeneous frame-rates and resolution can offer advantages. Prior knowledge or information obtained from earlier samples can be used to restrict the possible range of solutions (e.g. smoothness assumption and motion prediction). My goal is to obtain fundamental answers to many of those question based on thorough theoretical analysis combined with practical algorithms that are proven on real applications.
Max ERC Funding
1 757 422 €
Duration
Start date: 2008-08-01, End date: 2013-11-30
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 AGNES
Project ACTIVE AGEING – RESILIENCE AND EXTERNAL SUPPORT AS MODIFIERS OF THE DISABLEMENT OUTCOME
Researcher (PI) Taina Tuulikki RANTANEN
Host Institution (HI) JYVASKYLAN YLIOPISTO
Call Details Advanced Grant (AdG), SH3, ERC-2015-AdG
Summary The goals are 1. To develop a scale assessing the diversity of active ageing with four dimensions that are ability (what people can do), activity (what people do do), ambition (what are the valued activities that people want to do), and autonomy (how satisfied people are with the opportunity to do valued activities); 2. To examine health and physical and psychological functioning as the determinants and social and build environment, resilience and personal skills as modifiers of active ageing; 3. To develop a multicomponent sustainable intervention aiming to promote active ageing (methods: counselling, information technology, help from volunteers); 4. To test the feasibility and effectiveness on the intervention; and 5. To study cohort effects on the phenotypes on the pathway to active ageing.
“If You Can Measure It, You Can Change It.” Active ageing assessment needs conceptual progress, which I propose to do. A quantifiable scale will be developed that captures the diversity of active ageing stemming from the WHO definition of active ageing as the process of optimizing opportunities for health and participation in the society for all people in line with their needs, goals and capacities as they age. I will collect cross-sectional data (N=1000, ages 75, 80 and 85 years) and model the pathway to active ageing with state-of-the art statistical methods. By doing this I will create novel knowledge on preconditions for active ageing. The collected cohort data will be compared to a pre-existing cohort data that was collected 25 years ago to obtain knowledge about changes over time in functioning of older people. A randomized controlled trial (N=200) will be conducted to assess the effectiveness of the envisioned intervention promoting active ageing through participation. The project will regenerate ageing research by launching a novel scale, by training young scientists, by creating new concepts and theory development and by producing evidence for active ageing promotion
Summary
The goals are 1. To develop a scale assessing the diversity of active ageing with four dimensions that are ability (what people can do), activity (what people do do), ambition (what are the valued activities that people want to do), and autonomy (how satisfied people are with the opportunity to do valued activities); 2. To examine health and physical and psychological functioning as the determinants and social and build environment, resilience and personal skills as modifiers of active ageing; 3. To develop a multicomponent sustainable intervention aiming to promote active ageing (methods: counselling, information technology, help from volunteers); 4. To test the feasibility and effectiveness on the intervention; and 5. To study cohort effects on the phenotypes on the pathway to active ageing.
“If You Can Measure It, You Can Change It.” Active ageing assessment needs conceptual progress, which I propose to do. A quantifiable scale will be developed that captures the diversity of active ageing stemming from the WHO definition of active ageing as the process of optimizing opportunities for health and participation in the society for all people in line with their needs, goals and capacities as they age. I will collect cross-sectional data (N=1000, ages 75, 80 and 85 years) and model the pathway to active ageing with state-of-the art statistical methods. By doing this I will create novel knowledge on preconditions for active ageing. The collected cohort data will be compared to a pre-existing cohort data that was collected 25 years ago to obtain knowledge about changes over time in functioning of older people. A randomized controlled trial (N=200) will be conducted to assess the effectiveness of the envisioned intervention promoting active ageing through participation. The project will regenerate ageing research by launching a novel scale, by training young scientists, by creating new concepts and theory development and by producing evidence for active ageing promotion
Max ERC Funding
2 044 364 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym AMSEL
Project Atomic Force Microscopy for Molecular Structure Elucidation
Researcher (PI) Leo Gross
Host Institution (HI) IBM RESEARCH GMBH
Call Details Consolidator Grant (CoG), PE4, ERC-2015-CoG
Summary Molecular structure elucidation is of great importance in synthetic chemistry, pharmacy, life sciences, energy and environmental sciences, and technology applications. To date structure elucidation by atomic force microscopy (AFM) has been demonstrated for a few, small and mainly planar molecules. In this project high-risk, high-impact scientific questions will be solved using structure elucidation with the AFM employing a novel tool and novel methodologies.
