Project acronym AEROSOL
Project Astrochemistry of old stars: direct probing of unique chemical laboratories
Researcher (PI) Leen Katrien Els Decin
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Country Belgium
Call Details Consolidator Grant (CoG), PE9, ERC-2014-CoG
Summary The gas and dust in the interstellar medium (ISM) drive the chemical evolution of galaxies, the formation of stars and planets, and the synthesis of complex prebiotic molecules. The prime birth places for this interstellar material are the winds of evolved (super)giant stars. These winds are unique chemical laboratories, in which a large variety of gas and dust species radially expand away from the star.
Recent progress on the observations of these winds has been impressive thanks to Herschel and ALMA. The next challenge is to unravel the wealth of chemical information contained in these data. This is an ambitious task since (1) a plethora of physical and chemical processes interact in a complex way, (2) laboratory data to interpret these interactions are lacking, and (3) theoretical tools to analyse the data do not meet current needs.
To boost the knowledge of the physics and chemistry characterizing these winds, I propose a world-leading multi-disciplinary project combining (1) high-quality data, (2) novel theoretical wind models, and (3) targeted laboratory experiments. The aim is to pinpoint the dominant chemical pathways, unravel the transition from gas-phase to dust species, elucidate the role of clumps on the overall wind structure, and study the reciprocal effect between various dynamical and chemical phenomena.
Now is the right time for this ambitious project thanks to the availability of (1) high-quality multi-wavelength data, including ALMA and Herschel data of the PI, (2) supercomputers enabling a homogeneous analysis of the data using sophisticated theoretical wind models, and (3) novel laboratory equipment to measure the gas-phase reaction rates of key species.
This project will have far-reaching impact on (1) the field of evolved stars, (2) the understanding of the chemical lifecycle of the ISM, (3) chemical studies of dynamically more complex systems, such as exoplanets, protostars, supernovae etc., and (4) it will guide new instrument development.
Summary
The gas and dust in the interstellar medium (ISM) drive the chemical evolution of galaxies, the formation of stars and planets, and the synthesis of complex prebiotic molecules. The prime birth places for this interstellar material are the winds of evolved (super)giant stars. These winds are unique chemical laboratories, in which a large variety of gas and dust species radially expand away from the star.
Recent progress on the observations of these winds has been impressive thanks to Herschel and ALMA. The next challenge is to unravel the wealth of chemical information contained in these data. This is an ambitious task since (1) a plethora of physical and chemical processes interact in a complex way, (2) laboratory data to interpret these interactions are lacking, and (3) theoretical tools to analyse the data do not meet current needs.
To boost the knowledge of the physics and chemistry characterizing these winds, I propose a world-leading multi-disciplinary project combining (1) high-quality data, (2) novel theoretical wind models, and (3) targeted laboratory experiments. The aim is to pinpoint the dominant chemical pathways, unravel the transition from gas-phase to dust species, elucidate the role of clumps on the overall wind structure, and study the reciprocal effect between various dynamical and chemical phenomena.
Now is the right time for this ambitious project thanks to the availability of (1) high-quality multi-wavelength data, including ALMA and Herschel data of the PI, (2) supercomputers enabling a homogeneous analysis of the data using sophisticated theoretical wind models, and (3) novel laboratory equipment to measure the gas-phase reaction rates of key species.
This project will have far-reaching impact on (1) the field of evolved stars, (2) the understanding of the chemical lifecycle of the ISM, (3) chemical studies of dynamically more complex systems, such as exoplanets, protostars, supernovae etc., and (4) it will guide new instrument development.
Max ERC Funding
2 605 897 €
Duration
Start date: 2016-01-01, End date: 2021-12-31
Project acronym ART
Project Aberrant RNA degradation in T-cell leukemia
Researcher (PI) Jan Cools
Host Institution (HI) VIB VZW
Country Belgium
Call Details Consolidator Grant (CoG), LS4, ERC-2013-CoG
Summary "The deregulation of transcription is an important driver of leukemia development. Typically, transcription in leukemia cells is altered by the ectopic expression of transcription factors, by modulation of signaling pathways or by epigenetic changes. In addition to these factors that affect the production of RNAs, also changes in the processing of RNA (its splicing, transport and decay) may contribute to determine steady-state RNA levels in leukemia cells. Indeed, acquired mutations in various genes encoding RNA splice factors have recently been identified in myeloid leukemias and in chronic lymphocytic leukemia. In our study of T-cell acute lymphoblastic leukemia (T-ALL), we have identified mutations in RNA decay factors, including mutations in CNOT3, a protein believed to function in deadenylation of mRNA. It remains, however, unclear how mutations in RNA processing can contribute to the development of leukemia.
