Project acronym 1D-Engine
Project 1D-electrons coupled to dissipation: a novel approach for understanding and engineering superconducting materials and devices
Researcher (PI) Adrian KANTIAN
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary Correlated electrons are at the forefront of condensed matter theory. Interacting quasi-1D electrons have seen vast progress in analytical and numerical theory, and thus in fundamental understanding and quantitative prediction. Yet, in the 1D limit fluctuations preclude important technological use, particularly of superconductors. In contrast, high-Tc superconductors in 2D/3D are not precluded by fluctuations, but lack a fundamental theory, making prediction and engineering of their properties, a major goal in physics, very difficult. This project aims to combine the advantages of both areas by making major progress in the theory of quasi-1D electrons coupled to an electron bath, in part building on recent breakthroughs (with the PIs extensive involvement) in simulating 1D and 2D electrons with parallelized density matrix renormalization group (pDMRG) numerics. Such theory will fundamentally advance the study of open electron systems, and show how to use 1D materials as elements of new superconducting (SC) devices and materials: 1) It will enable a new state of matter, 1D electrons with true SC order. Fluctuations from the electronic liquid, such as graphene, could also enable nanoscale wires to appear SC at high temperatures. 2) A new approach for the deliberate engineering of a high-Tc superconductor. In 1D, how electrons pair by repulsive interactions is understood and can be predicted. Stabilization by reservoir - formed by a parallel array of many such 1D systems - offers a superconductor for which all factors setting Tc are known and can be optimized. 3) Many existing superconductors with repulsive electron pairing, all presently not understood, can be cast as 1D electrons coupled to a bath. Developing chain-DMFT theory based on pDMRG will allow these materials SC properties to be simulated and understood for the first time. 4) The insights gained will be translated to 2D superconductors to study how they could be enhanced by contact with electronic liquids.
Summary
Correlated electrons are at the forefront of condensed matter theory. Interacting quasi-1D electrons have seen vast progress in analytical and numerical theory, and thus in fundamental understanding and quantitative prediction. Yet, in the 1D limit fluctuations preclude important technological use, particularly of superconductors. In contrast, high-Tc superconductors in 2D/3D are not precluded by fluctuations, but lack a fundamental theory, making prediction and engineering of their properties, a major goal in physics, very difficult. This project aims to combine the advantages of both areas by making major progress in the theory of quasi-1D electrons coupled to an electron bath, in part building on recent breakthroughs (with the PIs extensive involvement) in simulating 1D and 2D electrons with parallelized density matrix renormalization group (pDMRG) numerics. Such theory will fundamentally advance the study of open electron systems, and show how to use 1D materials as elements of new superconducting (SC) devices and materials: 1) It will enable a new state of matter, 1D electrons with true SC order. Fluctuations from the electronic liquid, such as graphene, could also enable nanoscale wires to appear SC at high temperatures. 2) A new approach for the deliberate engineering of a high-Tc superconductor. In 1D, how electrons pair by repulsive interactions is understood and can be predicted. Stabilization by reservoir - formed by a parallel array of many such 1D systems - offers a superconductor for which all factors setting Tc are known and can be optimized. 3) Many existing superconductors with repulsive electron pairing, all presently not understood, can be cast as 1D electrons coupled to a bath. Developing chain-DMFT theory based on pDMRG will allow these materials SC properties to be simulated and understood for the first time. 4) The insights gained will be translated to 2D superconductors to study how they could be enhanced by contact with electronic liquids.
