Project acronym BIGSEA
Project Biogeochemical and ecosystem interactions with socio-economic activity in the global ocean
Researcher (PI) Eric Douglas Galbraith
Host Institution (HI) UNIVERSITAT AUTONOMA DE BARCELONA
Call Details Consolidator Grant (CoG), PE10, ERC-2015-CoG
Summary The global marine ecosystem is being deeply altered by human activity. On the one hand, rising concentrations of atmospheric greenhouse gases are changing the physical and chemical state of the ocean, exerting pressure from the bottom up. Meanwhile, the global fishery has provided large economic benefits, but in so doing has restructured ecosystems by removing most of the large animal biomass, a major top-down change. Although there has been a tremendous amount of research into isolated aspects of these impacts, the development of a holistic understanding of the full interactions between physics, chemistry, ecology and economic activity might appear impossible, given the myriad complexities. This proposal lays out a strategy to assemble a team of trans-disciplinary expertise, that will develop a unified, data-constrained, grid-based modeling framework to represent the most important interactions of the global human-ocean system. Building this framework requires solving a series of fundamental problems that currently hinder the development of the full model. If these problems can be solved, the resulting model will reveal novel emergent properties and open the doors to a range of previously unexplored questions of high impact across a range of disciplines. Key questions include the ways in which animals interact with oxygen minimum zones with implications for fisheries, the impacts fish harvesting may have on nutrient recycling, spatio-temporal interactions between managed and unmanaged fisheries, and fundamental questions about the relationships between fish price, fishing cost, and multiple markets in a changing world. Just as the first coupled ocean-atmosphere models revealed a wealth of new behaviours, the coupled human-ocean model proposed here has the potential to launch multiple new fields of enquiry. It is hoped that the novel approach will contribute to a paradigm shift that treats human activity as one component within the framework of the Earth System.
Summary
The global marine ecosystem is being deeply altered by human activity. On the one hand, rising concentrations of atmospheric greenhouse gases are changing the physical and chemical state of the ocean, exerting pressure from the bottom up. Meanwhile, the global fishery has provided large economic benefits, but in so doing has restructured ecosystems by removing most of the large animal biomass, a major top-down change. Although there has been a tremendous amount of research into isolated aspects of these impacts, the development of a holistic understanding of the full interactions between physics, chemistry, ecology and economic activity might appear impossible, given the myriad complexities. This proposal lays out a strategy to assemble a team of trans-disciplinary expertise, that will develop a unified, data-constrained, grid-based modeling framework to represent the most important interactions of the global human-ocean system. Building this framework requires solving a series of fundamental problems that currently hinder the development of the full model. If these problems can be solved, the resulting model will reveal novel emergent properties and open the doors to a range of previously unexplored questions of high impact across a range of disciplines. Key questions include the ways in which animals interact with oxygen minimum zones with implications for fisheries, the impacts fish harvesting may have on nutrient recycling, spatio-temporal interactions between managed and unmanaged fisheries, and fundamental questions about the relationships between fish price, fishing cost, and multiple markets in a changing world. Just as the first coupled ocean-atmosphere models revealed a wealth of new behaviours, the coupled human-ocean model proposed here has the potential to launch multiple new fields of enquiry. It is hoped that the novel approach will contribute to a paradigm shift that treats human activity as one component within the framework of the Earth System.
Max ERC Funding
1 600 000 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
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
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 CLIMAHAL
Project Climate dimension of natural halogens in the Earth system: Past, present, future
Researcher (PI) Alfonso SAIZ LOPEZ
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Consolidator Grant (CoG), PE10, ERC-2016-COG
Summary Naturally-emitted very short-lived halogens (VSLH) have a profound impact on the chemistry and composition of the atmosphere, destroying greenhouse gases and altering aerosol production, which together can change the Earth´s radiative balance. Therefore, natural halogens possess leverage to influence climate, although their contribution to climate change is not well established and most climate models have yet to consider their effects. Also, there is increasing evidence that natural halogens i) impact on the air quality of coastal cities, ii) accelerates the atmospheric deposition of mercury (a toxic heavy metal) and iii) that their natural ocean and ice emissions are controlled by biological and photochemical mechanisms that may respond to climate changes. Motivated by the above, this project aims to quantify the so far unrecognized natural halogen-climate feedbacks and the impact of these feedbacks on global atmospheric oxidizing capacity (AOC) and radiative forcing (RF) across pre-industrial, present and future climates. Answering these questions is essential to predict if these climate-mediated feedbacks can reduce or amplify future climate change. To this end we will develop a multidisciplinary research approach using laboratory and field observations and models interactively that will allow us to peel apart the detailed physical processes behind the contribution of natural halogens to global climate change. Furthermore, the work plan also involves examining past-future climate impacts of natural halogens within a holistic Earth System model, where we will develop the multidirectional halogen interactions in the land-ocean-ice-biosphere-atmosphere coupled system. This will provide a breakthrough in our understanding of the importance of these natural processes for the composition and oxidation capacity of the Earth´s atmosphere and climate, both in the presence and absence of human influence.
