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Displaying 1 - 10 of 30. Show 10 | 20 results per page.
Project acronym BARRAGE
Project Cell compartmentalization, individuation and diversity
Researcher (PI) Yves Barral
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Summary Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.
Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.
Project acronym CILIARYDISEASE
Project Deciphering mechanisms of ciliary disease
Researcher (PI) Heiko Lickert
Host Institution (HI) HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Summary Ciliopathies are pleiotropic diseases with a wide spectrum of human phenotypes. These include cyst formation in the liver and pancreas, respiratory disorders and a predisposition to diabetes and cancer. The pleiotropic nature of these disorders may reflect the many roles cilia play in physiology and signalling, highlighting the clinical importance of understanding their function in organ development and homeostasis. Despite the biological importance of cilia and decades of research, many aspects of cilia assembly and disassembly remain elusive. The earliest steps of cilia assembly involve conversion of the centrosome into a basal body, which anchors the cilia to the plasma membrane. Odf2 is one of the only proteins known to be important for this process, thus Ofd2 mutant cells lack cilia. During cell cycle re-entry primary cilia disassemble, the basal body dislodges from the plasma membrane and duplicates to serve as the mitotic centrosome. We recently identified Pitchfork, which functions in basal body-to-centrosome conversion and regulates embryonic patterning. The overall aim of this proposal is to better understand the cellular and bio-molecular mechanisms underlying ciliary disease. We will conditionally delete Odf2 and Pitchfork during embryogenesis and organogenesis. This will reveal the different requirements for the process of cilia assembly and disassembly in embryonic development, organ formation and homeostasis. The phenotypes will be analyzed at all levels of complexity. Subcellular imaging and identification of protein interaction partners will uncover the molecular basis of cilia assembly and disassembly. In summary, this project will decipher mechanisms underlying a wide spectrum of human ciliary disease and will open new avenues of clinical research.
Ciliopathies are pleiotropic diseases with a wide spectrum of human phenotypes. These include cyst formation in the liver and pancreas, respiratory disorders and a predisposition to diabetes and cancer. The pleiotropic nature of these disorders may reflect the many roles cilia play in physiology and signalling, highlighting the clinical importance of understanding their function in organ development and homeostasis. Despite the biological importance of cilia and decades of research, many aspects of cilia assembly and disassembly remain elusive. The earliest steps of cilia assembly involve conversion of the centrosome into a basal body, which anchors the cilia to the plasma membrane. Odf2 is one of the only proteins known to be important for this process, thus Ofd2 mutant cells lack cilia. During cell cycle re-entry primary cilia disassemble, the basal body dislodges from the plasma membrane and duplicates to serve as the mitotic centrosome. We recently identified Pitchfork, which functions in basal body-to-centrosome conversion and regulates embryonic patterning. The overall aim of this proposal is to better understand the cellular and bio-molecular mechanisms underlying ciliary disease. We will conditionally delete Odf2 and Pitchfork during embryogenesis and organogenesis. This will reveal the different requirements for the process of cilia assembly and disassembly in embryonic development, organ formation and homeostasis. The phenotypes will be analyzed at all levels of complexity. Subcellular imaging and identification of protein interaction partners will uncover the molecular basis of cilia assembly and disassembly. In summary, this project will decipher mechanisms underlying a wide spectrum of human ciliary disease and will open new avenues of clinical research.
Project acronym CRITICALBRAINCHANGES
Project Development and plasticity of multisensory functions to study the principles of age dependent learning plasticity in humans
Researcher (PI) Brigitte Roeder
Host Institution (HI) UNIVERSITAET HAMBURG
Summary Proposal summary: The present project will investigate the main principles of development and neuroplasticity in humans in the domain of multisensory processes (the interplay between sensory systems). It will be tested how learning plasticity of the human brain changes from childhood to adulthood and how early experience constraints neuroplasticity at later developmental stages as well as in adults. The project is based upon animal findings in sensory development and plasticity. Both a prospective (studies in children) and a retrospective (studies in people with a history of visual or auditory deprivation) approach are employed. Behavioural paradigms from experimental psychology addressing multisensory processes are combined with electroencephalographic recordings (EEG). First, we investigate the functional principles and neural correlates of multisensory development. Second, we investigate multisensory processes in people who suffered from a transient phase of sensory deprivation after birth: (a) in people who were born with bilateral dense cataracts that were removed later, and (b) in congenitally deaf individuals, who were equipped with a cochlear implant to restore hearing. This line of research will reveal the critical contribution of single sensory systems as well as the synchronized input across modalities with regard to the emergence of successful multisensory binding. Third, we will investigate whether it is possible to alleviate neural changes demarcating the end of sensitive phases or critical periods by implementing an incremental training procedure. Last, we will look at whether experimentally induced transient sensory deprivation increases neuroplasticity loss during a sensitive phase or critical period. We are convinced that basic research, such as the present, will reveal important principles of development and neuroplasticity which will be useful in applied setting to improve education, the rehabilitation of individuals with sensory defects and the treatment of developmental disorders.
