Project acronym 2-HIT
Project Genetic interaction networks: From C. elegans to human disease
Researcher (PI) Ben Lehner
Host Institution (HI) FUNDACIO CENTRE DE REGULACIO GENOMICA
Call Details Starting Grant (StG), LS2, ERC-2007-StG
Summary Most hereditary diseases in humans are genetically complex, resulting from combinations of mutations in multiple genes. However synthetic interactions between genes are very difficult to identify in population studies because of a lack of statistical power and we fundamentally do not understand how mutations interact to produce phenotypes. C. elegans is a unique animal in which genetic interactions can be rapidly identified in vivo using RNA interference, and we recently used this system to construct the first genetic interaction network for any animal, focused on signal transduction genes. The first objective of this proposal is to extend this work and map a comprehensive genetic interaction network for this model metazoan. This project will provide the first insights into the global properties of animal genetic interaction networks, and a comprehensive view of the functional relationships between genes in an animal. The second objective of the proposal is to use C. elegans to develop and validate experimentally integrated gene networks that connect genes to phenotypes and predict genetic interactions on a genome-wide scale. The methods that we develop and validate in C. elegans will then be applied to predict phenotypes and interactions for human genes. The final objective is to dissect the molecular mechanisms underlying genetic interactions, and to understand how these interactions evolve. The combined aim of these three objectives is to generate a framework for understanding and predicting how mutations interact to produce phenotypes, including in human disease.
Summary
Most hereditary diseases in humans are genetically complex, resulting from combinations of mutations in multiple genes. However synthetic interactions between genes are very difficult to identify in population studies because of a lack of statistical power and we fundamentally do not understand how mutations interact to produce phenotypes. C. elegans is a unique animal in which genetic interactions can be rapidly identified in vivo using RNA interference, and we recently used this system to construct the first genetic interaction network for any animal, focused on signal transduction genes. The first objective of this proposal is to extend this work and map a comprehensive genetic interaction network for this model metazoan. This project will provide the first insights into the global properties of animal genetic interaction networks, and a comprehensive view of the functional relationships between genes in an animal. The second objective of the proposal is to use C. elegans to develop and validate experimentally integrated gene networks that connect genes to phenotypes and predict genetic interactions on a genome-wide scale. The methods that we develop and validate in C. elegans will then be applied to predict phenotypes and interactions for human genes. The final objective is to dissect the molecular mechanisms underlying genetic interactions, and to understand how these interactions evolve. The combined aim of these three objectives is to generate a framework for understanding and predicting how mutations interact to produce phenotypes, including in human disease.
Max ERC Funding
1 100 000 €
Duration
Start date: 2008-09-01, End date: 2014-04-30
Project acronym 5COFM
Project Five Centuries of Marriages
Researcher (PI) Anna Cabré
Host Institution (HI) UNIVERSITAT AUTONOMA DE BARCELONA
Call Details Advanced Grant (AdG), SH6, ERC-2010-AdG_20100407
Summary This long-term research project is based on the data-mining of the Llibres d'Esposalles conserved at the Archives of the Barcelona Cathedral, an extraordinary data source comprising 244 books of marriage licenses records. It covers about 550.000 unions from over 250 parishes of the Diocese between 1451 and 1905. Its impeccable conservation is a miracle in a region where parish archives have undergone massive destruction. The books include data on the tax posed on each couple depending on their social class, on an eight-tiered scale. These data allow for research on multiple aspects of demographic research, especially on the very long run, such as: population estimates, marriage dynamics, cycles, and indirect estimations for fertility, migration and survival, as well as socio-economic studies related to social homogamy, social mobility, and transmission of social and occupational position. Being continuous over five centuries, the source constitutes a unique instrument to study the dynamics of population distribution, the expansion of the city of Barcelona and the constitution of its metropolitan area, as well as the chronology and the geography in the constitution of new social classes.
To this end, a digital library and a database, the Barcelona Historical Marriages Database (BHiMaD), are to be created and completed. An ERC-AG will help doing so while undertaking the research analysis of the database in parallel.