In this project, we aim to further characterize the mechanisms of RNA regulation in T-cell acute lymphoblastic leukemia (T-ALL) to obtain insight in the interplay between RNA generation and RNA decay and its role in leukemia development. We will study RNA decay in human T-ALL cells and mouse models of T-ALL, with the aim to identify the molecular consequences that contribute to leukemia development. We will use new technologies such as RNA-sequencing in combination with bromouridine labeling of RNA to measure RNA transcription and decay rates in a transcriptome wide manner allowing unbiased discoveries. These studies will be complemented with screens in Drosophila melanogaster using an established eye cancer model, previously also successfully used for the studies of T-ALL oncogenes.
This study will contribute to our understanding of the pathogenesis of T-ALL and may identify new targets for therapy of this leukemia. In addition, our study will provide a better understanding of how RNA processing is implicated in cancer development in general."
Summary
"The deregulation of transcription is an important driver of leukemia development. Typically, transcription in leukemia cells is altered by the ectopic expression of transcription factors, by modulation of signaling pathways or by epigenetic changes. In addition to these factors that affect the production of RNAs, also changes in the processing of RNA (its splicing, transport and decay) may contribute to determine steady-state RNA levels in leukemia cells. Indeed, acquired mutations in various genes encoding RNA splice factors have recently been identified in myeloid leukemias and in chronic lymphocytic leukemia. In our study of T-cell acute lymphoblastic leukemia (T-ALL), we have identified mutations in RNA decay factors, including mutations in CNOT3, a protein believed to function in deadenylation of mRNA. It remains, however, unclear how mutations in RNA processing can contribute to the development of leukemia.
In this project, we aim to further characterize the mechanisms of RNA regulation in T-cell acute lymphoblastic leukemia (T-ALL) to obtain insight in the interplay between RNA generation and RNA decay and its role in leukemia development. We will study RNA decay in human T-ALL cells and mouse models of T-ALL, with the aim to identify the molecular consequences that contribute to leukemia development. We will use new technologies such as RNA-sequencing in combination with bromouridine labeling of RNA to measure RNA transcription and decay rates in a transcriptome wide manner allowing unbiased discoveries. These studies will be complemented with screens in Drosophila melanogaster using an established eye cancer model, previously also successfully used for the studies of T-ALL oncogenes.
This study will contribute to our understanding of the pathogenesis of T-ALL and may identify new targets for therapy of this leukemia. In addition, our study will provide a better understanding of how RNA processing is implicated in cancer development in general."
Max ERC Funding
1 998 300 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym ASEA
Project The aftermath of slavery in East Africa
Researcher (PI) Felicitas Maria BECKER
Host Institution (HI) UNIVERSITEIT GENT
Country Belgium
Call Details Consolidator Grant (CoG), SH6, ERC-2018-COG
Summary Legacies of slavery tend to affect societies deeply, but in inland East Africa have remained little explored. This project aims [1] to establish what happened to the hundreds of thousands of slaves present in mainland East Africa in ca. 1900 and to their descendants over the twentieth century, [2] to explain why the aftermath of slavery is so little discussed in the written sources and historiography of the region, and [3] to trace the social and political legacies of slavery up to the present. It will combine historical and anthropological methods, and, besides post-slavery, addresses questions pertaining to public history, social mobility, marginality and inequality, gender, and understandings of freedom. It pursues them through a series of place-specific case-studies tracing different courses and outcomes within the region, and through comparative work, both between the case studies and with studies on the aftermath of slavery in West Africa, the Indian Ocean and the Americas.