Proposal summary: The present project will investigate the main principles of development and neuroplasticity in humans in the domain of multisensory processes (the interplay between sensory systems). It will be tested how learning plasticity of the human brain changes from childhood to adulthood and how early experience constraints neuroplasticity at later developmental stages as well as in adults. The project is based upon animal findings in sensory development and plasticity. Both a prospective (studies in children) and a retrospective (studies in people with a history of visual or auditory deprivation) approach are employed. Behavioural paradigms from experimental psychology addressing multisensory processes are combined with electroencephalographic recordings (EEG). First, we investigate the functional principles and neural correlates of multisensory development. Second, we investigate multisensory processes in people who suffered from a transient phase of sensory deprivation after birth: (a) in people who were born with bilateral dense cataracts that were removed later, and (b) in congenitally deaf individuals, who were equipped with a cochlear implant to restore hearing. This line of research will reveal the critical contribution of single sensory systems as well as the synchronized input across modalities with regard to the emergence of successful multisensory binding. Third, we will investigate whether it is possible to alleviate neural changes demarcating the end of sensitive phases or critical periods by implementing an incremental training procedure. Last, we will look at whether experimentally induced transient sensory deprivation increases neuroplasticity loss during a sensitive phase or critical period. We are convinced that basic research, such as the present, will reveal important principles of development and neuroplasticity which will be useful in applied setting to improve education, the rehabilitation of individuals with sensory defects and the treatment of developmental disorders.
Project acronym DMD
Project Dynamic Mechanism Design: Theory and Applications
Researcher (PI) Benedict Moldovanu
Host Institution (HI) RHEINISCHE FRIEDRICH-WILHELMS-UNIVERSITAT BONN
Summary We plan to construct a theoretical bridge between classical dynamic allocation models used in Operations Research/Management Science, and between the modern theory of mechanism design. Our theoretical results will generate insights for the construction of applied pricing schemes and testable implications about the pattern of observed prices. The Economics literature has focused on information and incentive issues in static models, whereas the Operations Research/Management Science literature has looked at dynamic models that were often lacking strategic/ informational aspects. There is an increased recent interest in combining these bodies of knowledge, spurred by studies of yield management, and of decentralized platforms for interaction/ communication among agents. A general mechanism design analysis starts with the characterization of all dynamically implementable allocation policies. Variational arguments can be used then to characterize optimal policies. The research will focus on models with multidimensional incomplete information, such as: 1) Add incomplete information to the dynamic &amp; stochastic knapsack problem; 2) Allow for strategic purchase time in dynamic pricing models; 3)Allow for competing mechanism designers. The ensuing control problems are often not standard and require special tools. An additional attack line will be devoted to models that combine design with learning about the environment. The information revealed by an agent affects then both the value of the current allocation, and the option value of future allocations. We plan to: 1) Derive the properties of learning processes that allow efficient, dynamic implementation; 2) Characterize second-best mechanism in cases where adaptive learning and efficiency are not compatible with each other.
We plan to construct a theoretical bridge between classical dynamic allocation models used in Operations Research/Management Science, and between the modern theory of mechanism design. Our theoretical results will generate insights for the construction of applied pricing schemes and testable implications about the pattern of observed prices. The Economics literature has focused on information and incentive issues in static models, whereas the Operations Research/Management Science literature has looked at dynamic models that were often lacking strategic/ informational aspects. There is an increased recent interest in combining these bodies of knowledge, spurred by studies of yield management, and of decentralized platforms for interaction/ communication among agents. A general mechanism design analysis starts with the characterization of all dynamically implementable allocation policies. Variational arguments can be used then to characterize optimal policies. The research will focus on models with multidimensional incomplete information, such as: 1) Add incomplete information to the dynamic &amp; stochastic knapsack problem; 2) Allow for strategic purchase time in dynamic pricing models; 3)Allow for competing mechanism designers. The ensuing control problems are often not standard and require special tools. An additional attack line will be devoted to models that combine design with learning about the environment. The information revealed by an agent affects then both the value of the current allocation, and the option value of future allocations. We plan to: 1) Derive the properties of learning processes that allow efficient, dynamic implementation; 2) Characterize second-best mechanism in cases where adaptive learning and efficiency are not compatible with each other.
