Project acronym 3DBIOLUNG
Project Bioengineering lung tissue using extracellular matrix based 3D bioprinting
Researcher (PI) Darcy WAGNER
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS9, ERC-2018-STG
Summary Chronic lung diseases are increasing in prevalence with over 65 million patients worldwide. Lung transplantation remains the only potential option at end-stage disease. Around 4000 patients receive lung transplants annually with more awaiting transplantation, including 1000 patients in Europe. New options to increase available tissue for lung transplantation are desperately needed.
An exciting new research area focuses on generating lung tissue ex vivo using bioengineering approaches. Scaffolds can be generated from synthetic or biologically-derived (acellular) materials, seeded with cells and grown in a bioreactor prior to transplantation. Ideally, scaffolds would be seeded with cells derived from the transplant recipient, thus obviating the need for long-term immunosuppression. However, functional regeneration has yet to be achieved. New advances in 3D printing and 3D bioprinting (when cells are printed) indicate that this once thought of science-fiction concept might finally be mature enough for complex tissues, including lung. 3D bioprinting addresses a number of concerns identified in previous approaches, such as a) patient heterogeneity in acellular human scaffolds, b) anatomical differences in xenogeneic sources, c) lack of biological cues on synthetic materials and d) difficulty in manufacturing the complex lung architecture. 3D bioprinting could be a reproducible, scalable, and controllable approach for generating functional lung tissue.
The aim of this proposal is to use custom 3D bioprinters to generate constructs mimicking lung tissue using an innovative approach combining primary cells, the engineering reproducibility of synthetic materials, and the biologically conductive properties of acellular lung (hybrid). We will 3D bioprint hybrid murine and human lung tissue models and test gas exchange, angiogenesis and in vivo immune responses. This proposal will be a critical first step in demonstrating feasibility of 3D bioprinting lung tissue.
Summary
Chronic lung diseases are increasing in prevalence with over 65 million patients worldwide. Lung transplantation remains the only potential option at end-stage disease. Around 4000 patients receive lung transplants annually with more awaiting transplantation, including 1000 patients in Europe. New options to increase available tissue for lung transplantation are desperately needed.
An exciting new research area focuses on generating lung tissue ex vivo using bioengineering approaches. Scaffolds can be generated from synthetic or biologically-derived (acellular) materials, seeded with cells and grown in a bioreactor prior to transplantation. Ideally, scaffolds would be seeded with cells derived from the transplant recipient, thus obviating the need for long-term immunosuppression. However, functional regeneration has yet to be achieved. New advances in 3D printing and 3D bioprinting (when cells are printed) indicate that this once thought of science-fiction concept might finally be mature enough for complex tissues, including lung. 3D bioprinting addresses a number of concerns identified in previous approaches, such as a) patient heterogeneity in acellular human scaffolds, b) anatomical differences in xenogeneic sources, c) lack of biological cues on synthetic materials and d) difficulty in manufacturing the complex lung architecture. 3D bioprinting could be a reproducible, scalable, and controllable approach for generating functional lung tissue.
The aim of this proposal is to use custom 3D bioprinters to generate constructs mimicking lung tissue using an innovative approach combining primary cells, the engineering reproducibility of synthetic materials, and the biologically conductive properties of acellular lung (hybrid). We will 3D bioprint hybrid murine and human lung tissue models and test gas exchange, angiogenesis and in vivo immune responses. This proposal will be a critical first step in demonstrating feasibility of 3D bioprinting lung tissue.
Max ERC Funding
1 499 975 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
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 AGINGSEXDIFF
Project Aging Differently: Understanding Sex Differences in Reproductive, Demographic and Functional Senescence
Researcher (PI) Alexei Maklakov
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a
long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not
only in how long they live and when they start to senesce, but also in how they react to
environmental interventions aimed at prolonging their life span or decelerating the onset of aging.
Therefore, sex differences in life span and aging have important implications beyond the questions
posed by fundamental science. Both evolutionary reasons and medical implications of sex
differences in demographic, reproductive and physiological senescence are and will be crucial
targets of present and future research in the biology of aging. Here I propose a two-step approach
that can provide a significant breakthrough in our understanding of the biological basis of sex
differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific
mortality rate in sex differences in aging by developing a series of targeted experimental
evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I
address the role of intra-locus sexual conflict in the evolution of aging by combining novel
methodology from nutritional ecology – the Geometric Framework – with artificial selection
approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will
directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the
adaptive evolution of diet choice. By combining techniques from evolutionary biology and
nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to
the training of young scientists in this rapidly developing field.
