Project acronym EURECA
Project Eukaryotic Regulated RNA Catabolism
Researcher (PI) Torben Heick Jensen
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Advanced Grant (AdG), LS1, ERC-2013-ADG
Summary "Regulation and fidelity of gene expression is fundamental to the differentiation and maintenance of all living organisms. While historically attention has been focused on the process of transcriptional activation, we predict that RNA turnover pathways are equally important for gene expression regulation. This has been implied for selected protein-coding RNAs (mRNAs) but is virtually unexplored for non-protein-coding RNAs (ncRNAs).
The intention of the EURECA proposal is to establish cutting-edge research to characterize mammalian nuclear RNA turnover; its factor utility, substrate specificity and regulatory capacity. We foresee that RNA turnover is at the core of gene expression regulation - forming intricate connection to RNA productive systems – thus, being centrally placed to determine RNA fate. EURECA seeks to dramatically improve our understanding of cellular decision processes impacting RNA levels and to establish models for how regulated RNA turnover helps control key biological processes.
The realization that the number of ncRNA producing genes was previously grossly underestimated foretells that ncRNA regulation will impact on most aspects of cell biology. Consistently, aberrant ncRNA levels correlate with human disease phenotypes and RNA turnover complexes are linked to disease biology. Still, solid models for how ncRNA turnover regulate biological processes in higher eukaryotes are not available. Moreover, which ncRNAs retain function and which are merely transcriptional by-products remain a major challenge to sort out. The circumstances and kinetics of ncRNA turnover are therefore important to delineate as these will ultimately relate to the likelihood of molecular function. A fundamental challenge here is to also discern which protein complements of non-coding ribonucleoprotein particles (ncRNPs) are (in)compatible with function. Balancing single transcript/factor analysis with high-throughput methodology, EURECA will address these questions."
Summary
"Regulation and fidelity of gene expression is fundamental to the differentiation and maintenance of all living organisms. While historically attention has been focused on the process of transcriptional activation, we predict that RNA turnover pathways are equally important for gene expression regulation. This has been implied for selected protein-coding RNAs (mRNAs) but is virtually unexplored for non-protein-coding RNAs (ncRNAs).
The intention of the EURECA proposal is to establish cutting-edge research to characterize mammalian nuclear RNA turnover; its factor utility, substrate specificity and regulatory capacity. We foresee that RNA turnover is at the core of gene expression regulation - forming intricate connection to RNA productive systems – thus, being centrally placed to determine RNA fate. EURECA seeks to dramatically improve our understanding of cellular decision processes impacting RNA levels and to establish models for how regulated RNA turnover helps control key biological processes.
The realization that the number of ncRNA producing genes was previously grossly underestimated foretells that ncRNA regulation will impact on most aspects of cell biology. Consistently, aberrant ncRNA levels correlate with human disease phenotypes and RNA turnover complexes are linked to disease biology. Still, solid models for how ncRNA turnover regulate biological processes in higher eukaryotes are not available. Moreover, which ncRNAs retain function and which are merely transcriptional by-products remain a major challenge to sort out. The circumstances and kinetics of ncRNA turnover are therefore important to delineate as these will ultimately relate to the likelihood of molecular function. A fundamental challenge here is to also discern which protein complements of non-coding ribonucleoprotein particles (ncRNPs) are (in)compatible with function. Balancing single transcript/factor analysis with high-throughput methodology, EURECA will address these questions."
Max ERC Funding
2 497 960 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym LYSOSOME
Project Lysosomes as targets for cancer therapy
Researcher (PI) Marja Helena Jaeaettelae
Host Institution (HI) KRAEFTENS BEKAEMPELSE
Country Denmark
Call Details Advanced Grant (AdG), LS7, ERC-2013-ADG
Summary "Knowing that the lysosomes contain a powerful cocktail of hydrolases capable of digesting cells and entire tissues, it is obvious that the maintenance of lysosomal membrane integrity is of utmost importance for all cells, and especially for cancer cells with dramatically increased lysosomal activity. Yet, the mechanisms that regulate lysosomal membrane stability have remained obscure, largely due to the lack of methods sensitive enough to detect partial lysosomal leakage and suitable for screening purposes. We have finally succeeded in developing such a method, which allows me to propose here a project whose major aim is to reveal how cells maintain the integrity of lysosomal membranes. Based on our emerging data that firmly connect heat shock protein 70 and sphingolipid metabolism to lysosomal membrane stability, we will devote a large part of the project to the molecular details of these connections and to the characterization of the effects of new and already approved (cationic amphiphilic drugs) sphingolipid-regulating drugs on lysosomal membrane stability and cell survival. Additionally, we will screen selected siRNA libraries to identify signaling networks and lysosome-associated proteins essential for lysosomal membrane integrity, and small molecule libraries to identify compounds that induce lysosomal cell death. The next step is to identify lysosome-stabilizing mechanisms that are especially important for cancer cell survival. And the ultimate goal is to validate corresponding drug targets and drugs (old and new) for the induction of lysosomal cell death in therapy resistant cancers. As a “by-product” we expect to identify putative drug targets for the treatment of degenerative diseases and lipid storage disorders, where the stabilization of the lysosomal membranes promotes cell survival."
