text:
(-) Remove Advanced Grant (AdG) (23) filter Advanced Grant (AdG) (23)
Project acronym Angiolnc
Project Endothelial long non-coding RNAs
Researcher (PI) Stefanie Dimmeler
Host Institution (HI) JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN
Summary Endothelial cells comprise the inner cellular cover of the vasculature, which delivers metabolites and oxygen to the tissue. Dysfunction of endothelial cells as it occurs during aging or metabolic syndromes can result in atherosclerosis, which can lead to myocardial infarction or stroke, whereas pathological angiogenesis contributes to tumor growth and diabetic retinopathy. Thus, endothelial cells play central roles in pathophysiological processes of many diseases including cardiovascular diseases and cancer. Many studies explored the regulation of endothelial cell functions by growth factors, but the impact of epigenetic mechanisms and particularly the role of novel non-coding RNAs is largely unknown. More than 70 % of the human genome encodes for non-coding RNAs (ncRNAs) and increasing evidence suggests that a significant portion of these ncRNAs are functionally active as RNA molecules. Angiolnc aims to explore the function of long ncRNAs (lncRNAs) and particular circular RNAs (circRNAs) in the endothelium. LncRNAs comprise a heterogenic class of RNAs with a length of > 200 nucleotides and circRNAs are generated by back splicing. Angiolnc is based on the discovery of novel endothelial hypoxia-regulated lncRNAs and circRNAs by next generation sequencing. To begin to understand the potential functions of lncRNAs in the endothelium, we will study two lncRNAs, named Angiolnc1 und Angiolnc2, as prototypical examples of endothelial cell-enriched lncRNAs that are regulated by oxygen levels. We will further dissect the epigenetic mechanisms, by which these lncRNAs regulate endothelial cell function. In the second part of the application, we will determine the regulation and function of circRNAs, which may act as molecular sponges in the cytoplasm. Finally, we will study the function of identified lncRNAs and circRNAs in mouse models and measure their expression in human specimens in order to determine their role as therapeutic targets or diagnostic tools.
Endothelial cells comprise the inner cellular cover of the vasculature, which delivers metabolites and oxygen to the tissue. Dysfunction of endothelial cells as it occurs during aging or metabolic syndromes can result in atherosclerosis, which can lead to myocardial infarction or stroke, whereas pathological angiogenesis contributes to tumor growth and diabetic retinopathy. Thus, endothelial cells play central roles in pathophysiological processes of many diseases including cardiovascular diseases and cancer. Many studies explored the regulation of endothelial cell functions by growth factors, but the impact of epigenetic mechanisms and particularly the role of novel non-coding RNAs is largely unknown. More than 70 % of the human genome encodes for non-coding RNAs (ncRNAs) and increasing evidence suggests that a significant portion of these ncRNAs are functionally active as RNA molecules. Angiolnc aims to explore the function of long ncRNAs (lncRNAs) and particular circular RNAs (circRNAs) in the endothelium. LncRNAs comprise a heterogenic class of RNAs with a length of > 200 nucleotides and circRNAs are generated by back splicing. Angiolnc is based on the discovery of novel endothelial hypoxia-regulated lncRNAs and circRNAs by next generation sequencing. To begin to understand the potential functions of lncRNAs in the endothelium, we will study two lncRNAs, named Angiolnc1 und Angiolnc2, as prototypical examples of endothelial cell-enriched lncRNAs that are regulated by oxygen levels. We will further dissect the epigenetic mechanisms, by which these lncRNAs regulate endothelial cell function. In the second part of the application, we will determine the regulation and function of circRNAs, which may act as molecular sponges in the cytoplasm. Finally, we will study the function of identified lncRNAs and circRNAs in mouse models and measure their expression in human specimens in order to determine their role as therapeutic targets or diagnostic tools.
Project acronym AUROMYC
Project N-Myc and Aurora A: From Protein Stability to Chromosome TopologyN-Myc and Aurora A: From Protein Stability to Chromosome TopologyMyc and Aurora A: From Protein Stability to Chromosome Topology
Researcher (PI) Martin Eilers
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Summary There is an intense interest in the function of human Myc proteins that stems from their pervasive role in the genesis of human tumors. A large body of evidence has established that expression levels of one of three closely related Myc proteins are enhanced in the majority of all human tumors and that multiple tumor entities depend on elevated Myc function, arguing that targeting Myc will have significant therapeutic efficacy. This hope awaits clinical confirmation, since the strategies that are currently under investigation to target Myc function or expression have yet to enter the clinic. Myc proteins are global regulators of transcription, but their mechanism of action is poorly understood. Myc proteins are highly unstable in normal cells and rapidly turned over by the ubiquitin/proteasome system. In contrast, they are stabilized in tumor cells. Work by us and by others has shown that stabilization of Myc is required for tumorigenesis and has identified strategies to destabilize Myc for tumor therapy. This work has also led to the surprising observation that the N-Myc protein, which drives neuroendocrine tumorigenesis, is stabilized by association with the Aurora-A kinase and that clinically available Aurora-A inhibitors can dissociate the complex and destabilize N-Myc. Aurora-A has not previously been implicated in transcription, prompting us to use protein crystallography, proteomics and shRNA screening to understand its interaction with N-Myc. We have now identified a novel protein complex of N-Myc and Aurora-A that provides an unexpected and potentially groundbreaking insight into Myc function. We have also solved the crystal structure of the N-Myc/Aurora-A complex. Collectively, both findings open new strategies to target Myc function for tumor therapy.
There is an intense interest in the function of human Myc proteins that stems from their pervasive role in the genesis of human tumors. A large body of evidence has established that expression levels of one of three closely related Myc proteins are enhanced in the majority of all human tumors and that multiple tumor entities depend on elevated Myc function, arguing that targeting Myc will have significant therapeutic efficacy. This hope awaits clinical confirmation, since the strategies that are currently under investigation to target Myc function or expression have yet to enter the clinic. Myc proteins are global regulators of transcription, but their mechanism of action is poorly understood. Myc proteins are highly unstable in normal cells and rapidly turned over by the ubiquitin/proteasome system. In contrast, they are stabilized in tumor cells. Work by us and by others has shown that stabilization of Myc is required for tumorigenesis and has identified strategies to destabilize Myc for tumor therapy. This work has also led to the surprising observation that the N-Myc protein, which drives neuroendocrine tumorigenesis, is stabilized by association with the Aurora-A kinase and that clinically available Aurora-A inhibitors can dissociate the complex and destabilize N-Myc. Aurora-A has not previously been implicated in transcription, prompting us to use protein crystallography, proteomics and shRNA screening to understand its interaction with N-Myc. We have now identified a novel protein complex of N-Myc and Aurora-A that provides an unexpected and potentially groundbreaking insight into Myc function. We have also solved the crystal structure of the N-Myc/Aurora-A complex. Collectively, both findings open new strategies to target Myc function for tumor therapy.
Project acronym CELLPLASTICITY
Project New Frontiers in Cellular Reprogramming: Exploiting Cellular Plasticity
Researcher (PI) Manuel SERRANO MARUGAN
Host Institution (HI) FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Summary "Our research group has worked over the years at the interface between cancer and ageing, with a strong emphasis on mouse models. More recently, we became interested in cellular reprogramming because we hypothesized that understanding cellular plasticity could yield new insights into cancer and ageing. Indeed, during the previous ERC Advanced Grant, we made relevant contributions to the fields of cellular reprogramming (Nature 2013), cellular senescence (Cell 2013), cancer (Cancer Cell 2012), and ageing (Cell Metabolism 2012). Now, we take advantage of our diverse background and integrate the above processes. Our unifying hypothesis is that cellular plasticity lies at the basis of tissue regeneration ("adaptive cellular plasticity"), as well as at the origin of cancer ("maladaptive gain of cellular plasticity") and ageing ("maladaptive loss of cellular plasticity"). A key experimental system will be our "reprogrammable mice" (with inducible expression of the four Yamanaka factors), which we regard as a tool to induce cellular plasticity in vivo. The project is divided as follows: Objective #1 – Cellular plasticity and cancer: role of tumour suppressors in in vivo de-differentiation and reprogramming / impact of transient de-differentiation on tumour initiation / lineage tracing of Oct4 to determine whether a transient pluripotent-state occurs during cancer. Objective #2 – Cellular plasticity in tissue regeneration and ageing: impact of transient de-differentiation on tissue regeneration / contribution of the damage-induced microenvironment to tissue regeneration / impact of transient de-differentiation on ageing. Objective #3: New frontiers in cellular plasticity: chemical manipulation of cellular plasticity in vivo / new states of pluripotency / characterization of in vivo induced pluripotency and its unique properties. We anticipate that the completion of this project will yield new fundamental insights into cancer, regeneration and ageing."
