Project acronym EpiTrack
Project Single-cell temporal tracking of epigenetic DNA marks
Researcher (PI) Saulius KLIMASAUSKAS
Host Institution (HI) VILNIAUS UNIVERSITETAS
Call Details Advanced Grant (AdG), LS9, ERC-2016-ADG
Summary Over the past decade, epigenetic phenomena have taken centre stage in our understanding of gene regulation, cellular differentiation and human disease. DNA methylation is a prevalent epigenetic modification in mammals, which is brought about by enzymatic transfer of methyl groups from the S-adenosylmethionine (SAM) cofactor by three known DNA methyltransferases (DNMTs). The most dramatic epigenomic reprogramming in mammalian development occurs after fertilization, whereby a global loss of DNA methylation is followed by massive reinstatement of new methylation patterns, different for each cell type. Although DNA methylation has been extensively investigated, key mechanistic aspects of these fascinating events remain obscure. The goal of this proposal is to bridge the gap in our understanding of how the genomic methylation patterns are established and how they govern cell plasticity and variability during differentiation and development. These questions could only be answered by precise determination of where and when methylation marks are deposited by the individual DNMTs, and how these methylation marks affect gene expression. To achieve this ambitious goal, we will metabolically engineer mouse cells to permit SAM analog-based chemical pulse-tagging of their methylation sites in vivo. We will then advance profiling of DNA modifications to the single cell level via innovative integration of microdroplet-based barcoding, precise genomic mapping and super-resolution imaging. Using this unique experimental system we will determine, with unprecedented detail and throughput, the dynamics and variability of DNA methylation and gene expression patterns during differentiation of mouse embryonic cells to neural and other lineages. This project will give a comprehensive, time-resolved view of the roles that the DNMTs play in mammalian development, which will open new horizons in epigenomic research and will advance our understanding of human development and disease.
Summary
Over the past decade, epigenetic phenomena have taken centre stage in our understanding of gene regulation, cellular differentiation and human disease. DNA methylation is a prevalent epigenetic modification in mammals, which is brought about by enzymatic transfer of methyl groups from the S-adenosylmethionine (SAM) cofactor by three known DNA methyltransferases (DNMTs). The most dramatic epigenomic reprogramming in mammalian development occurs after fertilization, whereby a global loss of DNA methylation is followed by massive reinstatement of new methylation patterns, different for each cell type. Although DNA methylation has been extensively investigated, key mechanistic aspects of these fascinating events remain obscure. The goal of this proposal is to bridge the gap in our understanding of how the genomic methylation patterns are established and how they govern cell plasticity and variability during differentiation and development. These questions could only be answered by precise determination of where and when methylation marks are deposited by the individual DNMTs, and how these methylation marks affect gene expression. To achieve this ambitious goal, we will metabolically engineer mouse cells to permit SAM analog-based chemical pulse-tagging of their methylation sites in vivo. We will then advance profiling of DNA modifications to the single cell level via innovative integration of microdroplet-based barcoding, precise genomic mapping and super-resolution imaging. Using this unique experimental system we will determine, with unprecedented detail and throughput, the dynamics and variability of DNA methylation and gene expression patterns during differentiation of mouse embryonic cells to neural and other lineages. This project will give a comprehensive, time-resolved view of the roles that the DNMTs play in mammalian development, which will open new horizons in epigenomic research and will advance our understanding of human development and disease.
Max ERC Funding
2 499 875 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym Sip-Vol+
Project Stress-Induced Plant Volatiles in Biosphere-Atmosphere System
Researcher (PI) Ülo Niinemets
Host Institution (HI) EESTI MAAULIKOOL
Call Details Advanced Grant (AdG), LS8, ERC-2012-ADG_20120314
Summary Vegetation forms a key interface between Earth surface and atmosphere. The important role of vegetation carbon, water and energy exchanges is well established, but the overall impact of plant trace gas (VOC) emission for large-scale Earth processes is poorly understood. Although it is widely accepted that VOCs play major roles in the formation of ozone, secondary organic aerosols (SOA) and cloud condensation nuclei (CNN) with potentially profound impacts on air quality and Earth radiative balance, the research has so far focused only on constitutive emissions from species considered “emitters”. However, differently from constitutive VOCs emitted only by certain species, all plant species can be triggered to emit induced VOCs under abiotic and biotic stress. So far, induced high-reactivity VOCs are not considered in global VOC budget, and thus, this proposal tests the key assumption that VOC emissions worldwide have been vastly underestimated. As global change is resulting in higher level of stress in Earth ecosystems, the relevance of induced emissions is further expected to gain in importance. The current project has the overall objective to evaluate the effect of plant-generated VOC emissions on air composition and environment under global change, with particular emphasis on the role of VOCs induced in response to environmental stress. The study first quantifies the VOC production vs. stress severity relationships across species with differing stress tolerance and advances and parameterizes the qualitative induced VOC model developed by PI. The novel quantitative model is further verified by flux measurements and scaled up to regional and global scales to assess the contribution of induced emissions to overall VOC budget, and study the feedbacks between stress, ozone, SOA and CNN formation and the Earth climate using an hierarchy of available models. This highly cross-disciplinary project is expected to result in key contributions in two research fields of major significance: plant stress tolerance from molecules to globe and the role of vegetation component in atmospheric reactivity and Earth climate. The first part of the study provides fundamental insight into the stress responsiveness of plants with differing tolerance to environmental limitations, extending “leaf economics spectrum”, a hotspot of current plant ecology research. The second part provides quantitative information on large-scale importance of plant VOCs in globally changing climates with major relevance for understanding the role of plants in the Earth’s large scale processes.
Summary
Vegetation forms a key interface between Earth surface and atmosphere. The important role of vegetation carbon, water and energy exchanges is well established, but the overall impact of plant trace gas (VOC) emission for large-scale Earth processes is poorly understood. Although it is widely accepted that VOCs play major roles in the formation of ozone, secondary organic aerosols (SOA) and cloud condensation nuclei (CNN) with potentially profound impacts on air quality and Earth radiative balance, the research has so far focused only on constitutive emissions from species considered “emitters”. However, differently from constitutive VOCs emitted only by certain species, all plant species can be triggered to emit induced VOCs under abiotic and biotic stress. So far, induced high-reactivity VOCs are not considered in global VOC budget, and thus, this proposal tests the key assumption that VOC emissions worldwide have been vastly underestimated. As global change is resulting in higher level of stress in Earth ecosystems, the relevance of induced emissions is further expected to gain in importance. The current project has the overall objective to evaluate the effect of plant-generated VOC emissions on air composition and environment under global change, with particular emphasis on the role of VOCs induced in response to environmental stress. The study first quantifies the VOC production vs. stress severity relationships across species with differing stress tolerance and advances and parameterizes the qualitative induced VOC model developed by PI. The novel quantitative model is further verified by flux measurements and scaled up to regional and global scales to assess the contribution of induced emissions to overall VOC budget, and study the feedbacks between stress, ozone, SOA and CNN formation and the Earth climate using an hierarchy of available models. This highly cross-disciplinary project is expected to result in key contributions in two research fields of major significance: plant stress tolerance from molecules to globe and the role of vegetation component in atmospheric reactivity and Earth climate. The first part of the study provides fundamental insight into the stress responsiveness of plants with differing tolerance to environmental limitations, extending “leaf economics spectrum”, a hotspot of current plant ecology research. The second part provides quantitative information on large-scale importance of plant VOCs in globally changing climates with major relevance for understanding the role of plants in the Earth’s large scale processes.
Max ERC Funding
2 259 366 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