Summary
Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a
long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not
only in how long they live and when they start to senesce, but also in how they react to
environmental interventions aimed at prolonging their life span or decelerating the onset of aging.
Therefore, sex differences in life span and aging have important implications beyond the questions
posed by fundamental science. Both evolutionary reasons and medical implications of sex
differences in demographic, reproductive and physiological senescence are and will be crucial
targets of present and future research in the biology of aging. Here I propose a two-step approach
that can provide a significant breakthrough in our understanding of the biological basis of sex
differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific
mortality rate in sex differences in aging by developing a series of targeted experimental
evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I
address the role of intra-locus sexual conflict in the evolution of aging by combining novel
methodology from nutritional ecology – the Geometric Framework – with artificial selection
approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will
directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the
adaptive evolution of diet choice. By combining techniques from evolutionary biology and
nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to
the training of young scientists in this rapidly developing field.
Max ERC Funding
1 391 904 €
Duration
Start date: 2010-12-01, End date: 2016-05-31
Project acronym ANSR
Project Ab initio approach to nuclear structure and reactions (++)
Researcher (PI) Christian Erik Forssen
Host Institution (HI) CHALMERS TEKNISKA HOEGSKOLA AB
Country Sweden
Call Details Starting Grant (StG), PE2, ERC-2009-StG
Summary Today, much interest in several fields of physics is devoted to the study of small, open quantum systems, whose properties are profoundly affected by the environment; i.e., the continuum of decay channels. In nuclear physics, these problems were originally studied in the context of nuclear reactions but their importance has been reestablished with the advent of radioactive-beam physics and the resulting interest in exotic nuclei. In particular, strong theory initiatives in this area of research will be instrumental for the success of the experimental program at the Facility for Antiproton and Ion Research (FAIR) in Germany. In addition, many of the aspects of open quantum systems are also being explored in the rapidly evolving research on ultracold atomic gases, quantum dots, and other nanodevices. A first-principles description of open quantum systems presents a substantial theoretical and computational challenge. However, the current availability of enormous computing power has allowed theorists to make spectacular progress on problems that were previously thought intractable. The importance of computational methods to study quantum many-body systems is stressed in this proposal. Our approach is based on the ab initio no-core shell model (NCSM), which is a well-established theoretical framework aimed originally at an exact description of nuclear structure starting from realistic inter-nucleon forces. A successful completion of this project requires extensions of the NCSM mathematical framework and the development of highly advanced computer codes. The '++' in the project title indicates the interdisciplinary aspects of the present research proposal and the ambition to make a significant impact on connected fields of many-body physics.
Summary
Today, much interest in several fields of physics is devoted to the study of small, open quantum systems, whose properties are profoundly affected by the environment; i.e., the continuum of decay channels. In nuclear physics, these problems were originally studied in the context of nuclear reactions but their importance has been reestablished with the advent of radioactive-beam physics and the resulting interest in exotic nuclei. In particular, strong theory initiatives in this area of research will be instrumental for the success of the experimental program at the Facility for Antiproton and Ion Research (FAIR) in Germany. In addition, many of the aspects of open quantum systems are also being explored in the rapidly evolving research on ultracold atomic gases, quantum dots, and other nanodevices. A first-principles description of open quantum systems presents a substantial theoretical and computational challenge. However, the current availability of enormous computing power has allowed theorists to make spectacular progress on problems that were previously thought intractable. The importance of computational methods to study quantum many-body systems is stressed in this proposal. Our approach is based on the ab initio no-core shell model (NCSM), which is a well-established theoretical framework aimed originally at an exact description of nuclear structure starting from realistic inter-nucleon forces. A successful completion of this project requires extensions of the NCSM mathematical framework and the development of highly advanced computer codes. The '++' in the project title indicates the interdisciplinary aspects of the present research proposal and the ambition to make a significant impact on connected fields of many-body physics.