Max ERC Funding
1 491 013 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym Born-Immune
Project Shaping of the Human Immune System by Primal Environmental Exposures In the Newborn Child
Researcher (PI) Klas Erik Petter Brodin
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS6, ERC-2015-STG
Summary Immune systems are highly variable, but the sources of this variation are poorly understood. Genetic variation only explains a minor fraction of this, and we are unable to accurately predict the risk of immune mediated disease or severe infection in any given individual. I recently found that immune cells and proteins in healthy twins vary because of non-heritable influences (infections, vaccines, microbiota etc.), with only minor influences from heritable factors (Brodin, et al, Cell 2015). When and how such environmental influences shape our immune system is now important to understand. Birth represents the most transformational change in environment during the life of any individual. I propose, that environmental influences at birth, and during the first months of life could be particularly influential by imprinting on the regulatory mechanisms forming in the developing immune system. Adaptive changes in immune cell frequencies and functional states induced by early-life exposures could determine both the immune competence of the newborn, but potentially also its long-term trajectory towards immunological health or disease. Here, I propose a study of 1000 newborn children, followed longitudinally during their first 1000 days of life. By monitoring immune profiles and recording many environmental influences, we hope to understand how early life exposures can influence human immune system development. We have established a new assay based on Mass Cytometry and necessary data analysis tools (Brodin, et al, PNAS 2014), to simultaneously monitor the frequencies, phenotypes and functional states of more than 200 blood immune cell populations from only 100 microliters of blood. By monitoring environmental influences at regular follow-up visits, by questionnaires, serum measurements of infection, and gut microbiome sequencing, we aim to provide the most comprehensive analysis to date of immune system development in newborn children.
Summary
Immune systems are highly variable, but the sources of this variation are poorly understood. Genetic variation only explains a minor fraction of this, and we are unable to accurately predict the risk of immune mediated disease or severe infection in any given individual. I recently found that immune cells and proteins in healthy twins vary because of non-heritable influences (infections, vaccines, microbiota etc.), with only minor influences from heritable factors (Brodin, et al, Cell 2015). When and how such environmental influences shape our immune system is now important to understand. Birth represents the most transformational change in environment during the life of any individual. I propose, that environmental influences at birth, and during the first months of life could be particularly influential by imprinting on the regulatory mechanisms forming in the developing immune system. Adaptive changes in immune cell frequencies and functional states induced by early-life exposures could determine both the immune competence of the newborn, but potentially also its long-term trajectory towards immunological health or disease. Here, I propose a study of 1000 newborn children, followed longitudinally during their first 1000 days of life. By monitoring immune profiles and recording many environmental influences, we hope to understand how early life exposures can influence human immune system development. We have established a new assay based on Mass Cytometry and necessary data analysis tools (Brodin, et al, PNAS 2014), to simultaneously monitor the frequencies, phenotypes and functional states of more than 200 blood immune cell populations from only 100 microliters of blood. By monitoring environmental influences at regular follow-up visits, by questionnaires, serum measurements of infection, and gut microbiome sequencing, we aim to provide the most comprehensive analysis to date of immune system development in newborn children.
Max ERC Funding
1 422 339 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym CAAXPROCESSINGHUMDIS
Project CAAX Protein Processing in Human DIsease: From Cancer to Progeria
Researcher (PI) Martin Olof Bergö
Host Institution (HI) GOETEBORGS UNIVERSITET
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary My objective is to understand the physiologic and medical importance of the posttranslational processing of CAAX proteins (e.g., K-RAS and prelamin A) and to define the suitability of the CAAX protein processing enzymes as therapeutic targets for the treatment of cancer and progeria. CAAX proteins undergo three posttranslational processing steps at a carboxyl-terminal CAAX motif. These processing steps, which are mediated by four different enzymes (FTase, GGTase-I, RCE1, and ICMT), increase the hydrophobicity of the carboxyl terminus of the protein and thereby facilitate interactions with membrane surfaces. Somatic mutations in K-RAS deregulate cell growth and are etiologically involved in the pathogenesis of many forms of cancer. A mutation in prelamin A causes Hutchinson-Gilford progeria syndrome—a pediatric progeroid syndrome associated with misshaped cell nuclei and a host of aging-like disease phenotypes. One strategy to render the mutant K-RAS and prelamin A less harmful is to interfere with their ability to bind to membrane surfaces (e.g., the plasma membrane and the nuclear envelope). This could be accomplished by inhibiting the enzymes that modify the CAAX motif. My Specific Aims are: (1) To define the suitability of the CAAX processing enzymes as therapeutic targets in the treatment of K-RAS-induced lung cancer and leukemia; and (2) To test the hypothesis that inactivation of FTase or ICMT will ameliorate disease phenotypes of progeria. I have developed genetic strategies to produce lung cancer or leukemia in mice by activating an oncogenic K-RAS and simultaneously inactivating different CAAX processing enzymes. I will also inactivate several CAAX processing enzymes in mice with progeria—both before the emergence of phenotypes and after the development of advanced disease phenotypes. These experiments should reveal whether the absence of the different CAAX processing enzymes affects the onset, progression, or regression of cancer and progeria.
