Project acronym CancerADAPT
Project Targeting the adaptive capacity of prostate cancer through the manipulation of transcriptional and metabolic traits
Researcher (PI) Arkaitz CARRACEDO PEREZ
Host Institution (HI) ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOCIENCIAS
Country Spain
Call Details Consolidator Grant (CoG), LS4, ERC-2018-COG
Summary The composition and molecular features of tumours vary during the course of the disease, and the selection pressure imposed by the environment is a central component in this process. Evolutionary principles have been exploited to explain the genomic aberrations in cancer. However, the phenotypic changes underlying disease progression remain poorly understood. In the past years, I have contributed to identify and characterise the therapeutic implications underlying metabolic alterations that are intrinsic to primary tumours or metastasis. In CancerADAPT I postulate that cancer cells rely on adaptive transcriptional & metabolic mechanisms [converging on a Metabolic Phenotype] in order to rapidly succeed in their establishment in new microenvironments along disease progression. I aim to predict the molecular cues that govern the adaptive properties in prostate cancer (PCa), one of the most commonly diagnosed cancers in men and an important source of cancer-related deaths. I will exploit single cell RNASeq, spatial transcriptomics and multiregional OMICs in order to identify the transcriptional and metabolic diversity within tumours and along disease progression. I will complement experimental strategies with computational analyses that identify and classify the predicted adaptation strategies of PCa cells in response to variations in the tumour microenvironment. Metabolic phenotypes postulated to sustain PCa adaptability will be functionally and mechanistically deconstructed. We will identify therapeutic strategies emanating from these results through in silico methodologies and small molecule high-throughput screening, and evaluate their potential to hamper the adaptability of tumour cells in vitro and in vivo, in two specific aspects: metastasis and therapy response. CancerADAPT will generate fundamental understanding on how cancer cells adapt in our organism, in turn leading to therapeutic strategies that increase the efficacy of current treatments.
Summary
The composition and molecular features of tumours vary during the course of the disease, and the selection pressure imposed by the environment is a central component in this process. Evolutionary principles have been exploited to explain the genomic aberrations in cancer. However, the phenotypic changes underlying disease progression remain poorly understood. In the past years, I have contributed to identify and characterise the therapeutic implications underlying metabolic alterations that are intrinsic to primary tumours or metastasis. In CancerADAPT I postulate that cancer cells rely on adaptive transcriptional & metabolic mechanisms [converging on a Metabolic Phenotype] in order to rapidly succeed in their establishment in new microenvironments along disease progression. I aim to predict the molecular cues that govern the adaptive properties in prostate cancer (PCa), one of the most commonly diagnosed cancers in men and an important source of cancer-related deaths. I will exploit single cell RNASeq, spatial transcriptomics and multiregional OMICs in order to identify the transcriptional and metabolic diversity within tumours and along disease progression. I will complement experimental strategies with computational analyses that identify and classify the predicted adaptation strategies of PCa cells in response to variations in the tumour microenvironment. Metabolic phenotypes postulated to sustain PCa adaptability will be functionally and mechanistically deconstructed. We will identify therapeutic strategies emanating from these results through in silico methodologies and small molecule high-throughput screening, and evaluate their potential to hamper the adaptability of tumour cells in vitro and in vivo, in two specific aspects: metastasis and therapy response. CancerADAPT will generate fundamental understanding on how cancer cells adapt in our organism, in turn leading to therapeutic strategies that increase the efficacy of current treatments.
