Project acronym 3DCellPhase-
Project In situ Structural Analysis of Molecular Crowding and Phase Separation
Researcher (PI) Julia MAHAMID
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Country Germany
Call Details Starting Grant (StG), LS1, ERC-2017-STG
Summary This proposal brings together two fields in biology, namely the emerging field of phase-separated assemblies in cell biology and state-of-the-art cellular cryo-electron tomography, to advance our understanding on a fundamental, yet illusive, question: the molecular organization of the cytoplasm.
Eukaryotes organize their biochemical reactions into functionally distinct compartments. Intriguingly, many, if not most, cellular compartments are not membrane enclosed. Rather, they assemble dynamically by phase separation, typically triggered upon a specific event. Despite significant progress on reconstituting such liquid-like assemblies in vitro, we lack information as to whether these compartments in vivo are indeed amorphous liquids, or whether they exhibit structural features such as gels or fibers. My recent work on sample preparation of cells for cryo-electron tomography, including cryo-focused ion beam thinning, guided by 3D correlative fluorescence microscopy, shows that we can now prepare site-specific ‘electron-transparent windows’ in suitable eukaryotic systems, which allow direct examination of structural features of cellular compartments in their cellular context. Here, we will use these techniques to elucidate the structural principles and cytoplasmic environment driving the dynamic assembly of two phase-separated compartments: Stress granules, which are RNA bodies that form rapidly in the cytoplasm upon cellular stress, and centrosomes, which are sites of microtubule nucleation. We will combine these studies with a quantitative description of the crowded nature of cytoplasm and of its local variations, to provide a direct readout of the impact of excluded volume on molecular assembly in living cells. Taken together, these studies will provide fundamental insights into the structural basis by which cells form biochemical compartments.
Summary
This proposal brings together two fields in biology, namely the emerging field of phase-separated assemblies in cell biology and state-of-the-art cellular cryo-electron tomography, to advance our understanding on a fundamental, yet illusive, question: the molecular organization of the cytoplasm.
Eukaryotes organize their biochemical reactions into functionally distinct compartments. Intriguingly, many, if not most, cellular compartments are not membrane enclosed. Rather, they assemble dynamically by phase separation, typically triggered upon a specific event. Despite significant progress on reconstituting such liquid-like assemblies in vitro, we lack information as to whether these compartments in vivo are indeed amorphous liquids, or whether they exhibit structural features such as gels or fibers. My recent work on sample preparation of cells for cryo-electron tomography, including cryo-focused ion beam thinning, guided by 3D correlative fluorescence microscopy, shows that we can now prepare site-specific ‘electron-transparent windows’ in suitable eukaryotic systems, which allow direct examination of structural features of cellular compartments in their cellular context. Here, we will use these techniques to elucidate the structural principles and cytoplasmic environment driving the dynamic assembly of two phase-separated compartments: Stress granules, which are RNA bodies that form rapidly in the cytoplasm upon cellular stress, and centrosomes, which are sites of microtubule nucleation. We will combine these studies with a quantitative description of the crowded nature of cytoplasm and of its local variations, to provide a direct readout of the impact of excluded volume on molecular assembly in living cells. Taken together, these studies will provide fundamental insights into the structural basis by which cells form biochemical compartments.
Max ERC Funding
1 228 125 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym ACROSS
Project Australasian Colonization Research: Origins of Seafaring to Sahul
Researcher (PI) Rosemary Helen FARR
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Country United Kingdom
Call Details Starting Grant (StG), SH6, ERC-2017-STG
Summary One of the most exciting research questions within archaeology is that of the peopling of Australasia by at least c.50,000 years ago. This represents some of the earliest evidence of modern human colonization outside Africa, yet, even at the greatest sea-level lowstand, this migration would have involved seafaring. It is the maritime nature of this dispersal which makes it so important to questions of technological, cognitive and social human development. These issues have traditionally been the preserve of archaeologists, but with a multidisciplinary approach that embraces cutting-edge marine geophysical, hydrodynamic and archaeogenetic analyses, we now have the opportunity to examine the When, Where, Who and How of the earliest seafaring in world history.