Project acronym DNADEMETHYLASE
Project Functions and mechanism of active DNA demethylation
Researcher (PI) Heinz Christof Niehrs
Host Institution (HI) INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH
Summary Epigenetic gene regulation is of central importance for development and disease. Despite dramatic progress in epigenetics during the past decade, DNA demethylation remains one of the last big frontiers and very little is known about it. DNA demethylation is a widespread phenomenon and occurs in plants as well as in animals, during development, in the adult, and during somatic cell reprogramming of pluripotency genes. The molecular identity of the DNA demethylase in animal cells remained unresolved and has hampered progress in the field for decades. In 2007 we published that Growth Arrest and DNA Damage 45 a (Gadd45a) is a key player in active DNA demethylation, which opened new avenues in the study of this elusive process. The goal of this project is to further analyze the mechanism of DNA demethylation as well as the role played by Gadd45 in development. Given the many unresolved questions in this burgeoning field, our work promises to be ground-breaking and therefore have a profound impact in unraveling one of the least understood processes of gene regulation. Specifically we will address the following points. I) The biological role of Gadd45 mediated DNA demethylation in mouse embryos and adults is unknown. We have obtained mouse mutants for Gadd45a,b, and g and we will analyze them for developmental defects and dissect the methylation regulation of relevant genes. II) The targeting mechanism by which Gadd45 is binding to and demethylating specific sites in the genome is a central unresolved issue. We have identified a candidate DNA binding protein interacting with Gadd45 and we will analyze its role in site specific targeting of DNA demethylation in vitro and in mouse. III) We found that Gadd45 is an RNA binding protein and we will therefore analyze how non-coding RNAs are involved in targeting and/or activating Gadd45 during DNA demethylation.
Epigenetic gene regulation is of central importance for development and disease. Despite dramatic progress in epigenetics during the past decade, DNA demethylation remains one of the last big frontiers and very little is known about it. DNA demethylation is a widespread phenomenon and occurs in plants as well as in animals, during development, in the adult, and during somatic cell reprogramming of pluripotency genes. The molecular identity of the DNA demethylase in animal cells remained unresolved and has hampered progress in the field for decades. In 2007 we published that Growth Arrest and DNA Damage 45 a (Gadd45a) is a key player in active DNA demethylation, which opened new avenues in the study of this elusive process. The goal of this project is to further analyze the mechanism of DNA demethylation as well as the role played by Gadd45 in development. Given the many unresolved questions in this burgeoning field, our work promises to be ground-breaking and therefore have a profound impact in unraveling one of the least understood processes of gene regulation. Specifically we will address the following points. I) The biological role of Gadd45 mediated DNA demethylation in mouse embryos and adults is unknown. We have obtained mouse mutants for Gadd45a,b, and g and we will analyze them for developmental defects and dissect the methylation regulation of relevant genes. II) The targeting mechanism by which Gadd45 is binding to and demethylating specific sites in the genome is a central unresolved issue. We have identified a candidate DNA binding protein interacting with Gadd45 and we will analyze its role in site specific targeting of DNA demethylation in vitro and in mouse. III) We found that Gadd45 is an RNA binding protein and we will therefore analyze how non-coding RNAs are involved in targeting and/or activating Gadd45 during DNA demethylation.