"Our research group has worked over the years at the interface between cancer and ageing, with a strong emphasis on mouse models. More recently, we became interested in cellular reprogramming because we hypothesized that understanding cellular plasticity could yield new insights into cancer and ageing. Indeed, during the previous ERC Advanced Grant, we made relevant contributions to the fields of cellular reprogramming (Nature 2013), cellular senescence (Cell 2013), cancer (Cancer Cell 2012), and ageing (Cell Metabolism 2012). Now, we take advantage of our diverse background and integrate the above processes. Our unifying hypothesis is that cellular plasticity lies at the basis of tissue regeneration ("adaptive cellular plasticity"), as well as at the origin of cancer ("maladaptive gain of cellular plasticity") and ageing ("maladaptive loss of cellular plasticity"). A key experimental system will be our "reprogrammable mice" (with inducible expression of the four Yamanaka factors), which we regard as a tool to induce cellular plasticity in vivo. The project is divided as follows: Objective #1 – Cellular plasticity and cancer: role of tumour suppressors in in vivo de-differentiation and reprogramming / impact of transient de-differentiation on tumour initiation / lineage tracing of Oct4 to determine whether a transient pluripotent-state occurs during cancer. Objective #2 – Cellular plasticity in tissue regeneration and ageing: impact of transient de-differentiation on tissue regeneration / contribution of the damage-induced microenvironment to tissue regeneration / impact of transient de-differentiation on ageing. Objective #3: New frontiers in cellular plasticity: chemical manipulation of cellular plasticity in vivo / new states of pluripotency / characterization of in vivo induced pluripotency and its unique properties. We anticipate that the completion of this project will yield new fundamental insights into cancer, regeneration and ageing."
Project acronym Com4Com
Project Collective modes in 4d-metal compounds and heterostructures
Researcher (PI) Bernhard Keimer
Summary Compounds of transition metals with 4d valence electrons ("4d metals") play eminent roles in many areas of condensed matter physics ranging from unconventional superconductivity to oxide electronics, but fundamental questions about the interplay between the spin-orbit coupling and electronic correlations at the atomic scale remain unanswered. Momentum-resolved spectroscopies of collective electronic excitations yield detailed insight into the magnitude and spatial range of the electronic correlations, and have thus decisively shaped the conceptual understanding of quantum many-body phenomena in 3d-electron systems. We will devise and build a novel resonant inelastic x-ray scattering (RIXS) instrument capable of determining the dispersion relations of electronic collective modes in 4d-metal compounds with full momentum-space coverage, high energy resolution, and monolayer sensitivity. Data from this instrument will yield comprehensive information about the interaction parameters specifying the electronic Hamiltonians of 4d-electron materials, unique insight into the spin-orbital composition of their excited-state wavefunctions, and definitive tests of proposals to realize Kitaev models with spin-liquid states that are potentially relevant in topological quantum computation. The element-specificity of RIXS will also allow us to determine the microscopic exchange interactions in complex materials with both 3d and 4d valence electrons, and its high sensitivity will enable experiments on operational device structures comprising only a few monolayers. We will thus be able to tightly integrate momentum-resolved spectroscopy with state-of-the-art, monolayer-by-monolayer deposition methods of 4d metal-oxide films and heterostructures. The results will fuel a feedback loop comprising synthesis, characterization, and modeling, which will greatly advance our ability to design materials and devices whose functionality derives from the collective organization of electrons.
Compounds of transition metals with 4d valence electrons ("4d metals") play eminent roles in many areas of condensed matter physics ranging from unconventional superconductivity to oxide electronics, but fundamental questions about the interplay between the spin-orbit coupling and electronic correlations at the atomic scale remain unanswered. Momentum-resolved spectroscopies of collective electronic excitations yield detailed insight into the magnitude and spatial range of the electronic correlations, and have thus decisively shaped the conceptual understanding of quantum many-body phenomena in 3d-electron systems. We will devise and build a novel resonant inelastic x-ray scattering (RIXS) instrument capable of determining the dispersion relations of electronic collective modes in 4d-metal compounds with full momentum-space coverage, high energy resolution, and monolayer sensitivity. Data from this instrument will yield comprehensive information about the interaction parameters specifying the electronic Hamiltonians of 4d-electron materials, unique insight into the spin-orbital composition of their excited-state wavefunctions, and definitive tests of proposals to realize Kitaev models with spin-liquid states that are potentially relevant in topological quantum computation. The element-specificity of RIXS will also allow us to determine the microscopic exchange interactions in complex materials with both 3d and 4d valence electrons, and its high sensitivity will enable experiments on operational device structures comprising only a few monolayers. We will thus be able to tightly integrate momentum-resolved spectroscopy with state-of-the-art, monolayer-by-monolayer deposition methods of 4d metal-oxide films and heterostructures. The results will fuel a feedback loop comprising synthesis, characterization, and modeling, which will greatly advance our ability to design materials and devices whose functionality derives from the collective organization of electrons.
Project acronym DENOVOSTEM
Project DE NOVO GENERATION OF SOMATIC STEM CELLS: REGULATION AND MECHANISMS OF CELL PLASTICITY
Researcher (PI) Stefano Piccolo
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Summary The possibility to artificially induce and expand in vitro tissue-specific stem cells (SCs) is an important goal for regenerative medicine, to understand organ physiology, for in vitro modeling of human diseases and many other applications. Here we found that this goal can be achieved in the culture dish by transiently inducing expression of YAP or TAZ - nuclear effectors of the Hippo and biomechanical pathways - into primary/terminally differentiated cells of distinct tissue origins. Moreover, YAP/TAZ are essential endogenous factors that preserve ex-vivo naturally arising SCs of distinct tissues. In this grant, we aim to gain insights into YAP/TAZ molecular networks (upstream regulators and downstream targets) involved in somatic SC reprogramming and SC identity. Our studies will entail the identification of the genetic networks and epigenetic changes controlled by YAP/TAZ during cell de-differentiation and the re-acquisition of SC-traits in distinct cell types. We will also investigate upstream inputs establishing YAP/TAZ activity, with particular emphasis on biomechanical and cytoskeletal cues that represent overarching regulators of YAP/TAZ in tissues. For many tumors, it appears that acquisition of an immature, stem-like state is a prerequisite for tumor progression and an early step in oncogene-mediated transformation. YAP/TAZ activation is widespread in human tumors. However, a connection between YAP/TAZ and oncogene-induced cell plasticity has never been investigated. We will also pursue some intriguing preliminary results and investigate how oncogenes and chromatin remodelers may link to cell mechanics, and the plasticity of the differentiated and SC states by controlling YAP/TAZ. In sum, this research should advance our understanding of the cellular and molecular basis underpinning organ growth, tissue regeneration and tumor initiation.
The possibility to artificially induce and expand in vitro tissue-specific stem cells (SCs) is an important goal for regenerative medicine, to understand organ physiology, for in vitro modeling of human diseases and many other applications. Here we found that this goal can be achieved in the culture dish by transiently inducing expression of YAP or TAZ - nuclear effectors of the Hippo and biomechanical pathways - into primary/terminally differentiated cells of distinct tissue origins. Moreover, YAP/TAZ are essential endogenous factors that preserve ex-vivo naturally arising SCs of distinct tissues. In this grant, we aim to gain insights into YAP/TAZ molecular networks (upstream regulators and downstream targets) involved in somatic SC reprogramming and SC identity. Our studies will entail the identification of the genetic networks and epigenetic changes controlled by YAP/TAZ during cell de-differentiation and the re-acquisition of SC-traits in distinct cell types. We will also investigate upstream inputs establishing YAP/TAZ activity, with particular emphasis on biomechanical and cytoskeletal cues that represent overarching regulators of YAP/TAZ in tissues. For many tumors, it appears that acquisition of an immature, stem-like state is a prerequisite for tumor progression and an early step in oncogene-mediated transformation. YAP/TAZ activation is widespread in human tumors. However, a connection between YAP/TAZ and oncogene-induced cell plasticity has never been investigated. We will also pursue some intriguing preliminary results and investigate how oncogenes and chromatin remodelers may link to cell mechanics, and the plasticity of the differentiated and SC states by controlling YAP/TAZ. In sum, this research should advance our understanding of the cellular and molecular basis underpinning organ growth, tissue regeneration and tumor initiation.
Project acronym Filmcolors
Project Film Colors. An Interdisciplinary Approach.
Researcher (PI) Barbara Flueckiger
Summary Film is in essence colored light projected onto a screen. Its aesthetics are thus highly determined by the material properties of film and the optical configuration of the cinematic apparatus. To this day, however, there is no systematic study of the relationship between the technology and aesthetics of film colors, despite the fact that, following the digital turn in film production and distribution, the understanding of this relationship is more essential than ever before. Over 200 film color processes were developed since the invention of film. They are presented on the Timeline of Historical Film Colors, which will be an integral part of the project. The groundbreaking nature of this project lies in a truly interdisciplinary research design with a novel methodology to explore the interaction of technological advances and limitations with film color aesthetics, identifying diachronic patterns of stylistic means. To this end it develops a tool through recent advancements in digital humanities for crowd-sourcing of color analyses of large groups of films. In-depth studies of technical papers and scientific measurements of film colors will investigate the technical basis of films' aesthetic appearance. These insights will be applied to the digitization and restoration of historical films to explore and disseminate the results. While every serious art restoration connects scientific analyses with art-historical and aesthetic investigations, a similar approach is rarely applied to film. In summary, the present research proposal capitalizes on the principal investigator's preceding studies to bridge the gap between technology and aesthetics. With the methods described here, the results will trace previously hidden roots of aesthetic developments of film colors. While the project is ambitious, it builds on a sizable methodological foundation to optimize risk management and guarantee significant advances in the understanding of film colors.
