Project acronym AcTafactors
Project AcTafactors: Tumor Necrosis Factor-based immuno-cytokines with superior therapeutic indexes
Researcher (PI) Jan Honoré L Tavernier
Host Institution (HI) VIB
Call Details Proof of Concept (PoC), ERC-2015-PoC, ERC-2015-PoC
Summary Tumor Necrosis Factor (TNF) is a homotrimeric pro-inflammatory cytokine that was originally discovered based on its extraordinary antitumor activity. However, its shock-inducing properties, causing hypotension, leukopenia and multiple organ failure, prevented its systemic use in cancer treatment. With this proof-of-concept study we want to evaluate a novel class of cell-targeted TNFs with strongly reduced systemic toxicities (AcTafactors). In these engineered immuno-cytokines, single-chain TNFs that harbor mutations to reduce the affinity for its receptor(s) are fused to a cell- specific targeting domain. Whilst almost no biological activity is observed on non-targeted cells, thus preventing systemic toxicity, avidity effects at the targeted cell membrane lead to recovery of over 90% of the TNF signaling activity. In this project we propose a lead optimization program to further improve the lead AcTafactors identified in the context of the ERC Advanced Grant project and to evaluate the resulting molecules for their ability to target the tumor (neo)vasculature in clinically relevant murine tumor models. The pre-clinical proof-of-concept we aim for represents a first step towards clinical development and ultimately potential market approval of an effective AcTafactor anti-cancer therapy.
Summary
Tumor Necrosis Factor (TNF) is a homotrimeric pro-inflammatory cytokine that was originally discovered based on its extraordinary antitumor activity. However, its shock-inducing properties, causing hypotension, leukopenia and multiple organ failure, prevented its systemic use in cancer treatment. With this proof-of-concept study we want to evaluate a novel class of cell-targeted TNFs with strongly reduced systemic toxicities (AcTafactors). In these engineered immuno-cytokines, single-chain TNFs that harbor mutations to reduce the affinity for its receptor(s) are fused to a cell- specific targeting domain. Whilst almost no biological activity is observed on non-targeted cells, thus preventing systemic toxicity, avidity effects at the targeted cell membrane lead to recovery of over 90% of the TNF signaling activity. In this project we propose a lead optimization program to further improve the lead AcTafactors identified in the context of the ERC Advanced Grant project and to evaluate the resulting molecules for their ability to target the tumor (neo)vasculature in clinically relevant murine tumor models. The pre-clinical proof-of-concept we aim for represents a first step towards clinical development and ultimately potential market approval of an effective AcTafactor anti-cancer therapy.
Max ERC Funding
149 320 €
Duration
Start date: 2015-11-01, End date: 2017-04-30
Project acronym AD-VIP
Project Alzheimer’s disease and AAV9: Use of a virus-based delivery system for vectored immunoprophylaxis in dementia.
Researcher (PI) MATTHEW GUY HOLT
Host Institution (HI) VIB
Call Details Proof of Concept (PoC), PC1, ERC-2015-PoC
Summary Alzheimer’s disease (AD) is the most common form of dementia in the Western World, representing an economic and social cost of billions of euros a year. Given the changing demographics of society, these costs will only increase over the coming decades.
Amyloid plaques, composed of amyloid beta peptide (Abeta), are a defining characteristic of AD. Evidence now suggests that Abeta is central to disease pathogenesis due to its toxicity, which leads to cell loss and eventual cognitive decline. Abeta is generated by proteolytic cleavage of amyloid precursor protein, a process that involves the protein BACE1.
Knock-down of BACE1 is sufficient to prevent amyloid pathology and cognitive deficits in transgenic mouse models of AD, so BACE1 is an attractive target for therapeutic intervention. Although many small molecule inhibitors of BACE1 have been developed, many have problems with imperfect selectivity, posing a substantial risk for off-target toxicity in vivo. In contrast, antibody-based therapeutics provide an attractive alternative given their excellent molecular selectivity. However, the success of antibody therapies in AD is limited by the blood brain barrier, which limits antibody entry into the brain from the systemic circulation.