The voyage from Sunda (South East Asia) to Sahul (Australasia) provides evidence for the earliest ‘open water’ crossing in the world. A combination of the sparse number of early archaeological finds and the significant changes in the palaeolandscape and submergence of the broad north western Australian continental shelf, mean that little is known about the routes taken and what these crossings may have entailed.
This project will combine research of the submerged palaeolandscape of the continental shelf to refine our knowledge of the onshore/offshore environment, identify potential submerged prehistoric sites and enhance our understanding of the palaeoshoreline and tidal regime. This will be combined with archaeogenetic research targeting mtDNA and Y-chromosome data to resolve questions of demography and dating.
For the first time this project takes a truly multidisciplinary approach to address the colonization of Sahul, providing an unique opportunity to tackle some of the most important questions about human origins, the relationship between humans and the changing environment, population dynamics and migration, seafaring technology, social organisation and cognition.
Summary
One of the most exciting research questions within archaeology is that of the peopling of Australasia by at least c.50,000 years ago. This represents some of the earliest evidence of modern human colonization outside Africa, yet, even at the greatest sea-level lowstand, this migration would have involved seafaring. It is the maritime nature of this dispersal which makes it so important to questions of technological, cognitive and social human development. These issues have traditionally been the preserve of archaeologists, but with a multidisciplinary approach that embraces cutting-edge marine geophysical, hydrodynamic and archaeogenetic analyses, we now have the opportunity to examine the When, Where, Who and How of the earliest seafaring in world history.
The voyage from Sunda (South East Asia) to Sahul (Australasia) provides evidence for the earliest ‘open water’ crossing in the world. A combination of the sparse number of early archaeological finds and the significant changes in the palaeolandscape and submergence of the broad north western Australian continental shelf, mean that little is known about the routes taken and what these crossings may have entailed.
This project will combine research of the submerged palaeolandscape of the continental shelf to refine our knowledge of the onshore/offshore environment, identify potential submerged prehistoric sites and enhance our understanding of the palaeoshoreline and tidal regime. This will be combined with archaeogenetic research targeting mtDNA and Y-chromosome data to resolve questions of demography and dating.
For the first time this project takes a truly multidisciplinary approach to address the colonization of Sahul, providing an unique opportunity to tackle some of the most important questions about human origins, the relationship between humans and the changing environment, population dynamics and migration, seafaring technology, social organisation and cognition.
Max ERC Funding
1 134 928 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym ACTIVE_NEUROGENESIS
Project Activity-dependent signaling in radial glial cells and their neuronal progeny
Researcher (PI) Colin Akerman
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Starting Grant (StG), LS5, ERC-2009-StG
Summary A significant advance in the field of development has been the appreciation that radial glial cells are progenitors and give birth to neurons in the brain. In order to advance this exciting area of biology, we need approaches that combine structural and functional studies of these cells. This is reflected by the emerging realisation that dynamic interactions involving radial glia may be critical for the regulation of their proliferative behaviour. It has been observed that radial glia experience transient elevations in intracellular Ca2+ but the nature of these signals, and the information that they convey, is not known. The inability to observe these cells in vivo and over the course of their development has also meant that basic questions remain unexplored. For instance, how does the behaviour of a radial glial cell at one point in development, influence the final identity of its progeny? I propose to build a research team that will capitalise upon methods we have developed for observing individual radial glia and their progeny in an intact vertebrate nervous system. The visual system of Xenopus Laevis tadpoles offers non-invasive optical access to the brain, making time-lapse imaging of single cells feasible over minutes and weeks. The system s anatomy lends itself to techniques that measure the activity of the cells in a functional sensory network. We will use this to examine signalling mechanisms in radial glia and how a radial glial cell s experience influences its proliferative behaviour and the types of neuron it generates. We will also examine the interactions that continue between a radial glial cell and its daughter neurons. Finally, we will explore the relationships that exist within neuronal progeny derived from a single radial glial cell.