Max ERC Funding
1 999 882 €
Duration
Start date: 2019-11-01, End date: 2024-10-31
Project acronym GALACTICNUCLEUS
Project The Fingerprint of a Galactic Nucleus: A Multi-Wavelength, High-Angular Resolution, Near-Infrared Study of the Centre of the Milky Way
Researcher (PI) Rainer Schoedel
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Country Spain
Call Details Consolidator Grant (CoG), PE9, ERC-2013-CoG
Summary Galactic stellar nuclei are very common in all types of galaxies and are marked by the presence of nuclear star clusters, the densest and most massive star clusters in the present-day Universe. Their formation is still an unresolved puzzle. The centre of the Milky Way contains a massive black hole and a stellar nucleus and is orders of magnitude closer than any comparable target. It is the only galactic nucleus and the most extreme astrophysical environment that we can examine on scales of milli-parsecs. It is therefore a crucial laboratory for studying galactic nuclei and their role in the context of galaxy evolution. Yet, suitable data that would allow us to examine the stellar component of the Galactic Centre exist for less than 1% of its projected area. Moreover, the well-explored regions are extraordinary, like the central parsec around the massive black hole, and therefore probably not representative for the overall environment. Fundamental questions on the stellar population, structure and assembly history of the Galactic Centre remain therefore unanswered. This project aims at addressing the open questions by obtaining accurate, high-angular resolution, multi-wavelength near-infrared photometry for an area of several 100 pc^2, a more than ten-fold increase compared to the current state of affairs. The Galactic Centre presents unique observational challenges because of a combination of high extinction and extreme stellar crowding. It is therefore not adequately covered by existing or upcoming imaging surveys. I present a project that is specifically tailored to overcome these observational challenges. In particular, I have developed a key technique to obtain the necessary sensitive, high-angular resolution images with a stable point spread function over large, crowded fields. It works with a range of existing ground-based instruments and will serve to complement existing data to provide a global and detailed picture of the stellar nucleus of the Milky Way.
Summary
Galactic stellar nuclei are very common in all types of galaxies and are marked by the presence of nuclear star clusters, the densest and most massive star clusters in the present-day Universe. Their formation is still an unresolved puzzle. The centre of the Milky Way contains a massive black hole and a stellar nucleus and is orders of magnitude closer than any comparable target. It is the only galactic nucleus and the most extreme astrophysical environment that we can examine on scales of milli-parsecs. It is therefore a crucial laboratory for studying galactic nuclei and their role in the context of galaxy evolution. Yet, suitable data that would allow us to examine the stellar component of the Galactic Centre exist for less than 1% of its projected area. Moreover, the well-explored regions are extraordinary, like the central parsec around the massive black hole, and therefore probably not representative for the overall environment. Fundamental questions on the stellar population, structure and assembly history of the Galactic Centre remain therefore unanswered. This project aims at addressing the open questions by obtaining accurate, high-angular resolution, multi-wavelength near-infrared photometry for an area of several 100 pc^2, a more than ten-fold increase compared to the current state of affairs. The Galactic Centre presents unique observational challenges because of a combination of high extinction and extreme stellar crowding. It is therefore not adequately covered by existing or upcoming imaging surveys. I present a project that is specifically tailored to overcome these observational challenges. In particular, I have developed a key technique to obtain the necessary sensitive, high-angular resolution images with a stable point spread function over large, crowded fields. It works with a range of existing ground-based instruments and will serve to complement existing data to provide a global and detailed picture of the stellar nucleus of the Milky Way.
Max ERC Funding
1 547 657 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym LArcHer
Project Breaking barriers between Science and Heritage approaches to Levantine Rock Art through Archaeology, Heritage Science and IT
Researcher (PI) Ines DOMINGO SANZ
Host Institution (HI) UNIVERSITAT DE BARCELONA
Country Spain
Call Details Consolidator Grant (CoG), SH6, ERC-2018-COG
Summary LArcHer project aims at pioneering a new and more comprehensive way of understanding one of Europe’s most extraordinary bodies of prehistoric art, awarded Unesco World Heritage status in 1998: Levantine rock art (LRA). The ground-breaking nature of the project relies on combining a multidisciplinary (Archaeology, Heritage Science and IT) and multiscale approach (from microanalysis to landscape perspectives) to gain a holistic view of this art. It also aims at closing existing gaps between science and heritage mainstreams, to better understand the values and threats affecting this tradition and bring about a change in the way we understand, care, use and manage this millenary legacy. LArcHer aims are: a) Use cross-disciplinary knowledge and methods to redefine LRA (i.e. new dating techniques to refine chronology, new analytical methods to understand the creative process); b) Use LRA as a proxy to raise new questions of global interest on the evolution of creative thinking and human cognition (i.e. the timing and driving forces behind the birth of anthropocentrism and visual narratives in the history of prehistoric art); c) Develop new research agendas to set off complementary goals between science and heritage and define best practices for open air rock art conservation and management.