Max ERC Funding
1 304 800 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym B-DOMINANCE
Project B Cell Immunodominance in Antiviral Immunity
Researcher (PI) Davide Angeletti
Host Institution (HI) GOETEBORGS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS6, ERC-2019-STG
Summary This proposal aims at understanding how B cell specificity and immunodominance shape primary and secondary humoral responses to influenza A virus. Influenza A virus is a relevant human pathogen causing a considerable yearly death toll and economic burden to society. Immunodominance is a major driving force of adaptive immunity and defines the hierarchical recognition of epitopes on the same antigen. Previous studies analysing B cell dynamics in primary and secondary responses have been mainly focusing on simple antigens and competition between B cell clones of the same family. Investigation using complex antigens and examining interclonal competition are surprisingly scarce. Influenza hemagglutinin (HA) is a prime candidate to study immunodominance in B cells. I have generated a set of mutant viruses that will allow for an unprecedented investigation into immunodominance and B cell interclonal competition in primary and secondary responses. These viruses can be used to isolate and enumerate antibody and B cells specific for different epitopes on the same complex antigen (HA). I will use these unique tools in combination with state-of-the-art immunological methods, multi-colour flow cytometry and single cells RNA sequencing paired with B cell receptor sequencing to gain fundamental insights into B cell regulation and anti-viral humoral responses. I will i) study the link between B cell receptor characteristics, specificity and B cell fate decisions in primary responses, ii) characterize the relative contribution of pre-existing B cells, serum antibodies and CD4 T cells for immunodominance of secondary responses, iii) define immunodominance in human individuals, repeatedly exposed to influenza virus. I expect this project to critically improve our understanding of basic B cell biology with the long-term benefit of improving current vaccination against variable viral pathogens.
Summary
This proposal aims at understanding how B cell specificity and immunodominance shape primary and secondary humoral responses to influenza A virus. Influenza A virus is a relevant human pathogen causing a considerable yearly death toll and economic burden to society. Immunodominance is a major driving force of adaptive immunity and defines the hierarchical recognition of epitopes on the same antigen. Previous studies analysing B cell dynamics in primary and secondary responses have been mainly focusing on simple antigens and competition between B cell clones of the same family. Investigation using complex antigens and examining interclonal competition are surprisingly scarce. Influenza hemagglutinin (HA) is a prime candidate to study immunodominance in B cells. I have generated a set of mutant viruses that will allow for an unprecedented investigation into immunodominance and B cell interclonal competition in primary and secondary responses. These viruses can be used to isolate and enumerate antibody and B cells specific for different epitopes on the same complex antigen (HA). I will use these unique tools in combination with state-of-the-art immunological methods, multi-colour flow cytometry and single cells RNA sequencing paired with B cell receptor sequencing to gain fundamental insights into B cell regulation and anti-viral humoral responses. I will i) study the link between B cell receptor characteristics, specificity and B cell fate decisions in primary responses, ii) characterize the relative contribution of pre-existing B cells, serum antibodies and CD4 T cells for immunodominance of secondary responses, iii) define immunodominance in human individuals, repeatedly exposed to influenza virus. I expect this project to critically improve our understanding of basic B cell biology with the long-term benefit of improving current vaccination against variable viral pathogens.
Max ERC Funding
1 481 697 €
Duration
Start date: 2019-12-01, End date: 2024-11-30
Project acronym BEE NATURAL
Project A sustainable future for honeybees by unravelling the mechanisms of natural disease resistance
Researcher (PI) Barbara Locke Grander
Host Institution (HI) SVERIGES LANTBRUKSUNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS9, ERC-2020-STG
Summary The ectoparasitic mite, Varroa destructor, vectors lethal honeybee viruses, in particular Deformed wing virus (DWV) and is unarguably the leading cause of honeybee (Apis mellifera) colony mortality world-wide causing critical economic and ecological consequences for pollination-dependent crop production and wild plant biodiversity, respectively. Since the introduction of the mite in the 1970s and 1980s, wild honeybees in Europe and North America have been nearly completely eradicated and managed honeybees only survive through mite control treatment, or otherwise die within 1-2 years. These treatments remove the selective pressure necessary to establish a stable host-parasite relationship, which hampers the evolution of resistance and obstructs fundamental research on natural selection host‒parasite coevolution in this new host‒parasite system, which is now only possible in a few small honeybee populations surviving long-term (>20 years) without varroa control in Sweden, France and Norway. These rare and valuable naturally selected populations offer unique insight into the natural adaptive capacity of honeybees, yet little is understood about their mechanisms of resistance or tolerance to varroa mites and the viruses they vector.