Summary
A significant advance in the field of development has been the appreciation that radial glial cells are progenitors and give birth to neurons in the brain. In order to advance this exciting area of biology, we need approaches that combine structural and functional studies of these cells. This is reflected by the emerging realisation that dynamic interactions involving radial glia may be critical for the regulation of their proliferative behaviour. It has been observed that radial glia experience transient elevations in intracellular Ca2+ but the nature of these signals, and the information that they convey, is not known. The inability to observe these cells in vivo and over the course of their development has also meant that basic questions remain unexplored. For instance, how does the behaviour of a radial glial cell at one point in development, influence the final identity of its progeny? I propose to build a research team that will capitalise upon methods we have developed for observing individual radial glia and their progeny in an intact vertebrate nervous system. The visual system of Xenopus Laevis tadpoles offers non-invasive optical access to the brain, making time-lapse imaging of single cells feasible over minutes and weeks. The system s anatomy lends itself to techniques that measure the activity of the cells in a functional sensory network. We will use this to examine signalling mechanisms in radial glia and how a radial glial cell s experience influences its proliferative behaviour and the types of neuron it generates. We will also examine the interactions that continue between a radial glial cell and its daughter neurons. Finally, we will explore the relationships that exist within neuronal progeny derived from a single radial glial cell.
Max ERC Funding
1 284 808 €
Duration
Start date: 2010-02-01, End date: 2015-01-31
Project acronym activeFly
Project Circuit mechanisms of self-movement estimation during walking
Researcher (PI) M Eugenia CHIAPPE
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Country Portugal
Call Details Starting Grant (StG), LS5, ERC-2017-STG
Summary The brain evolves, develops, and operates in the context of animal movements. As a consequence, fundamental brain functions such as spatial perception and motor control critically depend on the precise knowledge of the ongoing body motion. An accurate internal estimate of self-movement is thought to emerge from sensorimotor integration; nonetheless, which circuits perform this internal estimation, and exactly how motor-sensory coordination is implemented within these circuits are basic questions that remain to be poorly understood. There is growing evidence suggesting that, during locomotion, motor-related and visual signals interact at early stages of visual processing. In mammals, however, it is not clear what the function of this interaction is. Recently, we have shown that a population of Drosophila optic-flow processing neurons —neurons that are sensitive to self-generated visual flow, receives convergent visual and walking-related signals to form a faithful representation of the fly’s walking movements. Leveraging from these results, and combining quantitative analysis of behavior with physiology, optogenetics, and modelling, we propose to investigate circuit mechanisms of self-movement estimation during walking. We will:1) use cell specific manipulations to identify what cells are necessary to generate the motor-related activity in the population of visual neurons, 2) record from the identified neurons and correlate their activity with specific locomotor parameters, and 3) perturb the activity of different cell-types within the identified circuits to test their role in the dynamics of the visual neurons, and on the fly’s walking behavior. These experiments will establish unprecedented causal relationships among neural activity, the formation of an internal representation, and locomotor control. The identified sensorimotor principles will establish a framework that can be tested in other scenarios or animal systems with implications both in health and disease.