Spread across Mediterranean Iberia, LRA is the only European body of figurative art dominated by humans engaged in dynamic narratives of hunting, violence, warfare, dances and so forth. These scenes are unique to explore past social dynamics, human behaviour and cultural practices. As such, it is the only body of European rock art with potential to answer some of the new questions raised by LArcHer.
Key to LArcHer are the systematic recording and analysis of the art through 3D Digital technologies, management and data storage systems, GIS, physicochemical analysis of pigments and bedrock and comparative analysis with other major bodies of art with equivalent developments.
Summary
LArcHer project aims at pioneering a new and more comprehensive way of understanding one of Europe’s most extraordinary bodies of prehistoric art, awarded Unesco World Heritage status in 1998: Levantine rock art (LRA). The ground-breaking nature of the project relies on combining a multidisciplinary (Archaeology, Heritage Science and IT) and multiscale approach (from microanalysis to landscape perspectives) to gain a holistic view of this art. It also aims at closing existing gaps between science and heritage mainstreams, to better understand the values and threats affecting this tradition and bring about a change in the way we understand, care, use and manage this millenary legacy. LArcHer aims are: a) Use cross-disciplinary knowledge and methods to redefine LRA (i.e. new dating techniques to refine chronology, new analytical methods to understand the creative process); b) Use LRA as a proxy to raise new questions of global interest on the evolution of creative thinking and human cognition (i.e. the timing and driving forces behind the birth of anthropocentrism and visual narratives in the history of prehistoric art); c) Develop new research agendas to set off complementary goals between science and heritage and define best practices for open air rock art conservation and management.
Spread across Mediterranean Iberia, LRA is the only European body of figurative art dominated by humans engaged in dynamic narratives of hunting, violence, warfare, dances and so forth. These scenes are unique to explore past social dynamics, human behaviour and cultural practices. As such, it is the only body of European rock art with potential to answer some of the new questions raised by LArcHer.
Key to LArcHer are the systematic recording and analysis of the art through 3D Digital technologies, management and data storage systems, GIS, physicochemical analysis of pigments and bedrock and comparative analysis with other major bodies of art with equivalent developments.
Max ERC Funding
1 991 178 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym LATTAL
Project The Latin Talmud and its Influence on Christian-Jewish Polemic
Researcher (PI) Alexander Fidora
Host Institution (HI) UNIVERSIDAD AUTONOMA DE BARCELONA
Country Spain
Call Details Consolidator Grant (CoG), SH5, ERC-2013-CoG
Summary "While polemics and dialogue between Judaism and Christianity are as old as the Christian religion itself, one can clearly distinguish different periods, trends and intensities in the relations between the faiths. A significant landmark in this long and complex history is the Latin translation of large sections of the Talmud, the most important Jewish post-biblical text and the basis for the development of Rabbinic Judaism.
When during the 13th century Christian theologians started to examine and translate the Talmud from Hebrew and Aramaic into Latin, they were faced with a huge body of texts which represented centuries of legalistic and homiletic materials. The discovery of this immense post-biblical Jewish literature became a source of fascination for Christians who believed that this text, which encompasses every aspect of Jewish life, was fundamental both for refuting the Jewish faith and for substantiating the truth of Christianity. This realization heralded a rethinking of the place of Jews in Christian society and redefined Christian-Jewish dialogue and polemic.
The purpose of our project is to edit and publish the largest extant collection of Talmudic passages translated from Hebrew into Latin, that is, the ""Extractiones de Talmud"", while studying this ground-breaking document in the context of the trial and burning of the Talmud in 1240-42 and its aftermath.
This project addresses vital questions of Jewish and Christian identity, still relevant to the 21st century, and can only be carried out by a transdisciplinary research team including specialists from Latin Philology, Hebrew Studies and History."
Summary
"While polemics and dialogue between Judaism and Christianity are as old as the Christian religion itself, one can clearly distinguish different periods, trends and intensities in the relations between the faiths. A significant landmark in this long and complex history is the Latin translation of large sections of the Talmud, the most important Jewish post-biblical text and the basis for the development of Rabbinic Judaism.