The project is ground-breaking through its long-term time frame, its wide-ranging combination of methods, and in questioning established assumptions, e.g. about the meaning of ‘freedom’ for ex-slaves. It is high-risk in the sense that the field researchers leading the case studies will need good knowledge of Swahili, good social contacts and the flexibility to identify and follow emerging leads wherever they take them. It is feasible because the proposed research program and conceptual frameworks can be adapted as the work develops, and given the obscurity of the regions, groups and questions involved, the resulting gains to knowledge will be major. It is high-gain because it will fill a gaping hole in current knowledge, and establish how people in East Africa coped with the toxic legacy of slavery, which often presents intractable problems, apparently with little disruption. The resulting comparisons will contribute to a better understanding of tensions in other post-slavery societies.
Summary
Legacies of slavery tend to affect societies deeply, but in inland East Africa have remained little explored. This project aims [1] to establish what happened to the hundreds of thousands of slaves present in mainland East Africa in ca. 1900 and to their descendants over the twentieth century, [2] to explain why the aftermath of slavery is so little discussed in the written sources and historiography of the region, and [3] to trace the social and political legacies of slavery up to the present. It will combine historical and anthropological methods, and, besides post-slavery, addresses questions pertaining to public history, social mobility, marginality and inequality, gender, and understandings of freedom. It pursues them through a series of place-specific case-studies tracing different courses and outcomes within the region, and through comparative work, both between the case studies and with studies on the aftermath of slavery in West Africa, the Indian Ocean and the Americas.
The project is ground-breaking through its long-term time frame, its wide-ranging combination of methods, and in questioning established assumptions, e.g. about the meaning of ‘freedom’ for ex-slaves. It is high-risk in the sense that the field researchers leading the case studies will need good knowledge of Swahili, good social contacts and the flexibility to identify and follow emerging leads wherever they take them. It is feasible because the proposed research program and conceptual frameworks can be adapted as the work develops, and given the obscurity of the regions, groups and questions involved, the resulting gains to knowledge will be major. It is high-gain because it will fill a gaping hole in current knowledge, and establish how people in East Africa coped with the toxic legacy of slavery, which often presents intractable problems, apparently with little disruption. The resulting comparisons will contribute to a better understanding of tensions in other post-slavery societies.
Max ERC Funding
1 921 250 €
Duration
Start date: 2019-11-01, End date: 2024-10-31
Project acronym BantuFirst
Project The First Bantu Speakers South of the Rainforest: A Cross-Disciplinary Approach to Human Migration, Language Spread, Climate Change and Early Farming in Late Holocene Central Africa
Researcher (PI) Koen Andre G. BOSTOEN
Host Institution (HI) UNIVERSITEIT GENT
Country Belgium
Call Details Consolidator Grant (CoG), SH6, ERC-2016-COG
Summary The Bantu Expansion is not only the main linguistic, cultural and demographic process in Late Holocene Africa. It is also one of the most controversial issues in African History that still has political repercussions today. It has sparked debate across the disciplines and far beyond Africanist circles in an attempt to understand how the young Bantu language family (ca. 5000 years) could spread over large parts of Central, Eastern and Southern Africa. This massive dispersal is commonly seen as the result of a single migratory macro-event driven by agriculture, but many questions about the movement and subsistence of ancestral Bantu speakers are still open. They can only be answered through real interdisciplinary collaboration. This project will unite researchers with outstanding expertise in African archaeology, archaeobotany and historical linguistics to form a unique cross-disciplinary team that will shed new light on the first Bantu-speaking village communities south of the rainforest. Fieldwork is planned in parts of the Democratic Republic of Congo, the Republic of Congo and Angola that are terra incognita for archaeologists to determine the timing, location and archaeological signature of the earliest villagers and to establish how they interacted with autochthonous hunter-gatherers. Special attention will be paid to archaeobotanical and palaeoenvironmental data to get an idea of their subsistence, diet and habitat. Historical linguistics will be pushed beyond the boundaries of vocabulary-based phylogenetics and open new pathways in lexical reconstruction, especially regarding subsistence and land use of early Bantu speakers. Through interuniversity collaboration archaeozoological, palaeoenvironmental and genetic data and phylogenetic modelling will be brought into the cross-disciplinary approach to acquire a new holistic view on the interconnections between human migration, language spread, climate change and early farming in Late Holocene Central Africa.