The research team, at the U. Autònoma de Barcelona, involves researchers from the Center for Demo-graphic Studies and the Computer Vision Center experts in historical databases and computer-aided recognition of ancient manuscripts. 5CofM will serve the preservation of the original “Llibres d’Esposalles” and unlock the full potential embedded in the collection.
Summary
This long-term research project is based on the data-mining of the Llibres d'Esposalles conserved at the Archives of the Barcelona Cathedral, an extraordinary data source comprising 244 books of marriage licenses records. It covers about 550.000 unions from over 250 parishes of the Diocese between 1451 and 1905. Its impeccable conservation is a miracle in a region where parish archives have undergone massive destruction. The books include data on the tax posed on each couple depending on their social class, on an eight-tiered scale. These data allow for research on multiple aspects of demographic research, especially on the very long run, such as: population estimates, marriage dynamics, cycles, and indirect estimations for fertility, migration and survival, as well as socio-economic studies related to social homogamy, social mobility, and transmission of social and occupational position. Being continuous over five centuries, the source constitutes a unique instrument to study the dynamics of population distribution, the expansion of the city of Barcelona and the constitution of its metropolitan area, as well as the chronology and the geography in the constitution of new social classes.
To this end, a digital library and a database, the Barcelona Historical Marriages Database (BHiMaD), are to be created and completed. An ERC-AG will help doing so while undertaking the research analysis of the database in parallel.
The research team, at the U. Autònoma de Barcelona, involves researchers from the Center for Demo-graphic Studies and the Computer Vision Center experts in historical databases and computer-aided recognition of ancient manuscripts. 5CofM will serve the preservation of the original “Llibres d’Esposalles” and unlock the full potential embedded in the collection.
Max ERC Funding
1 847 400 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym Aftermath
Project THE AFTERMATH OF THE EAST ASIAN WAR OF 1592-1598.
Researcher (PI) Rebekah CLEMENTS
Host Institution (HI) UNIVERSITAT AUTONOMA DE BARCELONA
Call Details Starting Grant (StG), SH6, ERC-2017-STG
Summary Aftermath seeks to understand the legacy of the East Asian War of 1592-1598. This conflict involved over 500,000 combatants from Japan, China, and Korea; up to 100,000 Korean civilians were abducted to Japan. The war caused momentous demographic upheaval and widespread destruction, but also had long-lasting cultural impact as a result of the removal to Japan of Korean technology and skilled labourers. The conflict and its aftermath bear striking parallels to events in East Asia during World War 2, and memories of the 16th century war remain deeply resonant in the region. However, the war and its immediate aftermath are also significant because they occurred at the juncture of periods often characterized as “medieval” and “early modern” in the East Asian case. What were the implications for the social, economic, and cultural contours of early modern East Asia? What can this conflict tell us about war “aftermath” across historical periods and about such periodization itself? There is little Western scholarship on the war and few studies in any language cross linguistic, disciplinary, and national boundaries to achieve a regional perspective that reflects the interconnected history of East Asia. Aftermath will radically alter our understanding of the region’s history by providing the first analysis of the state of East Asia as a result of the war. The focus will be on the period up to the middle of the 17th century, but not precluding ongoing effects. The team, with expertise covering Japan, Korea, and China, will investigate three themes: the movement of people and demographic change, the impact on the natural environment, and technological diffusion. The project will be the first large scale investigation to use Japanese, Korean, and Chinese sources to understand the war’s aftermath. It will broaden understandings of the early modern world, and push the boundaries of war legacy studies by exploring the meanings of “aftermath” in the early modern East Asian context.