Summary
Naturally-emitted very short-lived halogens (VSLH) have a profound impact on the chemistry and composition of the atmosphere, destroying greenhouse gases and altering aerosol production, which together can change the Earth´s radiative balance. Therefore, natural halogens possess leverage to influence climate, although their contribution to climate change is not well established and most climate models have yet to consider their effects. Also, there is increasing evidence that natural halogens i) impact on the air quality of coastal cities, ii) accelerates the atmospheric deposition of mercury (a toxic heavy metal) and iii) that their natural ocean and ice emissions are controlled by biological and photochemical mechanisms that may respond to climate changes. Motivated by the above, this project aims to quantify the so far unrecognized natural halogen-climate feedbacks and the impact of these feedbacks on global atmospheric oxidizing capacity (AOC) and radiative forcing (RF) across pre-industrial, present and future climates. Answering these questions is essential to predict if these climate-mediated feedbacks can reduce or amplify future climate change. To this end we will develop a multidisciplinary research approach using laboratory and field observations and models interactively that will allow us to peel apart the detailed physical processes behind the contribution of natural halogens to global climate change. Furthermore, the work plan also involves examining past-future climate impacts of natural halogens within a holistic Earth System model, where we will develop the multidirectional halogen interactions in the land-ocean-ice-biosphere-atmosphere coupled system. This will provide a breakthrough in our understanding of the importance of these natural processes for the composition and oxidation capacity of the Earth´s atmosphere and climate, both in the presence and absence of human influence.
Max ERC Funding
1 979 112 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym CutLoops
Project Loop amplitudes in quantum field theory
Researcher (PI) Ruth Britto
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Consolidator Grant (CoG), PE2, ERC-2014-CoG
Summary The traditional formulation of relativistic quantum theory is ill-equipped to handle the range of difficult computations needed to describe particle collisions at the Large Hadron Collider (LHC) within a suitable time frame. Yet, recent work shows that probability amplitudes in quantum gauge field theories, such as those describing the Standard Model and its extensions, take surprisingly simple forms. The simplicity indicates deep structure in gauge theory that has already led to dramatic computational improvements, but remains to be fully understood. For precision calculations and investigations of the deep structure of gauge theory, a comprehensive method for computing multi-loop amplitudes systematically and efficiently must be found.
The goal of this proposal is to construct a new and complete approach to computing amplitudes from a detailed understanding of their singularities, based on prior successes of so-called on-shell methods combined with the latest developments in the mathematics of Feynman integrals. Scattering processes relevant to the LHC and to formal investigations of quantum field theory will be computed within the new framework.
Summary
The traditional formulation of relativistic quantum theory is ill-equipped to handle the range of difficult computations needed to describe particle collisions at the Large Hadron Collider (LHC) within a suitable time frame. Yet, recent work shows that probability amplitudes in quantum gauge field theories, such as those describing the Standard Model and its extensions, take surprisingly simple forms. The simplicity indicates deep structure in gauge theory that has already led to dramatic computational improvements, but remains to be fully understood. For precision calculations and investigations of the deep structure of gauge theory, a comprehensive method for computing multi-loop amplitudes systematically and efficiently must be found.
The goal of this proposal is to construct a new and complete approach to computing amplitudes from a detailed understanding of their singularities, based on prior successes of so-called on-shell methods combined with the latest developments in the mathematics of Feynman integrals. Scattering processes relevant to the LHC and to formal investigations of quantum field theory will be computed within the new framework.
Max ERC Funding
1 954 065 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
Project acronym eLightning
Project Lightning propagation and high-energy emissions within coupled multi-model simulations
Researcher (PI) Alejandro Luque Estepa
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Consolidator Grant (CoG), PE10, ERC-2015-CoG
Summary More than 250 years after establishing the electrical nature of the lightning flash, we still do not understand how a lightning channel advances. Most of these channels progress not continuously but in a series of sudden jumps and, as they jump, they emit bursts of energetic radiation. Despite increasingly accurate observations, there is no accepted explanation for this stepped progression.