Summary
My objective is to understand the physiologic and medical importance of the posttranslational processing of CAAX proteins (e.g., K-RAS and prelamin A) and to define the suitability of the CAAX protein processing enzymes as therapeutic targets for the treatment of cancer and progeria. CAAX proteins undergo three posttranslational processing steps at a carboxyl-terminal CAAX motif. These processing steps, which are mediated by four different enzymes (FTase, GGTase-I, RCE1, and ICMT), increase the hydrophobicity of the carboxyl terminus of the protein and thereby facilitate interactions with membrane surfaces. Somatic mutations in K-RAS deregulate cell growth and are etiologically involved in the pathogenesis of many forms of cancer. A mutation in prelamin A causes Hutchinson-Gilford progeria syndrome—a pediatric progeroid syndrome associated with misshaped cell nuclei and a host of aging-like disease phenotypes. One strategy to render the mutant K-RAS and prelamin A less harmful is to interfere with their ability to bind to membrane surfaces (e.g., the plasma membrane and the nuclear envelope). This could be accomplished by inhibiting the enzymes that modify the CAAX motif. My Specific Aims are: (1) To define the suitability of the CAAX processing enzymes as therapeutic targets in the treatment of K-RAS-induced lung cancer and leukemia; and (2) To test the hypothesis that inactivation of FTase or ICMT will ameliorate disease phenotypes of progeria. I have developed genetic strategies to produce lung cancer or leukemia in mice by activating an oncogenic K-RAS and simultaneously inactivating different CAAX processing enzymes. I will also inactivate several CAAX processing enzymes in mice with progeria—both before the emergence of phenotypes and after the development of advanced disease phenotypes. These experiments should reveal whether the absence of the different CAAX processing enzymes affects the onset, progression, or regression of cancer and progeria.
Max ERC Funding
1 689 600 €
Duration
Start date: 2008-06-01, End date: 2013-05-31
Project acronym CACTUS
Project developmental social Cognition and ACTion UnderStanding
Researcher (PI) Kjell Gustaf Gredebäck
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), SH4, ERC-2012-StG_20111124
Summary Humans are social creatures throughout life. This proposal aims to advance our knowledge of the mechanisms that mediate understanding of others’ actions from a developmental perspective. A special emphasis will be devoted to mirror neuron and teleological frameworks. The former framework focuses on reciprocal motor activation during action execution and observation whereas the later framework emphasizes the application of abstract principles to observed events. The mechanisms that guide both processes will be investigated in isolation, but special attention will also be devoted to understanding how these diverse forms of action understanding jointly contribute to action understanding. The project encompasses three essential research objectives, illustrated by three research questions. How do mirror neuron and teleological processes influence action understanding? How does action understanding enable social action evaluation (empathy and pro-social preferences)? How is action understanding expressed during real-life social interactions? These questions will be addressed by presenting infants and toddlers with social events of varying complexity (from simple actions and animated sequences to complex everyday social events), relating empirical findings to predictions derived from the teleological and motor cognitive frameworks. The overarching aim is to provide a computational model of early emerging social cognitive capabilities, with a focus on action understanding and action evaluation, while passively observing others and while partaking in social interactions with others.