Summary
Aftermath seeks to understand the legacy of the East Asian War of 1592-1598. This conflict involved over 500,000 combatants from Japan, China, and Korea; up to 100,000 Korean civilians were abducted to Japan. The war caused momentous demographic upheaval and widespread destruction, but also had long-lasting cultural impact as a result of the removal to Japan of Korean technology and skilled labourers. The conflict and its aftermath bear striking parallels to events in East Asia during World War 2, and memories of the 16th century war remain deeply resonant in the region. However, the war and its immediate aftermath are also significant because they occurred at the juncture of periods often characterized as “medieval” and “early modern” in the East Asian case. What were the implications for the social, economic, and cultural contours of early modern East Asia? What can this conflict tell us about war “aftermath” across historical periods and about such periodization itself? There is little Western scholarship on the war and few studies in any language cross linguistic, disciplinary, and national boundaries to achieve a regional perspective that reflects the interconnected history of East Asia. Aftermath will radically alter our understanding of the region’s history by providing the first analysis of the state of East Asia as a result of the war. The focus will be on the period up to the middle of the 17th century, but not precluding ongoing effects. The team, with expertise covering Japan, Korea, and China, will investigate three themes: the movement of people and demographic change, the impact on the natural environment, and technological diffusion. The project will be the first large scale investigation to use Japanese, Korean, and Chinese sources to understand the war’s aftermath. It will broaden understandings of the early modern world, and push the boundaries of war legacy studies by exploring the meanings of “aftermath” in the early modern East Asian context.
Max ERC Funding
1 444 980 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym AGRIWESTMED
Project Origins and spread of agriculture in the south-western Mediterranean region
Researcher (PI) Maria Leonor Peña Chocarro
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), SH6, ERC-2008-AdG
Summary This project focuses on one of the most fascinating events of the long history of the human species: the origins and spread of agriculture. Research over the past 40 years has provided an invaluable dataset on crop domestication and the spread of agriculture into Europe. However, despite the enormous advances in research there are important areas that remain almost unexplored, some of immense interest. This is the case of the western Mediterranean region from where our knowledge is still limited (Iberian Peninsula) or almost inexistent (northern Morocco). The last few years have witnessed a considerable increase in archaeobotany and the effort of a group of Spanish researchers working together in different aspects of agriculture has started to produce the first results. My proposal will approach the study of the arrival of agriculture to the western Mediterranean by exploring different interrelated research areas. The project involves the
application of different techniques (analysis of charred plant remains, pollen and non-pollen microfossils, phytoliths, micro-wear analyses, isotopes, soil micromorphology, genetics, and ethnoarchaeology) which will help to define the emergence and spread of agriculture in the area, its likely place of origin, its main technological attributes as well as the range crop husbandry practices carried out. The interaction between the different approaches and the methodologies involved will allow achieving a greater understanding of the type of agriculture that characterized the first farming communities in the most south-western part of Europe.
Summary
This project focuses on one of the most fascinating events of the long history of the human species: the origins and spread of agriculture. Research over the past 40 years has provided an invaluable dataset on crop domestication and the spread of agriculture into Europe. However, despite the enormous advances in research there are important areas that remain almost unexplored, some of immense interest. This is the case of the western Mediterranean region from where our knowledge is still limited (Iberian Peninsula) or almost inexistent (northern Morocco). The last few years have witnessed a considerable increase in archaeobotany and the effort of a group of Spanish researchers working together in different aspects of agriculture has started to produce the first results. My proposal will approach the study of the arrival of agriculture to the western Mediterranean by exploring different interrelated research areas. The project involves the
application of different techniques (analysis of charred plant remains, pollen and non-pollen microfossils, phytoliths, micro-wear analyses, isotopes, soil micromorphology, genetics, and ethnoarchaeology) which will help to define the emergence and spread of agriculture in the area, its likely place of origin, its main technological attributes as well as the range crop husbandry practices carried out. The interaction between the different approaches and the methodologies involved will allow achieving a greater understanding of the type of agriculture that characterized the first farming communities in the most south-western part of Europe.