Project acronym DRAMANET
Project Early Modern European Drama and the Cultural Net
Researcher (PI) Joachim Rudolf Otto Küpper
Host Institution (HI) FREIE UNIVERSITAET BERLIN
Summary The project pursues a historical and a theoretical objective. First, it aims at giving a comprehensive analysis of (Western) European early modern drama as the first phenomenon of mass media in human history. Second, it aims at exploring the explanatory value of the metaphor of culture as a net. In that period, drama as performance casts the basis of modern mass media; it establishes for the first time in human history the cultural practice of a public visual culture that is not bound to ritual patterns and the ensuing constraints. In terms of theory, the project will investigate the productivity of the metaphor of culture as a net. A net is a non-hierarchical structure without a centre. There is no entelechical form of a net. Nets are never complete. Nets may thus extend and branch out to regions which are completely unknown to those who set them up initially. Since they are constructed by humans, nets are subject to human will as to their transport capacity. Material may be allowed to float freely or it may be submitted to scrutiny. The control logic may be belief-driven, power-driven or money-driven. The floating material may circulate in different degrees of formal organization. The outlined approach will open up perspectives for investigating European drama beyond the boundaries of national cultures. Transculturality will thus be considered to be the standard case, while nationality of cultural artefacts will be considered the particular case. Common traits between texts / cultural artefacts stemming from different eras or from different areas will no longer be difficult to explain. Reception in later times or in other regions can be accounted for with regard to the aforementioned three basic control mechanisms. Basic formal standards, whose accomplishment can be observed in all European national cultures, can be explained as a floating of material at differing levels of formal organization.
The project pursues a historical and a theoretical objective. First, it aims at giving a comprehensive analysis of (Western) European early modern drama as the first phenomenon of mass media in human history. Second, it aims at exploring the explanatory value of the metaphor of culture as a net. In that period, drama as performance casts the basis of modern mass media; it establishes for the first time in human history the cultural practice of a public visual culture that is not bound to ritual patterns and the ensuing constraints. In terms of theory, the project will investigate the productivity of the metaphor of culture as a net. A net is a non-hierarchical structure without a centre. There is no entelechical form of a net. Nets are never complete. Nets may thus extend and branch out to regions which are completely unknown to those who set them up initially. Since they are constructed by humans, nets are subject to human will as to their transport capacity. Material may be allowed to float freely or it may be submitted to scrutiny. The control logic may be belief-driven, power-driven or money-driven. The floating material may circulate in different degrees of formal organization. The outlined approach will open up perspectives for investigating European drama beyond the boundaries of national cultures. Transculturality will thus be considered to be the standard case, while nationality of cultural artefacts will be considered the particular case. Common traits between texts / cultural artefacts stemming from different eras or from different areas will no longer be difficult to explain. Reception in later times or in other regions can be accounted for with regard to the aforementioned three basic control mechanisms. Basic formal standards, whose accomplishment can be observed in all European national cultures, can be explained as a floating of material at differing levels of formal organization.
Project acronym ESEI
Project Engineering Social and Economic Institutions
Researcher (PI) Jacob Goeree
Host Institution (HI) UNIVERSITAT ZURICH
Summary The advent of the Internet and the increased power of modern day computing have dramatically changed the economic landscape. Billions of dollars worth of goods are being auctioned among geographically dispersed buyers; online brokerages are used to find jobs, trade stocks, make travel arrangements, etc. The architecture of these online (trading) platforms is typically rooted in their pre-Internet counterparts, and advances in the theory of market design combined with increased computing capabilities prompt a careful re-evaluation. This proposal concerns the creation of novel, more flexible institutions using an approach that combines theory, laboratory experiments, and practical policy. The first project enhances our understanding of newly designed package auctions by developing equilibrium models of competitive bidding and measuring the efficacy of alternative formats in controlled experiments. The next project studies novel market forms that allow for all-or-nothing trades to alleviate inefficiencies and enhance dynamic stability when complementarities exist. The third project concerns the design of market regulation and procurement contests to create better incentives for research and development. The fourth project addresses information aggregation properties of alternative voting institutions, suggesting improvements for referenda and jury/committee voting. The Internet has also dramatically altered the nature of social interactions. Emerging institutions such as online social networking tools, rating systems, and web-community Q&amp;A services reduce social distances and catalyze opportunities for social learning. The final project focuses on social learning in a variety of settings and on the impact of social networks on behavior. Combined these projects generate insights that apply to a broad array of social and economic environments and that will guide practitioners to the use of better designed institutions.