Summary
The brain evolves, develops, and operates in the context of animal movements. As a consequence, fundamental brain functions such as spatial perception and motor control critically depend on the precise knowledge of the ongoing body motion. An accurate internal estimate of self-movement is thought to emerge from sensorimotor integration; nonetheless, which circuits perform this internal estimation, and exactly how motor-sensory coordination is implemented within these circuits are basic questions that remain to be poorly understood. There is growing evidence suggesting that, during locomotion, motor-related and visual signals interact at early stages of visual processing. In mammals, however, it is not clear what the function of this interaction is. Recently, we have shown that a population of Drosophila optic-flow processing neurons —neurons that are sensitive to self-generated visual flow, receives convergent visual and walking-related signals to form a faithful representation of the fly’s walking movements. Leveraging from these results, and combining quantitative analysis of behavior with physiology, optogenetics, and modelling, we propose to investigate circuit mechanisms of self-movement estimation during walking. We will:1) use cell specific manipulations to identify what cells are necessary to generate the motor-related activity in the population of visual neurons, 2) record from the identified neurons and correlate their activity with specific locomotor parameters, and 3) perturb the activity of different cell-types within the identified circuits to test their role in the dynamics of the visual neurons, and on the fly’s walking behavior. These experiments will establish unprecedented causal relationships among neural activity, the formation of an internal representation, and locomotor control. The identified sensorimotor principles will establish a framework that can be tested in other scenarios or animal systems with implications both in health and disease.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym AfricanNeo
Project The African Neolithic: A genetic perspective
Researcher (PI) Carina SCHLEBUSCH
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), SH6, ERC-2017-STG
Summary The spread of farming practices in various parts of the world had a marked influence on how humans live today and how we are distributed around the globe. Around 10,000 years ago, warmer conditions lead to population increases, coinciding with the invention of farming in several places around the world. Archaeological evidence attest to the spread of these practices to neighboring regions. In many cases this lead to whole continents being converted from hunter-gatherer to farming societies. It is however difficult to see from archaeological records if only the farming culture spread to other places or whether the farming people themselves migrated. Investigating patterns of genetic variation for farming populations and for remaining hunter-gatherer groups can help to resolve questions on population movements co-occurring with the spread of farming practices. It can further shed light on the routes of migration and dates when migrants arrived.
The spread of farming to Europe has been thoroughly investigated in the fields of archaeology, linguistics and genetics, while on other continents these events have been less investigated. In Africa, mainly linguistic and archaeological studies have attempted to elucidate the spread of farming and herding practices. I propose to investigate the movement of farmer and pastoral groups in Africa, by typing densely spaced genome-wide variant positions in a large number of African populations. The data will be used to infer how farming and pastoralism was introduced to various regions, where the incoming people originated from and when these (potential) population movements occurred. Through this study, the Holocene history of Africa will be revealed and placed into a global context of migration, mobility and cultural transitions. Additionally the study will give due credence to one of the largest Neolithic expansion events, the Bantu-expansion, which caused a pronounced change in the demographic landscape of the African continent
Summary
The spread of farming practices in various parts of the world had a marked influence on how humans live today and how we are distributed around the globe. Around 10,000 years ago, warmer conditions lead to population increases, coinciding with the invention of farming in several places around the world. Archaeological evidence attest to the spread of these practices to neighboring regions. In many cases this lead to whole continents being converted from hunter-gatherer to farming societies. It is however difficult to see from archaeological records if only the farming culture spread to other places or whether the farming people themselves migrated. Investigating patterns of genetic variation for farming populations and for remaining hunter-gatherer groups can help to resolve questions on population movements co-occurring with the spread of farming practices. It can further shed light on the routes of migration and dates when migrants arrived.
The spread of farming to Europe has been thoroughly investigated in the fields of archaeology, linguistics and genetics, while on other continents these events have been less investigated. In Africa, mainly linguistic and archaeological studies have attempted to elucidate the spread of farming and herding practices. I propose to investigate the movement of farmer and pastoral groups in Africa, by typing densely spaced genome-wide variant positions in a large number of African populations. The data will be used to infer how farming and pastoralism was introduced to various regions, where the incoming people originated from and when these (potential) population movements occurred. Through this study, the Holocene history of Africa will be revealed and placed into a global context of migration, mobility and cultural transitions. Additionally the study will give due credence to one of the largest Neolithic expansion events, the Bantu-expansion, which caused a pronounced change in the demographic landscape of the African continent
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym AFRIVAL
Project African river basins: catchment-scale carbon fluxes and transformations
Researcher (PI) Steven Bouillon
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Country Belgium
Call Details Starting Grant (StG), PE10, ERC-2009-StG
Summary This proposal wishes to fundamentally improve our understanding of the role of tropical freshwater ecosystems in carbon (C) cycling on the catchment scale. It uses an unprecedented combination of state-of-the-art proxies such as stable isotope, 14C and biomarker signatures to characterize organic matter, radiogenic isotope signatures to determine particle residence times, as well as field measurements of relevant biogeochemical processes. We focus on tropical systems since there is a striking lack of data on such systems, even though riverine C transport is thought to be disproportionately high in tropical areas. Furthermore, the presence of landscape-scale contrasts in vegetation (in particular, C3 vs. C4 plants) are an important asset in the use of stable isotopes as natural tracers of C cycling processes on this scale. Freshwater ecosystems are an important component in the global C cycle, and the primary link between terrestrial and marine ecosystems. Recent estimates indicate that ~2 Pg C y-1 (Pg=Petagram) enter freshwater systems, i.e., about twice the estimated global terrestrial C sink. More than half of this is thought to be remineralized before it reaches the coastal zone, and for the Amazon basin this has even been suggested to be ~90% of the lateral C inputs. The question how general these patterns are is a matter of debate, and assessing the mechanisms determining the degree of processing versus transport of organic carbon in lakes and river systems is critical to further constrain their role in the global C cycle. This proposal provides an interdisciplinary approach to describe and quantify catchment-scale C transport and cycling in tropical river basins. Besides conceptual and methodological advances, and a significant expansion of our dataset on C processes in such systems, new data gathered in this project are likely to provide exciting and novel hypotheses on the functioning of freshwater systems and their linkage to the terrestrial C budget.