Recent studies have shown that adeno-associated virus serotype 9 (AAV9) effectively crosses the blood brain barrier. Here, we propose evaluating the use of AAV9 as a delivery system for a highly specific and potent inhibitory nanobody targeted against BACE1 as a treatment for AD.
Summary
Alzheimer’s disease (AD) is the most common form of dementia in the Western World, representing an economic and social cost of billions of euros a year. Given the changing demographics of society, these costs will only increase over the coming decades.
Amyloid plaques, composed of amyloid beta peptide (Abeta), are a defining characteristic of AD. Evidence now suggests that Abeta is central to disease pathogenesis due to its toxicity, which leads to cell loss and eventual cognitive decline. Abeta is generated by proteolytic cleavage of amyloid precursor protein, a process that involves the protein BACE1.
Knock-down of BACE1 is sufficient to prevent amyloid pathology and cognitive deficits in transgenic mouse models of AD, so BACE1 is an attractive target for therapeutic intervention. Although many small molecule inhibitors of BACE1 have been developed, many have problems with imperfect selectivity, posing a substantial risk for off-target toxicity in vivo. In contrast, antibody-based therapeutics provide an attractive alternative given their excellent molecular selectivity. However, the success of antibody therapies in AD is limited by the blood brain barrier, which limits antibody entry into the brain from the systemic circulation.
Recent studies have shown that adeno-associated virus serotype 9 (AAV9) effectively crosses the blood brain barrier. Here, we propose evaluating the use of AAV9 as a delivery system for a highly specific and potent inhibitory nanobody targeted against BACE1 as a treatment for AD.
Max ERC Funding
150 000 €
Duration
Start date: 2016-12-01, End date: 2018-05-31
Project acronym AdOMiS
Project Adaptive Optical Microscopy Systems: Unifying theory, practice and applications
Researcher (PI) Martin BOOTH
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), PE7, ERC-2015-AdG
Summary Recent technological advances in optical microscopy have vastly broadened the possibilities for applications in the biomedical sciences. Fluorescence microscopy is the central tool for investigation of molecular structures and dynamics that take place in the cellular and tissue environment. Coupled with progress in labeling methods, these microscopes permit observation of biological structures and processes with unprecedented sensitivity and resolution. This work has been enabled by the engineering development of diverse optical systems that provide different capabilities for the imaging toolkit. All such methods rely upon high fidelity optics to provide optimal resolution and efficiency, but they all suffer from aberrations caused by refractive index variations within the specimen. It is widely accepted that in many applications this fundamental problem prevents optimum operation and limits capability. Adaptive optics (AO) has been introduced to overcome these limitations by correcting aberrations and a range of demonstrations has shown clearly its potential. Indeed, it shows great promise to improve virtually all types of research or commercial microscopes, but significant challenges must still be met before AO can be widely implemented in routine imaging. Current advances are being made through development of bespoke AO solutions to individual imaging tasks. However, the diversity of microscopy methods means that individual solutions are often not translatable to other systems. This proposal is directed towards the creation of theoretical and practical frameworks that tie together AO concepts and provide a suite of scientific tools with broad application. This will be achieved through a systems approach that encompasses theoretical modelling, optical engineering and the requirements of biological applications. Additional outputs will include practical designs, operating protocols and software algorithms that will support next generation AO microscope systems.