This proposal addresses this open question. First, we propose a methodological breakthrough that will allow us to tackle the main bottleneck in the theoretical understanding of lightning: the wide disparity between length-scales within a lightning flash. We plan to apply techniques that have succeeded in other fields, such as multi-model coupled simulations and moving-mesh finite elements methods. Acting as a computational microscope, these techniques will reveal the small-scale electrodynamics around a lightning channel.
We will then apply these techniques to elucidate the intertwined problems of lightning channel stepping and thunderstorm-related high-energy emissions. The main hypothesis that we will test is that stepping is due to the formation of low-conductivity spots within the filamentary-discharge region that surrounds a lightning channel. This idea is motivated by observations from high-altitude atmospheric discharges. By resolving the small-scale dynamics, with our numerical method, we will also test hypothesis for high-energy emissions from the lighting channel, which crucially depend on the microscopic distribution of electric fields.
This interdisciplinary proposal, straddling between geophysics and gas discharge physics, seeks a double breakthrough: the methodological one of building multi-scale lightning simulations and the hypothesis-driven one of finding out the reason for stepping. If it succeeds, it will achieve a leap forward in our knowledge of lightning, undoubtedly one of the greatest spectacles in our planet's repertoire.
Summary
More than 250 years after establishing the electrical nature of the lightning flash, we still do not understand how a lightning channel advances. Most of these channels progress not continuously but in a series of sudden jumps and, as they jump, they emit bursts of energetic radiation. Despite increasingly accurate observations, there is no accepted explanation for this stepped progression.
This proposal addresses this open question. First, we propose a methodological breakthrough that will allow us to tackle the main bottleneck in the theoretical understanding of lightning: the wide disparity between length-scales within a lightning flash. We plan to apply techniques that have succeeded in other fields, such as multi-model coupled simulations and moving-mesh finite elements methods. Acting as a computational microscope, these techniques will reveal the small-scale electrodynamics around a lightning channel.
We will then apply these techniques to elucidate the intertwined problems of lightning channel stepping and thunderstorm-related high-energy emissions. The main hypothesis that we will test is that stepping is due to the formation of low-conductivity spots within the filamentary-discharge region that surrounds a lightning channel. This idea is motivated by observations from high-altitude atmospheric discharges. By resolving the small-scale dynamics, with our numerical method, we will also test hypothesis for high-energy emissions from the lighting channel, which crucially depend on the microscopic distribution of electric fields.
This interdisciplinary proposal, straddling between geophysics and gas discharge physics, seeks a double breakthrough: the methodological one of building multi-scale lightning simulations and the hypothesis-driven one of finding out the reason for stepping. If it succeeds, it will achieve a leap forward in our knowledge of lightning, undoubtedly one of the greatest spectacles in our planet's repertoire.
Max ERC Funding
1 960 826 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym FRAGMENT
Project FRontiers in dust minerAloGical coMposition and its Effects upoN climaTe
Researcher (PI) Carlos Perez Garcia-Pando
Host Institution (HI) BARCELONA SUPERCOMPUTING CENTER - CENTRO NACIONAL DE SUPERCOMPUTACION
Call Details Consolidator Grant (CoG), PE10, ERC-2017-COG
Summary Soil dust aerosols are mixtures of different minerals, whose relative abundances, particle size distribution (PSD), shape, surface topography and mixing state influence their effect upon climate. However, Earth System Models typically assume that dust aerosols have a globally uniform composition, neglecting the known regional variations in the mineralogy of the sources. The goal of FRAGMENT is to understand and constrain the global mineralogical composition of dust along with its effects upon climate. The representation of the global dust mineralogy is hindered by our limited knowledge of the global soil mineral content and our incomplete understanding of the emitted dust PSD in terms of its constituent minerals that results from the fragmentation of soil aggregates during wind erosion. The emitted PSD affects the duration of particle transport and thus each mineral’s global distribution, along with its specific effect upon climate. Coincident observations of the emitted dust and soil PSD are scarce and do not characterize the mineralogy. In addition, the existing theoretical paradigms disagree fundamentally on multiple aspects. We will contribute new fundamental understanding of the size-resolved mineralogy of dust at emission and its relationship with the parent soil, based on an unprecedented ensemble of measurement campaigns that have been designed to thoroughly test our theoretical hypotheses. To improve knowledge of the global soil mineral content, we will evaluate and use available remote hyperspectral imaging, which is unprecedented in the context of dust modelling. Our new methods will anticipate the coming innovation of retrieving soil mineralogy through high-quality spaceborne hyperspectral measurements. Finally, we will generate integrated and quantitative knowledge of the role of dust mineralogy in dust-radiation, dust-chemistry and dust-cloud interactions based on modeling experiments constrained with our theoretical innovations and field measurements.