Summary
This proposal wishes to fundamentally improve our understanding of the role of tropical freshwater ecosystems in carbon (C) cycling on the catchment scale. It uses an unprecedented combination of state-of-the-art proxies such as stable isotope, 14C and biomarker signatures to characterize organic matter, radiogenic isotope signatures to determine particle residence times, as well as field measurements of relevant biogeochemical processes. We focus on tropical systems since there is a striking lack of data on such systems, even though riverine C transport is thought to be disproportionately high in tropical areas. Furthermore, the presence of landscape-scale contrasts in vegetation (in particular, C3 vs. C4 plants) are an important asset in the use of stable isotopes as natural tracers of C cycling processes on this scale. Freshwater ecosystems are an important component in the global C cycle, and the primary link between terrestrial and marine ecosystems. Recent estimates indicate that ~2 Pg C y-1 (Pg=Petagram) enter freshwater systems, i.e., about twice the estimated global terrestrial C sink. More than half of this is thought to be remineralized before it reaches the coastal zone, and for the Amazon basin this has even been suggested to be ~90% of the lateral C inputs. The question how general these patterns are is a matter of debate, and assessing the mechanisms determining the degree of processing versus transport of organic carbon in lakes and river systems is critical to further constrain their role in the global C cycle. This proposal provides an interdisciplinary approach to describe and quantify catchment-scale C transport and cycling in tropical river basins. Besides conceptual and methodological advances, and a significant expansion of our dataset on C processes in such systems, new data gathered in this project are likely to provide exciting and novel hypotheses on the functioning of freshwater systems and their linkage to the terrestrial C budget.
Max ERC Funding
1 745 262 €
Duration
Start date: 2009-10-01, End date: 2014-09-30
Project acronym Aftermath
Project THE AFTERMATH OF THE EAST ASIAN WAR OF 1592-1598.
Researcher (PI) Rebekah CLEMENTS
Host Institution (HI) UNIVERSIDAD AUTONOMA DE BARCELONA
Country Spain
Call Details Starting Grant (StG), SH6, ERC-2017-STG
Summary Aftermath seeks to understand the legacy of the East Asian War of 1592-1598. This conflict involved over 500,000 combatants from Japan, China, and Korea; up to 100,000 Korean civilians were abducted to Japan. The war caused momentous demographic upheaval and widespread destruction, but also had long-lasting cultural impact as a result of the removal to Japan of Korean technology and skilled labourers. The conflict and its aftermath bear striking parallels to events in East Asia during World War 2, and memories of the 16th century war remain deeply resonant in the region. However, the war and its immediate aftermath are also significant because they occurred at the juncture of periods often characterized as “medieval” and “early modern” in the East Asian case. What were the implications for the social, economic, and cultural contours of early modern East Asia? What can this conflict tell us about war “aftermath” across historical periods and about such periodization itself? There is little Western scholarship on the war and few studies in any language cross linguistic, disciplinary, and national boundaries to achieve a regional perspective that reflects the interconnected history of East Asia. Aftermath will radically alter our understanding of the region’s history by providing the first analysis of the state of East Asia as a result of the war. The focus will be on the period up to the middle of the 17th century, but not precluding ongoing effects. The team, with expertise covering Japan, Korea, and China, will investigate three themes: the movement of people and demographic change, the impact on the natural environment, and technological diffusion. The project will be the first large scale investigation to use Japanese, Korean, and Chinese sources to understand the war’s aftermath. It will broaden understandings of the early modern world, and push the boundaries of war legacy studies by exploring the meanings of “aftermath” in the early modern East Asian context.