Summary
Humans are social creatures throughout life. This proposal aims to advance our knowledge of the mechanisms that mediate understanding of others’ actions from a developmental perspective. A special emphasis will be devoted to mirror neuron and teleological frameworks. The former framework focuses on reciprocal motor activation during action execution and observation whereas the later framework emphasizes the application of abstract principles to observed events. The mechanisms that guide both processes will be investigated in isolation, but special attention will also be devoted to understanding how these diverse forms of action understanding jointly contribute to action understanding. The project encompasses three essential research objectives, illustrated by three research questions. How do mirror neuron and teleological processes influence action understanding? How does action understanding enable social action evaluation (empathy and pro-social preferences)? How is action understanding expressed during real-life social interactions? These questions will be addressed by presenting infants and toddlers with social events of varying complexity (from simple actions and animated sequences to complex everyday social events), relating empirical findings to predictions derived from the teleological and motor cognitive frameworks. The overarching aim is to provide a computational model of early emerging social cognitive capabilities, with a focus on action understanding and action evaluation, while passively observing others and while partaking in social interactions with others.
Max ERC Funding
1 498 920 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym ELECTRONOPERA
Project Electron dynamics to the Attosecond time scale and Angstrom length scale on low dimensional structures in Operation
Researcher (PI) Anders Mikkelsen
Host Institution (HI) LUNDS UNIVERSITET
Call Details Starting Grant (StG), PE3, ERC-2010-StG_20091028
Summary We will develop and use imaging techniques for direct probing of electron dynamics in low dimensional structures with orders of
magnitude improvements in time and spatial resolution. We will perform our measurements not only on static structures, but on
complex structures under operating conditions. Finally as our equipment can also probe structural properties from microns to
single atom defects we can directly correlate our observations of electron dynamics with knowledge of geometrical structure. We
hope to directly answer central questions in nanophysics on how complex geometric structure on several length-scales induces
new and surprising electron dynamics and thus properties in nanoscale objects.
The low dimensional semiconductors and metal (nano) structures studied will be chosen to have unique novel properties that will
have potential applications in IT, life-science and renewable energy.
To radically increase our diagnostics capabilities we will combine PhotoEmission Electron Microscopy and attosecond XUV/IR
laser technology to directly image surface electron dynamics with attosecond time resolution and nanometer lateral resolution.
Exploring a completely new realm in terms of timescale with nm resolution we will start with rather simple structure such as Au
nanoparticles and arrays nanoholes in ultrathin metal films, and gradually increase complexity.
As the first group in the world we have shown that atomic resolved structural and electrical measurements by Scanning Tunneling
Microscopy is possible on complex 1D semiconductors heterostructures. Importantly, our new method allows for direct studies of
nanowires in devices.
We can now measure atomic scale surface chemistry and surface electronic/geometric structure directly on operational/operating
nanoscale devices. This is important both from a technology point of view, and is an excellent playground for understanding the
fundamental interplay between electronic and structural properties.
Summary
We will develop and use imaging techniques for direct probing of electron dynamics in low dimensional structures with orders of
magnitude improvements in time and spatial resolution. We will perform our measurements not only on static structures, but on
complex structures under operating conditions. Finally as our equipment can also probe structural properties from microns to
single atom defects we can directly correlate our observations of electron dynamics with knowledge of geometrical structure. We
hope to directly answer central questions in nanophysics on how complex geometric structure on several length-scales induces
new and surprising electron dynamics and thus properties in nanoscale objects.
The low dimensional semiconductors and metal (nano) structures studied will be chosen to have unique novel properties that will
have potential applications in IT, life-science and renewable energy.
To radically increase our diagnostics capabilities we will combine PhotoEmission Electron Microscopy and attosecond XUV/IR
laser technology to directly image surface electron dynamics with attosecond time resolution and nanometer lateral resolution.
Exploring a completely new realm in terms of timescale with nm resolution we will start with rather simple structure such as Au
nanoparticles and arrays nanoholes in ultrathin metal films, and gradually increase complexity.
As the first group in the world we have shown that atomic resolved structural and electrical measurements by Scanning Tunneling
Microscopy is possible on complex 1D semiconductors heterostructures. Importantly, our new method allows for direct studies of
nanowires in devices.
We can now measure atomic scale surface chemistry and surface electronic/geometric structure directly on operational/operating
nanoscale devices. This is important both from a technology point of view, and is an excellent playground for understanding the
fundamental interplay between electronic and structural properties.