Film is in essence colored light projected onto a screen. Its aesthetics are thus highly determined by the material properties of film and the optical configuration of the cinematic apparatus. To this day, however, there is no systematic study of the relationship between the technology and aesthetics of film colors, despite the fact that, following the digital turn in film production and distribution, the understanding of this relationship is more essential than ever before. Over 200 film color processes were developed since the invention of film. They are presented on the Timeline of Historical Film Colors, which will be an integral part of the project. The groundbreaking nature of this project lies in a truly interdisciplinary research design with a novel methodology to explore the interaction of technological advances and limitations with film color aesthetics, identifying diachronic patterns of stylistic means. To this end it develops a tool through recent advancements in digital humanities for crowd-sourcing of color analyses of large groups of films. In-depth studies of technical papers and scientific measurements of film colors will investigate the technical basis of films' aesthetic appearance. These insights will be applied to the digitization and restoration of historical films to explore and disseminate the results. While every serious art restoration connects scientific analyses with art-historical and aesthetic investigations, a similar approach is rarely applied to film. In summary, the present research proposal capitalizes on the principal investigator's preceding studies to bridge the gap between technology and aesthetics. With the methods described here, the results will trace previously hidden roots of aesthetic developments of film colors. While the project is ambitious, it builds on a sizable methodological foundation to optimize risk management and guarantee significant advances in the understanding of film colors.
Project acronym GTCMR
Project Global Terrorism and Collective Moral Responsibility: Redesigning Military, Police and Intelligence Institutions in Liberal Democracies
Researcher (PI) Seumas Miller
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Summary International terrorism, e.g. Al Qaeda, IS, is a major global security threat. Counter-terrorism is a morally complex enterprise involving police, military, intelligence agencies and non-security agencies. Counter-terrorism should be framed as a collective moral responsibility of governments, security institutions and citizens. (1) How is international terrorism to be defined? (2) What is the required theoretical notion of collective moral responsibility? (3) What counter-terrorist strategies and tactics are effective, morally permissible and consistent with liberal democracy? Tactics: targeted killing, drone warfare, preventative detention, and bulk metadata collection (e.g. by NSA); (4) How is this inchoate collective moral responsibility to be institutionally embedded in security agencies? (i) How are security institutions to be redesigned to enable them to realise and coordinate their counter-terrorism strategies without over-reaching their various core institutional purposes which have hitherto been disparate, (e.g. law enforcement versus military combat), and without compromising human rights, (e.g. right to life of innocent civilians, right to freedom, right to privacy), including by means of morally unacceptable counter-terrorism tactics? (ii) How are these tactics to be integrated with a broad-based counter-terrorism strategy which has such measures as anti-radicalisation and state-to-state engagement to address key sources of terrorism, such as the dissemination of extremist religious ideology (e.g. militant Wahhabi ideology emanating from Saudi Arabia) and the legitimate grievances of some terrorist groups (e.g. Palestinian state)? What ought a morally permissible and efficacious (i) structure of counter-terrorist institutional arrangements, and (ii) set of counter-terrorist tactics, for a contemporary liberal democracy collaborating with other liberal democracies facing the common problem of international terrorism consist of?
International terrorism, e.g. Al Qaeda, IS, is a major global security threat. Counter-terrorism is a morally complex enterprise involving police, military, intelligence agencies and non-security agencies. Counter-terrorism should be framed as a collective moral responsibility of governments, security institutions and citizens. (1) How is international terrorism to be defined? (2) What is the required theoretical notion of collective moral responsibility? (3) What counter-terrorist strategies and tactics are effective, morally permissible and consistent with liberal democracy? Tactics: targeted killing, drone warfare, preventative detention, and bulk metadata collection (e.g. by NSA); (4) How is this inchoate collective moral responsibility to be institutionally embedded in security agencies? (i) How are security institutions to be redesigned to enable them to realise and coordinate their counter-terrorism strategies without over-reaching their various core institutional purposes which have hitherto been disparate, (e.g. law enforcement versus military combat), and without compromising human rights, (e.g. right to life of innocent civilians, right to freedom, right to privacy), including by means of morally unacceptable counter-terrorism tactics? (ii) How are these tactics to be integrated with a broad-based counter-terrorism strategy which has such measures as anti-radicalisation and state-to-state engagement to address key sources of terrorism, such as the dissemination of extremist religious ideology (e.g. militant Wahhabi ideology emanating from Saudi Arabia) and the legitimate grievances of some terrorist groups (e.g. Palestinian state)? What ought a morally permissible and efficacious (i) structure of counter-terrorist institutional arrangements, and (ii) set of counter-terrorist tactics, for a contemporary liberal democracy collaborating with other liberal democracies facing the common problem of international terrorism consist of?
Project acronym INSULATRONICS
Project Controlling Electric Signals with Insulating Antiferromagnets and Insulating Ferromagnets
Researcher (PI) Arne Brataas
Host Institution (HI) NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Summary The proposal aims to facilitate a revolution of information and communication technologies by controlling electric signals with antiferromagnetic insulators and ferromagnetic insulators. We recently discovered that antiferromagnets can be active components in spintronics devices despite their lack of a macroscopic magnetic moment, and even when they are insulating. Conventional electronics- and spintronics-based logic and memory devices, interconnects, and microwave oscillators are based on (spin-polarized) charge transport, which inherently dissipates power due to ohmic losses. The research proposed seeks to determine the extents to which "Insulatronics" has the potential to control the electric and thermal signal generation, transmission, and detection in more power-efficient ways. Insulatronics is profoundly different because there are no moving charges involved so the power reduction is significant. We hope to establish the extents to which spin-waves and coherent magnons in antiferromagnetic insulators and ferromagnetic insulators can be strongly coupled to electric and thermal currents in adjacent conductors and utilize this coupling to control electric signals. The coupling will be facilitated by spin-transfer torques and spin-pumping – a technique we pioneered – as well as spin-orbit torques and its reciprocal process of charge-pumping. The core of this project focuses on the theoretical and fundamental challenges facing Insulatronics. Beyond the duration of the project, if we are successful, the use of spin signals in insulators with extremely low power dissipation may enable superior low-power technologies such as oscillators, logic devices, interconnects, non-volatile random access memories, and perhaps even quantum information processing.
The proposal aims to facilitate a revolution of information and communication technologies by controlling electric signals with antiferromagnetic insulators and ferromagnetic insulators. We recently discovered that antiferromagnets can be active components in spintronics devices despite their lack of a macroscopic magnetic moment, and even when they are insulating. Conventional electronics- and spintronics-based logic and memory devices, interconnects, and microwave oscillators are based on (spin-polarized) charge transport, which inherently dissipates power due to ohmic losses. The research proposed seeks to determine the extents to which "Insulatronics" has the potential to control the electric and thermal signal generation, transmission, and detection in more power-efficient ways. Insulatronics is profoundly different because there are no moving charges involved so the power reduction is significant. We hope to establish the extents to which spin-waves and coherent magnons in antiferromagnetic insulators and ferromagnetic insulators can be strongly coupled to electric and thermal currents in adjacent conductors and utilize this coupling to control electric signals. The coupling will be facilitated by spin-transfer torques and spin-pumping – a technique we pioneered – as well as spin-orbit torques and its reciprocal process of charge-pumping. The core of this project focuses on the theoretical and fundamental challenges facing Insulatronics. Beyond the duration of the project, if we are successful, the use of spin signals in insulators with extremely low power dissipation may enable superior low-power technologies such as oscillators, logic devices, interconnects, non-volatile random access memories, and perhaps even quantum information processing.
Project acronym K4U
Project Knowledge For Use [K4U]: Making the Most of Social Science to Build Better Policies
Researcher (PI) Nancy Cartwright
Host Institution (HI) UNIVERSITY OF DURHAM
Summary 'Research is an investment in our future' says Horizon 2020. That's only true if you know what to do with it. When it comes to social policy, we don't really know how to put our research results to use. K4U aims to remedy this. K4U will construct a radically new picture of how to use social science to build better social policies. This picture will be founded on an ambitious philosophical study of the technology of social science including a thorough reconceptualisation of objectivity, deliberation and the role of values in the science/society interface. Current work, primarily by the evidence-based policy and practice movement, focusses on knowledge production: encouraging high quality studies and vetting them. Little attention goes to knowledge use: How is social science knowledge to be used in policy design and deliberation – how should it be used so that policy outcomes are more effective and more reliably predictable and competing values and points of view are respected in policy choice and implementation? K4U will provide not just a theoretical but a practical understanding— for users: intelligible and practically helpful to those who need to estimate and balance the effectiveness, the evidence, the chances of success, the costs, the benefits, the winners and losers, and the social, moral, political and cultural acceptability of proposed policies. The philosophical approach of K4U is broadly Popperian. It views 'science and technology as a means of understanding social problems and responding to them' and it emphasises the concrete and detailed, where the real content of general philosophical concepts and claims is embodied and interrogated. K4U is a showcase for the kind of philosophy that makes a difference to real life -- philosophy for practice. And it will launch an entire new field in philosophy: the philosophy of social technology.