Summary
Recent technological advances in optical microscopy have vastly broadened the possibilities for applications in the biomedical sciences. Fluorescence microscopy is the central tool for investigation of molecular structures and dynamics that take place in the cellular and tissue environment. Coupled with progress in labeling methods, these microscopes permit observation of biological structures and processes with unprecedented sensitivity and resolution. This work has been enabled by the engineering development of diverse optical systems that provide different capabilities for the imaging toolkit. All such methods rely upon high fidelity optics to provide optimal resolution and efficiency, but they all suffer from aberrations caused by refractive index variations within the specimen. It is widely accepted that in many applications this fundamental problem prevents optimum operation and limits capability. Adaptive optics (AO) has been introduced to overcome these limitations by correcting aberrations and a range of demonstrations has shown clearly its potential. Indeed, it shows great promise to improve virtually all types of research or commercial microscopes, but significant challenges must still be met before AO can be widely implemented in routine imaging. Current advances are being made through development of bespoke AO solutions to individual imaging tasks. However, the diversity of microscopy methods means that individual solutions are often not translatable to other systems. This proposal is directed towards the creation of theoretical and practical frameworks that tie together AO concepts and provide a suite of scientific tools with broad application. This will be achieved through a systems approach that encompasses theoretical modelling, optical engineering and the requirements of biological applications. Additional outputs will include practical designs, operating protocols and software algorithms that will support next generation AO microscope systems.
Max ERC Funding
3 234 789 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym AGATM
Project A Global Anthropology of Transforming Marriage
Researcher (PI) Janet CARSTEN
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Advanced Grant (AdG), SH5, ERC-2015-AdG
Summary This research will create a new theoretical vision of the importance of marriage as an agent of transformation in human sociality. Marriage globally is undergoing profound change, provoking intense debate and anxiety. These concerns refract wider instabilities in political, economic, and familial institutions. They signal the critical role of marriage in bringing together - and separating - intimate, personal, and familial life with wider state institutions. But we have little up to date comparative research or general theory of how marriage changes or the long-term significance of such change. Paradoxically, social scientific and public discourse emphasise the conservative and normative aspects of marriage. This underlines the need for a new theoretical frame that takes account of cultural and historical specificity to grasp the importance of marriage as both vehicle of and engine for transformation. AGATM overturns conventional understandings by viewing marriage as inherently transformative, indeed at the heart of social and cultural change. The research will investigate current transformations of marriage in two distinct senses. First, it will undertake an ethnographic investigation of new forms of marriage in selected sites in Europe, N. America, Asia, and Africa. Second, it will subject ‘marriage’ to a rigorous theoretical critique that will denaturalise marriage and reintegrate it into the new anthropology of kinship. Research on five complementary and contrastive sub-projects examining emerging forms of marriage in different locations will be structured through the themes of care, property, and ritual forms. The overarching analytic of temporality will frame the theoretical vision of the research and connect the themes. The resulting six monographs, journal articles, and exhibition will together revitalise the study of kinship by placing the moral, practical, political, and imaginative significance of marriage over time at its centre.
Summary
This research will create a new theoretical vision of the importance of marriage as an agent of transformation in human sociality. Marriage globally is undergoing profound change, provoking intense debate and anxiety. These concerns refract wider instabilities in political, economic, and familial institutions. They signal the critical role of marriage in bringing together - and separating - intimate, personal, and familial life with wider state institutions. But we have little up to date comparative research or general theory of how marriage changes or the long-term significance of such change. Paradoxically, social scientific and public discourse emphasise the conservative and normative aspects of marriage. This underlines the need for a new theoretical frame that takes account of cultural and historical specificity to grasp the importance of marriage as both vehicle of and engine for transformation. AGATM overturns conventional understandings by viewing marriage as inherently transformative, indeed at the heart of social and cultural change. The research will investigate current transformations of marriage in two distinct senses. First, it will undertake an ethnographic investigation of new forms of marriage in selected sites in Europe, N. America, Asia, and Africa. Second, it will subject ‘marriage’ to a rigorous theoretical critique that will denaturalise marriage and reintegrate it into the new anthropology of kinship. Research on five complementary and contrastive sub-projects examining emerging forms of marriage in different locations will be structured through the themes of care, property, and ritual forms. The overarching analytic of temporality will frame the theoretical vision of the research and connect the themes. The resulting six monographs, journal articles, and exhibition will together revitalise the study of kinship by placing the moral, practical, political, and imaginative significance of marriage over time at its centre.