A combined low-temperature scanning tunneling microscope/atomic force microscope (LT-STM/AFM) with high throughput and in situ electrospray deposition method will be developed. Chemical resolution will be achieved by novel measurement techniques, in particular the usage of different and novel tip functionalizations and combination with Kelvin probe force microscopy. Elements will be identified using substructure recognition provided by a database that will be erected and by refined theory and simulations.
The developed tools and techniques will be applied to molecules of increasing fragility, complexity, size, and three-dimensionality. In particular samples that are challenging to characterize with conventional methods will be studied. Complex molecular mixtures will be investigated molecule-by-molecule taking advantage of the single-molecule sensitivity. The absolute stereochemistry of molecules will be determined, resolving molecules with multiple stereocenters. The operation of single molecular machines as nanocars and molecular gears will be investigated. Reactive intermediates generated with atomic manipulation will be characterized and their on-surface reactivity will be studied by AFM.
Summary
Molecular structure elucidation is of great importance in synthetic chemistry, pharmacy, life sciences, energy and environmental sciences, and technology applications. To date structure elucidation by atomic force microscopy (AFM) has been demonstrated for a few, small and mainly planar molecules. In this project high-risk, high-impact scientific questions will be solved using structure elucidation with the AFM employing a novel tool and novel methodologies.
A combined low-temperature scanning tunneling microscope/atomic force microscope (LT-STM/AFM) with high throughput and in situ electrospray deposition method will be developed. Chemical resolution will be achieved by novel measurement techniques, in particular the usage of different and novel tip functionalizations and combination with Kelvin probe force microscopy. Elements will be identified using substructure recognition provided by a database that will be erected and by refined theory and simulations.
The developed tools and techniques will be applied to molecules of increasing fragility, complexity, size, and three-dimensionality. In particular samples that are challenging to characterize with conventional methods will be studied. Complex molecular mixtures will be investigated molecule-by-molecule taking advantage of the single-molecule sensitivity. The absolute stereochemistry of molecules will be determined, resolving molecules with multiple stereocenters. The operation of single molecular machines as nanocars and molecular gears will be investigated. Reactive intermediates generated with atomic manipulation will be characterized and their on-surface reactivity will be studied by AFM.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym Antibodyomics
Project Vaccine profiling and immunodiagnostic discovery by high-throughput antibody repertoire analysis
Researcher (PI) Sai Tota Reddy
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), LS7, ERC-2015-STG
Summary Vaccines and immunodiagnostics have been vital for public health and medicine, however a quantitative molecular understanding of vaccine-induced antibody responses is lacking. Antibody research is currently going through a big-data driven revolution, largely due to progress in next-generation sequencing (NGS) and bioinformatic analysis of antibody repertoires. A main advantage of high-throughput antibody repertoire analysis is that it provides a wealth of quantitative information not possible with other classical methods of antibody analysis (i.e., serum titers); this information includes: clonal distribution and diversity, somatic hypermutation patterns, and lineage tracing. In preliminary work my group has established standardized methods for antibody repertoire NGS, including an experimental-bioinformatic pipeline for error and bias correction that enables highly accurate repertoire sequencing and analysis. The overall goal of this proposal will be to apply high-throughput antibody repertoire analysis for quantitative vaccine profiling and discovery of next-generation immunodiagnostics. Using mouse subunit vaccination as our model system, we will answer for the first time, a fundamental biological question within the context of antibody responses - what is the link between genotype (antibody repertoire) and phenotype (serum antibodies)? We will expand upon this approach for improved rational vaccine design by quantitatively determining the impact of a comprehensive set of subunit vaccination parameters on complete antibody landscapes. Finally, we will develop advanced bioinformatic methods to discover immunodiagnostics based on antibody repertoire sequences. In summary, this proposal lays the foundation for fundamentally new approaches in the quantitative analysis of antibody responses, which long-term will promote the development of next-generation vaccines and immunodiagnostics.