Summary
Soil dust aerosols are mixtures of different minerals, whose relative abundances, particle size distribution (PSD), shape, surface topography and mixing state influence their effect upon climate. However, Earth System Models typically assume that dust aerosols have a globally uniform composition, neglecting the known regional variations in the mineralogy of the sources. The goal of FRAGMENT is to understand and constrain the global mineralogical composition of dust along with its effects upon climate. The representation of the global dust mineralogy is hindered by our limited knowledge of the global soil mineral content and our incomplete understanding of the emitted dust PSD in terms of its constituent minerals that results from the fragmentation of soil aggregates during wind erosion. The emitted PSD affects the duration of particle transport and thus each mineral’s global distribution, along with its specific effect upon climate. Coincident observations of the emitted dust and soil PSD are scarce and do not characterize the mineralogy. In addition, the existing theoretical paradigms disagree fundamentally on multiple aspects. We will contribute new fundamental understanding of the size-resolved mineralogy of dust at emission and its relationship with the parent soil, based on an unprecedented ensemble of measurement campaigns that have been designed to thoroughly test our theoretical hypotheses. To improve knowledge of the global soil mineral content, we will evaluate and use available remote hyperspectral imaging, which is unprecedented in the context of dust modelling. Our new methods will anticipate the coming innovation of retrieving soil mineralogy through high-quality spaceborne hyperspectral measurements. Finally, we will generate integrated and quantitative knowledge of the role of dust mineralogy in dust-radiation, dust-chemistry and dust-cloud interactions based on modeling experiments constrained with our theoretical innovations and field measurements.
Max ERC Funding
2 000 000 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym HYMNS
Project High-sensitivitY Measurements of key stellar Nucleo-Synthesis reactions
Researcher (PI) Cesar Domingo Pardo
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Consolidator Grant (CoG), PE2, ERC-2015-CoG
Summary The origin of the heavy elements in the Universe is one of the main open questions in modern science. Beyond iron the two main mechanisms of nucleosynthesis are the slow (s) and rapid (r) neutron capture processes operating in giant stars and explosive stellar environments, respectively. Modern s-nucleosynthesis studies are based on the combination of i) stellar models, ii) observed abundances and iii) neutron capture rates measured over many years using several techniques. HYMNS is aimed at a paradigm shift in the sensitivity of s-process neutron capture measurements; The most advanced and accurate methods allow one to measure the neutron capture rate as a function of the neutron energy by combining the time-of-flight technique with radiation detectors, either calorimeters or total energy detectors. These systems are sensitive only to the radiation energy, which ultimately limits the attainable detection sensitivity. State-of-the-art detection systems require drastic innovation if we are to access the stellar (n,g) rates of several key radioactive nuclei, where only small amounts of sample material are available. Such unstable nuclides are of pivotal importance for nucleosynthesis studies because they act as branching points in the s-path and are thus extremely sensitive to the stellar physical conditions. The aim of HYMNS is to develop and apply a novel detection system in the field of (n,g) measurements called total-energy detector with imaging capability (i-TED), which is capable of measuring both the energy and the trajectory of the g-rays, thus enabling a superior level of background discrimination. HYMNS is structured to enable the first measurements for key s-process branching nuclei over the stellar energy range. The first application will be to determine the neutron capture cross section of 79Se, which will provide the most stringent constraint for the thermal conditions and their time-dependence in state-of-the-art evolution models of massive stars.