'Research is an investment in our future' says Horizon 2020. That's only true if you know what to do with it. When it comes to social policy, we don't really know how to put our research results to use. K4U aims to remedy this. K4U will construct a radically new picture of how to use social science to build better social policies. This picture will be founded on an ambitious philosophical study of the technology of social science including a thorough reconceptualisation of objectivity, deliberation and the role of values in the science/society interface. Current work, primarily by the evidence-based policy and practice movement, focusses on knowledge production: encouraging high quality studies and vetting them. Little attention goes to knowledge use: How is social science knowledge to be used in policy design and deliberation – how should it be used so that policy outcomes are more effective and more reliably predictable and competing values and points of view are respected in policy choice and implementation? K4U will provide not just a theoretical but a practical understanding— for users: intelligible and practically helpful to those who need to estimate and balance the effectiveness, the evidence, the chances of success, the costs, the benefits, the winners and losers, and the social, moral, political and cultural acceptability of proposed policies. The philosophical approach of K4U is broadly Popperian. It views 'science and technology as a means of understanding social problems and responding to them' and it emphasises the concrete and detailed, where the real content of general philosophical concepts and claims is embodied and interrogated. K4U is a showcase for the kind of philosophy that makes a difference to real life -- philosophy for practice. And it will launch an entire new field in philosophy: the philosophy of social technology.
Project acronym LightNet
Project LightNet - Tracking the Coherent Light Path in Photosynthetic Networks
Researcher (PI) Niek van Hulst
Host Institution (HI) FUNDACIO INSTITUT DE CIENCIES FOTONIQUES
Summary ature has developed photosynthesis to power life. Networks of light harvesting antennas capture the sunlight to funnel the photonic energy towards reaction centres. Surprisingly, quantum coherences are observed in the energy transfer of photosynthetic complexes, even at room temperature. Does nature exploit quantum concepts? Does the coherence help to find an optimal path for robust or efficient transfer? How are the coherences sustained? What is their spatial extent in a real light-harvesting network? So far only solutions of complexes were studied, far from the natural network operation, putting on hold conclusions as to a biological role of the coherences. My group recently succeeded in the first detection of coherent oscillations of a single photo-synthetic complex at physiological conditions, and non-classical photon emission of individual complexes. These pioneering results, together with our expertise in nanophotonics, pave the way to address photosynthetic networks in real nano-space and on femtosecond timescale. Specific objectives are: --Ultrafast single protein detection: tracing the fs coherent energy transfer path of an individual complex; addressing the very nature of the persistent coherences. -Beyond fluorescence: light harvesting complex are designed for light transport, not emission. I will explore innovative alternatives: optical antennas to enhance quantum efficiency; detection of stimulated emission; and electrical read-out on graphene. -Nanoscale light transport: using local excitation and detection by nanoholes, nanoslits and scanning antenna probes I will spatially map the extent of the inter-complex transfer. -The network: combining both coherent fs excitation and localized nanoscale excitation/detection I will track the extent of coherences throughout the network. The impact of this first exploration of light transport in a nanoscale bionetwork ranges to solar energy management, molecular biology, polymer chemistry and material science.
ature has developed photosynthesis to power life. Networks of light harvesting antennas capture the sunlight to funnel the photonic energy towards reaction centres. Surprisingly, quantum coherences are observed in the energy transfer of photosynthetic complexes, even at room temperature. Does nature exploit quantum concepts? Does the coherence help to find an optimal path for robust or efficient transfer? How are the coherences sustained? What is their spatial extent in a real light-harvesting network? So far only solutions of complexes were studied, far from the natural network operation, putting on hold conclusions as to a biological role of the coherences. My group recently succeeded in the first detection of coherent oscillations of a single photo-synthetic complex at physiological conditions, and non-classical photon emission of individual complexes. These pioneering results, together with our expertise in nanophotonics, pave the way to address photosynthetic networks in real nano-space and on femtosecond timescale. Specific objectives are: --Ultrafast single protein detection: tracing the fs coherent energy transfer path of an individual complex; addressing the very nature of the persistent coherences. -Beyond fluorescence: light harvesting complex are designed for light transport, not emission. I will explore innovative alternatives: optical antennas to enhance quantum efficiency; detection of stimulated emission; and electrical read-out on graphene. -Nanoscale light transport: using local excitation and detection by nanoholes, nanoslits and scanning antenna probes I will spatially map the extent of the inter-complex transfer. -The network: combining both coherent fs excitation and localized nanoscale excitation/detection I will track the extent of coherences throughout the network. The impact of this first exploration of light transport in a nanoscale bionetwork ranges to solar energy management, molecular biology, polymer chemistry and material science.
Project acronym MALMECC
Project Music and Late Medieval European Court Cultures: Towards a Trans-Disciplinary and Post-National Cultural Poetics of the Performative Arts
Researcher (PI) Karl Kuegle
Summary Late medieval European court cultures have traditionally been studied from a mono-disciplinary and national(ist) perspective. This focus has obscured much of the interplay of cultural performances that informed "courtly life". Recent research has begun to reverse this, focusing on issues such as the tensions between orality, writing, and performance; the sociocultural dimensions of making and owning manuscripts (musical and otherwise); the interstices between musical, literary and visual texts and political, social and religious rituals; and the impact of gender, kinship, and social status on the genesis and transmission of culture and music. These "new medievalist" studies have significantly enhanced our understanding of the cultural meanings of singing, listening, and sound in late medieval times. Taking a decisive step further, MALMECC will, for the first time, systematically explore late medieval (c. 1280-1450) court cultures and their music synoptically across Europe. England, the Low Countries, Avignon, Bohemia, south-eastern Germany/Salzburg, Savoy, and Cyprus have been selected for study as each was a vibrant site of cultural production but has been relatively neglected due to prevailing discursive formations favouring "centres" like Paris and Florence. Linking these courts in a large-scale comparative study focused on the role of music in courtly life but embedded within a multidisciplinary framework encompassing all the arts as well as politics and religion will reveal the complex ecology of late medieval performances of noblesse in unheard-of depth while at the same time throwing the unique qualities of each court into distinct relief. The project will apply an innovative research paradigm that develops a trans-disciplinary and post-national(ist), "relational" approach to the study of music in late-medieval court cultures. In doing so it will integrate all late medieval arts and re-constitute the fullness of their potential meanings.
Late medieval European court cultures have traditionally been studied from a mono-disciplinary and national(ist) perspective. This focus has obscured much of the interplay of cultural performances that informed "courtly life". Recent research has begun to reverse this, focusing on issues such as the tensions between orality, writing, and performance; the sociocultural dimensions of making and owning manuscripts (musical and otherwise); the interstices between musical, literary and visual texts and political, social and religious rituals; and the impact of gender, kinship, and social status on the genesis and transmission of culture and music. These "new medievalist" studies have significantly enhanced our understanding of the cultural meanings of singing, listening, and sound in late medieval times. Taking a decisive step further, MALMECC will, for the first time, systematically explore late medieval (c. 1280-1450) court cultures and their music synoptically across Europe. England, the Low Countries, Avignon, Bohemia, south-eastern Germany/Salzburg, Savoy, and Cyprus have been selected for study as each was a vibrant site of cultural production but has been relatively neglected due to prevailing discursive formations favouring "centres" like Paris and Florence. Linking these courts in a large-scale comparative study focused on the role of music in courtly life but embedded within a multidisciplinary framework encompassing all the arts as well as politics and religion will reveal the complex ecology of late medieval performances of noblesse in unheard-of depth while at the same time throwing the unique qualities of each court into distinct relief. The project will apply an innovative research paradigm that develops a trans-disciplinary and post-national(ist), "relational" approach to the study of music in late-medieval court cultures. In doing so it will integrate all late medieval arts and re-constitute the fullness of their potential meanings.
Project acronym MMUVR
Project Elucidating the role of ultraviolet radiation in melanoma
Researcher (PI) Richard Marais
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Summary Melanoma incidence continues to increase across Europe and compared to other cancers, it disproportionately affects young people, causing a significant loss in life-years in those affected. Ultraviolet radiation (UVR) is the only environmental risk factor in melanoma, but the underlying genetic constitution of the individual also plays an important role. However, our knowledge of the gene-gene and gene-environment interactions in melanomagenesis is still very limited and here we will use various cutting-edge technologies to investigate the role of UVR in melanoma initiation and progression. We have developed mouse models of UVR-driven melanoma that closely mimic UVR-driven melanoma in humans and these provide an unprecedented opportunity to dissect how different wavelengths and patterns of UVR exposure affect melanomagenesis. We propose a multidisciplinary programme of work to examine how host genetic susceptibility factors and responses such as DNA damage repair and inflammation affect melanoma development and progression following UVR exposure. We will integrate knowledge from our animal experiments with epidemiological, histopathological, clinical, and genetic features of human tumours to improve stratification of human melanoma and thereby assist clinical management of this deadly disease. Our overarching aim is to develop a validated stratification approach to melanoma patients that will assist in the development of effective public health campaigns for individuals at risk across Europe.