When during the 13th century Christian theologians started to examine and translate the Talmud from Hebrew and Aramaic into Latin, they were faced with a huge body of texts which represented centuries of legalistic and homiletic materials. The discovery of this immense post-biblical Jewish literature became a source of fascination for Christians who believed that this text, which encompasses every aspect of Jewish life, was fundamental both for refuting the Jewish faith and for substantiating the truth of Christianity. This realization heralded a rethinking of the place of Jews in Christian society and redefined Christian-Jewish dialogue and polemic.
The purpose of our project is to edit and publish the largest extant collection of Talmudic passages translated from Hebrew into Latin, that is, the ""Extractiones de Talmud"", while studying this ground-breaking document in the context of the trial and burning of the Talmud in 1240-42 and its aftermath.
This project addresses vital questions of Jewish and Christian identity, still relevant to the 21st century, and can only be carried out by a transdisciplinary research team including specialists from Latin Philology, Hebrew Studies and History."
Max ERC Funding
1 292 700 €
Duration
Start date: 2014-10-01, End date: 2018-09-30
Project acronym MAGNESIA
Project The impact of highly magnetic neutron stars in the explosive and transient Universe
Researcher (PI) Nanda Rea
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Country Spain
Call Details Consolidator Grant (CoG), PE9, ERC-2018-COG
Summary The gravitational wave window is now open. It is then imperative to build quantitative models of neutron stars that use all the available tracers to constrain fundamental physics at the highest densities and magnetic fields. The most magnetic neutron stars, the magnetars, have been recently suggested to be powering a large variety of explosive and transient events. The enormous rotational power at birth, and the magnetic energy they can release via large flares, put the magnetars in the (yet) hand-wavy interpretations of gamma-ray bursts, the early phases of double neutron star mergers, super-luminous supernovae, hypernovae, fast radio bursts, and ultra-luminous X-ray sources. However, despite knowing about 30 magnetars, we are lacking a census of how many we expect within the pulsar population, nor we have robust constraints on their flaring rates. The recent discovery of transient magnetars, of magnetar-like flares from sources with measured low dipolar magnetic fields and from typical radio pulsars, clearly showed that the magnetar census in our Galaxy is largely under-estimated. This hampers our understanding not only of the pulsar and magnetar populations, but also of them as possibly related to many of Universe’s explosive events. MAGNESIA will infer a sound Magnetar Census via an innovative approach that will build the first Pulsar Population Synthesis model able to cope with constraints/limits from multi-band observations, and taking into account 3D magnetic field evolution models and flaring rates for neutron stars. Combining expertise in multi-band observations, numerical modeling, nuclear physics, and computation, MAGNESIA will solve the physics, the observational systematic errors, and the computational challenges that inhibited previous works, to finally constrain the spin period and magnetic field distribution at birth of the neutron star population.
Summary
The gravitational wave window is now open. It is then imperative to build quantitative models of neutron stars that use all the available tracers to constrain fundamental physics at the highest densities and magnetic fields. The most magnetic neutron stars, the magnetars, have been recently suggested to be powering a large variety of explosive and transient events. The enormous rotational power at birth, and the magnetic energy they can release via large flares, put the magnetars in the (yet) hand-wavy interpretations of gamma-ray bursts, the early phases of double neutron star mergers, super-luminous supernovae, hypernovae, fast radio bursts, and ultra-luminous X-ray sources. However, despite knowing about 30 magnetars, we are lacking a census of how many we expect within the pulsar population, nor we have robust constraints on their flaring rates. The recent discovery of transient magnetars, of magnetar-like flares from sources with measured low dipolar magnetic fields and from typical radio pulsars, clearly showed that the magnetar census in our Galaxy is largely under-estimated. This hampers our understanding not only of the pulsar and magnetar populations, but also of them as possibly related to many of Universe’s explosive events. MAGNESIA will infer a sound Magnetar Census via an innovative approach that will build the first Pulsar Population Synthesis model able to cope with constraints/limits from multi-band observations, and taking into account 3D magnetic field evolution models and flaring rates for neutron stars. Combining expertise in multi-band observations, numerical modeling, nuclear physics, and computation, MAGNESIA will solve the physics, the observational systematic errors, and the computational challenges that inhibited previous works, to finally constrain the spin period and magnetic field distribution at birth of the neutron star population.