The advent of the Internet and the increased power of modern day computing have dramatically changed the economic landscape. Billions of dollars worth of goods are being auctioned among geographically dispersed buyers; online brokerages are used to find jobs, trade stocks, make travel arrangements, etc. The architecture of these online (trading) platforms is typically rooted in their pre-Internet counterparts, and advances in the theory of market design combined with increased computing capabilities prompt a careful re-evaluation. This proposal concerns the creation of novel, more flexible institutions using an approach that combines theory, laboratory experiments, and practical policy. The first project enhances our understanding of newly designed package auctions by developing equilibrium models of competitive bidding and measuring the efficacy of alternative formats in controlled experiments. The next project studies novel market forms that allow for all-or-nothing trades to alleviate inefficiencies and enhance dynamic stability when complementarities exist. The third project concerns the design of market regulation and procurement contests to create better incentives for research and development. The fourth project addresses information aggregation properties of alternative voting institutions, suggesting improvements for referenda and jury/committee voting. The Internet has also dramatically altered the nature of social interactions. Emerging institutions such as online social networking tools, rating systems, and web-community Q&amp;A services reduce social distances and catalyze opportunities for social learning. The final project focuses on social learning in a variety of settings and on the impact of social networks on behavior. Combined these projects generate insights that apply to a broad array of social and economic environments and that will guide practitioners to the use of better designed institutions.
Project acronym ETHIO-SPARE
Project Cultural Heritage of Christian Ethiopia: Salvation, Preservation and Research
Researcher (PI) Denis Nosnitsin
Summary Ethiopia is one of the countries with the most ancient Christian history, and the only country in Africa where Christianity became official religion as early as in the 4th century A.D. It is also the only country in the region where the history has been documented in written sources: manuscripts in possession of ca. 600 monasteries and 20,000 churches, some of which date back to early Middle Ages, have been estimated to number up to ca. 200,000. Only a minor part of these archives have so far received scholarly evaluation, only less than one tenth of manuscripts have been microfilmed or digitalized, and only those that have come in possession of European libraries have been duly catalogued and are well protected. A great part of this unique heritage is on the verge of extinction, and urgent action needs to be taken to save it from complete disappearance. A thorough research into the texts will grant insight into the mentality of this African region and provide parallels to the ways other African regions without ancient written tradition may have developed, as well as to the ways Christianity spread in medieval Europe: in monastic Ethiopia some features now lost in the civilized world may still be observed. The project will unite scholars working in the fields of philology, codicology, digital philology, religious studies, anthropology, art history, and book preservation, who will secure the most important pieces of historical written evidence and carry out first-hand in-depth research into the witnesses. Local history and oral traditions collected during field research will allow a comprehensive and complete evaluation of the sources. Focus on historiographic and legal documents will allow a detailed reconstruction of local history of selected regions.
Ethiopia is one of the countries with the most ancient Christian history, and the only country in Africa where Christianity became official religion as early as in the 4th century A.D. It is also the only country in the region where the history has been documented in written sources: manuscripts in possession of ca. 600 monasteries and 20,000 churches, some of which date back to early Middle Ages, have been estimated to number up to ca. 200,000. Only a minor part of these archives have so far received scholarly evaluation, only less than one tenth of manuscripts have been microfilmed or digitalized, and only those that have come in possession of European libraries have been duly catalogued and are well protected. A great part of this unique heritage is on the verge of extinction, and urgent action needs to be taken to save it from complete disappearance. A thorough research into the texts will grant insight into the mentality of this African region and provide parallels to the ways other African regions without ancient written tradition may have developed, as well as to the ways Christianity spread in medieval Europe: in monastic Ethiopia some features now lost in the civilized world may still be observed. The project will unite scholars working in the fields of philology, codicology, digital philology, religious studies, anthropology, art history, and book preservation, who will secure the most important pieces of historical written evidence and carry out first-hand in-depth research into the witnesses. Local history and oral traditions collected during field research will allow a comprehensive and complete evaluation of the sources. Focus on historiographic and legal documents will allow a detailed reconstruction of local history of selected regions.
Project acronym FORCEDLABOURAFRICA
Project Forced labour: an Afro-European heritage in sub-Saharan Africa (1930-1975)?