Max ERC Funding
1 545 169 €
Duration
Start date: 2009-04-01, End date: 2013-03-31
Project acronym ArtEmpire
Project An ARTery of EMPIRE. Conquest, Commerce, Crisis, Culture and the Panamanian Junction (1513-1671)
Researcher (PI) Bethany Aram Worzella
Host Institution (HI) UNIVERSIDAD PABLO DE OLAVIDE
Call Details Consolidator Grant (CoG), SH6, ERC-2014-CoG
Summary European incursions onto the narrow isthmian pass that divided and connected the Atlantic and Pacific oceans made it a strategic node of the Spanish Empire and a crucial site for early modern globalization. On the front lines of the convergence of four continents, Old Panama offers an unusual opportunity for examining the diverse, often asymmetrical impacts of cultural and commercial contacts. The role of Italian, Portuguese, British, Dutch, and French interests in the area, as well as an influx of African slaves and Asian merchandise, have left a unique material legacy that requires an integrated, interdisciplinary approach to its varied sources. Bones, teeth and artifacts on this artery of Empire offer the possibility of new insights into the cultural and biological impact of early globalization. They also invite an interdisciplinary approach to different groups’ tactics for survival, including possible dietary changes, and the pursuit of profit. Such strategies may have led the diverse peoples inhabiting this junction, from indigenous allies to African and Asian bandits to European corsairs, to develop and to favor local production and Pacific trade networks at the expense of commerce with the metropolis.
This project applies historical, archaeological and archaeometric methodologies to evidence of encounters between peoples and goods from Europe, America, Africa and Asia that took place on the Isthmus of Panama during the sixteenth and seventeenth centuries. Forging an interdisciplinary approach to early globalization, it challenges both Euro-centric and Hispano-phobic interpretations of the impact of the conquest of America, traditionally seen as a demographic catastrophe that reached its nadir in the so-called seventeenth-century crisis. Rather than applying quantitative methods to incomplete source material, researchers will adopt a contextualized, inter-disciplinary, qualitative approach to diverse agents involved in cultural and commercial exchange.
Summary
European incursions onto the narrow isthmian pass that divided and connected the Atlantic and Pacific oceans made it a strategic node of the Spanish Empire and a crucial site for early modern globalization. On the front lines of the convergence of four continents, Old Panama offers an unusual opportunity for examining the diverse, often asymmetrical impacts of cultural and commercial contacts. The role of Italian, Portuguese, British, Dutch, and French interests in the area, as well as an influx of African slaves and Asian merchandise, have left a unique material legacy that requires an integrated, interdisciplinary approach to its varied sources. Bones, teeth and artifacts on this artery of Empire offer the possibility of new insights into the cultural and biological impact of early globalization. They also invite an interdisciplinary approach to different groups’ tactics for survival, including possible dietary changes, and the pursuit of profit. Such strategies may have led the diverse peoples inhabiting this junction, from indigenous allies to African and Asian bandits to European corsairs, to develop and to favor local production and Pacific trade networks at the expense of commerce with the metropolis.
This project applies historical, archaeological and archaeometric methodologies to evidence of encounters between peoples and goods from Europe, America, Africa and Asia that took place on the Isthmus of Panama during the sixteenth and seventeenth centuries. Forging an interdisciplinary approach to early globalization, it challenges both Euro-centric and Hispano-phobic interpretations of the impact of the conquest of America, traditionally seen as a demographic catastrophe that reached its nadir in the so-called seventeenth-century crisis. Rather than applying quantitative methods to incomplete source material, researchers will adopt a contextualized, inter-disciplinary, qualitative approach to diverse agents involved in cultural and commercial exchange.