Max ERC Funding
2 263 148 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym MarsFirstWater
Project The physicochemical nature of water on early Mars
Researcher (PI) Alberto Gonzalez Fairen
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Country Spain
Call Details Consolidator Grant (CoG), PE9, ERC-2018-COG
Summary Concepts of large bodies of glacial ice and liquid standing water, a robust hydrological cycle, and a rich Martian history of climate change are part of the current consensus model for early Mars. However, questions still poorly constrained include: a precise understanding of the inventory of water during the first billion years of Mars history and its early evolution on both global and local scales; whether liquid or solid H2O dominated, for what duration of time and where the water resided; what were the host-rock weathering rates and patterns and the physicochemical parameters defining such interactions; what specific landforms and mineralogies were generated during those periods; and what implications all these processes had on the possible inception of life on Mars. These fundamental questions represent large uncertainties and knowledge gaps. Therefore, a quantitative understanding of the basic characteristics of water on early Mars is very much needed and is the focus of this proposal.
This application outlines a plan for my research in the next five years, and explains how I propose to fully characterize the aqueous environments of early Mars through a quantitative and truly interdisciplinary investigation. Spacecraft mission-derived datasets will be consistently used to test hypotheses through paleogeomorphological reconstructions, geochemical modeling, mineralogical studies, and astrobiological investigations. The derived results will produce hard constraints on the physical evolution, chemical alteration and habitability of surface and near-surface aqueous environments on early Mars. The planned investigations will benefit from the combination of working with first-hand data from ongoing Mars missions and with the state-of-the-art laboratory tools at the host institution. The final expected result will be a complete understanding of the physicochemical nature of water on early Mars, also opening new paths for the astrobiological exploration of the planet.
Summary
Concepts of large bodies of glacial ice and liquid standing water, a robust hydrological cycle, and a rich Martian history of climate change are part of the current consensus model for early Mars. However, questions still poorly constrained include: a precise understanding of the inventory of water during the first billion years of Mars history and its early evolution on both global and local scales; whether liquid or solid H2O dominated, for what duration of time and where the water resided; what were the host-rock weathering rates and patterns and the physicochemical parameters defining such interactions; what specific landforms and mineralogies were generated during those periods; and what implications all these processes had on the possible inception of life on Mars. These fundamental questions represent large uncertainties and knowledge gaps. Therefore, a quantitative understanding of the basic characteristics of water on early Mars is very much needed and is the focus of this proposal.
This application outlines a plan for my research in the next five years, and explains how I propose to fully characterize the aqueous environments of early Mars through a quantitative and truly interdisciplinary investigation. Spacecraft mission-derived datasets will be consistently used to test hypotheses through paleogeomorphological reconstructions, geochemical modeling, mineralogical studies, and astrobiological investigations. The derived results will produce hard constraints on the physical evolution, chemical alteration and habitability of surface and near-surface aqueous environments on early Mars. The planned investigations will benefit from the combination of working with first-hand data from ongoing Mars missions and with the state-of-the-art laboratory tools at the host institution. The final expected result will be a complete understanding of the physicochemical nature of water on early Mars, also opening new paths for the astrobiological exploration of the planet.
Max ERC Funding
1 998 368 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym PALEOPLANT
Project Palaeolithic Plant Use in the Western Mediterranean
Researcher (PI) Lydia Zapata
Host Institution (HI) UNIVERSIDAD DEL PAIS VASCO/ EUSKAL HERRIKO UNIBERTSITATEA
Country Spain
Call Details Consolidator Grant (CoG), SH6, ERC-2013-CoG
Summary This project deals with one of the big gaps of knowledge in prehistory, how plant foods and resources were used by preagrarian societies. Plants have been fundamental for human societies across the planet. However, it is a blank when it comes to archaeological evidence of humans eating and exploiting them during most part of Prehistory. This work aims at changing the meat/hunting centred paradigm of Palaeolithic subsistence by readdressing human plant exploitation through a novel interdisciplinary approach. The main objectives are: 1) To assess wild plant exploitation among Palaeolithic-Epipalaeolithic societies, 2) To appraise resilience and change in Palaeolithic-Epipalaeolithic plant use, and 3) To improve archaeological methodology and fieldwork. The chronology of analysis –from the Late Middle Palaeolithic to the Epipalaeolithic- includes two extremely interesting periods: a) the transition from the middle to the upper Palaeolithic with neanderthal extinction and early presence of modern humans which gives us the opportunity to explore and compare whether these groups exploit plant resources in a different way, and b) the climatic change from the Late Pleistocene to the early Holocene which allows to evaluate how last hunter-gatherers from the region adapt to climatic change and new ecological conditions. The challenge of the work is to obtain archaeological visibility of plant use through and interdisciplinary approach that combines: pollen analysis, the study of plant macroremains including underground storage organs (USOs), micromorphology, analysis of microremains such as phytoliths and starch, ethnobotany and use-wear analyses on tools. The different types of evidence to be analysed come from relevant archaeological sites from Spain, Portugal and Morocco. Because a project at this scale has not been developed before, major scientific developments and impact in archaeological science can be safely expected.