Summary
The Bantu Expansion is not only the main linguistic, cultural and demographic process in Late Holocene Africa. It is also one of the most controversial issues in African History that still has political repercussions today. It has sparked debate across the disciplines and far beyond Africanist circles in an attempt to understand how the young Bantu language family (ca. 5000 years) could spread over large parts of Central, Eastern and Southern Africa. This massive dispersal is commonly seen as the result of a single migratory macro-event driven by agriculture, but many questions about the movement and subsistence of ancestral Bantu speakers are still open. They can only be answered through real interdisciplinary collaboration. This project will unite researchers with outstanding expertise in African archaeology, archaeobotany and historical linguistics to form a unique cross-disciplinary team that will shed new light on the first Bantu-speaking village communities south of the rainforest. Fieldwork is planned in parts of the Democratic Republic of Congo, the Republic of Congo and Angola that are terra incognita for archaeologists to determine the timing, location and archaeological signature of the earliest villagers and to establish how they interacted with autochthonous hunter-gatherers. Special attention will be paid to archaeobotanical and palaeoenvironmental data to get an idea of their subsistence, diet and habitat. Historical linguistics will be pushed beyond the boundaries of vocabulary-based phylogenetics and open new pathways in lexical reconstruction, especially regarding subsistence and land use of early Bantu speakers. Through interuniversity collaboration archaeozoological, palaeoenvironmental and genetic data and phylogenetic modelling will be brought into the cross-disciplinary approach to acquire a new holistic view on the interconnections between human migration, language spread, climate change and early farming in Late Holocene Central Africa.
Max ERC Funding
1 997 500 €
Duration
Start date: 2018-01-01, End date: 2023-06-30
Project acronym BAS-SBBT
Project Bacterial Amyloid Secretion: Structural Biology and Biotechnology.
Researcher (PI) Han Karel Remaut
Host Institution (HI) VIB VZW
Country Belgium
Call Details Consolidator Grant (CoG), LS1, ERC-2014-CoG
Summary Curli are functional amyloid fibers that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria. Unlike the protein misfolding and aggregation events seen in pathological amyloid diseases such as Alzheimer’s and Parkinson’s disease, curli are the product of a dedicated protein secretion machinery. Curli formation requires a specialised and mechanistically unique transporter in the bacterial outer membrane, as well as two soluble accessory proteins thought to facilitate the safe guidance of the curli subunits across the periplasm and to coordinate their self-assembly at cell surface.
In this interdisciplinary research program we will study the structural and molecular biology of E. coli curli biosynthesis and address the fundamental questions concerning the molecular processes that allow the spatially and temporally controlled transport and deposition of these pro-amyloidogenic polypeptides. We will structurally unravel the secretion machinery, trap and analyse critical secretion intermediates and through in vitro reconstitution, assemble a minimal, self-sufficient peptide transport and fiber assembly system.
The new insights gained will set the stage for targeted interventions in curli -mediated biofilm formation and this research project will develop a new framework to harness the unique properties found in curli structure and biosynthesis for biotechnological applications as in patterned functionalized nanowires and directed, selective peptide carriers.
Summary
Curli are functional amyloid fibers that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria. Unlike the protein misfolding and aggregation events seen in pathological amyloid diseases such as Alzheimer’s and Parkinson’s disease, curli are the product of a dedicated protein secretion machinery. Curli formation requires a specialised and mechanistically unique transporter in the bacterial outer membrane, as well as two soluble accessory proteins thought to facilitate the safe guidance of the curli subunits across the periplasm and to coordinate their self-assembly at cell surface.
In this interdisciplinary research program we will study the structural and molecular biology of E. coli curli biosynthesis and address the fundamental questions concerning the molecular processes that allow the spatially and temporally controlled transport and deposition of these pro-amyloidogenic polypeptides. We will structurally unravel the secretion machinery, trap and analyse critical secretion intermediates and through in vitro reconstitution, assemble a minimal, self-sufficient peptide transport and fiber assembly system.
The new insights gained will set the stage for targeted interventions in curli -mediated biofilm formation and this research project will develop a new framework to harness the unique properties found in curli structure and biosynthesis for biotechnological applications as in patterned functionalized nanowires and directed, selective peptide carriers.