Melanoma incidence continues to increase across Europe and compared to other cancers, it disproportionately affects young people, causing a significant loss in life-years in those affected. Ultraviolet radiation (UVR) is the only environmental risk factor in melanoma, but the underlying genetic constitution of the individual also plays an important role. However, our knowledge of the gene-gene and gene-environment interactions in melanomagenesis is still very limited and here we will use various cutting-edge technologies to investigate the role of UVR in melanoma initiation and progression. We have developed mouse models of UVR-driven melanoma that closely mimic UVR-driven melanoma in humans and these provide an unprecedented opportunity to dissect how different wavelengths and patterns of UVR exposure affect melanomagenesis. We propose a multidisciplinary programme of work to examine how host genetic susceptibility factors and responses such as DNA damage repair and inflammation affect melanoma development and progression following UVR exposure. We will integrate knowledge from our animal experiments with epidemiological, histopathological, clinical, and genetic features of human tumours to improve stratification of human melanoma and thereby assist clinical management of this deadly disease. Our overarching aim is to develop a validated stratification approach to melanoma patients that will assist in the development of effective public health campaigns for individuals at risk across Europe.
Project acronym Mulosige
Project Multilingual locals, significant geographies: a new approach to world literature
Researcher (PI) Francesca Orsini
Host Institution (HI) SCHOOL OF ORIENTAL AND AFRICAN STUDIES ROYAL CHARTER
Summary "World literature is literature that circulates globally. It is mostly in English. Its main genre is the novel." These are caricatures of how World literature as a set of discourses is shaping the field of literary studies, but in fact Non-Western literatures are positioned with reference to a single global timeline and a single map, and translations supposedly ensure that worthy texts enter the global canon. What does not circulate globally is provincial, not good enough, not "world literature". This picture bears little resemblance to the multilingual world of literature, which consists not of a single map but of many "significant geographies" specific to language, group, and genre. By exploring the often fractured "multilingual locals" and "significant geographies" of literature in north India, Morocco, and Ethiopia—each with different experiences of literary multilingualism, colonial diglossia, and continuing oral traditions—we seek to establish a multilingual and located approach to world literature in place of meta-categories like "global" and "world". Mindful of older histories and networks of literary multilingualism and critical of the monolingual straitjacket of modern literary histories that partition Anglophone and Francophone literature from Arabic, Amharic, and Hindi/Urdu, we focus on three periods: imperial consolidation, decolonization, and the current globalizing moment. We will study local transculturations, local debates on world literature, old and new forms of multilingualism, actors and technologies of print and orality, to highlight dynamics of appropriation rather than imitation, co-constitution rather than diffusion, and the multiplicity of choices and trajectories that together form local and transnational literary fields ("world literature"). The project will propose a theoretical approach, methods for multilingual training and research, and strategic dialogues with scholars and writers in Morocco, Ethiopia, India, UK and France.
"World literature is literature that circulates globally. It is mostly in English. Its main genre is the novel." These are caricatures of how World literature as a set of discourses is shaping the field of literary studies, but in fact Non-Western literatures are positioned with reference to a single global timeline and a single map, and translations supposedly ensure that worthy texts enter the global canon. What does not circulate globally is provincial, not good enough, not "world literature". This picture bears little resemblance to the multilingual world of literature, which consists not of a single map but of many "significant geographies" specific to language, group, and genre. By exploring the often fractured "multilingual locals" and "significant geographies" of literature in north India, Morocco, and Ethiopia—each with different experiences of literary multilingualism, colonial diglossia, and continuing oral traditions—we seek to establish a multilingual and located approach to world literature in place of meta-categories like "global" and "world". Mindful of older histories and networks of literary multilingualism and critical of the monolingual straitjacket of modern literary histories that partition Anglophone and Francophone literature from Arabic, Amharic, and Hindi/Urdu, we focus on three periods: imperial consolidation, decolonization, and the current globalizing moment. We will study local transculturations, local debates on world literature, old and new forms of multilingualism, actors and technologies of print and orality, to highlight dynamics of appropriation rather than imitation, co-constitution rather than diffusion, and the multiplicity of choices and trajectories that together form local and transnational literary fields ("world literature"). The project will propose a theoretical approach, methods for multilingual training and research, and strategic dialogues with scholars and writers in Morocco, Ethiopia, India, UK and France.
Project acronym OxygenSensing
Project Molecular mechanisms of acute oxygen sensing.
Researcher (PI) Jose Lopez Barneo
Host Institution (HI) UNIVERSIDAD DE SEVILLA
Summary Oxygen (O2) is essential for life on Earth. This proposal deals with the study of the molecular mechanisms underlying acute O2 sensing by cells, a long-standing issue that is yet to be elucidated. In recent years, the discovery of hypoxia inducible transcription factors and their regulation by the O2-dependent hydroxylases has provided a solid framework for understanding genetic responses to sustained (chronic) hypoxia. However the mechanisms of acute O2 sensing, necessary for the activation of rapid, life-saving, compensatory respiratory and cardiovascular reflexes (e.g. hyperventilation and sympathetic activation), are unknown. While the primary goal of the project is to characterize the molecular mechanisms underlying acute O2 sensing by arterial chemoreceptors (carotid body –CB- and adrenal medulla –AM-), we will also extend our study to other organs (e.g. pulmonary and systemic arteries) of the homeostatic acute O2-sensing system. We will investigate the role of mitochondria, in particular complex I (MCI), in acute O2 sensing. Previous data from our group demonstrated that rotenone, a MCI blocker, selectively occludes responsiveness to hypoxia in CB cells. In addition, our unpublished data indicate that sensitivity to hypoxia (but not to other stimuli) is lost in mice with genetic disruption of MCI genes in CB and AM cells. We have shown that the adult CB is a plastic organ that contains a population of multipotent neural stem cells. Hence, another objective of the project is to study the role of these stem cells in CB modulation (over- or infra-activation), which may participate in the pathogenesis of diseases. In the past, our group has made seminal contributions to unveiling the cellular bases of arterial chemoreception. The discovery of stem cells in the CB and the generation of new genetically modified mouse models, put us in a leading position to elucidate the molecular bases of acute O2 sensing and their biomedical implications.
Oxygen (O2) is essential for life on Earth. This proposal deals with the study of the molecular mechanisms underlying acute O2 sensing by cells, a long-standing issue that is yet to be elucidated. In recent years, the discovery of hypoxia inducible transcription factors and their regulation by the O2-dependent hydroxylases has provided a solid framework for understanding genetic responses to sustained (chronic) hypoxia. However the mechanisms of acute O2 sensing, necessary for the activation of rapid, life-saving, compensatory respiratory and cardiovascular reflexes (e.g. hyperventilation and sympathetic activation), are unknown. While the primary goal of the project is to characterize the molecular mechanisms underlying acute O2 sensing by arterial chemoreceptors (carotid body –CB- and adrenal medulla –AM-), we will also extend our study to other organs (e.g. pulmonary and systemic arteries) of the homeostatic acute O2-sensing system. We will investigate the role of mitochondria, in particular complex I (MCI), in acute O2 sensing. Previous data from our group demonstrated that rotenone, a MCI blocker, selectively occludes responsiveness to hypoxia in CB cells. In addition, our unpublished data indicate that sensitivity to hypoxia (but not to other stimuli) is lost in mice with genetic disruption of MCI genes in CB and AM cells. We have shown that the adult CB is a plastic organ that contains a population of multipotent neural stem cells. Hence, another objective of the project is to study the role of these stem cells in CB modulation (over- or infra-activation), which may participate in the pathogenesis of diseases. In the past, our group has made seminal contributions to unveiling the cellular bases of arterial chemoreception. The discovery of stem cells in the CB and the generation of new genetically modified mouse models, put us in a leading position to elucidate the molecular bases of acute O2 sensing and their biomedical implications.
Project acronym PICOPROP
Project Photo Induced Collective Properties of Hybrid Halide Perovskites
Researcher (PI) Laszlo Forro
Summary The recent discovery of the organo-inorganic perovskite CH3NH3PbI3 as very efficient material in photoelectric conversion is multifaceted: it turns out that this compound is promising not only in photovoltaics, but it is lasing, it gives bright light emitting diodes, promising in water splitting and we are persuaded that it can play an important role in basic sciences, as well. We have recently realized that under white light illumination the photoelectrons, due to their very long recombination time, stay in the conduction band and the resistivity of a single crystal shows a metallic behavior. If the lifetime is sufficiently long and the density of these excited carrier is high enough they could condense into a Fermi sea. The project's goal is to realize this highly unusual state and to document its properties by magneto-transport and spectroscopic techniques. We will check in our model compound the long-sought superconductivity of photo-excited carriers, extensively searched for in cuprates, if we could stabilize it by fine tuning the interactions by hydrostatic pressure under constant illumination. The availability of high quality samples is primordial for this program. It turns out that CH3NH3PbI3 is ideal compound, it seems to be almost free of charged defects (its room temperature resistance is 5 orders of magnitude higher than that of Phosphorus doped Silicon at 1013 cm-3 doping concentration) and we can grow excellent single crystals of it. Furthermore, it has a flexibility in material design: one can vary all the constituents, and even the dimensionality by making layered materials with the main chemical motifs. A special effort will be devoted to tune the spin-orbit coupling by different elements, since this could be at the origin of the long recombination time of the photo-electrons. We suspect that the highly tunable, clean and disorder-free doping obtained by shining light on these ionic crystals opens a new era in material discovery.
