Project acronym 2DMATER
Project Controlled Synthesis of Two-Dimensional Nanomaterials for Energy Storage and Conversion
Researcher (PI) Xinliang Feng
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2012-StG_20111012
Summary "Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."
Summary
"Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-09-01, End date: 2017-08-31
Project acronym 2O2ACTIVATION
Project Development of Direct Dehydrogenative Couplings mediated by Dioxygen
Researcher (PI) Frederic William Patureau
Host Institution (HI) RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2016-STG
Summary The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research.
The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation.
The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event.
Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.
Summary
The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research.
The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation.
The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event.
Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.
Max ERC Funding
1 489 823 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym 3DCellPhase-
Project In situ Structural Analysis of Molecular Crowding and Phase Separation
Researcher (PI) Julia MAHAMID
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Country Germany
Call Details Starting Grant (StG), LS1, ERC-2017-STG
Summary This proposal brings together two fields in biology, namely the emerging field of phase-separated assemblies in cell biology and state-of-the-art cellular cryo-electron tomography, to advance our understanding on a fundamental, yet illusive, question: the molecular organization of the cytoplasm.
Eukaryotes organize their biochemical reactions into functionally distinct compartments. Intriguingly, many, if not most, cellular compartments are not membrane enclosed. Rather, they assemble dynamically by phase separation, typically triggered upon a specific event. Despite significant progress on reconstituting such liquid-like assemblies in vitro, we lack information as to whether these compartments in vivo are indeed amorphous liquids, or whether they exhibit structural features such as gels or fibers. My recent work on sample preparation of cells for cryo-electron tomography, including cryo-focused ion beam thinning, guided by 3D correlative fluorescence microscopy, shows that we can now prepare site-specific ‘electron-transparent windows’ in suitable eukaryotic systems, which allow direct examination of structural features of cellular compartments in their cellular context. Here, we will use these techniques to elucidate the structural principles and cytoplasmic environment driving the dynamic assembly of two phase-separated compartments: Stress granules, which are RNA bodies that form rapidly in the cytoplasm upon cellular stress, and centrosomes, which are sites of microtubule nucleation. We will combine these studies with a quantitative description of the crowded nature of cytoplasm and of its local variations, to provide a direct readout of the impact of excluded volume on molecular assembly in living cells. Taken together, these studies will provide fundamental insights into the structural basis by which cells form biochemical compartments.
Summary
This proposal brings together two fields in biology, namely the emerging field of phase-separated assemblies in cell biology and state-of-the-art cellular cryo-electron tomography, to advance our understanding on a fundamental, yet illusive, question: the molecular organization of the cytoplasm.
Eukaryotes organize their biochemical reactions into functionally distinct compartments. Intriguingly, many, if not most, cellular compartments are not membrane enclosed. Rather, they assemble dynamically by phase separation, typically triggered upon a specific event. Despite significant progress on reconstituting such liquid-like assemblies in vitro, we lack information as to whether these compartments in vivo are indeed amorphous liquids, or whether they exhibit structural features such as gels or fibers. My recent work on sample preparation of cells for cryo-electron tomography, including cryo-focused ion beam thinning, guided by 3D correlative fluorescence microscopy, shows that we can now prepare site-specific ‘electron-transparent windows’ in suitable eukaryotic systems, which allow direct examination of structural features of cellular compartments in their cellular context. Here, we will use these techniques to elucidate the structural principles and cytoplasmic environment driving the dynamic assembly of two phase-separated compartments: Stress granules, which are RNA bodies that form rapidly in the cytoplasm upon cellular stress, and centrosomes, which are sites of microtubule nucleation. We will combine these studies with a quantitative description of the crowded nature of cytoplasm and of its local variations, to provide a direct readout of the impact of excluded volume on molecular assembly in living cells. Taken together, these studies will provide fundamental insights into the structural basis by which cells form biochemical compartments.