Summary
This project deals with one of the big gaps of knowledge in prehistory, how plant foods and resources were used by preagrarian societies. Plants have been fundamental for human societies across the planet. However, it is a blank when it comes to archaeological evidence of humans eating and exploiting them during most part of Prehistory. This work aims at changing the meat/hunting centred paradigm of Palaeolithic subsistence by readdressing human plant exploitation through a novel interdisciplinary approach. The main objectives are: 1) To assess wild plant exploitation among Palaeolithic-Epipalaeolithic societies, 2) To appraise resilience and change in Palaeolithic-Epipalaeolithic plant use, and 3) To improve archaeological methodology and fieldwork. The chronology of analysis –from the Late Middle Palaeolithic to the Epipalaeolithic- includes two extremely interesting periods: a) the transition from the middle to the upper Palaeolithic with neanderthal extinction and early presence of modern humans which gives us the opportunity to explore and compare whether these groups exploit plant resources in a different way, and b) the climatic change from the Late Pleistocene to the early Holocene which allows to evaluate how last hunter-gatherers from the region adapt to climatic change and new ecological conditions. The challenge of the work is to obtain archaeological visibility of plant use through and interdisciplinary approach that combines: pollen analysis, the study of plant macroremains including underground storage organs (USOs), micromorphology, analysis of microremains such as phytoliths and starch, ethnobotany and use-wear analyses on tools. The different types of evidence to be analysed come from relevant archaeological sites from Spain, Portugal and Morocco. Because a project at this scale has not been developed before, major scientific developments and impact in archaeological science can be safely expected.
Max ERC Funding
384 345 €
Duration
Start date: 2014-07-01, End date: 2015-12-31
Project acronym ReadCalibration
Project Phonemic representations in speech perception and production: Recalibration by readingacquisition
Researcher (PI) Clara, Dominique, Sylvie Martin
Host Institution (HI) BCBL BASQUE CENTER ON COGNITION BRAIN AND LANGUAGE
Country Spain
Call Details Consolidator Grant (CoG), SH4, ERC-2018-COG
Summary The main goal of this project is to demonstrate that reading acquisition (RA) drastically reshapes our phonemic inventory, and to investigate the time-course and fine-grained properties of this recalibration. The main innovative and ground-breaking aspect of this project is the merging of two research fields, (1) reading acquisition and (2) phonemic recalibration, together with a deep and extensive exploration of the (3) perception-production link, which results in a new research line that pushes the boundaries of our understanding of the complex interactions between auditory and visual language perception and production.
We will demonstrate that phonemic representations (PRs) become more stable (less dispersed) during the process of learning to read, and that this recalibration varies according to the grapheme-phoneme conversion rules of the reading system. We will explore such recalibration by means of the first cross-linguistic longitudinal study examining the position and dispersion of PRs, both in perception and production of phonemes and words. Secondly, we will explore how recalibration develops when RA is impaired as is the case in dyslexic children –informing the research field on (4) dyslexia– and when pre-reading PRs are unstable as is the case in deaf children with cochlear implants –informing the research field on (5) deafness. Finally, the research will also be extended to PR recalibration during RA in a second language –informing the research on (6) bilingualism.
This proposal provides the first systematic investigation of phonemic recalibration during literacy acquisition, and will provide important insight for pragmatic research and theoretical accounts of language perception and production and phonemic recalibration. This project will also have major implications for the clinical field (theories and remediation of dyslexia and deafness) and for social policies and education (bilingualism, spoken and written language teaching).