Max ERC Funding
1 989 489 €
Duration
Start date: 2015-06-01, End date: 2020-11-30
Project acronym BEAL
Project Bioenergetics in microalgae : regulation modes of mitochondrial respiration, photosynthesis, and fermentative pathways, and their interactions in secondary algae
Researcher (PI) Pierre Antoine Georges Cardol
Host Institution (HI) UNIVERSITE DE LIEGE
Country Belgium
Call Details Consolidator Grant (CoG), LS8, ERC-2015-CoG
Summary During the course of eukaryote evolution, photosynthesis was propagated from primary eukaryotic algae to non-photosynthetic organisms through multiple secondary endosymbiotic events. Collectively referred to as “secondary algae”, these photosynthetic organisms account for only 1-2% of the total global biomass, but produce a far larger part of the global annual fixation of carbon on Earth.
ATP is the universal chemical energy carrier in living cells. In photosynthetic eukaryotes, it is produced by two major cellular processes: photosynthesis and respiration taking place in chloroplasts and mitochondria, respectively. Both processes support the production of biomass and govern gas (O2 and CO2) exchanges. On the other hand, anaerobic fermentative enzymes have also been identified in several primary and secondary algae. The regulation modes and interactions of respiration, photosynthesis and fermentation are fairly well understood in primary green algae. Conversely, the complex evolutionary history of secondary algae implies a great variety of original regulatory mechanisms that have been barely investigated to date.
Over the last years my laboratory has developed and optimized a range of multidisciplinary approaches that now allow us, within the frame of the BEAL (BioEnergetics in microALgae) project, to (i) characterize and compare the photosynthetic regulation modes by biophysical approaches, (ii) use genetic and biochemical approaches to gain fundamental knowledge on aerobic respiration and anaerobic fermentative pathways, and (iii) investigate and compare interconnections between respiration, photosynthesis, and fermentation in organisms resulting from distinct evolutionary scenarios. On a long term, these developments will be instrumental to unravel bioenergetics constraints on growth in microalgae, a required knowledge to exploit the microalgal diversity in a biotechnological perspective, and to understand the complexity of the marine phytoplankton.
Summary
During the course of eukaryote evolution, photosynthesis was propagated from primary eukaryotic algae to non-photosynthetic organisms through multiple secondary endosymbiotic events. Collectively referred to as “secondary algae”, these photosynthetic organisms account for only 1-2% of the total global biomass, but produce a far larger part of the global annual fixation of carbon on Earth.
ATP is the universal chemical energy carrier in living cells. In photosynthetic eukaryotes, it is produced by two major cellular processes: photosynthesis and respiration taking place in chloroplasts and mitochondria, respectively. Both processes support the production of biomass and govern gas (O2 and CO2) exchanges. On the other hand, anaerobic fermentative enzymes have also been identified in several primary and secondary algae. The regulation modes and interactions of respiration, photosynthesis and fermentation are fairly well understood in primary green algae. Conversely, the complex evolutionary history of secondary algae implies a great variety of original regulatory mechanisms that have been barely investigated to date.
Over the last years my laboratory has developed and optimized a range of multidisciplinary approaches that now allow us, within the frame of the BEAL (BioEnergetics in microALgae) project, to (i) characterize and compare the photosynthetic regulation modes by biophysical approaches, (ii) use genetic and biochemical approaches to gain fundamental knowledge on aerobic respiration and anaerobic fermentative pathways, and (iii) investigate and compare interconnections between respiration, photosynthesis, and fermentation in organisms resulting from distinct evolutionary scenarios. On a long term, these developments will be instrumental to unravel bioenergetics constraints on growth in microalgae, a required knowledge to exploit the microalgal diversity in a biotechnological perspective, and to understand the complexity of the marine phytoplankton.
Max ERC Funding
1 837 625 €
Duration
Start date: 2016-06-01, End date: 2021-11-30
Project acronym BIONICbacteria
Project Integrating a novel layer of synthetic biology tools in Pseudomonas, inspired by bacterial viruses
Researcher (PI) Rob LAVIGNE
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Country Belgium
Call Details Consolidator Grant (CoG), LS9, ERC-2018-COG
Summary As nature’s first bioengineers, bacteriophages have evolved to modify, adapt and control their bacterial hosts through billions of years of interactions. Indeed, like modern synthetic biologists aspire to do, bacteriophages already evade bacterial silencing of their xenogeneic DNA, subvert host gene expression, and co-opt both the central and peripheral metabolisms of their hosts. Studying these key insights from a molecular systems biology perspective, inspired us to develop these evolutionary fully-adapted phage mechanisms as a next-level layer of synthetic biology tools. Thus, BIONICbacteria will provide conceptual novel synthetic biology tools that allow direct manipulation of specific protein activity, post-translational modifications, RNA stability, and metabolite concentrations.