Max ERC Funding
1 228 125 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym 3DPartForm
Project 3D-printing of PARTiculate FORMulations utilizing polymer microparticle-based voxels
Researcher (PI) Julian Thiele
Host Institution (HI) LEIBNIZ-INSTITUT FUR POLYMERFORSCHUNG DRESDEN EV
Country Germany
Call Details Starting Grant (StG), PE8, ERC-2019-STG
Summary New polymer materials are necessary to match the demand for highly integrated, multifunctional, responsive systems for sensing, information processing, soft robotics or multi-parametric implants. Both established
material design concepts based on lithography, and emerging engineering efforts based on additive manufacturing (AM) are currently not able to fully address the need for topologically complex, multifunctional
and stimuli-responsive polymer materials. This proposal aims at establishing a radically new approach for polymer material design, rethinking AM on both material and process level. Here, functionality will be already
embedded at the building block level to emerge into larger scales. The exact methodology relies on polymer microparticles as a novel material basis with arbitrary geometry, function, mechanics and responsiveness.
These microparticulate formulations will serve as predefined, voxel-like building blocks in AM yielding hierarchical assemblies with spatially defined voxel position and programmable, adaptive properties, which clearly go beyond existing functional material classes. With that, 3DPartForm will address the current lack of additive manufacturing providing multifunctional, stimuli-responsive materials, in which not only strongly different, but most importantly functional building blocks with intrinsic time axis will be processed into true 4D-polymer multimaterials. Products emerging from this approach will reach a previously unknown level of system integration, where optical transparency, electric and thermal conductivity as well as diffusivity and mechanical rigidity will become spatiotemporally tunable at single-voxel level. Coupled sensing and actuation operations will be realized by processing, transforming and manipulating single or combined input stimuli within these materials in the focus of 3DPartform, and platforms for biomimetics and cell-free biotechnology will be implemented as a long-term goal.
Summary
New polymer materials are necessary to match the demand for highly integrated, multifunctional, responsive systems for sensing, information processing, soft robotics or multi-parametric implants. Both established
material design concepts based on lithography, and emerging engineering efforts based on additive manufacturing (AM) are currently not able to fully address the need for topologically complex, multifunctional
and stimuli-responsive polymer materials. This proposal aims at establishing a radically new approach for polymer material design, rethinking AM on both material and process level. Here, functionality will be already
embedded at the building block level to emerge into larger scales. The exact methodology relies on polymer microparticles as a novel material basis with arbitrary geometry, function, mechanics and responsiveness.
These microparticulate formulations will serve as predefined, voxel-like building blocks in AM yielding hierarchical assemblies with spatially defined voxel position and programmable, adaptive properties, which clearly go beyond existing functional material classes. With that, 3DPartForm will address the current lack of additive manufacturing providing multifunctional, stimuli-responsive materials, in which not only strongly different, but most importantly functional building blocks with intrinsic time axis will be processed into true 4D-polymer multimaterials. Products emerging from this approach will reach a previously unknown level of system integration, where optical transparency, electric and thermal conductivity as well as diffusivity and mechanical rigidity will become spatiotemporally tunable at single-voxel level. Coupled sensing and actuation operations will be realized by processing, transforming and manipulating single or combined input stimuli within these materials in the focus of 3DPartform, and platforms for biomimetics and cell-free biotechnology will be implemented as a long-term goal.
Max ERC Funding
1 474 125 €
Duration
Start date: 2020-04-01, End date: 2025-03-31
Project acronym ActiDrops
Project Synthetic Active Droplets Inspired by Life
Researcher (PI) Job BOEKHOVEN
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2019-STG
Summary Active droplets are made of molecular building blocks that are activated and deactivated by a chemical reaction cycle. In the activation, a precursor is converted into a building block for droplets driven by the consumption of fuel. In the deactivation, the building blocks react back to the precursor. In other words, active droplets emerge when fuel is supplied, but decay when fuel is depleted. Theoretical studies show active droplets all evolve to the same size. Another work predicts that the droplets can spontaneously self-divide when energy is abundant. All of these exciting properties, i.e., emergence, decay, collective behavior, and self-division are pivotal to the functioning of life. If we could engineer these behaviors in synthetic materials, we would obtain a better understanding of active assembly which is directly relevant to biology and the origin of life.