Summary
The main goal of this project is to demonstrate that reading acquisition (RA) drastically reshapes our phonemic inventory, and to investigate the time-course and fine-grained properties of this recalibration. The main innovative and ground-breaking aspect of this project is the merging of two research fields, (1) reading acquisition and (2) phonemic recalibration, together with a deep and extensive exploration of the (3) perception-production link, which results in a new research line that pushes the boundaries of our understanding of the complex interactions between auditory and visual language perception and production.
We will demonstrate that phonemic representations (PRs) become more stable (less dispersed) during the process of learning to read, and that this recalibration varies according to the grapheme-phoneme conversion rules of the reading system. We will explore such recalibration by means of the first cross-linguistic longitudinal study examining the position and dispersion of PRs, both in perception and production of phonemes and words. Secondly, we will explore how recalibration develops when RA is impaired as is the case in dyslexic children –informing the research field on (4) dyslexia– and when pre-reading PRs are unstable as is the case in deaf children with cochlear implants –informing the research field on (5) deafness. Finally, the research will also be extended to PR recalibration during RA in a second language –informing the research on (6) bilingualism.
This proposal provides the first systematic investigation of phonemic recalibration during literacy acquisition, and will provide important insight for pragmatic research and theoretical accounts of language perception and production and phonemic recalibration. This project will also have major implications for the clinical field (theories and remediation of dyslexia and deafness) and for social policies and education (bilingualism, spoken and written language teaching).
Max ERC Funding
1 875 000 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym RSHEALTH
Project Investigating the causes and consequences of replication stress in mammalian health
Researcher (PI) Oscar Fernandez-Capetillo Ruiz
Host Institution (HI) FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III
Country Spain
Call Details Consolidator Grant (CoG), LS3, ERC-2013-CoG
Summary "DNA damage (DD) is the cause of several diseases, including cancer, and it is also linked to the organ decline that arises in ageing. Yet, the contribution of different sources of DD to these processes is not understood. Sources of DD such as chromosome breaks, eroded telomeres or oxidative stress are been heavily investigated. For establishing my group, I decided to focus on a source of DD that arises every time a cell replicates its DNA, and which is known as replication stress (RS). In short, RS stands for the excessive accumulation of single-stranded DNA at replication forks that, due to its recombinogenic nature, can initiate genomic rearrangements. Consistently, RS is now known to be a key source of genomic instability in human tumors. In mammalian cells, a signalling cascade initiated by ATR and Chk1 kinases suppresses RS. Unfortunately, the essential nature of these kinases significantly limited the study of the RS-response in mammals. In the initial years of our lab we have developed several tools that facilitate the study of RS in mammals. These include a cellular system where ATR can be activated at will, potent and selective ATR inhibitors, and mice with reduced or increased levels of ATR and Chk1 kinases. These tools have allowed us to start exploring how RS impacts on cancer and ageing, as well as to investigate the potential of targeting ATR for cancer therapy. Yet, the field of RS is still poorly developed, and many basic questions are still in the need of answers.
This application outlines a plan for our research in the next five years, and explains how I propose to investigate RS at molecular, cellular and animal levels. Whereas I plan to capitalize on the tools (published and unpublished) that we have generated within the last few years, I also propose several innovative strategies for the study of the RS-response in mammals. This grant would allow us to consolidate our still young group as a solid laboratory for the study of RS in mammals."
Summary
"DNA damage (DD) is the cause of several diseases, including cancer, and it is also linked to the organ decline that arises in ageing. Yet, the contribution of different sources of DD to these processes is not understood. Sources of DD such as chromosome breaks, eroded telomeres or oxidative stress are been heavily investigated. For establishing my group, I decided to focus on a source of DD that arises every time a cell replicates its DNA, and which is known as replication stress (RS). In short, RS stands for the excessive accumulation of single-stranded DNA at replication forks that, due to its recombinogenic nature, can initiate genomic rearrangements. Consistently, RS is now known to be a key source of genomic instability in human tumors. In mammalian cells, a signalling cascade initiated by ATR and Chk1 kinases suppresses RS. Unfortunately, the essential nature of these kinases significantly limited the study of the RS-response in mammals. In the initial years of our lab we have developed several tools that facilitate the study of RS in mammals. These include a cellular system where ATR can be activated at will, potent and selective ATR inhibitors, and mice with reduced or increased levels of ATR and Chk1 kinases. These tools have allowed us to start exploring how RS impacts on cancer and ageing, as well as to investigate the potential of targeting ATR for cancer therapy. Yet, the field of RS is still poorly developed, and many basic questions are still in the need of answers.