The goal of BIONICbacteria is to pioneer an unconventional way to perform synthetic biology, tapping an unlimited source of novel phage tools genetic circuits and phage modulators. To achieve these goals, we will apply and develop state-of-the-art technologies in molecular microbiology and focus on three principal aims:
(1) To exploit new phage-encoded genetic circuits as synthetic biology parts and as intricate biotechnological chassis.
(2) To build synthetic phage modulators (SPMs) as novel payloads to directly impact the bacterial metabolism in a targeted manner.
(3) To create designer bacteria by integrating SPMs-containing circuits into bacterial strains as proof-of-concepts for applications in industrial fermentations and vaccine design.
This proposed “plug-in” approach of evolutionary-adapted synthetic modules, will allow us to domesticate Pseudomonas strains in radically new ways. By building proofs-of-concept for applications in industrial fermentations and vaccine development, we address key problem in these areas with potentially high-gain solutions for society and industry.
Summary
As nature’s first bioengineers, bacteriophages have evolved to modify, adapt and control their bacterial hosts through billions of years of interactions. Indeed, like modern synthetic biologists aspire to do, bacteriophages already evade bacterial silencing of their xenogeneic DNA, subvert host gene expression, and co-opt both the central and peripheral metabolisms of their hosts. Studying these key insights from a molecular systems biology perspective, inspired us to develop these evolutionary fully-adapted phage mechanisms as a next-level layer of synthetic biology tools. Thus, BIONICbacteria will provide conceptual novel synthetic biology tools that allow direct manipulation of specific protein activity, post-translational modifications, RNA stability, and metabolite concentrations.
The goal of BIONICbacteria is to pioneer an unconventional way to perform synthetic biology, tapping an unlimited source of novel phage tools genetic circuits and phage modulators. To achieve these goals, we will apply and develop state-of-the-art technologies in molecular microbiology and focus on three principal aims:
(1) To exploit new phage-encoded genetic circuits as synthetic biology parts and as intricate biotechnological chassis.
(2) To build synthetic phage modulators (SPMs) as novel payloads to directly impact the bacterial metabolism in a targeted manner.
(3) To create designer bacteria by integrating SPMs-containing circuits into bacterial strains as proof-of-concepts for applications in industrial fermentations and vaccine design.
This proposed “plug-in” approach of evolutionary-adapted synthetic modules, will allow us to domesticate Pseudomonas strains in radically new ways. By building proofs-of-concept for applications in industrial fermentations and vaccine development, we address key problem in these areas with potentially high-gain solutions for society and industry.
Max ERC Funding
1 998 750 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym BOSS-WAVES
Project Back-reaction Of Solar plaSma to WAVES
Researcher (PI) Tom VAN DOORSSELAERE
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Country Belgium
Call Details Consolidator Grant (CoG), PE9, ERC-2016-COG
Summary "The solar coronal heating problem is a long-standing astrophysical problem. The slow DC (reconnection) heating models are well developed in detailed 3D numerical simulations. The fast AC (wave) heating mechanisms have traditionally been neglected since there were no wave observations.
Since 2007, we know that the solar atmosphere is filled with transverse waves, but still we have no adequate models (except for my own 1D analytical models) for their dissipation and plasma heating by these waves. We urgently need to know the contribution of these waves to the coronal heating problem.
In BOSS-WAVES, I will innovate the AC wave heating models by utilising novel 3D numerical simulations of propagating transverse waves. From previous results in my team, I know that the inclusion of the back-reaction of the solar plasma is crucial in understanding the energy dissipation: the wave heating leads to chromospheric evaporation and plasma mixing (by the Kelvin-Helmholtz instability).
BOSS-WAVES will bring the AC heating models to the same level of state-of-the-art DC heating models.