Summary
"Knowing that the lysosomes contain a powerful cocktail of hydrolases capable of digesting cells and entire tissues, it is obvious that the maintenance of lysosomal membrane integrity is of utmost importance for all cells, and especially for cancer cells with dramatically increased lysosomal activity. Yet, the mechanisms that regulate lysosomal membrane stability have remained obscure, largely due to the lack of methods sensitive enough to detect partial lysosomal leakage and suitable for screening purposes. We have finally succeeded in developing such a method, which allows me to propose here a project whose major aim is to reveal how cells maintain the integrity of lysosomal membranes. Based on our emerging data that firmly connect heat shock protein 70 and sphingolipid metabolism to lysosomal membrane stability, we will devote a large part of the project to the molecular details of these connections and to the characterization of the effects of new and already approved (cationic amphiphilic drugs) sphingolipid-regulating drugs on lysosomal membrane stability and cell survival. Additionally, we will screen selected siRNA libraries to identify signaling networks and lysosome-associated proteins essential for lysosomal membrane integrity, and small molecule libraries to identify compounds that induce lysosomal cell death. The next step is to identify lysosome-stabilizing mechanisms that are especially important for cancer cell survival. And the ultimate goal is to validate corresponding drug targets and drugs (old and new) for the induction of lysosomal cell death in therapy resistant cancers. As a “by-product” we expect to identify putative drug targets for the treatment of degenerative diseases and lipid storage disorders, where the stabilization of the lysosomal membranes promotes cell survival."
Max ERC Funding
2 499 960 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym PLAQNAP
Project Plasmon-based Functional and Quantum Nanophotonics
Researcher (PI) Sergey Bozhevolnyi
Host Institution (HI) SYDDANSK UNIVERSITET
Country Denmark
Call Details Advanced Grant (AdG), PE3, ERC-2013-ADG
Summary "Plasmon-based nanophotnics, an explosively growing research field concerned with surface-plasmon waveguides and circuitry, is oriented towards exploiting unique perspectives opened for radiation guiding along metal surfaces: extreme mode confinement (i.e., far beyond the diffraction limit) and seamless interfacing of electronic and photonic circuits (that both utilize the same metal circuitry). At the same time, unavoidable radiation absorption by metals results in the fundamental trade-off between the mode confinement and propagation loss, so that the problem of making the most of the above unique features becomes of paramount importance. The proposal encompasses two ground-breaking research directions in plasmonics that explore and utilize extremely confined plasmon-waveguide modes for functional and quantum nanophotonics. These directions of in-depth investigations concentrate within two interrelated and largely unexplored research areas within plasmonics: development of ultra-compact plasmonic configurations exhibiting unique functionalities and realization of strong coupling between extremely confined plasmonic modes and individual quantum emitters. Fundamental studies of ultimate mode confinement and coupling to quantum emitters would evolve into investigations carried out within forefront topics including (i) dynamic control of plasmon-waveguide modes using the same metal circuitry for both radiation guiding and its control with electrical signals; (ii) moulding the radiation flow by gradually varying waveguide cross sections in order to realize efficient nanofocusing of radiation, miniature ultra-dispersive wavelength-selective components and table-top models of plasmonic black holes, and (iii) quantum plasmonics with individual quantum emitters being strongly coupled to deep subwavelength surface plasmon modes, targeting the realization of a saturable waveguide mirror, single-photon transistor and long-distance entanglement of two remote quantum emitters."