Max ERC Funding
2 297 584 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym ALZSYN
Project Imaging synaptic contributors to dementia
Researcher (PI) Tara Spires-Jones
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Consolidator Grant (CoG), LS5, ERC-2015-CoG
Summary Alzheimer's disease, the most common cause of dementia in older people, is a devastating condition that is becoming a public health crisis as our population ages. Despite great progress recently in Alzheimer’s disease research, we have no disease modifying drugs and a decade with a 99.6% failure rate of clinical trials attempting to treat the disease. This project aims to develop relevant therapeutic targets to restore brain function in Alzheimer’s disease by integrating human and model studies of synapses. It is widely accepted in the field that alterations in amyloid beta initiate the disease process. However the cascade leading from changes in amyloid to widespread tau pathology and neurodegeneration remain unclear. Synapse loss is the strongest pathological correlate of dementia in Alzheimer’s, and mounting evidence suggests that synapse degeneration plays a key role in causing cognitive decline. Here I propose to test the hypothesis that the amyloid cascade begins at the synapse leading to tau pathology, synapse dysfunction and loss, and ultimately neural circuit collapse causing cognitive impairment. The team will use cutting-edge multiphoton and array tomography imaging techniques to test mechanisms downstream of amyloid beta at synapses, and determine whether intervening in the cascade allows recovery of synapse structure and function. Importantly, I will combine studies in robust models of familial Alzheimer’s disease with studies in postmortem human brain to confirm relevance of our mechanistic studies to human disease. Finally, human stem cell derived neurons will be used to test mechanisms and potential therapeutics in neurons expressing the human proteome. Together, these experiments are ground-breaking since they have the potential to further our understanding of how synapses are lost in Alzheimer’s disease and to identify targets for effective therapeutic intervention, which is a critical unmet need in today’s health care system.
Summary
Alzheimer's disease, the most common cause of dementia in older people, is a devastating condition that is becoming a public health crisis as our population ages. Despite great progress recently in Alzheimer’s disease research, we have no disease modifying drugs and a decade with a 99.6% failure rate of clinical trials attempting to treat the disease. This project aims to develop relevant therapeutic targets to restore brain function in Alzheimer’s disease by integrating human and model studies of synapses. It is widely accepted in the field that alterations in amyloid beta initiate the disease process. However the cascade leading from changes in amyloid to widespread tau pathology and neurodegeneration remain unclear. Synapse loss is the strongest pathological correlate of dementia in Alzheimer’s, and mounting evidence suggests that synapse degeneration plays a key role in causing cognitive decline. Here I propose to test the hypothesis that the amyloid cascade begins at the synapse leading to tau pathology, synapse dysfunction and loss, and ultimately neural circuit collapse causing cognitive impairment. The team will use cutting-edge multiphoton and array tomography imaging techniques to test mechanisms downstream of amyloid beta at synapses, and determine whether intervening in the cascade allows recovery of synapse structure and function. Importantly, I will combine studies in robust models of familial Alzheimer’s disease with studies in postmortem human brain to confirm relevance of our mechanistic studies to human disease. Finally, human stem cell derived neurons will be used to test mechanisms and potential therapeutics in neurons expressing the human proteome. Together, these experiments are ground-breaking since they have the potential to further our understanding of how synapses are lost in Alzheimer’s disease and to identify targets for effective therapeutic intervention, which is a critical unmet need in today’s health care system.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym AMEFOCT
Project Add-on module for optical coherence tomography with en-face view option
Researcher (PI) Adrian Podoleanu
Host Institution (HI) UNIVERSITY OF KENT
Call Details Proof of Concept (PoC), ERC-2015-PoC, ERC-2015-PoC
Summary By the end of the 4th year of the ERC Advanced grant, the PI has set up the basis of a unique procedure to perform optical coherence tomography (OCT) that is similar in outcome to time domain interferometry but has all advantages of spectral domain interferometry in terms of speed and sensitivity. The new method of OCT, termed as Master/Slave (MS), is characterised by several advantages: direct production of an en-face OCT image, tolerance to dispersion that allows MS-OCT to achieve the theoretical limit of axial resolution and sensitivity that can be tailored for no hardware and time cost, with the axial resolution. By excellence, the Master/Slave OCT method delivers en-face views direct, allowing lower cost hardware and faster provision of en-face slicing and visualisation. An essential advantage is that of parallel processing, that makes MS-OCT, ideally suited to novel parallel optical configurations and graphic processing units (GPU). These advantages can substantially increase the speed in providing volumes of the tissue, making the new OCT method superior to all other methods on the market. The POC support will help advance the MS-OCT closer to commercialisation. Four market strategies are identified with immediate products for the first two. OCT add-on modules, equipped with MS software, for: A. OCT developers, to accelerate their research and B. OCT developers that can modify existing commercial OCT systems, by making them accomplish the MS protocol. The module to be assembled and assessed for commercialisation will also pave the way to two more strategies: C. Companies already selling OCT systems on dedicated markets, where specialised agreements will widen the market and even D. A full OCT system created by the new company, an ultimate outcome that requires investment, based on revenue acquired by selling the add-on modules.