This application outlines a plan for our research in the next five years, and explains how I propose to investigate RS at molecular, cellular and animal levels. Whereas I plan to capitalize on the tools (published and unpublished) that we have generated within the last few years, I also propose several innovative strategies for the study of the RS-response in mammals. This grant would allow us to consolidate our still young group as a solid laboratory for the study of RS in mammals."
Max ERC Funding
1 997 819 €
Duration
Start date: 2014-03-01, End date: 2020-02-29
Project acronym SUBSILIENCE
Project Subsistence and human resilience to sudden climatic events in Europe during MIS3
Researcher (PI) ANA B. MARIN-ARROYO
Host Institution (HI) UNIVERSIDAD DE CANTABRIA
Country Spain
Call Details Consolidator Grant (CoG), SH6, ERC-2018-COG
Summary Climate has long been proposed as a possible trigger-factor for the extinction of Neanderthals and the rapid colonization of Europe by Anatomically Modern Humans (AMH). Abrupt and acute oscillations of climate, as recorded from polar ice sheets, are particularly threatening as they can push ecosystems towards catastrophic outcomes. Under these conditions, the survival of a species critically depends on their adaptive skills. Understanding the exact role that these episodes could have had in the Middle to Upper Palaeolithic transition is then essential to unravel the real causes of Neanderthal demise and AMH success. To do this, SUBSILIENCE will identify the subsistence strategies adopted by both human species in response to those climatic changes at 20 key archaeological sites located across southern European peninsulas. By applying zooarchaeological and taphonomic analyses, the behavioural flexibility and resilience of each human species will be assessed. In addition, to enable effective testing, local terrestrial climatic and environmental conditions will be accurately reconstructed using stable isotopes from animals consumed, producing a unique, continuous and properly-dated general environmental framework, improving existing knowledge. Finally, to further explore the problem, an innovative procedure to estimate prey abundance, ecology and human behaviour, involving the estimation of the ecosystem carrying capacity, will be developed. This multidisciplinary and novel approach will provide, for the first time, accurate answers to questions concerning a) which particular subsistence patterns (if any) favoured AMH over Neanderthals while coping with the changing environment and b) the extent to which climatic oscillations affected Neanderthal extinction. In this, it will be of relevance to the study of Prehistory on a pan-European scale.
Summary
Climate has long been proposed as a possible trigger-factor for the extinction of Neanderthals and the rapid colonization of Europe by Anatomically Modern Humans (AMH). Abrupt and acute oscillations of climate, as recorded from polar ice sheets, are particularly threatening as they can push ecosystems towards catastrophic outcomes. Under these conditions, the survival of a species critically depends on their adaptive skills. Understanding the exact role that these episodes could have had in the Middle to Upper Palaeolithic transition is then essential to unravel the real causes of Neanderthal demise and AMH success. To do this, SUBSILIENCE will identify the subsistence strategies adopted by both human species in response to those climatic changes at 20 key archaeological sites located across southern European peninsulas. By applying zooarchaeological and taphonomic analyses, the behavioural flexibility and resilience of each human species will be assessed. In addition, to enable effective testing, local terrestrial climatic and environmental conditions will be accurately reconstructed using stable isotopes from animals consumed, producing a unique, continuous and properly-dated general environmental framework, improving existing knowledge. Finally, to further explore the problem, an innovative procedure to estimate prey abundance, ecology and human behaviour, involving the estimation of the ecosystem carrying capacity, will be developed. This multidisciplinary and novel approach will provide, for the first time, accurate answers to questions concerning a) which particular subsistence patterns (if any) favoured AMH over Neanderthals while coping with the changing environment and b) the extent to which climatic oscillations affected Neanderthal extinction. In this, it will be of relevance to the study of Prehistory on a pan-European scale.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-06-01, End date: 2024-05-31