Summary
"Plasmon-based nanophotnics, an explosively growing research field concerned with surface-plasmon waveguides and circuitry, is oriented towards exploiting unique perspectives opened for radiation guiding along metal surfaces: extreme mode confinement (i.e., far beyond the diffraction limit) and seamless interfacing of electronic and photonic circuits (that both utilize the same metal circuitry). At the same time, unavoidable radiation absorption by metals results in the fundamental trade-off between the mode confinement and propagation loss, so that the problem of making the most of the above unique features becomes of paramount importance. The proposal encompasses two ground-breaking research directions in plasmonics that explore and utilize extremely confined plasmon-waveguide modes for functional and quantum nanophotonics. These directions of in-depth investigations concentrate within two interrelated and largely unexplored research areas within plasmonics: development of ultra-compact plasmonic configurations exhibiting unique functionalities and realization of strong coupling between extremely confined plasmonic modes and individual quantum emitters. Fundamental studies of ultimate mode confinement and coupling to quantum emitters would evolve into investigations carried out within forefront topics including (i) dynamic control of plasmon-waveguide modes using the same metal circuitry for both radiation guiding and its control with electrical signals; (ii) moulding the radiation flow by gradually varying waveguide cross sections in order to realize efficient nanofocusing of radiation, miniature ultra-dispersive wavelength-selective components and table-top models of plasmonic black holes, and (iii) quantum plasmonics with individual quantum emitters being strongly coupled to deep subwavelength surface plasmon modes, targeting the realization of a saturable waveguide mirror, single-photon transistor and long-distance entanglement of two remote quantum emitters."
Max ERC Funding
2 278 636 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym PREAS
Project Predicting the arsenic content in groundwater of the floodplains in SE Asia
Researcher (PI) Diederik Jan Postma
Host Institution (HI) Geological Survey of Denmark and Greenland
Country Denmark
Call Details Advanced Grant (AdG), PE10, ERC-2013-ADG
Summary More than 100 million people living on the floodplains of the Ganges-Brahmaputra-Meghna, Mekong and Red River, all draining the Himalayas, are consuming arsenic contaminated water. Providing safe drinking water for these people requires a quantitative understanding of the processes regulating the groundwater arsenic content and this knowledge is presently not available. In PREDIAS we propose a revolutionary new approach to study these arsenic contaminated aquifers where sediments and groundwaters are considered as one reacting unit that is changing over time. The key hypothesis is that it is the aquifer sediment burial age that is the overall controlling parameter for the arsenic content. This new approach is explored by studying the groundwater chemistry as a function of sediment burial age, which is equivalent to the geological evolution over time, in part of the Red River floodplain in Vietnam. The investigations comprise delineating the sedimentological development over the last 9000 yrs as well as reconstructing hydrogeological conditions over that period. Process studies will reveal the effect of burial age on the chemical properties of the sediments and the arsenic release mechanisms. They comprise the binding and release mechanisms of arsenic to the aquifer sediment, and the reactivity of sedimentary organic carbon and iron oxides which drive the redox reactions controlling the water chemistry and arsenic mobilization. Information on the sedimentological and hydrogeological development over time as well as a quantification of the geochemical processes will be incorporated in a 3-D reactive transport model which over the last 9000 years, in steps of about 1000 years, can predict the evolution of the arsenic content over space and time in the groundwater of the studied area. The model can be extended in a more conceptual form to larger parts of the Red River delta and Bangladesh using satellite imaging to reveal the geological development in those areas.
Summary
More than 100 million people living on the floodplains of the Ganges-Brahmaputra-Meghna, Mekong and Red River, all draining the Himalayas, are consuming arsenic contaminated water. Providing safe drinking water for these people requires a quantitative understanding of the processes regulating the groundwater arsenic content and this knowledge is presently not available. In PREDIAS we propose a revolutionary new approach to study these arsenic contaminated aquifers where sediments and groundwaters are considered as one reacting unit that is changing over time. The key hypothesis is that it is the aquifer sediment burial age that is the overall controlling parameter for the arsenic content. This new approach is explored by studying the groundwater chemistry as a function of sediment burial age, which is equivalent to the geological evolution over time, in part of the Red River floodplain in Vietnam. The investigations comprise delineating the sedimentological development over the last 9000 yrs as well as reconstructing hydrogeological conditions over that period. Process studies will reveal the effect of burial age on the chemical properties of the sediments and the arsenic release mechanisms. They comprise the binding and release mechanisms of arsenic to the aquifer sediment, and the reactivity of sedimentary organic carbon and iron oxides which drive the redox reactions controlling the water chemistry and arsenic mobilization. Information on the sedimentological and hydrogeological development over time as well as a quantification of the geochemical processes will be incorporated in a 3-D reactive transport model which over the last 9000 years, in steps of about 1000 years, can predict the evolution of the arsenic content over space and time in the groundwater of the studied area. The model can be extended in a more conceptual form to larger parts of the Red River delta and Bangladesh using satellite imaging to reveal the geological development in those areas.
Max ERC Funding
1 619 932 €
Duration
Start date: 2014-01-01, End date: 2018-03-31