Summary
By the end of the 4th year of the ERC Advanced grant, the PI has set up the basis of a unique procedure to perform optical coherence tomography (OCT) that is similar in outcome to time domain interferometry but has all advantages of spectral domain interferometry in terms of speed and sensitivity. The new method of OCT, termed as Master/Slave (MS), is characterised by several advantages: direct production of an en-face OCT image, tolerance to dispersion that allows MS-OCT to achieve the theoretical limit of axial resolution and sensitivity that can be tailored for no hardware and time cost, with the axial resolution. By excellence, the Master/Slave OCT method delivers en-face views direct, allowing lower cost hardware and faster provision of en-face slicing and visualisation. An essential advantage is that of parallel processing, that makes MS-OCT, ideally suited to novel parallel optical configurations and graphic processing units (GPU). These advantages can substantially increase the speed in providing volumes of the tissue, making the new OCT method superior to all other methods on the market. The POC support will help advance the MS-OCT closer to commercialisation. Four market strategies are identified with immediate products for the first two. OCT add-on modules, equipped with MS software, for: A. OCT developers, to accelerate their research and B. OCT developers that can modify existing commercial OCT systems, by making them accomplish the MS protocol. The module to be assembled and assessed for commercialisation will also pave the way to two more strategies: C. Companies already selling OCT systems on dedicated markets, where specialised agreements will widen the market and even D. A full OCT system created by the new company, an ultimate outcome that requires investment, based on revenue acquired by selling the add-on modules.
Max ERC Funding
149 917 €
Duration
Start date: 2015-11-01, End date: 2017-04-30
Project acronym APPELS
Project A Probe of the Periodic Elements for Life in the Sea
Researcher (PI) Rosalind Emily Mayors Rickaby
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Consolidator Grant (CoG), PE10, ERC-2015-CoG
Summary "Chemical elements are the building blocks of life. The major elements, C, H. O, N, P, S are easily recognised as essential nutrients, but their use by life relies on metalloproteins. The identity of the metal centres of these metalloproteins and even the broader palette of trace elements fundamental to life are remarkably poorly known. Whole genomes remain opaque to decoding of this bioinorganic dimension, and optimal trace element concentrations for physiological function. Defining the elemental requirements for maximum growth rate of photosynthesising phytoplankton in the ocean, is critical to understanding Earth's climate. Although microscopic in stature, phytoplankton exert a gigantic influence on the biological pumping of carbon from the atmosphere to the deep ocean. Yet their metal requirements are poorly constrained, being inferred from cellular quotas and "nutrient-like" ocean metal distributions, susceptible to ambiguity between mistaken cellular uptake and use.
APPELS will undertake a two-pronged approach to define the modern marine metallome/metalloproteome. I will explore the expanse of the periodic table for novel required elements by growing phytoplankton, representative of the broadest chemotypes, in manipulated media, to delineate optimal conditions for growth whereby any limitation at lowered concentrations implies use. The second prong uses cutting-edge techniques that unite methods from proteomics with geochemical mass-spectrometry to allow both metals and their associated proteins to be examined comprehensively. APPELS will transform our understanding of the essential elements in the ocean and how the biological pump of carbon is geared to ocean chemistry in an evolving world. More broadly, APPELS will provide a step change in documented protein-metal binding centres, with implications for discovery of novel biochemical pathways, and optimal nutrition."