Researcher (PI) Alexander Keese
Host Institution (HI) HUMBOLDT-UNIVERSITAET ZU BERLIN
Summary This project analyses the structures of colonial systems of forced labour, in an attempt to come to a comparison of the different trajectories of African populations under distinct European administrations. Through the interpretation of case studies from different West African and Central African territories, it will be possible to understand the techniques of organising an involuntary labour force, and their evolution until and beyond independence. The slow process of the abolition of forced labour from World War II did not exclude continuities in clandestine practices of forcing African (rural) populations to work without remuneration. Another form of continuity connects colonial practices to the postcolonial re-institution of systems of forced labour: many postcolonial African governments were inclined to rely themselves on respective practices under the impression of dire budgetary situations. The different case studies will highlight the existence of forced labour as an Afro-European heritage in the social structures of African societies, and link that heritage back to the experiences of African populations in the local arena. For cases from Ghana, Senegal, São Tomé e Príncipe, and a larger Central African region consisting of sub-cases from Angola, Gabon, and Zambia, the project will address the question how structures of and changes in forced labour had an impact on relations of power inside of the local societies. In particular, forced labour was, in the colonial period, not only a means for colonial officials to shape socio-economic realities in the colonies according to their ideas, but it also was an instrument in the hands of chiefs ( traditional rulers ) who were eager to employ it as a weapon to discipline any existing opposition among their populations. African voices, both from archival sources and from interviews, will be in the focus of this analysis: they will show the importance of the particular experience of forced labour for African social evolution
This project analyses the structures of colonial systems of forced labour, in an attempt to come to a comparison of the different trajectories of African populations under distinct European administrations. Through the interpretation of case studies from different West African and Central African territories, it will be possible to understand the techniques of organising an involuntary labour force, and their evolution until and beyond independence. The slow process of the abolition of forced labour from World War II did not exclude continuities in clandestine practices of forcing African (rural) populations to work without remuneration. Another form of continuity connects colonial practices to the postcolonial re-institution of systems of forced labour: many postcolonial African governments were inclined to rely themselves on respective practices under the impression of dire budgetary situations. The different case studies will highlight the existence of forced labour as an Afro-European heritage in the social structures of African societies, and link that heritage back to the experiences of African populations in the local arena. For cases from Ghana, Senegal, São Tomé e Príncipe, and a larger Central African region consisting of sub-cases from Angola, Gabon, and Zambia, the project will address the question how structures of and changes in forced labour had an impact on relations of power inside of the local societies. In particular, forced labour was, in the colonial period, not only a means for colonial officials to shape socio-economic realities in the colonies according to their ideas, but it also was an instrument in the hands of chiefs ( traditional rulers ) who were eager to employ it as a weapon to discipline any existing opposition among their populations. African voices, both from archival sources and from interviews, will be in the focus of this analysis: they will show the importance of the particular experience of forced labour for African social evolution
Project acronym FPMICROGLIA
Project Towards a dynamic quantitative understanding of neuronal microglial interactions
Researcher (PI) Francesca Peri
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Summary A significant proportion of neurons in the brain undergo programmed cell death. In order to prevent the diffusion of damaging degradation products, dying neurons are quickly collected by microglia, specialised phagocytes that are resident in the brain. Despite the importance of these cells in several neuronal pathologies, many fundamental questions concerning microglial-neuronal interactions remain unaddressed. How these cells collectively ensure that the entire brain is surveyed and how they react to damage with high precision is still entirely unknown. Recent findings suggest that diffusible molecules such as lipids and nucleotides could attract microglia in response to neuronal apoptosis and injury, respectively. While these molecules can trigger dynamic changes in microglia motility in vitro, elucidating how their activity is controlled within the intact brain, both in space and time, remains the most important challenge in understanding this fascinating biological problem. We aim to further exploit the massive imaging potential of the transparent zebrafish embryo for studying microglial biology in vivo. By combining forward and reverse genetic approaches with quantitative imaging technology, we will directly address the mechanisms underlying the attraction of microglia towards apoptotic, sick and injured neurons. For the first time, we will define the collective behaviour of an entire microglial network within an intact brain under both physiological and pathological conditions.
A significant proportion of neurons in the brain undergo programmed cell death. In order to prevent the diffusion of damaging degradation products, dying neurons are quickly collected by microglia, specialised phagocytes that are resident in the brain. Despite the importance of these cells in several neuronal pathologies, many fundamental questions concerning microglial-neuronal interactions remain unaddressed. How these cells collectively ensure that the entire brain is surveyed and how they react to damage with high precision is still entirely unknown. Recent findings suggest that diffusible molecules such as lipids and nucleotides could attract microglia in response to neuronal apoptosis and injury, respectively. While these molecules can trigger dynamic changes in microglia motility in vitro, elucidating how their activity is controlled within the intact brain, both in space and time, remains the most important challenge in understanding this fascinating biological problem. We aim to further exploit the massive imaging potential of the transparent zebrafish embryo for studying microglial biology in vivo. By combining forward and reverse genetic approaches with quantitative imaging technology, we will directly address the mechanisms underlying the attraction of microglia towards apoptotic, sick and injured neurons. For the first time, we will define the collective behaviour of an entire microglial network within an intact brain under both physiological and pathological conditions.