Max ERC Funding
1 998 875 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym ARTSOUNDSCAPES
Project The sound of special places: exploring rock art soundscapes and the sacred
Researcher (PI) A. Margarita DIAZ-ANDREU
Host Institution (HI) UNIVERSITAT DE BARCELONA
Call Details Advanced Grant (AdG), SH6, ERC-2017-ADG
Summary The ARTSOUNDSCAPES project deals with sound, rock art and sacred landscapes among past hunter-gatherers and early agricultural societies around the world. The potential of sound to stimulate powerful emotions makes it a common medium for conferring places with extraordinary agency. Ethnographic and ethnohistorical sources indicate that these sites are often endowed with a sacred significance and, in many cases, they also receive special treatment, including the production of rock paintings. Despite the aural experience being an integral component of the human condition and a key element in ritual, archaeology has largely been unable to study it systematically. Rock art landscapes are no exception and, although some studies have been made, they have largely been reproached for their lack of scientific rigour and subjectivity. ARTSOUNDSCAPES will fully address this weakness by investigating the perception of sound in rock art landscapes from an interdisciplinary approach. Borrowing methods developed in acoustic engineering, the project will assess, from an objective and quantitative perspective, the acoustic properties of rock art landscapes in selected areas around the world: the Western/Central Mediterranean in Europe, Siberia in Asia, and Baja California in North America. Human experiences associated with altered or mystical states invoked by the identified special sonic characteristics of these landscapes will be further tested by exploring the psychoacoustic effects these soundscapes have on people and their neural correlate to brain activity. The project will also thoroughly survey ethnographic attitudes to sacred soundscapes based on both current premodern societies and ethnohistorical sources. The groundbreaking combination of this array of interdisciplinary approaches will facilitate the ultimate aim of the project: to propose a phenomenological understanding of sacred soundscapes among late hunter-gatherers and early agriculturalists around the world.
Summary
The ARTSOUNDSCAPES project deals with sound, rock art and sacred landscapes among past hunter-gatherers and early agricultural societies around the world. The potential of sound to stimulate powerful emotions makes it a common medium for conferring places with extraordinary agency. Ethnographic and ethnohistorical sources indicate that these sites are often endowed with a sacred significance and, in many cases, they also receive special treatment, including the production of rock paintings. Despite the aural experience being an integral component of the human condition and a key element in ritual, archaeology has largely been unable to study it systematically. Rock art landscapes are no exception and, although some studies have been made, they have largely been reproached for their lack of scientific rigour and subjectivity. ARTSOUNDSCAPES will fully address this weakness by investigating the perception of sound in rock art landscapes from an interdisciplinary approach. Borrowing methods developed in acoustic engineering, the project will assess, from an objective and quantitative perspective, the acoustic properties of rock art landscapes in selected areas around the world: the Western/Central Mediterranean in Europe, Siberia in Asia, and Baja California in North America. Human experiences associated with altered or mystical states invoked by the identified special sonic characteristics of these landscapes will be further tested by exploring the psychoacoustic effects these soundscapes have on people and their neural correlate to brain activity. The project will also thoroughly survey ethnographic attitudes to sacred soundscapes based on both current premodern societies and ethnohistorical sources. The groundbreaking combination of this array of interdisciplinary approaches will facilitate the ultimate aim of the project: to propose a phenomenological understanding of sacred soundscapes among late hunter-gatherers and early agriculturalists around the world.
Max ERC Funding
2 239 375 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym BCLYM
Project Molecular mechanisms of mature B cell lymphomagenesis
Researcher (PI) Almudena Ramiro
Host Institution (HI) CENTRO NACIONAL DE INVESTIGACIONESCARDIOVASCULARES CARLOS III (F.S.P.)
Call Details Starting Grant (StG), LS3, ERC-2007-StG
Summary Most of the lymphomas diagnosed in the western world are originated from mature B cells. The hallmark of these malignancies is the presence of recurrent chromosome translocations that usually involve the immunoglobulin loci and a proto-oncogene. As a result of the translocation event the proto-oncogene becomes deregulated under the influence of immunoglobulin cis sequences thus playing an important role in the etiology of the disease. Upon antigen encounter mature B cells engage in the germinal center reaction, a complex differentiation program of critical importance to the development of the secondary immune response. The germinal center reaction entails the somatic remodelling of immunoglobulin genes by the somatic hypermutation and class switch recombination reactions, both of which are triggered by Activation Induced Deaminase (AID). We have previously shown that AID also initiates lymphoma-associated c-myc/IgH chromosome translocations. In addition, the germinal center reaction involves a fine-tuned balance between intense B cell proliferation and program cell death. This environment seems to render B cells particularly vulnerable to malignant transformation. We aim at studying the molecular events responsible for B cell susceptibility to lymphomagenesis from two perspectives. First, we will address the role of AID in the generation of lymphomagenic lesions in the context of AID specificity and transcriptional activation. Second, we will approach the regulatory function of microRNAs of AID-dependent, germinal center events. The proposal aims at the molecular understanding of a process that lies in the interface of immune regulation and oncogenic transformation and therefore the results will have profound implications both to basic and clinical understanding of lymphomagenesis.