The recent discovery of the organo-inorganic perovskite CH3NH3PbI3 as very efficient material in photoelectric conversion is multifaceted: it turns out that this compound is promising not only in photovoltaics, but it is lasing, it gives bright light emitting diodes, promising in water splitting and we are persuaded that it can play an important role in basic sciences, as well. We have recently realized that under white light illumination the photoelectrons, due to their very long recombination time, stay in the conduction band and the resistivity of a single crystal shows a metallic behavior. If the lifetime is sufficiently long and the density of these excited carrier is high enough they could condense into a Fermi sea. The project's goal is to realize this highly unusual state and to document its properties by magneto-transport and spectroscopic techniques. We will check in our model compound the long-sought superconductivity of photo-excited carriers, extensively searched for in cuprates, if we could stabilize it by fine tuning the interactions by hydrostatic pressure under constant illumination. The availability of high quality samples is primordial for this program. It turns out that CH3NH3PbI3 is ideal compound, it seems to be almost free of charged defects (its room temperature resistance is 5 orders of magnitude higher than that of Phosphorus doped Silicon at 1013 cm-3 doping concentration) and we can grow excellent single crystals of it. Furthermore, it has a flexibility in material design: one can vary all the constituents, and even the dimensionality by making layered materials with the main chemical motifs. A special effort will be devoted to tune the spin-orbit coupling by different elements, since this could be at the origin of the long recombination time of the photo-electrons. We suspect that the highly tunable, clean and disorder-free doping obtained by shining light on these ionic crystals opens a new era in material discovery.
Project acronym POLTDES
Project Interacting polaritons in two-dimensional electron systems
Researcher (PI) Atac Imamoglu
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Summary Reversible coupling of excitons and photons in a microcavity leads to the formation of mixed light-matter quasiparticles, called cavity-polaritons. Weakly interacting polaritons constitute a rich system for studying nonequilibrium condensation and superfluidity. While exciton-polaritons have been studied mostly in intrinsic semiconductors with no free electrons, two-dimensional modulation-doped semiconductors with strong interactions between electrons have played a central role in unravelling many-body physics using transport. In this project, we combine these two fields of research and explore the complex interplay between cavity-polaritons and strongly correlated states of two dimensional electrons embedded inside microcavities. Our principal objective is the realization of polariton mediated superconductivity of electrons in gallium arsenide. Besides demonstrating a new mechanism for Cooper-pair formation, such an observation could revolutionize the search for systems that exhibit topological order. In a reciprocal approach, we will exploit the many-body nature of optical excitations in a two-dimensional electron gas to enhance polariton-polariton interactions. This will allow us to reach the polariton blockade regime, paving the way for realization of nonequilibrium strongly interacting polaritons. In parallel, we will explore cavity-magneto-polariton excitations out of fractional quantum Hall ground states: the objective in this part is to use the strong filling factor dependence of polariton splitting to realize nonlinear optical devices which derive their photon-photon interaction from light-absorption induced transition between compressible and incompressible ground states. Concurrently, we will study charged-exciton-polaritons in monolayer transition metal dichalcogenides positioned inside a microcavity, where a large polariton Berry-curvature allows for the observation of valley Hall effect and could be used to realize topological polaritons.
Reversible coupling of excitons and photons in a microcavity leads to the formation of mixed light-matter quasiparticles, called cavity-polaritons. Weakly interacting polaritons constitute a rich system for studying nonequilibrium condensation and superfluidity. While exciton-polaritons have been studied mostly in intrinsic semiconductors with no free electrons, two-dimensional modulation-doped semiconductors with strong interactions between electrons have played a central role in unravelling many-body physics using transport. In this project, we combine these two fields of research and explore the complex interplay between cavity-polaritons and strongly correlated states of two dimensional electrons embedded inside microcavities. Our principal objective is the realization of polariton mediated superconductivity of electrons in gallium arsenide. Besides demonstrating a new mechanism for Cooper-pair formation, such an observation could revolutionize the search for systems that exhibit topological order. In a reciprocal approach, we will exploit the many-body nature of optical excitations in a two-dimensional electron gas to enhance polariton-polariton interactions. This will allow us to reach the polariton blockade regime, paving the way for realization of nonequilibrium strongly interacting polaritons. In parallel, we will explore cavity-magneto-polariton excitations out of fractional quantum Hall ground states: the objective in this part is to use the strong filling factor dependence of polariton splitting to realize nonlinear optical devices which derive their photon-photon interaction from light-absorption induced transition between compressible and incompressible ground states. Concurrently, we will study charged-exciton-polaritons in monolayer transition metal dichalcogenides positioned inside a microcavity, where a large polariton Berry-curvature allows for the observation of valley Hall effect and could be used to realize topological polaritons.
Project acronym QuDeT
Project Quantum devices in topological matter: carbon nanotubes, graphene, and novel superfluids
Researcher (PI) Pertti Hakonen
Summary The project addresses quantum devices in hybrid systems formed using carbon nanotubes, graphene, and 3He superfluid, all with particular topological characteristics. Topological properties of these non-trivial materials can be drastically modified by introducing defects or interfaces into them, like single layer graphene into superfluid helium, boron nitride between graphene sheets, carbon nanotubes in 3He superfluid, or misfit dislocation layers into HOPG graphite. We are particularly interested in graphene/3He systems where graphene acts as an interface/substrate of interacting atomic ensembles. The atomic interactions across graphene are expected to provide novel mesoscopic condensates. By studying the topological phases of thin 3He layers and graphene immersed into superfluid 3He, we will investigate pairing across the graphene interface, deduce the origin of supercurrents, and look for excitonic superfluidity in these systems. Single walled carbon nanotubes provide high-quality nanomechanical resonators with extraordinary properties. By using proximity-induced superconductivity, these objects will be integrated into circuit optomechanics in a way that facilitates strong coupling between the mechanical motion and the microwave cavity. By using adiabatic nuclear refrigeration, these non-linear quantum objects will be cooled below 1 mK, at the temperature of which the quantum ground state is reached. The cooling relies on immersion of the SWNT into superfluid 3He which, in the limit T -> 0, provides a quantum vacuum with unique topological properties. Intriguingly, the characteristics of this vacuum can be probed by ultrasensitive detectors provided by the suspended SWNTs. Finally, besides non-classical phonon states, e.g. Fock states in the mechanical resonator, reaching the ground state of such an anharmonic oscillator will allow studies of quantum tunnelling of a macroscopic object from its metastable minimum when biased with a large gate voltage.
The project addresses quantum devices in hybrid systems formed using carbon nanotubes, graphene, and 3He superfluid, all with particular topological characteristics. Topological properties of these non-trivial materials can be drastically modified by introducing defects or interfaces into them, like single layer graphene into superfluid helium, boron nitride between graphene sheets, carbon nanotubes in 3He superfluid, or misfit dislocation layers into HOPG graphite. We are particularly interested in graphene/3He systems where graphene acts as an interface/substrate of interacting atomic ensembles. The atomic interactions across graphene are expected to provide novel mesoscopic condensates. By studying the topological phases of thin 3He layers and graphene immersed into superfluid 3He, we will investigate pairing across the graphene interface, deduce the origin of supercurrents, and look for excitonic superfluidity in these systems. Single walled carbon nanotubes provide high-quality nanomechanical resonators with extraordinary properties. By using proximity-induced superconductivity, these objects will be integrated into circuit optomechanics in a way that facilitates strong coupling between the mechanical motion and the microwave cavity. By using adiabatic nuclear refrigeration, these non-linear quantum objects will be cooled below 1 mK, at the temperature of which the quantum ground state is reached. The cooling relies on immersion of the SWNT into superfluid 3He which, in the limit T -> 0, provides a quantum vacuum with unique topological properties. Intriguingly, the characteristics of this vacuum can be probed by ultrasensitive detectors provided by the suspended SWNTs. Finally, besides non-classical phonon states, e.g. Fock states in the mechanical resonator, reaching the ground state of such an anharmonic oscillator will allow studies of quantum tunnelling of a macroscopic object from its metastable minimum when biased with a large gate voltage.
Project acronym SICLE
Project Saadian Intellectual and Cultural Life
Researcher (PI) François Déroche
Host Institution (HI) COLLEGE DE FRANCE
Summary The aim of the interdisciplinary investigation project SICLE is to investigate in a completely new way the intellectual and cultural history of the Saadian period in Morocco (1554-1660), using primarily the Saadian sultans' library, exceptionally preserved as a 'time capsule' in the El Escorial monastery following king Felipe III's decision to include it in his own library. The period is a time of direct involvement of Morocco in international politics and exchanges, both in their East-West (with the Ottoman empire) and North-South (with Europe) dimensions, without forgetting Timbuktu and the Songhay empire conquered by Ahmad al-Mansur, the most brilliant ruler of the dynasty. The manuscripts kept in El Escorial mirror the interests and the tastes of the Saadian rulers and of the elite at large. The paratextual information they contain (but ignored by the catalogues) like the various notes, the colophons, the illuminations or the bindings will be systematically collected and analyzed in a trans-disciplinary approach which can be defined as an 'archaeology of the book', combining codicology, philology, archaeometry, anthropology and art history. The same approach will be applied to the books of the 'ordinary people' from Saadian times preserved in Moroccan collections. SICLE goals are to offer: a) a history of the Saadian sultans' library and an analysis of their interests; b) a cultural and intellectual history of Morocco during the 16th century, with groundbreaking studies on the history of the book, on its economy and on education; c) an evaluation of the relationship with the 'outside' (Christian Europe, the Ottoman empire and sub-Saharan Africa) and the possible influence it had on Saadian intellectual production. Special attention will be paid to the Jewish and Morisco communities in their role of culture brokers.