I thus aim to synthesize active droplets and study their life-like properties. Two types of active droplets will be investigated; one type based on oil-molecules that phase separate in water, and one type based on cationic peptides in a complex coacervate with RNA. My team will develop reaction cycles that drive the droplet formation, thereby making them active. We will study their spontaneous emergence in response to energy, and disappearance when energy is scarce. Moreover, we study their collective behavior, like how they grow into one large droplet, or all converge to the same droplet volume. Finally, we test their division into daughter droplets. Our systematic approach will test how kinetic parameters, like the activation rate, affect the behavior of the droplets.
The results will mark a massive step forward in the engineering of materials with life-like behaviors, which can also serve as experimental models for membrane-less organelles. We expect to elucidate mechanisms that could have played a role in the origin of life. Finally, our findings could form stepping stones towards a synthetic cel.
Summary
Active droplets are made of molecular building blocks that are activated and deactivated by a chemical reaction cycle. In the activation, a precursor is converted into a building block for droplets driven by the consumption of fuel. In the deactivation, the building blocks react back to the precursor. In other words, active droplets emerge when fuel is supplied, but decay when fuel is depleted. Theoretical studies show active droplets all evolve to the same size. Another work predicts that the droplets can spontaneously self-divide when energy is abundant. All of these exciting properties, i.e., emergence, decay, collective behavior, and self-division are pivotal to the functioning of life. If we could engineer these behaviors in synthetic materials, we would obtain a better understanding of active assembly which is directly relevant to biology and the origin of life.
I thus aim to synthesize active droplets and study their life-like properties. Two types of active droplets will be investigated; one type based on oil-molecules that phase separate in water, and one type based on cationic peptides in a complex coacervate with RNA. My team will develop reaction cycles that drive the droplet formation, thereby making them active. We will study their spontaneous emergence in response to energy, and disappearance when energy is scarce. Moreover, we study their collective behavior, like how they grow into one large droplet, or all converge to the same droplet volume. Finally, we test their division into daughter droplets. Our systematic approach will test how kinetic parameters, like the activation rate, affect the behavior of the droplets.
The results will mark a massive step forward in the engineering of materials with life-like behaviors, which can also serve as experimental models for membrane-less organelles. We expect to elucidate mechanisms that could have played a role in the origin of life. Finally, our findings could form stepping stones towards a synthetic cel.
Max ERC Funding
1 491 350 €
Duration
Start date: 2020-02-01, End date: 2025-01-31
Project acronym ADONIS
Project Attosecond Dynamics On Interfaces and Solids
Researcher (PI) Reinhard Kienberger
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Country Germany
Call Details Starting Grant (StG), PE2, ERC-2007-StG
Summary New insight into ever smaller microscopic units of matter as well as in ever faster evolving chemical, physical or atomic processes pushes the frontiers in many fields in science. Pump/probe experiments turned out to be the most direct approach to time-domain investigations of fast-evolving microscopic processes. Accessing atomic and molecular inner-shell processes directly in the time-domain requires a combination of short wavelengths in the few hundred eV range and sub-femtosecond pulse duration. The concept of light-field-controlled XUV photoemission employs an XUV pulse achieved by High-order Harmonic Generation (HHG) as a pump and the light pulse as a probe or vice versa. The basic prerequisite, namely the generation and measurement of isolated sub-femtosecond XUV pulses synchronized to a strong few-cycle light pulse with attosecond precision, opens up a route to time-resolved inner-shell atomic and molecular spectroscopy with present day sources. Studies of attosecond electronic motion (1 as = 10-18 s) in solids and on surfaces and interfaces have until now remained out of reach. The unprecedented time resolution of the aforementioned technique will enable for the first time monitoring of sub-fs dynamics of such systems in the time domain. These dynamics – of electronic excitation, relaxation, and wave packet motion – are of broad scientific interest and pertinent to the development of many modern technologies including semiconductor and molecular electronics, optoelectronics, information processing, photovoltaics, and optical nano-structuring. The purpose of this project is to investigate phenomena like the temporal evolution of direct photoemission, interference effects in resonant photoemission, fast adsorbate-substrate charge transfer, and electronic dynamics in supramolecular assemblies, in a series of experiments in order to overcome the temporal limits of measurements in solid state physics and to better understand processes in microcosm.