Summary
Aftermath seeks to understand the legacy of the East Asian War of 1592-1598. This conflict involved over 500,000 combatants from Japan, China, and Korea; up to 100,000 Korean civilians were abducted to Japan. The war caused momentous demographic upheaval and widespread destruction, but also had long-lasting cultural impact as a result of the removal to Japan of Korean technology and skilled labourers. The conflict and its aftermath bear striking parallels to events in East Asia during World War 2, and memories of the 16th century war remain deeply resonant in the region. However, the war and its immediate aftermath are also significant because they occurred at the juncture of periods often characterized as “medieval” and “early modern” in the East Asian case. What were the implications for the social, economic, and cultural contours of early modern East Asia? What can this conflict tell us about war “aftermath” across historical periods and about such periodization itself? There is little Western scholarship on the war and few studies in any language cross linguistic, disciplinary, and national boundaries to achieve a regional perspective that reflects the interconnected history of East Asia. Aftermath will radically alter our understanding of the region’s history by providing the first analysis of the state of East Asia as a result of the war. The focus will be on the period up to the middle of the 17th century, but not precluding ongoing effects. The team, with expertise covering Japan, Korea, and China, will investigate three themes: the movement of people and demographic change, the impact on the natural environment, and technological diffusion. The project will be the first large scale investigation to use Japanese, Korean, and Chinese sources to understand the war’s aftermath. It will broaden understandings of the early modern world, and push the boundaries of war legacy studies by exploring the meanings of “aftermath” in the early modern East Asian context.
Max ERC Funding
1 444 980 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym AGEnTh
Project Atomic Gauge and Entanglement Theories
Researcher (PI) Marcello DALMONTE
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Country Italy
Call Details Starting Grant (StG), PE2, ERC-2017-STG
Summary AGEnTh is an interdisciplinary proposal which aims at theoretically investigating atomic many-body systems (cold atoms and trapped ions) in close connection to concepts from quantum information, condensed matter, and high energy physics. The main goals of this programme are to:
I) Find to scalable schemes for the measurements of entanglement properties, and in particular entanglement spectra, by proposing a shifting paradigm to access entanglement focused on entanglement Hamiltonians and field theories instead of probing density matrices;
II) Show how atomic gauge theories (including dynamical gauge fields) are ideal candidates for the realization of long-sought, highly-entangled states of matter, in particular topological superconductors supporting parafermion edge modes, and novel classes of quantum spin liquids emerging from clustering;
III) Develop new implementation strategies for the realization of gauge symmetries of paramount importance, such as discrete and SU(N)xSU(2)xU(1) groups, and establish a theoretical framework for the understanding of atomic physics experiments within the light-from-chaos scenario pioneered in particle physics.
These objectives are at the cutting-edge of fundamental science, and represent a coherent effort aimed at underpinning unprecedented regimes of strongly interacting quantum matter by addressing the basic aspects of probing, many-body physics, and implementations. The results are expected to (i) build up and establish qualitatively new synergies between the aforementioned communities, and (ii) stimulate an intense theoretical and experimental activity focused on both entanglement and atomic gauge theories.
In order to achieve those, AGEnTh builds: (1) on my background working at the interface between atomic physics and quantum optics from one side, and many-body theory on the other, and (2) on exploratory studies which I carried out to mitigate the conceptual risks associated with its high-risk/high-gain goals.