Summary
"Chemical elements are the building blocks of life. The major elements, C, H. O, N, P, S are easily recognised as essential nutrients, but their use by life relies on metalloproteins. The identity of the metal centres of these metalloproteins and even the broader palette of trace elements fundamental to life are remarkably poorly known. Whole genomes remain opaque to decoding of this bioinorganic dimension, and optimal trace element concentrations for physiological function. Defining the elemental requirements for maximum growth rate of photosynthesising phytoplankton in the ocean, is critical to understanding Earth's climate. Although microscopic in stature, phytoplankton exert a gigantic influence on the biological pumping of carbon from the atmosphere to the deep ocean. Yet their metal requirements are poorly constrained, being inferred from cellular quotas and "nutrient-like" ocean metal distributions, susceptible to ambiguity between mistaken cellular uptake and use.
APPELS will undertake a two-pronged approach to define the modern marine metallome/metalloproteome. I will explore the expanse of the periodic table for novel required elements by growing phytoplankton, representative of the broadest chemotypes, in manipulated media, to delineate optimal conditions for growth whereby any limitation at lowered concentrations implies use. The second prong uses cutting-edge techniques that unite methods from proteomics with geochemical mass-spectrometry to allow both metals and their associated proteins to be examined comprehensively. APPELS will transform our understanding of the essential elements in the ocean and how the biological pump of carbon is geared to ocean chemistry in an evolving world. More broadly, APPELS will provide a step change in documented protein-metal binding centres, with implications for discovery of novel biochemical pathways, and optimal nutrition."
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym ARIADNE
Project ARgon ImAging DetectioN chambEr
Researcher (PI) Konstantinos Mavrokoridis
Host Institution (HI) THE UNIVERSITY OF LIVERPOOL
Call Details Starting Grant (StG), PE2, ERC-2015-STG
Summary This proposal outlines a plan to combine Charge Couple Device (CCD) camera technologies with two-phase Liquid Argon Time Projection Chambers (LAr TPCs) utilising THick Gas Electron Multipliers (THGEMs) to evolve a next generation neutrino detector. This will be an entirely new readout option, and will open the prospect of revolutionary discoveries in fundamental particle physics. Furthermore, the Compton imaging power of this technology will be developed, which will have diverse applications in novel medical imaging techniques and detection of concealed nuclear materials.
Colossal LAr TPCs are the future for long-baseline-neutrino-oscillation physics around which the international neutrino community is rallying, with the common goal of discovering new physics beyond the Standard Model, which holds the key to our understanding of phenomena such as dark matter and the matter-antimatter asymmetry.
I have successfully provided a first demonstration of photographic capturing of muon tracks and single gammas interacting in the Liverpool 40 l LAr TPC using a CCD camera and THGEM. I propose an ambitious project of extensive research to mature this innovative LAr optical readout technology. I will construct a 650 l LAr TPC with integrated CCD/THGEM readout, capable of containing sufficient tracking information for full development and characterisation of this novel detector, with the goal of realising this game-changing technology in the planned future giant LAr TPCs. Camera readout can replace the current charge readout technology and associated scalability complications, and the excellent energy thresholds will enhance detector performance as well as extend research avenues to lower energy fundamental physics.
Also, I will explore the Compton imaging capability of LAr CCD/THGEM technology; the superiority of the energy threshold and spatial resolution of this system can offer significant advancement to medical imaging and the detection of concealed nuclear materials.
Summary
This proposal outlines a plan to combine Charge Couple Device (CCD) camera technologies with two-phase Liquid Argon Time Projection Chambers (LAr TPCs) utilising THick Gas Electron Multipliers (THGEMs) to evolve a next generation neutrino detector. This will be an entirely new readout option, and will open the prospect of revolutionary discoveries in fundamental particle physics. Furthermore, the Compton imaging power of this technology will be developed, which will have diverse applications in novel medical imaging techniques and detection of concealed nuclear materials.