Having exclusive access to these populations, the BEE NATURAL project sets out to comprehensively describe their host resistant and tolerant phenotypes towards both mites and viruses, using a variety of innovative experimental designs, in order to deeper our fundamental understanding of host-parasite interactions. Genomic regions or target genes associated with resistant and tolerant traits will be identified using Next Generation Sequencing (NGS) technologies such as RNA-seq and whole genome sequencing (WGS), providing valuable information that can be applied towards developing marker-assisted selection: a powerful new approach for disease resistant breeding that can facilitate major advances in genetic stock improvement.
Summary
The ectoparasitic mite, Varroa destructor, vectors lethal honeybee viruses, in particular Deformed wing virus (DWV) and is unarguably the leading cause of honeybee (Apis mellifera) colony mortality world-wide causing critical economic and ecological consequences for pollination-dependent crop production and wild plant biodiversity, respectively. Since the introduction of the mite in the 1970s and 1980s, wild honeybees in Europe and North America have been nearly completely eradicated and managed honeybees only survive through mite control treatment, or otherwise die within 1-2 years. These treatments remove the selective pressure necessary to establish a stable host-parasite relationship, which hampers the evolution of resistance and obstructs fundamental research on natural selection host‒parasite coevolution in this new host‒parasite system, which is now only possible in a few small honeybee populations surviving long-term (>20 years) without varroa control in Sweden, France and Norway. These rare and valuable naturally selected populations offer unique insight into the natural adaptive capacity of honeybees, yet little is understood about their mechanisms of resistance or tolerance to varroa mites and the viruses they vector.
Having exclusive access to these populations, the BEE NATURAL project sets out to comprehensively describe their host resistant and tolerant phenotypes towards both mites and viruses, using a variety of innovative experimental designs, in order to deeper our fundamental understanding of host-parasite interactions. Genomic regions or target genes associated with resistant and tolerant traits will be identified using Next Generation Sequencing (NGS) technologies such as RNA-seq and whole genome sequencing (WGS), providing valuable information that can be applied towards developing marker-assisted selection: a powerful new approach for disease resistant breeding that can facilitate major advances in genetic stock improvement.
Max ERC Funding
1 499 703 €
Duration
Start date: 2021-01-01, End date: 2025-12-31
Project acronym BIOFINDER
Project New biomarkers for Alzheimer’s & Parkinson’s diseases - key tools for early diagnosis and drug development
Researcher (PI) Oskar Hansson
Host Institution (HI) MAX IV Laboratory, Lund University
Country Sweden
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
Summary Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity.
AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets.
We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays.
New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging
Summary
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity.
AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets.
We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays.
New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging
Max ERC Funding
1 500 000 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym BODY-OWNERSHIP
Project Neural mechanisms of body ownership and the projection of ownership onto artificial bodies
Researcher (PI) H. Henrik Ehrsson
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Starting Grant (StG), LS4, ERC-2007-StG
Summary How do we recognize that our limbs are part of our own body, and why do we feel that one’s self is located inside the body? These fundamental questions have been discussed in theology, philosophy and psychology for millennia. The aim of my ground-breaking research programme is to identify the neuronal mechanisms that produce the sense of ownership of the body, and the processes responsible for the feeling that the self is located inside the physical body. To solve these questions I will adopt an inter-disciplinary approach using state-of-the-art methods from the fields of imaging neuroscience, experimental psychology, computer science and robotics. My first hypothesis is that the mechanism for body ownership is the integration of information from different sensory modalities (vision, touch and muscle sense) in multi-sensory brain areas (ventral premotor and intraparietal cortex). My second hypothesis is that the sense of where you are located in the environment is mediated by allocentric spatial representations in medial temporal lobes. To test this, I will use perceptual illusions and virtual-reality techniques that allow me to manipulate body ownership and the perceived location of the self, in conjunction with non-invasive recordings of brain activity in healthy humans. Functional magnetic resonance imaging and electroencephalography will be used to identify the neuronal correlates of ownership and ‘in-body experiences’, while transcranial magnetic stimulation will be used to examine the causal relationship between neural activity and ownership. It is no overstatement to say that my pioneering work could define a new sub-field in cognitive neuroscience dealing with how the brain represents the self. These basic scientific discoveries will be used in new frontier applications. For example, the development of a prosthetic limb that feels just like a real limb, and a method of controlling humanoid robots by the illusion of ‘becoming the robot’.