Max ERC Funding
1 419 120 €
Duration
Start date: 2010-10-01, End date: 2015-09-30
Project acronym ELSI
Project Emotional Learning in Social Interaction
Researcher (PI) Andreas Olsson
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), SH4, ERC-2011-StG_20101124
Summary This project will open up new horizons in the study of emotional learning by describing and modeling its role in social interaction. It brings together a novel set of experimental manipulations with two hitherto unconnected lines of research; biology of aversive learning and social cognition, with the aim to answer four specific objectives, namely to identify the mechanisms of aversive learning (1) about others and its dependence on stimulus bound (e.g. ethnic group belonging) and conceptual (e.g. moral and social status) features; (2) from others through observation, and its dependence on processing of stimulus bound (e.g. emotional expressiveness) and conceptual (e.g. empathy and mental state attributions) features; (3) during interaction and its dependence social characteristics as described in 1 and 2; and (4) build and test a neural model of social-emotional learning. To achieve these objectives, this project proposes a multi-method research program using novel behavioral experimental paradigms and manipulated virtual environments, drawing on cognitive neuroscience, psychophysiology, and behavioral genetics. It is predicted that social emotional learning will be accomplished through the interaction of four, partially overlapping, neural networks coding for affective, associative, social cognitive and instrumental/goal directed aspects, respectively. Whereas it is expected that the two first networks will be common to classical conditioning and social learning, the latter is hypothesized to be distinguished by its reliance on the social-cognitive network. The fourth network is predicted to be integral to the social learning through interactions and the shaping of behavioral norms. The proposed research will enhance our understanding of important social phenomena, such as the emergence and maintanance of group conflicts and norm compliance. It will also shed light on common psychological disorders, such as social anxiety, autism and psychopathy that are characterized by dysfunctions of the social emotional learning system.
Summary
This project will open up new horizons in the study of emotional learning by describing and modeling its role in social interaction. It brings together a novel set of experimental manipulations with two hitherto unconnected lines of research; biology of aversive learning and social cognition, with the aim to answer four specific objectives, namely to identify the mechanisms of aversive learning (1) about others and its dependence on stimulus bound (e.g. ethnic group belonging) and conceptual (e.g. moral and social status) features; (2) from others through observation, and its dependence on processing of stimulus bound (e.g. emotional expressiveness) and conceptual (e.g. empathy and mental state attributions) features; (3) during interaction and its dependence social characteristics as described in 1 and 2; and (4) build and test a neural model of social-emotional learning. To achieve these objectives, this project proposes a multi-method research program using novel behavioral experimental paradigms and manipulated virtual environments, drawing on cognitive neuroscience, psychophysiology, and behavioral genetics. It is predicted that social emotional learning will be accomplished through the interaction of four, partially overlapping, neural networks coding for affective, associative, social cognitive and instrumental/goal directed aspects, respectively. Whereas it is expected that the two first networks will be common to classical conditioning and social learning, the latter is hypothesized to be distinguished by its reliance on the social-cognitive network. The fourth network is predicted to be integral to the social learning through interactions and the shaping of behavioral norms. The proposed research will enhance our understanding of important social phenomena, such as the emergence and maintanance of group conflicts and norm compliance. It will also shed light on common psychological disorders, such as social anxiety, autism and psychopathy that are characterized by dysfunctions of the social emotional learning system.
Max ERC Funding
1 498 244 €
Duration
Start date: 2012-12-01, End date: 2018-11-30
Project acronym FatemapB
Project High Resolution Mapping of Fetal and Adult B Cell Fates During Ontogeny
Researcher (PI) Joan YUAN
Host Institution (HI) LUNDS UNIVERSITET
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary FateMapB aims to understand how the unique differentiation potential of fetal hematopoietic stem and progenitor cells
(HSPCs) contribute to functionally distinct cell types of the adult immune system. While most immune cells are replenished
by HSPCs through life, others emerge during a limited window in fetal life and sustain through self-renewal in situ. The
lineage identity of fetal HSPCs, and the extent of their contribution to the adult immune repertoire remain surprisingly
unclear. I previously identified the fetal specific RNA binding protein Lin28b as a post-transcriptional molecular switch
capable of inducing fetal-like hematopoiesis in adult bone marrow HSPCs (Yuan et al. Science, 2012). This discovery has
afforded me with unique perspectives on the formation of the mammalian immune system. The concept that the mature
immune system is a mosaic of fetal and adult derived cell types is addressed herein with an emphasis on the B cell lineage.