The aim of the interdisciplinary investigation project SICLE is to investigate in a completely new way the intellectual and cultural history of the Saadian period in Morocco (1554-1660), using primarily the Saadian sultans' library, exceptionally preserved as a 'time capsule' in the El Escorial monastery following king Felipe III's decision to include it in his own library. The period is a time of direct involvement of Morocco in international politics and exchanges, both in their East-West (with the Ottoman empire) and North-South (with Europe) dimensions, without forgetting Timbuktu and the Songhay empire conquered by Ahmad al-Mansur, the most brilliant ruler of the dynasty. The manuscripts kept in El Escorial mirror the interests and the tastes of the Saadian rulers and of the elite at large. The paratextual information they contain (but ignored by the catalogues) like the various notes, the colophons, the illuminations or the bindings will be systematically collected and analyzed in a trans-disciplinary approach which can be defined as an 'archaeology of the book', combining codicology, philology, archaeometry, anthropology and art history. The same approach will be applied to the books of the 'ordinary people' from Saadian times preserved in Moroccan collections. SICLE goals are to offer: a) a history of the Saadian sultans' library and an analysis of their interests; b) a cultural and intellectual history of Morocco during the 16th century, with groundbreaking studies on the history of the book, on its economy and on education; c) an evaluation of the relationship with the 'outside' (Christian Europe, the Ottoman empire and sub-Saharan Africa) and the possible influence it had on Saadian intellectual production. Special attention will be paid to the Jewish and Morisco communities in their role of culture brokers.
Project acronym SORBET
Project Spin Orbitronics for Electronic Technologies
Researcher (PI) Stuart Parkin
Summary Spintronics is a vibrant field of research that involves the intimate interaction of magnetic structure on the atomic scale with spin currents and spin-polarized charge currents. SORBET is focussed on an emerging sub-field of spintronics, namely that of spin orbitronics. Recent discoveries in this field concern the interplay of several distinct spin orbit coupling derived phenomena that, together, allow for the highly efficient current induced motion of domain walls (DWs) in magnetic nanowires. It is proposed to explore two classes of domain-wall device concepts: a novel two terminal single-domain wall device composed of a spin-valve based structure that is deposited on a vertical wall or other 3D structure; and a 3D racetrack memory that involves multiple domain walls. The main objectives of the project involve the exploration of atomically engineered thin film magnetic nano-structures that could enable these revolutionary devices, and to unravel and exploit the new physics of this emerging field of research. To achieve these objectives fundamental breakthroughs are needed both in the thin film materials themselves and in the physics that determines the material properties and controls the motion of the DWs. These devices are innately three-dimensional and thus can overcome challenges that limit the scaling of existing two-dimensional electronic technologies. Novel methods to fabricate these devices will be explored, especially, the use of atomic layer deposition and 3D printing techniques. An important objective will be to understand the origin of the spin orbit torques that drive domain walls in nanowires and the detailed relationship of these torques to the DW structure; it is anticipated that this will enable even more complex 3D spin textures to be realized that have, for example, much lower threshold currents for motion than is currently possible, and that exhibit topological transport phenomena that could even be used to generate or detect domain walls.
Spintronics is a vibrant field of research that involves the intimate interaction of magnetic structure on the atomic scale with spin currents and spin-polarized charge currents. SORBET is focussed on an emerging sub-field of spintronics, namely that of spin orbitronics. Recent discoveries in this field concern the interplay of several distinct spin orbit coupling derived phenomena that, together, allow for the highly efficient current induced motion of domain walls (DWs) in magnetic nanowires. It is proposed to explore two classes of domain-wall device concepts: a novel two terminal single-domain wall device composed of a spin-valve based structure that is deposited on a vertical wall or other 3D structure; and a 3D racetrack memory that involves multiple domain walls. The main objectives of the project involve the exploration of atomically engineered thin film magnetic nano-structures that could enable these revolutionary devices, and to unravel and exploit the new physics of this emerging field of research. To achieve these objectives fundamental breakthroughs are needed both in the thin film materials themselves and in the physics that determines the material properties and controls the motion of the DWs. These devices are innately three-dimensional and thus can overcome challenges that limit the scaling of existing two-dimensional electronic technologies. Novel methods to fabricate these devices will be explored, especially, the use of atomic layer deposition and 3D printing techniques. An important objective will be to understand the origin of the spin orbit torques that drive domain walls in nanowires and the detailed relationship of these torques to the DW structure; it is anticipated that this will enable even more complex 3D spin textures to be realized that have, for example, much lower threshold currents for motion than is currently possible, and that exhibit topological transport phenomena that could even be used to generate or detect domain walls.
Project acronym StemBAT
Project New players in human BAT differentiation and activation: a human PSC-derived BAT approach combined with state of the art genome engineering and –omics based methodologies
Researcher (PI) Antonio Vidal-Puig
Host Institution (HI) GENOME RESEARCH LIMITED
Summary Here we propose a strategy to control body weight and prevent/reverse obesity based on targeting brown adipose tissue (BAT) to facilitate negative energy balance and prevent adaptive responses to dietary restriction. However, BAT in humans is limited and poorly characterised. Thus, we propose to use stem cells as a tool to gain unique insights into the biology of human brown adipocytes. The General Objective is to identify pathways and factors of potential therapeutic relevance that promote BAT development and/or activation/recruitment using a stem cell based BAT differentiation approach, and then to functionally validate the role of these factors in vitro by genome engineering human stem cell derived adipocytes and in vivo by transplanting these cells into mice. Specific Aims are: 1.To identify molecular mechanisms involved in human brown adipose tissue development and activation. 2. To investigate the molecular mechanisms involved in human white adipose tissue browning/beige cells recruitment 3. To identify new agents/compounds of therapeutic value, able to activate or recruit human brown adipose tissue/brite cells. Experimental strategy: We will use a UCP1-reporter human pluripotent stem cell (PSC) line differentiated into brown and white adipocytes to identify genetic factors that may contribute to brown adipocyte differentiation/activation and white adipocyte browning. Following the identification of candidate genes, we will knock out, constitutively and/or inducibly, both alleles of these genes in human PSC cells, producing a total loss of function. Following the in vitro phenotyping of the cells we will proceed to the in vivo validation of the functional properties/phenotype of human PSC derived brown/brite adipocytes (wild-type and loss of function) by transplanting these cells into mice. Using these reporter tools we will also perform in vitro pharmacological screening and in vivo validation of new compounds that stimulate BAT activation and WAT browning
Here we propose a strategy to control body weight and prevent/reverse obesity based on targeting brown adipose tissue (BAT) to facilitate negative energy balance and prevent adaptive responses to dietary restriction. However, BAT in humans is limited and poorly characterised. Thus, we propose to use stem cells as a tool to gain unique insights into the biology of human brown adipocytes. The General Objective is to identify pathways and factors of potential therapeutic relevance that promote BAT development and/or activation/recruitment using a stem cell based BAT differentiation approach, and then to functionally validate the role of these factors in vitro by genome engineering human stem cell derived adipocytes and in vivo by transplanting these cells into mice. Specific Aims are: 1.To identify molecular mechanisms involved in human brown adipose tissue development and activation. 2. To investigate the molecular mechanisms involved in human white adipose tissue browning/beige cells recruitment 3. To identify new agents/compounds of therapeutic value, able to activate or recruit human brown adipose tissue/brite cells. Experimental strategy: We will use a UCP1-reporter human pluripotent stem cell (PSC) line differentiated into brown and white adipocytes to identify genetic factors that may contribute to brown adipocyte differentiation/activation and white adipocyte browning. Following the identification of candidate genes, we will knock out, constitutively and/or inducibly, both alleles of these genes in human PSC cells, producing a total loss of function. Following the in vitro phenotyping of the cells we will proceed to the in vivo validation of the functional properties/phenotype of human PSC derived brown/brite adipocytes (wild-type and loss of function) by transplanting these cells into mice. Using these reporter tools we will also perform in vitro pharmacological screening and in vivo validation of new compounds that stimulate BAT activation and WAT browning
Project acronym SynDiv
Project A nanophysics approach to synthetic cell division
Researcher (PI) Cornelis Dekker
Summary Imagine building a living cell from basic components, a vesicle filled with biomolecules that can sustain itself and reproduce into similar offspring. Can this be done? This proposal addresses the most tantalizing aspect: synthetic cell division. We aim to build liposomes (lipid vesicles enclosing an aqueous solution with proteins and DNA) that can spontaneously divide through a contractile protein ring at the vesicle perimeter. To realize this, we employ an experimental biophysics approach that addresses both the actual division and the prerequisite spatial control, with: 1. Cells in nanofabricated shapes. We will study cell-division proteins and DNA in live E.coli bacteria that are molded into user-defined arbitrary shapes and sizes. Clarifying the effects of cell shape will elucidate the guiding principles for the spatiotemporal organization of the cell-division machinery. 2. Proteins and DNA in nanofabricated chambers. We will use a bottom up approach to study the basic divisome components in vitro exploiting the full control provided by nanochambers. This will resolve the spatial organization of the fascinating patterns of Min proteins and chromatin that dictate the localization of the division ring. 3. Liposomes on chip. We will develop a chip-based technology to generate liposomes for exploring synthetic cell division. We will use both microfluidic constrictions and a biomimetic approach (encapsulation of divisome proteins such as FtsZ) to induce autonomous liposome splitting, thus enabling a simplified but tightly controlled form of synthetic cell division. To our knowledge, this nanofabrication-based approach to synthetic division is unique. We expect to be able to make important contributions to understanding cell division, and anticipate that on a 5-year scale we indeed can master synthetic division. We believe that our mix of nanophysics and synthetic biology is bound to yield deep insight into the biophysical underpinnings of cellular reproduction.