The high-risk, high-gain goals are (1) to create a coronal loop heated by waves, starting from an "empty" corona, by evaporating chromospheric material, and (2) to pioneer models for whole active regions heated by transverse waves."
Summary
"The solar coronal heating problem is a long-standing astrophysical problem. The slow DC (reconnection) heating models are well developed in detailed 3D numerical simulations. The fast AC (wave) heating mechanisms have traditionally been neglected since there were no wave observations.
Since 2007, we know that the solar atmosphere is filled with transverse waves, but still we have no adequate models (except for my own 1D analytical models) for their dissipation and plasma heating by these waves. We urgently need to know the contribution of these waves to the coronal heating problem.
In BOSS-WAVES, I will innovate the AC wave heating models by utilising novel 3D numerical simulations of propagating transverse waves. From previous results in my team, I know that the inclusion of the back-reaction of the solar plasma is crucial in understanding the energy dissipation: the wave heating leads to chromospheric evaporation and plasma mixing (by the Kelvin-Helmholtz instability).
BOSS-WAVES will bring the AC heating models to the same level of state-of-the-art DC heating models.
The high-risk, high-gain goals are (1) to create a coronal loop heated by waves, starting from an "empty" corona, by evaporating chromospheric material, and (2) to pioneer models for whole active regions heated by transverse waves."
Max ERC Funding
1 991 960 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym CHAMELEON
Project Cellular Hypoxia Alters DNA MEthylation through Loss of Epigenome OxidatioN
Researcher (PI) Diether Lambrechts
Host Institution (HI) VIB VZW
Country Belgium
Call Details Consolidator Grant (CoG), LS2, ERC-2013-CoG
Summary "DNA methylation was originally described in the 1970s as an epigenetic mark involved in transcriptional silencing, but the existence of DNA demethylation and the enzymes involved in this process were only recently discovered. In particular, it was established that TET hydroxylases catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) through a reaction requiring oxygen (O2) and 2-oxoglutarate (2OG). DNA demethylation as mediated by TET hydroxylases has so far predominantly been studied in the context of stem cells, but its precise contribution to carcinogenesis remains largely enigmatic. Nevertheless, somatic mutations in TETs have been identified in numerous cancers.
Tumor hypoxia is linked to increased malignancy, poor prognosis and resistance to cancer therapies. In this proposal, we aim to assess how hypoxia directly impacts on the cancer epigenome through the dependence of TET-mediated DNA demethylation on O2. First of all, we will study the effect of O2 and 2OG concentration on TET hydroxylase activity, as well as the overall and locus-specific changes of their product (5hmC). Secondly, because much of the hypoxic response is executed through HIFs, we will investigate how HIF binding is influenced by DNA methylation and if so, whether TET hydroxylases are targeted to HIF (or other) binding sites to maintain them transcriptionally active. Thirdly, we will assess to what extent 5hmC profiles differ between tumor types and construct a comprehensive panel of (tumor-specific) 5hmC sites to assess the global and locus-specific relevance of 5hmC in various cancers. Finally, since hypoxia is a key regulator of the cancer stem cell (CSC) niche and within the tumor microenvironment also promotes metastasis, we will establish the in vivo relevance of DNA demethylation, as imposed by tumor hypoxia, in the CSC niche and during metastasis. Overall, we thus aim to establish the interplay between tumor hypoxia and the DNA methylome."
Summary
"DNA methylation was originally described in the 1970s as an epigenetic mark involved in transcriptional silencing, but the existence of DNA demethylation and the enzymes involved in this process were only recently discovered. In particular, it was established that TET hydroxylases catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) through a reaction requiring oxygen (O2) and 2-oxoglutarate (2OG). DNA demethylation as mediated by TET hydroxylases has so far predominantly been studied in the context of stem cells, but its precise contribution to carcinogenesis remains largely enigmatic. Nevertheless, somatic mutations in TETs have been identified in numerous cancers.