Summary
The origin of the heavy elements in the Universe is one of the main open questions in modern science. Beyond iron the two main mechanisms of nucleosynthesis are the slow (s) and rapid (r) neutron capture processes operating in giant stars and explosive stellar environments, respectively. Modern s-nucleosynthesis studies are based on the combination of i) stellar models, ii) observed abundances and iii) neutron capture rates measured over many years using several techniques. HYMNS is aimed at a paradigm shift in the sensitivity of s-process neutron capture measurements; The most advanced and accurate methods allow one to measure the neutron capture rate as a function of the neutron energy by combining the time-of-flight technique with radiation detectors, either calorimeters or total energy detectors. These systems are sensitive only to the radiation energy, which ultimately limits the attainable detection sensitivity. State-of-the-art detection systems require drastic innovation if we are to access the stellar (n,g) rates of several key radioactive nuclei, where only small amounts of sample material are available. Such unstable nuclides are of pivotal importance for nucleosynthesis studies because they act as branching points in the s-path and are thus extremely sensitive to the stellar physical conditions. The aim of HYMNS is to develop and apply a novel detection system in the field of (n,g) measurements called total-energy detector with imaging capability (i-TED), which is capable of measuring both the energy and the trajectory of the g-rays, thus enabling a superior level of background discrimination. HYMNS is structured to enable the first measurements for key s-process branching nuclei over the stellar energy range. The first application will be to determine the neutron capture cross section of 79Se, which will provide the most stringent constraint for the thermal conditions and their time-dependence in state-of-the-art evolution models of massive stars.
Max ERC Funding
1 886 558 €
Duration
Start date: 2016-06-01, End date: 2022-05-31
Project acronym IDRICA
Project Improving Drought Resistance in Crops and Arabidopsis
Researcher (PI) Ana Isabel Caño Delgado
Host Institution (HI) CENTRE DE RECERCA EN AGRIGENOMICA CSIC-IRTA-UAB-UB
Call Details Consolidator Grant (CoG), LS9, ERC-2015-CoG
Summary Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.
Summary
Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym INFANTLEUKEMIA
Project GENOMIC, CELLULAR AND DEVELOPMENTAL RECONSTRUCTION OFINFANT MLL-AF4+ ACUTE LYMPHOBLASTIC LEUKEMIA
Researcher (PI) Pablo Menendez Buján
Host Institution (HI) FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS
Call Details Consolidator Grant (CoG), LS4, ERC-2014-CoG
Summary Infant cancer is very distinct to adult cancer and it is progressively seen as a developmental disease. An intriguing infant cancer is the t(4;11) acute lymphoblastic leukemia (ALL) characterized by the hallmark rearrangement MLL-AF4 (MA4), and associated with dismal prognosis. The 100% concordance in twins and its prenatal onset suggest an extremely rapid disease progression. Many key issues remain elusive:
Is MA4 leukemogenic?
Which are other relevant oncogenic drivers?
Which is the nature of the cell transformed by MA4?
Which is the leukemia-initiating cell (LIC)?
Does this ALL follow a hierarchical or stochastic cancer model?
How to explain therapy resistance and CNS involvement?
To what extent do genetics vs epigenetics contribute this ALL?
These questions remain a challenge due to: 1) the absence of prospective studies on diagnostic/remission-matched samples, 2) the lack of models which faithfully reproduce the disease and 3) a surprising genomic stability of this ALL.
I hypothesize that a Multilayer-Omics to function approach in patient blasts and early human hematopoietic stem/progenitor cells (HSPC) is required to fully scrutinize the biology underlying this life-threatening leukemia. I will perform genome-wide studies on the mutational landscape, DNA and H3K79 methylation profiles, and transcriptome on a uniquely available, large cohort of diagnostic/remission-matched samples. Omics data integration will provide unprecedented information about oncogenic drivers which must be analyzed in ground-breaking functional assays using patient blasts and early HSPCs carrying a CRISPR/Cas9-mediated locus/allele-specific t(4;11). Serial xenografts combined with exome-seq in paired diagnostic samples and xenografts will identify the LIC and determine whether variegated genetics may underlie clonal functional heterogeneity. This project will provide a precise understanding and a disease model for MA4+ ALL, offering a platform for new treatment strategies.
Summary
Infant cancer is very distinct to adult cancer and it is progressively seen as a developmental disease. An intriguing infant cancer is the t(4;11) acute lymphoblastic leukemia (ALL) characterized by the hallmark rearrangement MLL-AF4 (MA4), and associated with dismal prognosis. The 100% concordance in twins and its prenatal onset suggest an extremely rapid disease progression. Many key issues remain elusive:
Is MA4 leukemogenic?
Which are other relevant oncogenic drivers?
Which is the nature of the cell transformed by MA4?
Which is the leukemia-initiating cell (LIC)?
Does this ALL follow a hierarchical or stochastic cancer model?
How to explain therapy resistance and CNS involvement?
To what extent do genetics vs epigenetics contribute this ALL?
These questions remain a challenge due to: 1) the absence of prospective studies on diagnostic/remission-matched samples, 2) the lack of models which faithfully reproduce the disease and 3) a surprising genomic stability of this ALL.