Summary
How do we recognize that our limbs are part of our own body, and why do we feel that one’s self is located inside the body? These fundamental questions have been discussed in theology, philosophy and psychology for millennia. The aim of my ground-breaking research programme is to identify the neuronal mechanisms that produce the sense of ownership of the body, and the processes responsible for the feeling that the self is located inside the physical body. To solve these questions I will adopt an inter-disciplinary approach using state-of-the-art methods from the fields of imaging neuroscience, experimental psychology, computer science and robotics. My first hypothesis is that the mechanism for body ownership is the integration of information from different sensory modalities (vision, touch and muscle sense) in multi-sensory brain areas (ventral premotor and intraparietal cortex). My second hypothesis is that the sense of where you are located in the environment is mediated by allocentric spatial representations in medial temporal lobes. To test this, I will use perceptual illusions and virtual-reality techniques that allow me to manipulate body ownership and the perceived location of the self, in conjunction with non-invasive recordings of brain activity in healthy humans. Functional magnetic resonance imaging and electroencephalography will be used to identify the neuronal correlates of ownership and ‘in-body experiences’, while transcranial magnetic stimulation will be used to examine the causal relationship between neural activity and ownership. It is no overstatement to say that my pioneering work could define a new sub-field in cognitive neuroscience dealing with how the brain represents the self. These basic scientific discoveries will be used in new frontier applications. For example, the development of a prosthetic limb that feels just like a real limb, and a method of controlling humanoid robots by the illusion of ‘becoming the robot’.
Max ERC Funding
909 850 €
Duration
Start date: 2008-12-01, End date: 2013-11-30
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
Country Sweden
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 BRAINCELL
Project Charting the landscape of brain development by large-scale single-cell transcriptomics and phylogenetic lineage reconstruction
Researcher (PI) Sten Linnarsson
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary Embryogenesis is the temporal unfolding of cellular processes: proliferation, migration, differentiation, morphogenesis, apoptosis and functional specialization. These processes are well understood in specific tissues, and for specific cell types. Nevertheless, our systematic knowledge of the types of cells present in the developing and adult animal, and about their functional and lineage relationships, is limited. For example, there is no consensus on the number of cell types, and many important stem cells and progenitors remain to be discovered. Similarly, the lineage relationships between specific cell types are often poorly characterized. This is particularly true for the mammalian nervous system. We have developed (1) a reliable high-throghput method for sequencing all transcripts in 96 single cells at a time; and (2) a system for high-throughput phylogenetic lineage reconstruction. We now propose to characterize embryogenesis using a shotgun approach borrowed from genomics. Tissues will be dissected from multiple stages and dissociated to single cells. A total of 10,000 cells will be analyzed by RNA sequencing, revealing their functional cell type, their lineage relationships, and their current state (e.g. cell cycle phase). The novel approach proposed here will bring the powerful strategies pioneered in genomics into the field of developmental biology, including automation, digitization, and the random shotgun method. The data thus obtained will bring clarity to the concept of ‘cell type’; will provide a first catalog of mouse brain cell types with deep functional annotation; will provide markers for every cell type, including stem cells; and will serve as a basis for future comparative work, especially with human embryos.
Summary
Embryogenesis is the temporal unfolding of cellular processes: proliferation, migration, differentiation, morphogenesis, apoptosis and functional specialization. These processes are well understood in specific tissues, and for specific cell types. Nevertheless, our systematic knowledge of the types of cells present in the developing and adult animal, and about their functional and lineage relationships, is limited. For example, there is no consensus on the number of cell types, and many important stem cells and progenitors remain to be discovered. Similarly, the lineage relationships between specific cell types are often poorly characterized. This is particularly true for the mammalian nervous system. We have developed (1) a reliable high-throghput method for sequencing all transcripts in 96 single cells at a time; and (2) a system for high-throughput phylogenetic lineage reconstruction. We now propose to characterize embryogenesis using a shotgun approach borrowed from genomics. Tissues will be dissected from multiple stages and dissociated to single cells. A total of 10,000 cells will be analyzed by RNA sequencing, revealing their functional cell type, their lineage relationships, and their current state (e.g. cell cycle phase). The novel approach proposed here will bring the powerful strategies pioneered in genomics into the field of developmental biology, including automation, digitization, and the random shotgun method. The data thus obtained will bring clarity to the concept of ‘cell type’; will provide a first catalog of mouse brain cell types with deep functional annotation; will provide markers for every cell type, including stem cells; and will serve as a basis for future comparative work, especially with human embryos.
Max ERC Funding
1 496 032 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