Tumor hypoxia is linked to increased malignancy, poor prognosis and resistance to cancer therapies. In this proposal, we aim to assess how hypoxia directly impacts on the cancer epigenome through the dependence of TET-mediated DNA demethylation on O2. First of all, we will study the effect of O2 and 2OG concentration on TET hydroxylase activity, as well as the overall and locus-specific changes of their product (5hmC). Secondly, because much of the hypoxic response is executed through HIFs, we will investigate how HIF binding is influenced by DNA methylation and if so, whether TET hydroxylases are targeted to HIF (or other) binding sites to maintain them transcriptionally active. Thirdly, we will assess to what extent 5hmC profiles differ between tumor types and construct a comprehensive panel of (tumor-specific) 5hmC sites to assess the global and locus-specific relevance of 5hmC in various cancers. Finally, since hypoxia is a key regulator of the cancer stem cell (CSC) niche and within the tumor microenvironment also promotes metastasis, we will establish the in vivo relevance of DNA demethylation, as imposed by tumor hypoxia, in the CSC niche and during metastasis. Overall, we thus aim to establish the interplay between tumor hypoxia and the DNA methylome."
Max ERC Funding
1 920 000 €
Duration
Start date: 2014-09-01, End date: 2019-08-31
Project acronym cis-CONTROL
Project Decoding and controlling cell-state switching: A bottom-up approach based on enhancer logic
Researcher (PI) Stein Luc AERTS
Host Institution (HI) VIB
Country Belgium
Call Details Consolidator Grant (CoG), LS2, ERC-2016-COG
Summary Cell-state switching in cancer allows cells to transition from a proliferative to an invasive and drug-resistant phenotype. This plasticity plays an important role in cancer progression and tumour heterogeneity. We have made a striking observation that cancer cells of different origin can switch to a common survival state. During this epigenomic reprogramming, cancer cells re-activate genomic enhancers from specific regulatory programs, such as wound repair and epithelial-to-mesenchymal transition.
The goal of my project is to decipher the enhancer logic underlying this canalization effect towards a common survival state. We will then employ this new understanding of enhancer logic to engineer synthetic enhancers that are able to monitor and manipulate cell-state switching in real time. Furthermore, we will use enhancer models to identify cis-regulatory mutations that have an impact on cell-state switching and drug resistance. Such applications are currently hampered because there is a significant gap in our understanding of how enhancers work.
To tackle this problem we will use a combination of in vivo massively parallel enhancer-reporter assays, single-cell genomics on microfluidic devices, computational modelling, and synthetic enhancer design. Using these approaches we will pursue the following aims: (1) to identify functional enhancers regulating cell-state switching by performing in vivo genetic screens in mice; (2) to elucidate the dynamic trajectories whereby cells of different cancer types switch to a common survival cell-state, at single-cell resolution; (3) to create synthetic enhancer circuits that specifically kill cancer cells undergoing cell-state switching.
Our findings will have an impact on genome research, characterizing how cellular decision making is implemented by the cis-regulatory code; and on cancer research, employing enhancer logic in the context of cancer therapy.
Summary
Cell-state switching in cancer allows cells to transition from a proliferative to an invasive and drug-resistant phenotype. This plasticity plays an important role in cancer progression and tumour heterogeneity. We have made a striking observation that cancer cells of different origin can switch to a common survival state. During this epigenomic reprogramming, cancer cells re-activate genomic enhancers from specific regulatory programs, such as wound repair and epithelial-to-mesenchymal transition.
The goal of my project is to decipher the enhancer logic underlying this canalization effect towards a common survival state. We will then employ this new understanding of enhancer logic to engineer synthetic enhancers that are able to monitor and manipulate cell-state switching in real time. Furthermore, we will use enhancer models to identify cis-regulatory mutations that have an impact on cell-state switching and drug resistance. Such applications are currently hampered because there is a significant gap in our understanding of how enhancers work.
To tackle this problem we will use a combination of in vivo massively parallel enhancer-reporter assays, single-cell genomics on microfluidic devices, computational modelling, and synthetic enhancer design. Using these approaches we will pursue the following aims: (1) to identify functional enhancers regulating cell-state switching by performing in vivo genetic screens in mice; (2) to elucidate the dynamic trajectories whereby cells of different cancer types switch to a common survival cell-state, at single-cell resolution; (3) to create synthetic enhancer circuits that specifically kill cancer cells undergoing cell-state switching.
Our findings will have an impact on genome research, characterizing how cellular decision making is implemented by the cis-regulatory code; and on cancer research, employing enhancer logic in the context of cancer therapy.
Max ERC Funding
1 999 660 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