Summary
New insight into ever smaller microscopic units of matter as well as in ever faster evolving chemical, physical or atomic processes pushes the frontiers in many fields in science. Pump/probe experiments turned out to be the most direct approach to time-domain investigations of fast-evolving microscopic processes. Accessing atomic and molecular inner-shell processes directly in the time-domain requires a combination of short wavelengths in the few hundred eV range and sub-femtosecond pulse duration. The concept of light-field-controlled XUV photoemission employs an XUV pulse achieved by High-order Harmonic Generation (HHG) as a pump and the light pulse as a probe or vice versa. The basic prerequisite, namely the generation and measurement of isolated sub-femtosecond XUV pulses synchronized to a strong few-cycle light pulse with attosecond precision, opens up a route to time-resolved inner-shell atomic and molecular spectroscopy with present day sources. Studies of attosecond electronic motion (1 as = 10-18 s) in solids and on surfaces and interfaces have until now remained out of reach. The unprecedented time resolution of the aforementioned technique will enable for the first time monitoring of sub-fs dynamics of such systems in the time domain. These dynamics – of electronic excitation, relaxation, and wave packet motion – are of broad scientific interest and pertinent to the development of many modern technologies including semiconductor and molecular electronics, optoelectronics, information processing, photovoltaics, and optical nano-structuring. The purpose of this project is to investigate phenomena like the temporal evolution of direct photoemission, interference effects in resonant photoemission, fast adsorbate-substrate charge transfer, and electronic dynamics in supramolecular assemblies, in a series of experiments in order to overcome the temporal limits of measurements in solid state physics and to better understand processes in microcosm.
Max ERC Funding
1 296 000 €
Duration
Start date: 2008-10-01, End date: 2013-09-30
Project acronym AgeingStemCellFate
Project The Role of Ectopic Adipocyte Progenitors in Age-related Stem Cell Dysfunction, Systemic Inflammation, and Metabolic Disease
Researcher (PI) Tim Julius Schulz
Host Institution (HI) DEUTSCHES INSTITUT FUER ERNAEHRUNGSFORSCHUNG POTSDAM REHBRUECKE
Country Germany
Call Details Starting Grant (StG), LS4, ERC-2012-StG_20111109
Summary Ageing is accompanied by ectopic white adipose tissue depositions in skeletal muscle and other anatomical locations, such as brown adipose tissue and the bone marrow. Ectopic fat accrual contributes to organ dysfunction, systemic insulin resistance, and other perturbations that have been implicated in metabolic diseases.
This research proposal aims to identify the regulatory cues that control the development of ectopic progenitor cells that give rise to this type of fat. It is hypothesized that an age-related dysfunction of the stem cell niche leads to an imbalance between (1) tissue-specific stem cells and (2) fibroblast-like, primarily adipogenic progenitors that reside within many tissues. Novel methodologies that assess stem/progenitor cell characteristics on the single cell level will be combined with animal models of lineage tracing to determine the developmental origin of these adipogenic progenitors and processes that regulate their function.
Notch signalling is a key signalling pathway that relies on direct physical interaction to control stem cell fate. It is proposed that impaired Notch activity contributes to the phenotypical shift of precursor cell distribution in aged tissues.
Lastly, the role of the stem cell niche in ectopic adipocyte progenitor formation will be analyzed. External signals originating from the surrounding niche cells regulate the developmental fate of stem cells. Secreted factors and their role in the formation of ectopic adipocyte precursors during senescence will be identified using a combination of biochemical and systems biology approaches.
Accomplishment of these studies will help to understand the basic processes of stem cell ageing and identify mechanisms of age-related functional decline in tissue regeneration. By targeting the population of tissue-resident adipogenic progenitor cells, therapeutic strategies could be developed to counteract metabolic complications associated with the ageing process.
Summary
Ageing is accompanied by ectopic white adipose tissue depositions in skeletal muscle and other anatomical locations, such as brown adipose tissue and the bone marrow. Ectopic fat accrual contributes to organ dysfunction, systemic insulin resistance, and other perturbations that have been implicated in metabolic diseases.