Summary
AGEnTh is an interdisciplinary proposal which aims at theoretically investigating atomic many-body systems (cold atoms and trapped ions) in close connection to concepts from quantum information, condensed matter, and high energy physics. The main goals of this programme are to:
I) Find to scalable schemes for the measurements of entanglement properties, and in particular entanglement spectra, by proposing a shifting paradigm to access entanglement focused on entanglement Hamiltonians and field theories instead of probing density matrices;
II) Show how atomic gauge theories (including dynamical gauge fields) are ideal candidates for the realization of long-sought, highly-entangled states of matter, in particular topological superconductors supporting parafermion edge modes, and novel classes of quantum spin liquids emerging from clustering;
III) Develop new implementation strategies for the realization of gauge symmetries of paramount importance, such as discrete and SU(N)xSU(2)xU(1) groups, and establish a theoretical framework for the understanding of atomic physics experiments within the light-from-chaos scenario pioneered in particle physics.
These objectives are at the cutting-edge of fundamental science, and represent a coherent effort aimed at underpinning unprecedented regimes of strongly interacting quantum matter by addressing the basic aspects of probing, many-body physics, and implementations. The results are expected to (i) build up and establish qualitatively new synergies between the aforementioned communities, and (ii) stimulate an intense theoretical and experimental activity focused on both entanglement and atomic gauge theories.
In order to achieve those, AGEnTh builds: (1) on my background working at the interface between atomic physics and quantum optics from one side, and many-body theory on the other, and (2) on exploratory studies which I carried out to mitigate the conceptual risks associated with its high-risk/high-gain goals.
Max ERC Funding
1 055 317 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym AltCheM
Project In vivo functional screens to decipher mechanisms of stochastically- and mutationally-induced chemoresistance in Acute Myeloid Leukemia
Researcher (PI) Alexandre PUISSANT
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Country France
Call Details Starting Grant (StG), LS4, ERC-2017-STG
Summary Acute Myeloid Leukemia (AML), the most common leukemia diagnosed in adults, represents the paradigm of resistance to front-line therapies in hematology. Indeed, AML is so genetically complex that only few targeted therapies are currently tested in this disease and chemotherapy remains the only standard treatment for AML since the past four decades. Despite an initial sustained remission achieved by chemotherapeutic agents, almost all patients relapse with a chemoresistant minimal residual disease (MRD). The goal of my proposal is to characterize the still poorly understood biological mechanisms underlying persistence and emergence of MRD.
MRD is the consequence of the re-expansion of leukemia-initiating cells that are intrinsically more resistant to chemotherapy. This cell fraction may be stochastically more prone to survive front-line therapy regardless of their mutational status (the stochastic model), or genetically predetermined to resist by virtue of a collection of chemoprotective mutations (the mutational model).
I have already generated in mice, by consecutive rounds of chemotherapy, a stochastic MLL-AF9-driven chemoresistance model that I examined by RNA-sequencing. I will pursue the comprehensive cell autonomous and cell non-autonomous characterization of this chemoresistant AML disease using whole-exome and ChIP-sequencing.
To establish a mutationally-induced chemoresistant mouse model, I will conduct an innovative in vivo screen using pooled mutant open reading frame and shRNA libraries in order to predict which combinations of mutations, among those already known in AML, actively promote chemoresistance.
Finally, by combining genomic profiling and in vivo shRNA screening experiments, I will decipher the molecular mechanisms and identify the functional effectors of these two modes of resistance. Ultimately, I will then be able to firmly establish the fundamental relevance of the stochastic and/or the mutational model of chemoresistance for MRD genesis.
Summary
Acute Myeloid Leukemia (AML), the most common leukemia diagnosed in adults, represents the paradigm of resistance to front-line therapies in hematology. Indeed, AML is so genetically complex that only few targeted therapies are currently tested in this disease and chemotherapy remains the only standard treatment for AML since the past four decades. Despite an initial sustained remission achieved by chemotherapeutic agents, almost all patients relapse with a chemoresistant minimal residual disease (MRD). The goal of my proposal is to characterize the still poorly understood biological mechanisms underlying persistence and emergence of MRD.