We will use two complementary lineage-tracing technologies to stratify the immune system as a function of developmental
time, generating fundamental insight into the division of labor between fetal and adult HSPCs that ultimately provides
effective host protection.
Aim 1. Determine the qualitative and quantitative contribution of fetal HSPCs to the mature immune repertoire in situ
through Cre recombination mediated lineage-tracing.
Aim 2. Resolve the disputed lineage relationship between fetal derived B1a cells and adult derived B2 cells by single cell
lineage-tracing using cellular barcoding in vivo.
Aim 3. Characterize the mechanism and effector functions of Lin28b induced B1a cell development for assessing the
clinical utility of inducible fetal-like lymphopoiesis.
The implications of FateMapB extend beyond normal development to immune regeneration and age-related features of
leukemogenesis. Finally, our combinatorial lineage-tracing approach enables dissection of cell fates with previously
unattainable resolution.
Summary
FateMapB aims to understand how the unique differentiation potential of fetal hematopoietic stem and progenitor cells
(HSPCs) contribute to functionally distinct cell types of the adult immune system. While most immune cells are replenished
by HSPCs through life, others emerge during a limited window in fetal life and sustain through self-renewal in situ. The
lineage identity of fetal HSPCs, and the extent of their contribution to the adult immune repertoire remain surprisingly
unclear. I previously identified the fetal specific RNA binding protein Lin28b as a post-transcriptional molecular switch
capable of inducing fetal-like hematopoiesis in adult bone marrow HSPCs (Yuan et al. Science, 2012). This discovery has
afforded me with unique perspectives on the formation of the mammalian immune system. The concept that the mature
immune system is a mosaic of fetal and adult derived cell types is addressed herein with an emphasis on the B cell lineage.
We will use two complementary lineage-tracing technologies to stratify the immune system as a function of developmental
time, generating fundamental insight into the division of labor between fetal and adult HSPCs that ultimately provides
effective host protection.
Aim 1. Determine the qualitative and quantitative contribution of fetal HSPCs to the mature immune repertoire in situ
through Cre recombination mediated lineage-tracing.
Aim 2. Resolve the disputed lineage relationship between fetal derived B1a cells and adult derived B2 cells by single cell
lineage-tracing using cellular barcoding in vivo.
Aim 3. Characterize the mechanism and effector functions of Lin28b induced B1a cell development for assessing the
clinical utility of inducible fetal-like lymphopoiesis.
The implications of FateMapB extend beyond normal development to immune regeneration and age-related features of
leukemogenesis. Finally, our combinatorial lineage-tracing approach enables dissection of cell fates with previously
unattainable resolution.
Max ERC Funding
1 499 905 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym IMMUNOSWITCH
Project Switch recombination: a model system for DNA editing and repair in human lymphocytes with relevance for primary immunodeficiency and cancer formation
Researcher (PI) Qiang Pan Hammarström
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS6, ERC-2009-StG
Summary The aim of this project is to try to understand the complex molecular mechanisms involved in DNA editing, repair and recombination during immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). We have developed a series of PCR-based assays to study in vivo generated CSR junctions and the pattern of mutations introduced in the immunoglobulin variable region genes in human B cells, allowing us to characterize CSR and SHM in patients with immunodeficiency due to defect(s) in DNA repair/recombination. Novel in vitro CSR assays, based on GFP expression, allowing quantitative measurement of substrate recombination, are also being developed. In addition, we have initiated an evolutionary analysis of the function and structure of activation-induced deaminase, an essential molecule involved both in CSR and SHM, aiming to identify CSR specific-cofactor(s). Combining these approaches, we will be able to define the DNA repair pathways involved in CSR and SHM. The suggested project requires access to patients with various defects in the DNA repair pathways. Many of these diseases are exceedingly rare. However, through worldwide collaboration, we have obtained samples from a majority of the diagnosed patients. We are also refining the existing screening methods and developing novel methods, that will allow identification of additional patients both with recognized and new diseases caused by mutations in DNA repair pathways. Finally, we hope to be able to address the question whether illegitimate CSR events are associated with predisposition to lymphomagenesis in patients with immunodeficiency/DNA repair defect(s), by analyzing the CSR induced chromosomal breaks and translocations in these patients. A large-scale sequencing project is also planned to characterize the CSRnome in B-cell lymphoma samples.