Colossal LAr TPCs are the future for long-baseline-neutrino-oscillation physics around which the international neutrino community is rallying, with the common goal of discovering new physics beyond the Standard Model, which holds the key to our understanding of phenomena such as dark matter and the matter-antimatter asymmetry.
I have successfully provided a first demonstration of photographic capturing of muon tracks and single gammas interacting in the Liverpool 40 l LAr TPC using a CCD camera and THGEM. I propose an ambitious project of extensive research to mature this innovative LAr optical readout technology. I will construct a 650 l LAr TPC with integrated CCD/THGEM readout, capable of containing sufficient tracking information for full development and characterisation of this novel detector, with the goal of realising this game-changing technology in the planned future giant LAr TPCs. Camera readout can replace the current charge readout technology and associated scalability complications, and the excellent energy thresholds will enhance detector performance as well as extend research avenues to lower energy fundamental physics.
Also, I will explore the Compton imaging capability of LAr CCD/THGEM technology; the superiority of the energy threshold and spatial resolution of this system can offer significant advancement to medical imaging and the detection of concealed nuclear materials.
Max ERC Funding
1 837 911 €
Duration
Start date: 2016-03-01, End date: 2021-02-28
Project acronym ASSIMILES
Project Advanced Spectroscopy and Spectrometry for Imaging Metabolism using Isotopically-Labeled Endogenous Substrates
Researcher (PI) Arnaud Comment
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), PE4, ERC-2015-CoG
Summary A technological revolution is currently taking place making it possible to noninvasively study metabolism in mammals (incl. humans) in vivo with unprecedented temporal and spatial resolution. Central to these developments is the phenomenon of hyperpolarization, which transiently enhances the magnetic resonance (MR) signals so much that real-time metabolic imaging and spectroscopy becomes possible. The first clinical translation of hyperpolarization MR technology has recently been demonstrated with prostate cancer patients.
I have played an active role in these exciting developments, through design and construction of hyperpolarization MR setups that are defining the cutting-edge for in vivo preclinical metabolic studies. However, important obstacles still exist for the technology to fulfill its enormous potential.
With this highly interdisciplinary proposal, I will overcome the principal drawbacks of current hyperpolarization technology, namely: 1) A limited time window for hyperpolarized MR detection; 2) The conventional use of potentially toxic polarizing agents; 3) The necessity to use supra-physiological doses of metabolic substrates to reach detectable MR signal
I will develop a novel hyperpolarization instrument making use of photoexcited compounds as polarizing agents to produce hyperpolarized solutions containing exclusively endogenous compounds. It will become possible to deliver hyperpolarized solutions in a quasi-continuous manner, permitting infusion of physiological doses and greatly increasing sensitivity. I will also use a complementary isotope imaging technique, the so-called CryoNanoSIMS (developed at my institution over the last year), which can image isotopic distributions in frozen tissue sections and reveal the localization of injected substrates and their metabolites with subcellular spatial resolution. Case studies will include liver and brain cancer mouse models. This work is pioneering and will create a new frontier in molecular imaging.
Summary
A technological revolution is currently taking place making it possible to noninvasively study metabolism in mammals (incl. humans) in vivo with unprecedented temporal and spatial resolution. Central to these developments is the phenomenon of hyperpolarization, which transiently enhances the magnetic resonance (MR) signals so much that real-time metabolic imaging and spectroscopy becomes possible. The first clinical translation of hyperpolarization MR technology has recently been demonstrated with prostate cancer patients.
I have played an active role in these exciting developments, through design and construction of hyperpolarization MR setups that are defining the cutting-edge for in vivo preclinical metabolic studies. However, important obstacles still exist for the technology to fulfill its enormous potential.