This research proposal aims to identify the regulatory cues that control the development of ectopic progenitor cells that give rise to this type of fat. It is hypothesized that an age-related dysfunction of the stem cell niche leads to an imbalance between (1) tissue-specific stem cells and (2) fibroblast-like, primarily adipogenic progenitors that reside within many tissues. Novel methodologies that assess stem/progenitor cell characteristics on the single cell level will be combined with animal models of lineage tracing to determine the developmental origin of these adipogenic progenitors and processes that regulate their function.
Notch signalling is a key signalling pathway that relies on direct physical interaction to control stem cell fate. It is proposed that impaired Notch activity contributes to the phenotypical shift of precursor cell distribution in aged tissues.
Lastly, the role of the stem cell niche in ectopic adipocyte progenitor formation will be analyzed. External signals originating from the surrounding niche cells regulate the developmental fate of stem cells. Secreted factors and their role in the formation of ectopic adipocyte precursors during senescence will be identified using a combination of biochemical and systems biology approaches.
Accomplishment of these studies will help to understand the basic processes of stem cell ageing and identify mechanisms of age-related functional decline in tissue regeneration. By targeting the population of tissue-resident adipogenic progenitor cells, therapeutic strategies could be developed to counteract metabolic complications associated with the ageing process.
Max ERC Funding
1 496 444 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym AHH-OMICS
Project Understanding collective mechanisms of cell fate regulation using single-cell genomics
Researcher (PI) Steffen Rulands
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Country Germany
Call Details Starting Grant (StG), PE3, ERC-2020-STG
Summary Biological systems rely on an influx of energy to build and maintain complex spatio-temporal structures. A striking example of this is the self-organisation of cells into tissues, which relies on an interplay of molecular programs and tissue-level feedback. The mechanistic basis underlying these processes is poorly understood. The recent advent of single-cell sequencing technologies for the first time gives the opportunity to probe these processes with unprecedented molecular resolution in vivo. Biological function, however, relies on collective processes on the cellular scale which emerge from many interactions on the microscopic scale. But what can we learn about such collective processes from detailed empirical information on the molecular scale? Concepts from non-equilibrium statistical physics provide a powerful framework to understand collective processes underlying the self-organisation of cells. In the proposed research endeavour, we will combine the possibilities of novel single-cell technologies with methods from non-equilibrium statistical physics to understand collective processes regulating cellular behaviour. Using this conceptually new approach, we will 1) unveil collective epigenetic processes during differentiation, reprogramming and ageing, 2) determine how the interplay between different layers of regulation leads to the emergence of mesoscopic spatio-temporal structures in vivo, and 3) understand universal fluctuations in gene expression to unveil mechanistic principles of cellular decisions. Our theoretical work will be challenged by single-cell sequencing experiments performed by our collaborators. We will overcome important conceptual limitations in an emerging technology in biology and pioneer the application of methods from non-equilibrium statistical physics to single-cell genomics. At the same time, we take an interdisciplinary approach to tackle questions at the frontier of non-equilibrium physics.
Summary
Biological systems rely on an influx of energy to build and maintain complex spatio-temporal structures. A striking example of this is the self-organisation of cells into tissues, which relies on an interplay of molecular programs and tissue-level feedback. The mechanistic basis underlying these processes is poorly understood. The recent advent of single-cell sequencing technologies for the first time gives the opportunity to probe these processes with unprecedented molecular resolution in vivo. Biological function, however, relies on collective processes on the cellular scale which emerge from many interactions on the microscopic scale. But what can we learn about such collective processes from detailed empirical information on the molecular scale? Concepts from non-equilibrium statistical physics provide a powerful framework to understand collective processes underlying the self-organisation of cells. In the proposed research endeavour, we will combine the possibilities of novel single-cell technologies with methods from non-equilibrium statistical physics to understand collective processes regulating cellular behaviour. Using this conceptually new approach, we will 1) unveil collective epigenetic processes during differentiation, reprogramming and ageing, 2) determine how the interplay between different layers of regulation leads to the emergence of mesoscopic spatio-temporal structures in vivo, and 3) understand universal fluctuations in gene expression to unveil mechanistic principles of cellular decisions. Our theoretical work will be challenged by single-cell sequencing experiments performed by our collaborators. We will overcome important conceptual limitations in an emerging technology in biology and pioneer the application of methods from non-equilibrium statistical physics to single-cell genomics. At the same time, we take an interdisciplinary approach to tackle questions at the frontier of non-equilibrium physics.