Summary
The aim of this project is to try to understand the complex molecular mechanisms involved in DNA editing, repair and recombination during immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). We have developed a series of PCR-based assays to study in vivo generated CSR junctions and the pattern of mutations introduced in the immunoglobulin variable region genes in human B cells, allowing us to characterize CSR and SHM in patients with immunodeficiency due to defect(s) in DNA repair/recombination. Novel in vitro CSR assays, based on GFP expression, allowing quantitative measurement of substrate recombination, are also being developed. In addition, we have initiated an evolutionary analysis of the function and structure of activation-induced deaminase, an essential molecule involved both in CSR and SHM, aiming to identify CSR specific-cofactor(s). Combining these approaches, we will be able to define the DNA repair pathways involved in CSR and SHM. The suggested project requires access to patients with various defects in the DNA repair pathways. Many of these diseases are exceedingly rare. However, through worldwide collaboration, we have obtained samples from a majority of the diagnosed patients. We are also refining the existing screening methods and developing novel methods, that will allow identification of additional patients both with recognized and new diseases caused by mutations in DNA repair pathways. Finally, we hope to be able to address the question whether illegitimate CSR events are associated with predisposition to lymphomagenesis in patients with immunodeficiency/DNA repair defect(s), by analyzing the CSR induced chromosomal breaks and translocations in these patients. A large-scale sequencing project is also planned to characterize the CSRnome in B-cell lymphoma samples.
Max ERC Funding
1 888 166 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym LACOLA
Project Language, cognition and landscape: understanding cross-cultural and individual variation in geographical ontology
Researcher (PI) Niclas Burenhult
Host Institution (HI) LUNDS UNIVERSITET
Call Details Starting Grant (StG), SH4, ERC-2010-StG_20091209
Summary This project will break new ground in the language sciences by pursuing a linguistic inquiry into landscape. From the linguist s point of view, the geophysical environment is virtually unexplored. Yet it has vast potential for influence on the discipline. The project will play a pioneering role in situating landscape within linguistics as a fundamental domain of representational systems, opening up important links to other disciplines concerned with landscape that usually have little to do with language. It will achieve this by (1) exploring landscape categorization in a number of languages, (2) comparing such categorization, (3) developing a model for understanding categorization across languages and speakers, and (4) documenting vanishing landscape systems. The research team will study landscape categorization in six diverse language settings. Each setting is a case study carried out by a team member with expert knowledge and prior field experience of the setting. Each setting offers opportunities of studying closely related languages as well as individuals speaking the same language, making comparison possible not only among maximally diverse languages but also at finer levels of linguistic granularity. An exploratory psycholinguistic subproject will probe the relationship between language and cognition in the landscape domain. The project will blaze a trail in applying GIS to linguistic data, in testing advanced experimental techniques in the field, and in documenting domain-specific data from a global language sample. Cross-cultural variation in landscape ontology is a matter of great practical importance understanding the meaning and reference of landscape terms and place names is crucial to major fields of human cooperation, from navigation to international law.
Summary
This project will break new ground in the language sciences by pursuing a linguistic inquiry into landscape. From the linguist s point of view, the geophysical environment is virtually unexplored. Yet it has vast potential for influence on the discipline. The project will play a pioneering role in situating landscape within linguistics as a fundamental domain of representational systems, opening up important links to other disciplines concerned with landscape that usually have little to do with language. It will achieve this by (1) exploring landscape categorization in a number of languages, (2) comparing such categorization, (3) developing a model for understanding categorization across languages and speakers, and (4) documenting vanishing landscape systems. The research team will study landscape categorization in six diverse language settings. Each setting is a case study carried out by a team member with expert knowledge and prior field experience of the setting. Each setting offers opportunities of studying closely related languages as well as individuals speaking the same language, making comparison possible not only among maximally diverse languages but also at finer levels of linguistic granularity. An exploratory psycholinguistic subproject will probe the relationship between language and cognition in the landscape domain. The project will blaze a trail in applying GIS to linguistic data, in testing advanced experimental techniques in the field, and in documenting domain-specific data from a global language sample. Cross-cultural variation in landscape ontology is a matter of great practical importance understanding the meaning and reference of landscape terms and place names is crucial to major fields of human cooperation, from navigation to international law.