Summary
Most of the lymphomas diagnosed in the western world are originated from mature B cells. The hallmark of these malignancies is the presence of recurrent chromosome translocations that usually involve the immunoglobulin loci and a proto-oncogene. As a result of the translocation event the proto-oncogene becomes deregulated under the influence of immunoglobulin cis sequences thus playing an important role in the etiology of the disease. Upon antigen encounter mature B cells engage in the germinal center reaction, a complex differentiation program of critical importance to the development of the secondary immune response. The germinal center reaction entails the somatic remodelling of immunoglobulin genes by the somatic hypermutation and class switch recombination reactions, both of which are triggered by Activation Induced Deaminase (AID). We have previously shown that AID also initiates lymphoma-associated c-myc/IgH chromosome translocations. In addition, the germinal center reaction involves a fine-tuned balance between intense B cell proliferation and program cell death. This environment seems to render B cells particularly vulnerable to malignant transformation. We aim at studying the molecular events responsible for B cell susceptibility to lymphomagenesis from two perspectives. First, we will address the role of AID in the generation of lymphomagenic lesions in the context of AID specificity and transcriptional activation. Second, we will approach the regulatory function of microRNAs of AID-dependent, germinal center events. The proposal aims at the molecular understanding of a process that lies in the interface of immune regulation and oncogenic transformation and therefore the results will have profound implications both to basic and clinical understanding of lymphomagenesis.
Max ERC Funding
1 596 000 €
Duration
Start date: 2008-12-01, End date: 2014-11-30
Project acronym BETWEEN THE TIMES
Project “Between the Times”: Embattled Temporalities and Political Imagination in Interwar Europe
Researcher (PI) Liisi KEEDUS
Host Institution (HI) TALLINN UNIVERSITY
Call Details Starting Grant (StG), SH6, ERC-2017-STG
Summary The proposed project offers a new, pan-European intellectual history of the political imagination in the interwar period that places the demise of historicism and progressivism – and the emerging anti-teleological visions of time – at the center of some of its most innovative ethical, political and methodological pursuits. It argues that only a distinctively cross-disciplinary and European narrative can capture the full ramifications and legacies of a fundamental rupture in thought conventionally, yet inadequately confined to the German cultural space and termed “anti-historicism”. It innovates narratively by exploring politically and theoretically interlaced reinventions of temporality across and between different disciplines (theology, jurisprudence, classical studies, literary theory, linguistics, sociology, philosophy), as well as other creative fields. It experiments methodologically by reconstructing the dynamics of political thought prosopographically, through intellectual groupings at the forefront of the scholarly and political debates of the period. It challenges the sufficiency of the standard focus in interwar intellectual history on one or two, at most three (usually “Western” European) national contexts by following out the interactions of these groupings in France, Britain, Germany, Russia, Czechoslovakia, and Romania – groupings whose members frequently moved across national contexts. What were the political languages encoded in the reinventions of time, and vice versa – how were political aims translated into and advanced through theoretical innovation? How did these differ in different national contexts, and why? What are the fragmented legacies of this rupture, disbursed in and through the philosophical, methodological and political dicta and dogmas that rooted themselves in post-1945 thought? This project provides the first comprehensive answer to these fundamental questions about the intellectual identity of Europe and its historicities.