MRD is the consequence of the re-expansion of leukemia-initiating cells that are intrinsically more resistant to chemotherapy. This cell fraction may be stochastically more prone to survive front-line therapy regardless of their mutational status (the stochastic model), or genetically predetermined to resist by virtue of a collection of chemoprotective mutations (the mutational model).
I have already generated in mice, by consecutive rounds of chemotherapy, a stochastic MLL-AF9-driven chemoresistance model that I examined by RNA-sequencing. I will pursue the comprehensive cell autonomous and cell non-autonomous characterization of this chemoresistant AML disease using whole-exome and ChIP-sequencing.
To establish a mutationally-induced chemoresistant mouse model, I will conduct an innovative in vivo screen using pooled mutant open reading frame and shRNA libraries in order to predict which combinations of mutations, among those already known in AML, actively promote chemoresistance.
Finally, by combining genomic profiling and in vivo shRNA screening experiments, I will decipher the molecular mechanisms and identify the functional effectors of these two modes of resistance. Ultimately, I will then be able to firmly establish the fundamental relevance of the stochastic and/or the mutational model of chemoresistance for MRD genesis.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym AMPLITUDES
Project Manifesting the Simplicity of Scattering Amplitudes
Researcher (PI) Jacob BOURJAILY
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), PE2, ERC-2017-STG
Summary I propose a program of research that may forever change the way that we understand and use quantum field theory to make predictions for experiment. This will be achieved through the advancement of new, constructive frameworks to determine and represent scattering amplitudes in perturbation theory in terms that depend only on observable quantities, make manifest (all) the symmetries of the theory, and which can be efficiently evaluated while minimally spoiling the underlying simplicity of predictions. My research has already led to the discovery and development of several approaches of this kind.
This proposal describes the specific steps required to extend these ideas to more general theories and to higher orders of perturbation theory. Specifically, the plan of research I propose consists of three concrete goals: to fully characterize the discontinuities of loop amplitudes (`on-shell functions') for a broad class of theories; to develop powerful new representations of loop amplitude {\it integrands}, making manifest as much simplicity as possible; and to develop new techniques for loop amplitude {integration} that are compatible with and preserve the symmetries of observable quantities.
Progress toward any one of these objectives would have important theoretical implications and valuable practical applications. In combination, this proposal has the potential to significantly advance the state of the art for both our theoretical understanding and our computational reach for making predictions for experiment.
To achieve these goals, I will pursue a data-driven, `phenomenological' approach—involving the construction of new computational tools, developed in pursuit of concrete computational targets. For this work, my suitability and expertise is amply demonstrated by my research. I have not only played a key role in many of the most important theoretical developments in the past decade, but I have personally built the most powerful computational tools for their
Summary
I propose a program of research that may forever change the way that we understand and use quantum field theory to make predictions for experiment. This will be achieved through the advancement of new, constructive frameworks to determine and represent scattering amplitudes in perturbation theory in terms that depend only on observable quantities, make manifest (all) the symmetries of the theory, and which can be efficiently evaluated while minimally spoiling the underlying simplicity of predictions. My research has already led to the discovery and development of several approaches of this kind.
This proposal describes the specific steps required to extend these ideas to more general theories and to higher orders of perturbation theory. Specifically, the plan of research I propose consists of three concrete goals: to fully characterize the discontinuities of loop amplitudes (`on-shell functions') for a broad class of theories; to develop powerful new representations of loop amplitude {\it integrands}, making manifest as much simplicity as possible; and to develop new techniques for loop amplitude {integration} that are compatible with and preserve the symmetries of observable quantities.
Progress toward any one of these objectives would have important theoretical implications and valuable practical applications. In combination, this proposal has the potential to significantly advance the state of the art for both our theoretical understanding and our computational reach for making predictions for experiment.
To achieve these goals, I will pursue a data-driven, `phenomenological' approach—involving the construction of new computational tools, developed in pursuit of concrete computational targets. For this work, my suitability and expertise is amply demonstrated by my research. I have not only played a key role in many of the most important theoretical developments in the past decade, but I have personally built the most powerful computational tools for their
Max ERC Funding
1 499 695 €
Duration
Start date: 2018-02-01, End date: 2023-01-31