Imagine building a living cell from basic components, a vesicle filled with biomolecules that can sustain itself and reproduce into similar offspring. Can this be done? This proposal addresses the most tantalizing aspect: synthetic cell division. We aim to build liposomes (lipid vesicles enclosing an aqueous solution with proteins and DNA) that can spontaneously divide through a contractile protein ring at the vesicle perimeter. To realize this, we employ an experimental biophysics approach that addresses both the actual division and the prerequisite spatial control, with: 1. Cells in nanofabricated shapes. We will study cell-division proteins and DNA in live E.coli bacteria that are molded into user-defined arbitrary shapes and sizes. Clarifying the effects of cell shape will elucidate the guiding principles for the spatiotemporal organization of the cell-division machinery. 2. Proteins and DNA in nanofabricated chambers. We will use a bottom up approach to study the basic divisome components in vitro exploiting the full control provided by nanochambers. This will resolve the spatial organization of the fascinating patterns of Min proteins and chromatin that dictate the localization of the division ring. 3. Liposomes on chip. We will develop a chip-based technology to generate liposomes for exploring synthetic cell division. We will use both microfluidic constrictions and a biomimetic approach (encapsulation of divisome proteins such as FtsZ) to induce autonomous liposome splitting, thus enabling a simplified but tightly controlled form of synthetic cell division. To our knowledge, this nanofabrication-based approach to synthetic division is unique. We expect to be able to make important contributions to understanding cell division, and anticipate that on a 5-year scale we indeed can master synthetic division. We believe that our mix of nanophysics and synthetic biology is bound to yield deep insight into the biophysical underpinnings of cellular reproduction.
Project acronym TVOF
Project The values of French language and literature in the European Middle Ages
Researcher (PI) Simon Benjamin Gaunt
Summary Two questions about linguistic identity lie at the heart of this project. What is the relation historically between language and identity in Europe? How are cognate languages demarcated from each other? Normative models of national languages helped shape Europe. Yet they did not become hegemonic until the 19th century. Indeed, they were imposed (not always successfully) on a linguistic map of Europe more fluid and complex than most histories of national languages allow. In the Middle Ages multilingualism was common, as was the use of non-local languages, notably Latin, but also French. This project undertakes a revaluation of the nature and value of the use of French in Europe during a crucial period, 1100-1450, less in terms of its cultural prestige (the traditional focus of scholarship) than of its role as a supralocal, transnational language, particularly in Western Europe and the Eastern Mediterranean. The project fosters collaboration between, and cuts across, different intellectual and national scholarly traditions, drawing on expertise in codicology, critical theory, linguistics, literature, and philology; it involves scholars from a range of European countries and North America, entailing empirical research around a complex and widely disseminated textual tradition vital to medieval understandings of European history and identity, L'Histoire ancienne jusqu'à César. This case study will ground and stimulate broader speculative reflection on the two core questions concerning linguistic identity. While the project builds on prior critiques of the construction of, and investment in, national languages and literary traditions, it has a broad historical scope, and will offer an innovative, genuinely international perspective, in terms of both its object of study and method. Indeed, its final aim, through and beyond its consideration of French as a lingua franca, is to interrogate that language's role in the emergence of a European identity in the Middle Ages.
Two questions about linguistic identity lie at the heart of this project. What is the relation historically between language and identity in Europe? How are cognate languages demarcated from each other? Normative models of national languages helped shape Europe. Yet they did not become hegemonic until the 19th century. Indeed, they were imposed (not always successfully) on a linguistic map of Europe more fluid and complex than most histories of national languages allow. In the Middle Ages multilingualism was common, as was the use of non-local languages, notably Latin, but also French. This project undertakes a revaluation of the nature and value of the use of French in Europe during a crucial period, 1100-1450, less in terms of its cultural prestige (the traditional focus of scholarship) than of its role as a supralocal, transnational language, particularly in Western Europe and the Eastern Mediterranean. The project fosters collaboration between, and cuts across, different intellectual and national scholarly traditions, drawing on expertise in codicology, critical theory, linguistics, literature, and philology; it involves scholars from a range of European countries and North America, entailing empirical research around a complex and widely disseminated textual tradition vital to medieval understandings of European history and identity, L'Histoire ancienne jusqu'à César. This case study will ground and stimulate broader speculative reflection on the two core questions concerning linguistic identity. While the project builds on prior critiques of the construction of, and investment in, national languages and literary traditions, it has a broad historical scope, and will offer an innovative, genuinely international perspective, in terms of both its object of study and method. Indeed, its final aim, through and beyond its consideration of French as a lingua franca, is to interrogate that language's role in the emergence of a European identity in the Middle Ages.
Project acronym WATER
Project Probing the Structure and Dynamics of Water in its Various States
Researcher (PI) Anders Nilsson
Host Institution (HI) STOCKHOLMS UNIVERSITET
Summary We propose to address some of the most important outstanding questions for a microscopic understanding of water: What is the structure and dynamics of the hydrogen-bonding network that give rise to all the unique properties of water? How is the structure and dynamics affected by temperature, pressure and by perturbation through interaction with solutes and interfaces? Here we point to the opportunity to exploit the completely new avenues that the novel x-ray free-electron lasers open up for probing both structure and dynamics of water from hot temperatures down to the deeply supercooled regime where the anomalous properties become extreme. We plan to further develop fast cooling and ultrafast x-ray probing allowing access to below the homogeneous ice nucleation limit, to probe equilibrium dynamics through probe-probe techniques based on x-ray correlation spectroscopy, to access low-energy vibrational mode dynamics through THz pump and x-ray scattering probe and to transfer x-ray spectroscopies into the time domain. We will address one of the currently most debated issues related to a potential liquid-liquid transition and 2nd critical point in liquid water. The goal is to determine experimentally if water, as hypothesized in certain models, can really exist as two liquids, if there is reversible phase transition between the hypothesized liquids, evaluate if these hypothesized liquids can equilibrate on a time scale faster then the rate of ice nucleation and if there exists a critical point that can explain the fluctuations related to the diverging response functions. We will continue to critically investigate our proposed hypothesis that water at ambient temperature encompasses fluctuations around two local structures and that the dominating structure is a strongly distorted hydrogen bonded environment. We will investigate if these concepts can be used to describe the observed perturbations of water structure by solutes and interfaces.
We propose to address some of the most important outstanding questions for a microscopic understanding of water: What is the structure and dynamics of the hydrogen-bonding network that give rise to all the unique properties of water? How is the structure and dynamics affected by temperature, pressure and by perturbation through interaction with solutes and interfaces? Here we point to the opportunity to exploit the completely new avenues that the novel x-ray free-electron lasers open up for probing both structure and dynamics of water from hot temperatures down to the deeply supercooled regime where the anomalous properties become extreme. We plan to further develop fast cooling and ultrafast x-ray probing allowing access to below the homogeneous ice nucleation limit, to probe equilibrium dynamics through probe-probe techniques based on x-ray correlation spectroscopy, to access low-energy vibrational mode dynamics through THz pump and x-ray scattering probe and to transfer x-ray spectroscopies into the time domain. We will address one of the currently most debated issues related to a potential liquid-liquid transition and 2nd critical point in liquid water. The goal is to determine experimentally if water, as hypothesized in certain models, can really exist as two liquids, if there is reversible phase transition between the hypothesized liquids, evaluate if these hypothesized liquids can equilibrate on a time scale faster then the rate of ice nucleation and if there exists a critical point that can explain the fluctuations related to the diverging response functions. We will continue to critically investigate our proposed hypothesis that water at ambient temperature encompasses fluctuations around two local structures and that the dominating structure is a strongly distorted hydrogen bonded environment. We will investigate if these concepts can be used to describe the observed perturbations of water structure by solutes and interfaces.


Brighten your home office with these adorable Vancouver Island beeswax candles. Lightly scented with pine, juniper, and cedar wood essential oils, they'll make your office smell like a summer hike in the forest. Set of 2, the jade tea light doesn't have a label.