Summary
Vaccines and immunodiagnostics have been vital for public health and medicine, however a quantitative molecular understanding of vaccine-induced antibody responses is lacking. Antibody research is currently going through a big-data driven revolution, largely due to progress in next-generation sequencing (NGS) and bioinformatic analysis of antibody repertoires. A main advantage of high-throughput antibody repertoire analysis is that it provides a wealth of quantitative information not possible with other classical methods of antibody analysis (i.e., serum titers); this information includes: clonal distribution and diversity, somatic hypermutation patterns, and lineage tracing. In preliminary work my group has established standardized methods for antibody repertoire NGS, including an experimental-bioinformatic pipeline for error and bias correction that enables highly accurate repertoire sequencing and analysis. The overall goal of this proposal will be to apply high-throughput antibody repertoire analysis for quantitative vaccine profiling and discovery of next-generation immunodiagnostics. Using mouse subunit vaccination as our model system, we will answer for the first time, a fundamental biological question within the context of antibody responses - what is the link between genotype (antibody repertoire) and phenotype (serum antibodies)? We will expand upon this approach for improved rational vaccine design by quantitatively determining the impact of a comprehensive set of subunit vaccination parameters on complete antibody landscapes. Finally, we will develop advanced bioinformatic methods to discover immunodiagnostics based on antibody repertoire sequences. In summary, this proposal lays the foundation for fundamentally new approaches in the quantitative analysis of antibody responses, which long-term will promote the development of next-generation vaccines and immunodiagnostics.
Max ERC Funding
1 492 586 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym Antivessel-T-Cells
Project Development of Vascular-Disrupting Lymphocyte Therapy for Tumours
Researcher (PI) Georgios Coukos
Host Institution (HI) CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS
Call Details Advanced Grant (AdG), LS7, ERC-2012-ADG_20120314
Summary T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory.
I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.
Summary
T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory.
I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-08-01, End date: 2018-07-31
Project acronym ARTIVISM
Project Art and Activism : Creativity and Performance as Subversive Forms of Political Expression in Super-Diverse Cities
Researcher (PI) Monika Salzbrunn
Host Institution (HI) UNIVERSITE DE LAUSANNE
Call Details Consolidator Grant (CoG), SH5, ERC-2015-CoG
Summary ARTIVISM aims at exploring new artistic forms of political expression under difficult, precarious and/or oppressive conditions. It asks how social actors create belonging and multiple forms of resistance when they use art in activism or activism in art. What kind of alliances do these two forms of social practices generate in super-diverse places, in times of crisis and in precarious situations? Thus, ARTIVISM seeks to understand how social actors engage artistically in order to bring about social, economic and political change. Going beyond former research in urban and migration studies, and beyond the anthropology of art, ARTIVISM focuses on a broad range of artistic tools, styles and means of expression, namely festive events and parades, cartoons and comics and street art. By articulating performance studies, street anthropology and the sociology of celebration with migration and diversity studies, the project challenges former concepts, which took stable social groups for granted and reified them with ethnic lenses. The applied methodology considerably renews the field by bringing together event-, actor- and condition-centred approaches and a multi-sensory framework. Besides its multidisciplinary design, the ground-breaking nature of ARTIVISM lies in the application of the core concepts of performativity and liminality, as well as in an examination of the way to advance and refine these concepts and to create new analytical tools to respond to recent social phenomena. We have developed and tested innovative methods that respond to a postmodern type of fluid and temporary social action: audio-visual ethnography, urban event ethnography, street ethnography, field-crossing, and sensory ethnography (apprenticeship). Therefore, ARTIVISM develops new methods and theories in order to introduce a multi-faceted trans-disciplinary approach to the study of an emerging field of social transformations that is of challenging significance to the social sciences.
Summary
ARTIVISM aims at exploring new artistic forms of political expression under difficult, precarious and/or oppressive conditions. It asks how social actors create belonging and multiple forms of resistance when they use art in activism or activism in art. What kind of alliances do these two forms of social practices generate in super-diverse places, in times of crisis and in precarious situations? Thus, ARTIVISM seeks to understand how social actors engage artistically in order to bring about social, economic and political change. Going beyond former research in urban and migration studies, and beyond the anthropology of art, ARTIVISM focuses on a broad range of artistic tools, styles and means of expression, namely festive events and parades, cartoons and comics and street art. By articulating performance studies, street anthropology and the sociology of celebration with migration and diversity studies, the project challenges former concepts, which took stable social groups for granted and reified them with ethnic lenses. The applied methodology considerably renews the field by bringing together event-, actor- and condition-centred approaches and a multi-sensory framework. Besides its multidisciplinary design, the ground-breaking nature of ARTIVISM lies in the application of the core concepts of performativity and liminality, as well as in an examination of the way to advance and refine these concepts and to create new analytical tools to respond to recent social phenomena. We have developed and tested innovative methods that respond to a postmodern type of fluid and temporary social action: audio-visual ethnography, urban event ethnography, street ethnography, field-crossing, and sensory ethnography (apprenticeship). Therefore, ARTIVISM develops new methods and theories in order to introduce a multi-faceted trans-disciplinary approach to the study of an emerging field of social transformations that is of challenging significance to the social sciences.
Max ERC Funding
1 999 287 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
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