I hypothesize that a Multilayer-Omics to function approach in patient blasts and early human hematopoietic stem/progenitor cells (HSPC) is required to fully scrutinize the biology underlying this life-threatening leukemia. I will perform genome-wide studies on the mutational landscape, DNA and H3K79 methylation profiles, and transcriptome on a uniquely available, large cohort of diagnostic/remission-matched samples. Omics data integration will provide unprecedented information about oncogenic drivers which must be analyzed in ground-breaking functional assays using patient blasts and early HSPCs carrying a CRISPR/Cas9-mediated locus/allele-specific t(4;11). Serial xenografts combined with exome-seq in paired diagnostic samples and xenografts will identify the LIC and determine whether variegated genetics may underlie clonal functional heterogeneity. This project will provide a precise understanding and a disease model for MA4+ ALL, offering a platform for new treatment strategies.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym MITOSENSING
Project Decoding mitochondrial nutrient-sensing programs in POMC neurons as key determinants of metabolic health
Researcher (PI) Marc CLARET CARLES
Host Institution (HI) CONSORCI INSTITUT D'INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Call Details Consolidator Grant (CoG), LS4, ERC-2016-COG
Summary Nutrient-sensing by POMC neurons is a critical process to monitor the metabolic status of the organism and to coordinate adaptive neuroendocrine, behavioural and metabolic effectors of energy balance. Mitochondria, as central commanders of cellular energy production and primary sources of bioenergetic signals, are logical candidates to play a key role in metabolic control. However, a comprehensive understanding of the mitochondria as nutrient-sensors and modulators of systemic energy homeostasis is lacking. MITOSENSING hypothesizes that dedicated mitochondrial networks in POMC neurons are able to sense, integrate and respond to alterations in the nutritional milieu and engage physiological actions to maintain energy balance. Thus, defects in these mitochondrial nutrient-sensing programs in this subset of neurons underlie the development of metabolic conditions such as obesity and type-2 diabetes (T2D). To test it, we will pursue three aims: 1) to identify transcriptionally-modulated mitochondrial nutrient-sensing programs in POMC neurons; 2) to investigate whether disruption of specific nutrient-sensing programs in POMC neurons cause metabolic disorders; 3) to investigate whether the development of lifestyle-associated metabolic disorders are caused by defective mitochondrial nutrient-sensing programs in POMC neurons. By providing neuron-specific, integrative, functional and mechanistic in vivo strategies, MITOSENSING will represent a major step forward into the understanding of mitochondria as a nutrient-sensing entity, the gene programs involved and their physiological regulatory functions in the context of energy balance control. Adequate coordination of neuronal nutrient-sensing with energy balance control is critical to sustain life, and thus understanding the molecular mechanisms governing these physiological programs will have an enormous scientific impact and also potential therapeutical implications for obesity and T2D.
Summary
Nutrient-sensing by POMC neurons is a critical process to monitor the metabolic status of the organism and to coordinate adaptive neuroendocrine, behavioural and metabolic effectors of energy balance. Mitochondria, as central commanders of cellular energy production and primary sources of bioenergetic signals, are logical candidates to play a key role in metabolic control. However, a comprehensive understanding of the mitochondria as nutrient-sensors and modulators of systemic energy homeostasis is lacking. MITOSENSING hypothesizes that dedicated mitochondrial networks in POMC neurons are able to sense, integrate and respond to alterations in the nutritional milieu and engage physiological actions to maintain energy balance. Thus, defects in these mitochondrial nutrient-sensing programs in this subset of neurons underlie the development of metabolic conditions such as obesity and type-2 diabetes (T2D). To test it, we will pursue three aims: 1) to identify transcriptionally-modulated mitochondrial nutrient-sensing programs in POMC neurons; 2) to investigate whether disruption of specific nutrient-sensing programs in POMC neurons cause metabolic disorders; 3) to investigate whether the development of lifestyle-associated metabolic disorders are caused by defective mitochondrial nutrient-sensing programs in POMC neurons. By providing neuron-specific, integrative, functional and mechanistic in vivo strategies, MITOSENSING will represent a major step forward into the understanding of mitochondria as a nutrient-sensing entity, the gene programs involved and their physiological regulatory functions in the context of energy balance control. Adequate coordination of neuronal nutrient-sensing with energy balance control is critical to sustain life, and thus understanding the molecular mechanisms governing these physiological programs will have an enormous scientific impact and also potential therapeutical implications for obesity and T2D.
Max ERC Funding
1 999 573 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