Max ERC Funding
1 499 931 €
Duration
Start date: 2011-03-01, End date: 2016-02-29
Project acronym MAGNETIC-SPEED-LIMIT
Project Understanding the speed limits of magnetism
Researcher (PI) Stefano BONETTI
Host Institution (HI) STOCKHOLMS UNIVERSITET
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary While the origin of magnetic order in condensed matter is in the exchange and spin-orbit interactions, with time scales in the subpicosecond ranges, it has been long believed that magnetism could only be manipulated at nanosecond rates, exploiting dipolar interactions with external magnetic fields. However, in the past decade researchers have been able to observe ultrafast magnetic dynamics at its intrinsic time scales without the need for magnetic fields, thus revolutionising the view on the speed limits of magnetism. Despite many achievements in ultrafast magnetism, the understanding of the fundamental physics that allows for the ultrafast dissipation of angular momentum is still only partial, hampered by the lack of experimental techniques suited to fully explore these phenomena. However, the recent appearance of two new types of coherent radiation, single-cycle THz pulses and x-rays generated at free electron lasers (FELs), has provided researchers access to a whole new set of capabilities to tackle this challenge. This proposal suggests using these techniques to achieve an encompassing view of ultrafast magnetic dynamics in metallic ferromagnets, via the following three research objectives: (a) to reveal ultrafast dynamics driven by strong THz radiation in several magnetic systems using table-top femtosecond lasers; (b) to unravel the contribution of lattice dynamics to ultrafast demagnetization in different magnetic materials using the x-rays produced at FELs and (c) to directly image ultrafast spin currents by creating femtosecond movies with nanometre resolution. The proposed experiments are challenging and explore unchartered territories, but if successful, they will advance the understanding of the speed limits of magnetism, at the time scales of the exchange and spin-orbit interactions. They will also open up for future investigations of ultrafast magnetic phenomena in materials with large electronic correlations or spin-orbit coupling.
Summary
While the origin of magnetic order in condensed matter is in the exchange and spin-orbit interactions, with time scales in the subpicosecond ranges, it has been long believed that magnetism could only be manipulated at nanosecond rates, exploiting dipolar interactions with external magnetic fields. However, in the past decade researchers have been able to observe ultrafast magnetic dynamics at its intrinsic time scales without the need for magnetic fields, thus revolutionising the view on the speed limits of magnetism. Despite many achievements in ultrafast magnetism, the understanding of the fundamental physics that allows for the ultrafast dissipation of angular momentum is still only partial, hampered by the lack of experimental techniques suited to fully explore these phenomena. However, the recent appearance of two new types of coherent radiation, single-cycle THz pulses and x-rays generated at free electron lasers (FELs), has provided researchers access to a whole new set of capabilities to tackle this challenge. This proposal suggests using these techniques to achieve an encompassing view of ultrafast magnetic dynamics in metallic ferromagnets, via the following three research objectives: (a) to reveal ultrafast dynamics driven by strong THz radiation in several magnetic systems using table-top femtosecond lasers; (b) to unravel the contribution of lattice dynamics to ultrafast demagnetization in different magnetic materials using the x-rays produced at FELs and (c) to directly image ultrafast spin currents by creating femtosecond movies with nanometre resolution. The proposed experiments are challenging and explore unchartered territories, but if successful, they will advance the understanding of the speed limits of magnetism, at the time scales of the exchange and spin-orbit interactions. They will also open up for future investigations of ultrafast magnetic phenomena in materials with large electronic correlations or spin-orbit coupling.
Max ERC Funding
1 967 755 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