Summary
The proposed project offers a new, pan-European intellectual history of the political imagination in the interwar period that places the demise of historicism and progressivism – and the emerging anti-teleological visions of time – at the center of some of its most innovative ethical, political and methodological pursuits. It argues that only a distinctively cross-disciplinary and European narrative can capture the full ramifications and legacies of a fundamental rupture in thought conventionally, yet inadequately confined to the German cultural space and termed “anti-historicism”. It innovates narratively by exploring politically and theoretically interlaced reinventions of temporality across and between different disciplines (theology, jurisprudence, classical studies, literary theory, linguistics, sociology, philosophy), as well as other creative fields. It experiments methodologically by reconstructing the dynamics of political thought prosopographically, through intellectual groupings at the forefront of the scholarly and political debates of the period. It challenges the sufficiency of the standard focus in interwar intellectual history on one or two, at most three (usually “Western” European) national contexts by following out the interactions of these groupings in France, Britain, Germany, Russia, Czechoslovakia, and Romania – groupings whose members frequently moved across national contexts. What were the political languages encoded in the reinventions of time, and vice versa – how were political aims translated into and advanced through theoretical innovation? How did these differ in different national contexts, and why? What are the fragmented legacies of this rupture, disbursed in and through the philosophical, methodological and political dicta and dogmas that rooted themselves in post-1945 thought? This project provides the first comprehensive answer to these fundamental questions about the intellectual identity of Europe and its historicities.
Max ERC Funding
1 425 000 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym CBSCS
Project Physiology of the adult carotid body stem cell niche
Researcher (PI) Ricardo Pardal
Host Institution (HI) UNIVERSIDAD DE SEVILLA
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary The discovery of adult neural stem cells (NSCs) has broaden our view of the physiological plasticity of the nervous system,
and has opened new perspectives on the possibility of tissue regeneration and repair in the brain. NSCs reside in specialized
niches in the adult mammalian nervous system, where they are exposed to specific paracrine signals regulating their
behavior. These neural progenitors are generally in a quiescent state within their niche, and they activate their proliferation
depending on tissue regenerative and growth needs. Understanding the mechanisms by which NSCs enter and exit the
quiescent state is crucial for the comprehension of the physiology of the adult nervous system. In this project we will study
the behavior of a specific subpopulation of adult neural stem cells recently described by our group in the carotid body (CB).
This small organ constitutes the most important chemosensor of the peripheral nervous system and has neuronal glomus
cells responsible for the chemosensing, and glia-like sustentacular cells which were thought to have just a supportive role.
We recently described that these sustentacular cells are dormant stem cells able to activate their proliferation in response to a
physiological stimulus like hypoxia, and to differentiate into new glomus cells necessary for the adaptation of the organ.
Due to our precise experimental control of the activation and deactivation of the CB neurogenic niche, we believe the CB is
an ideal model to study fundamental questions about adult neural stem cell physiology and the interaction with the niche. We
propose to study the cellular and molecular mechanisms by which these carotid body stem cells enter and exit the quiescent
state, which will help us understand the physiology of adult neurogenic niches. Likewise, understanding this neurogenic
process will improve the efficacy of using glomus cells for cell therapy against neurological disease, and might help us
understand some neural tumors.
Summary
The discovery of adult neural stem cells (NSCs) has broaden our view of the physiological plasticity of the nervous system,
and has opened new perspectives on the possibility of tissue regeneration and repair in the brain. NSCs reside in specialized
niches in the adult mammalian nervous system, where they are exposed to specific paracrine signals regulating their
behavior. These neural progenitors are generally in a quiescent state within their niche, and they activate their proliferation
depending on tissue regenerative and growth needs. Understanding the mechanisms by which NSCs enter and exit the
quiescent state is crucial for the comprehension of the physiology of the adult nervous system. In this project we will study
the behavior of a specific subpopulation of adult neural stem cells recently described by our group in the carotid body (CB).
This small organ constitutes the most important chemosensor of the peripheral nervous system and has neuronal glomus
cells responsible for the chemosensing, and glia-like sustentacular cells which were thought to have just a supportive role.
We recently described that these sustentacular cells are dormant stem cells able to activate their proliferation in response to a
physiological stimulus like hypoxia, and to differentiate into new glomus cells necessary for the adaptation of the organ.