Max ERC Funding
1 489 500 €
Duration
Start date: 2021-01-01, End date: 2025-12-31
Project acronym AIM2 INFLAMMASOME
Project Cytosolic recognition of foreign nucleic acids: Molecular and functional characterization of AIM2, a central player in DNA-triggered inflammasome activation
Researcher (PI) Veit Hornung
Host Institution (HI) UNIVERSITATSKLINIKUM BONN
Country Germany
Call Details Starting Grant (StG), LS6, ERC-2009-StG
Summary Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.
Summary
Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.
Max ERC Funding
1 727 920 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym ALLERGENE
Project Allergic multimorbidity from birth to young adulthood: determinants, epigenetic regulation and inflammatory processes
Researcher (PI) Marie Standl
Host Institution (HI) HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Country Germany
Call Details Starting Grant (StG), LS7, ERC-2020-STG
Summary The prevalence of allergic diseases, such as atopic eczema, asthma and rhinitis, has increased over the past decades and is currently estimated to be up to 40%. Prevention strategies play a pivotal role, as there are no curative treatments available. Therefore, the aim of ALLERGENE is to understand the complex interplay of genetic, environmental and lifestyle factors and to identify involved mechanisms that distinguish between young adults free of allergic diseases and those suffering from allergic multimorbidity. Therefore, the aims of the present project are to: 1. Define allergic disease trajectories from birth to young adulthood, describe their determinants and identify risk and protective early-life environmental and lifestyle factors contributing to progression towards allergic multimorbidity or remission of allergic diseases. 2. Investigate molecular mechanisms of epigenetic regulation of allergic disease trajectories and test effect modification by inclusion of selected environmental and lifestyle factors. 3. Characterise the underlying inflammation profile of allergic disease trajectories and determine interactions with environmental and lifestyle factors The project makes use of two long-standing, prospective German birth cohort studies, GINIplus and LISA, with available data from birth to young adulthood, and an extensive examination planned at age 25. Within this project, a comprehensive characterisation of allergic disease trajectories, their determinants, comorbidities, risk and protective factors across the life-course will be obtained. ALLERGENE will enhance the understanding of how modifiable factors contribute to allergic disease aetiology. This will be an essential prerequisite to develop effective early intervention strategies for susceptible populations and to identify disease-specific biomarkers for the development and progression of allergic diseases in the future.
Summary
The prevalence of allergic diseases, such as atopic eczema, asthma and rhinitis, has increased over the past decades and is currently estimated to be up to 40%. Prevention strategies play a pivotal role, as there are no curative treatments available. Therefore, the aim of ALLERGENE is to understand the complex interplay of genetic, environmental and lifestyle factors and to identify involved mechanisms that distinguish between young adults free of allergic diseases and those suffering from allergic multimorbidity. Therefore, the aims of the present project are to: 1. Define allergic disease trajectories from birth to young adulthood, describe their determinants and identify risk and protective early-life environmental and lifestyle factors contributing to progression towards allergic multimorbidity or remission of allergic diseases. 2. Investigate molecular mechanisms of epigenetic regulation of allergic disease trajectories and test effect modification by inclusion of selected environmental and lifestyle factors. 3. Characterise the underlying inflammation profile of allergic disease trajectories and determine interactions with environmental and lifestyle factors The project makes use of two long-standing, prospective German birth cohort studies, GINIplus and LISA, with available data from birth to young adulthood, and an extensive examination planned at age 25. Within this project, a comprehensive characterisation of allergic disease trajectories, their determinants, comorbidities, risk and protective factors across the life-course will be obtained. ALLERGENE will enhance the understanding of how modifiable factors contribute to allergic disease aetiology. This will be an essential prerequisite to develop effective early intervention strategies for susceptible populations and to identify disease-specific biomarkers for the development and progression of allergic diseases in the future.
Max ERC Funding
1 493 330 €
Duration
Start date: 2021-03-01, End date: 2026-02-28