With this highly interdisciplinary proposal, I will overcome the principal drawbacks of current hyperpolarization technology, namely: 1) A limited time window for hyperpolarized MR detection; 2) The conventional use of potentially toxic polarizing agents; 3) The necessity to use supra-physiological doses of metabolic substrates to reach detectable MR signal
I will develop a novel hyperpolarization instrument making use of photoexcited compounds as polarizing agents to produce hyperpolarized solutions containing exclusively endogenous compounds. It will become possible to deliver hyperpolarized solutions in a quasi-continuous manner, permitting infusion of physiological doses and greatly increasing sensitivity. I will also use a complementary isotope imaging technique, the so-called CryoNanoSIMS (developed at my institution over the last year), which can image isotopic distributions in frozen tissue sections and reveal the localization of injected substrates and their metabolites with subcellular spatial resolution. Case studies will include liver and brain cancer mouse models. This work is pioneering and will create a new frontier in molecular imaging.
Max ERC Funding
2 199 146 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym ASYFAIR
Project Fair and Consistent Border Controls? A Critical, Multi-methodological and Interdisciplinary Study of Asylum Adjudication in Europe
Researcher (PI) Nicholas Mark Gill
Host Institution (HI) THE UNIVERSITY OF EXETER
Call Details Starting Grant (StG), SH3, ERC-2015-STG
Summary ‘Consistency’ is regularly cited as a desirable attribute of border control, but it has received little critical social scientific attention. This inter-disciplinary project, at the inter-face between critical human geography, border studies and law, will scrutinise the consistency of European asylum adjudication in order to develop richer theoretical understanding of this lynchpin concept. It will move beyond the administrative legal concepts of substantive and procedural consistency by advancing a three-fold conceptualisation of consistency – as everyday practice, discursive deployment of facts and disciplinary technique. In order to generate productive intellectual tension it will also employ an explicitly antagonistic conceptualisation of the relationship between geography and law that views law as seeking to constrain and systematise lived space. The project will employ an innovative combination of methodologies that will produce unique and rich data sets including quantitative analysis, multi-sited legal ethnography, discourse analysis and interviews, and the findings are likely to be of interest both to academic communities like geographers, legal and border scholars and to policy makers and activists working in border control settings. In 2013 the Common European Asylum System (CEAS) was launched to standardise the procedures of asylum determination. But as yet no sustained multi-methodological assessment of the claims of consistency inherent to the CEAS has been carried out. This project offers not only the opportunity to assess progress towards harmonisation of asylum determination processes in Europe, but will also provide a new conceptual framework with which to approach the dilemmas and risks of inconsistency in an area of law fraught with political controversy and uncertainty around the world. Most fundamentally, the project promises to debunk the myths surrounding the possibility of fair and consistent border controls in Europe and elsewhere.
Summary
‘Consistency’ is regularly cited as a desirable attribute of border control, but it has received little critical social scientific attention. This inter-disciplinary project, at the inter-face between critical human geography, border studies and law, will scrutinise the consistency of European asylum adjudication in order to develop richer theoretical understanding of this lynchpin concept. It will move beyond the administrative legal concepts of substantive and procedural consistency by advancing a three-fold conceptualisation of consistency – as everyday practice, discursive deployment of facts and disciplinary technique. In order to generate productive intellectual tension it will also employ an explicitly antagonistic conceptualisation of the relationship between geography and law that views law as seeking to constrain and systematise lived space. The project will employ an innovative combination of methodologies that will produce unique and rich data sets including quantitative analysis, multi-sited legal ethnography, discourse analysis and interviews, and the findings are likely to be of interest both to academic communities like geographers, legal and border scholars and to policy makers and activists working in border control settings. In 2013 the Common European Asylum System (CEAS) was launched to standardise the procedures of asylum determination. But as yet no sustained multi-methodological assessment of the claims of consistency inherent to the CEAS has been carried out. This project offers not only the opportunity to assess progress towards harmonisation of asylum determination processes in Europe, but will also provide a new conceptual framework with which to approach the dilemmas and risks of inconsistency in an area of law fraught with political controversy and uncertainty around the world. Most fundamentally, the project promises to debunk the myths surrounding the possibility of fair and consistent border controls in Europe and elsewhere.
Max ERC Funding
1 252 067 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