Due to our precise experimental control of the activation and deactivation of the CB neurogenic niche, we believe the CB is
an ideal model to study fundamental questions about adult neural stem cell physiology and the interaction with the niche. We
propose to study the cellular and molecular mechanisms by which these carotid body stem cells enter and exit the quiescent
state, which will help us understand the physiology of adult neurogenic niches. Likewise, understanding this neurogenic
process will improve the efficacy of using glomus cells for cell therapy against neurological disease, and might help us
understand some neural tumors.
Max ERC Funding
1 476 000 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym CELLDOCTOR
Project Quantitative understanding of a living system and its engineering as a cellular organelle
Researcher (PI) Luis Serrano
Host Institution (HI) FUNDACIO CENTRE DE REGULACIO GENOMICA
Call Details Advanced Grant (AdG), LS2, ERC-2008-AdG
Summary The idea of harnessing living organisms for treating human diseases is not new but, so far, the majority of the living vectors used in human therapy are viruses which have the disadvantage of the limited number of genes and networks that can contain. Bacteria allow the cloning of complex networks and the possibility of making a large plethora of compounds, naturally or through careful redesign. One of the main limitations for the use of bacteria to treat human diseases is their complexity, the existence of a cell wall that difficult the communication with the target cells, the lack of control over its growth and the immune response that will elicit on its target. Ideally one would like to have a very small bacterium (of a mitochondria size), with no cell wall, which could be grown in Vitro, be genetically manipulated, for which we will have enough data to allow a complete understanding of its behaviour and which could live as a human cell parasite. Such a microorganism could in principle be used as a living vector in which genes of interests, or networks producing organic molecules of medical relevance, could be introduced under in Vitro conditions and then inoculated on extracted human cells or in the organism, and then become a new organelle in the host. Then, it could produce and secrete into the host proteins which will be needed to correct a genetic disease, or drugs needed by the patient. To do that, we need to understand in excruciating detail the Biology of the target bacterium and how to interface with the host cell cycle (Systems biology aspect). Then we need to have engineering tools (network design, protein design, simulations) to modify the target bacterium to behave like an organelle once inside the cell (Synthetic biology aspect). M.pneumoniae could be such a bacterium. It is one of the smallest free-living bacterium known (680 genes), has no cell wall, can be cultivated in Vitro, can be genetically manipulated and can enter inside human cells.
Summary
The idea of harnessing living organisms for treating human diseases is not new but, so far, the majority of the living vectors used in human therapy are viruses which have the disadvantage of the limited number of genes and networks that can contain. Bacteria allow the cloning of complex networks and the possibility of making a large plethora of compounds, naturally or through careful redesign. One of the main limitations for the use of bacteria to treat human diseases is their complexity, the existence of a cell wall that difficult the communication with the target cells, the lack of control over its growth and the immune response that will elicit on its target. Ideally one would like to have a very small bacterium (of a mitochondria size), with no cell wall, which could be grown in Vitro, be genetically manipulated, for which we will have enough data to allow a complete understanding of its behaviour and which could live as a human cell parasite. Such a microorganism could in principle be used as a living vector in which genes of interests, or networks producing organic molecules of medical relevance, could be introduced under in Vitro conditions and then inoculated on extracted human cells or in the organism, and then become a new organelle in the host. Then, it could produce and secrete into the host proteins which will be needed to correct a genetic disease, or drugs needed by the patient. To do that, we need to understand in excruciating detail the Biology of the target bacterium and how to interface with the host cell cycle (Systems biology aspect). Then we need to have engineering tools (network design, protein design, simulations) to modify the target bacterium to behave like an organelle once inside the cell (Synthetic biology aspect). M.pneumoniae could be such a bacterium. It is one of the smallest free-living bacterium known (680 genes), has no cell wall, can be cultivated in Vitro, can be genetically manipulated and can enter inside human cells.
Max ERC Funding
2 400 000 €
Duration
Start date: 2009-03-01, End date: 2015-02-28