Project acronym 4-D nanoSCOPE
Project Advancing osteoporosis medicine by observing bone microstructure and remodelling using a four-dimensional nanoscope
Researcher (PI) Georg Schett
Host Institution (HI) UNIVERSITATSKLINIKUM ERLANGEN
Call Details Synergy Grants (SyG), SyG3PEb, ERC-2018-SyG
Summary Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function.
To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo.
The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.
Summary
Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function.
To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo.
The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.
Max ERC Funding
12 366 635 €
Duration
Start date: 2019-04-01, End date: 2025-03-31
Project acronym AXSIS
Project Frontiers in Attosecond X-ray Science: Imaging and Spectroscopy
Researcher (PI) Franz Xaver Kaertner
Host Institution (HI) STIFTUNG DEUTSCHES ELEKTRONEN-SYNCHROTRON DESY
Call Details Synergy Grants (SyG), SYG6, ERC-2013-SyG
Summary "X-ray crystallography yields atomic-resolution 3D images of the whole spectrum of molecules ranging from small inorganic clusters to large protein complexes constituting the macromolecular machinery of life. Life is not static, and many of the most important reactions in chemistry and biology are light induced and occur on ultrafast timescales. These have been studied with high time resolution primarily by ultrafast laser spectroscopy, but they reduce the vast complexity of the process to a few reaction coordinates. Here we develop attosecond serial crystallography and spectroscopy, to give a full description of ultrafast processes atomically resolved in real space and on the electronic energy landscape, from co-measurement of X-ray and optical spectra, and X-ray diffraction. This technique will revolutionize our understanding of structure and function at the atomic and molecular level and thereby unravel fundamental processes in chemistry and biology. We apply a fully coherent attosecond X-ray source based on coherent inverse Compton scattering off a free-electron crystal, developed in this project, to outrun radiation damage effects due to the necessary high X-ray irradiance required to acquire diffraction signals [A. Cho, ""Breakthrough of the year"", Science 388, 1530 (2012)]. Our synergistic project will optimize the entire instrumentation towards fundamental measurements of the mechanism of light absorption and excitation energy transfer. The multidisciplinary team optimizes X-ray pulse parameters, in tandem with sample delivery, crystal size, and advanced X-ray detectors. We will apply our new capabilities to one of the most important problems in structural biology, which is to elucidate the dynamics of light reactions, electron transfer and protein structure in photosynthesis. Also, the attosecond source can provide a coherent seed and will help to overcome peak flux limitations of X-ray FELs by introducing chirped pulse amplification to FEL technology."
Summary
"X-ray crystallography yields atomic-resolution 3D images of the whole spectrum of molecules ranging from small inorganic clusters to large protein complexes constituting the macromolecular machinery of life. Life is not static, and many of the most important reactions in chemistry and biology are light induced and occur on ultrafast timescales. These have been studied with high time resolution primarily by ultrafast laser spectroscopy, but they reduce the vast complexity of the process to a few reaction coordinates. Here we develop attosecond serial crystallography and spectroscopy, to give a full description of ultrafast processes atomically resolved in real space and on the electronic energy landscape, from co-measurement of X-ray and optical spectra, and X-ray diffraction. This technique will revolutionize our understanding of structure and function at the atomic and molecular level and thereby unravel fundamental processes in chemistry and biology. We apply a fully coherent attosecond X-ray source based on coherent inverse Compton scattering off a free-electron crystal, developed in this project, to outrun radiation damage effects due to the necessary high X-ray irradiance required to acquire diffraction signals [A. Cho, ""Breakthrough of the year"", Science 388, 1530 (2012)]. Our synergistic project will optimize the entire instrumentation towards fundamental measurements of the mechanism of light absorption and excitation energy transfer. The multidisciplinary team optimizes X-ray pulse parameters, in tandem with sample delivery, crystal size, and advanced X-ray detectors. We will apply our new capabilities to one of the most important problems in structural biology, which is to elucidate the dynamics of light reactions, electron transfer and protein structure in photosynthesis. Also, the attosecond source can provide a coherent seed and will help to overcome peak flux limitations of X-ray FELs by introducing chirped pulse amplification to FEL technology."
Max ERC Funding
13 884 200 €
Duration
Start date: 2014-08-01, End date: 2020-07-31
Project acronym BIOQ
Project Diamond Quantum Devices and Biology
Researcher (PI) Fedor Jelezko
Host Institution (HI) UNIVERSITAET ULM
Call Details Synergy Grants (SyG), SYG6, ERC-2012-SyG
Summary Many of the most remarkable contributions of modern science to society have arisen from interdisciplinary work of scientists enabling novel imaging and sensing technologies (NMR, X-ray diffraction, electron microscopy). BioQ will revolutionize the state of the art to create novel sensing technologies for the broad field of life sciences research that provide unprecedented access and insight into structure and function of individual bio-molecules under physiological conditions and apply these to the observation of biological processes down to the quantum level and with atomic resolution. At this level quantum properties are predicted to play an important role for the function of biological systems subject to environmental noise. BioQ will unravel the interplay of quantum coherent dynamics, molecular vibrations and environmental noise due to molecular vibrations in biological processes and design and carry out experimental tests of its predictions. BioQ will achieve new levels of understanding and control of biological systems, culminating in new ways to interface biological systems with quantum devices. To this end BioQ will exploit the ability of biological systems to arrange themselves into highly ordered structures to form novel hybrid materials of functionalized nano-diamonds that are capable of harnessing complex quantum dynamics at room temperature.
A deeper understanding of biological processes will open new roads towards drug design and bio-imaging. The elucidation of energy transport processes and dynamics may pave the way towards the design of more efficient light harvesting systems. Self-assembled hybrid bio-quantum devices provide a novel perspective towards quantum nanotechnology. The broad challenges that this ambitious programme present will be solved by an interdisciplinary team led by three PIs from experimental solid-state physics, theoretical quantum physics and bio-chemistry whose combination of expertise is essential for the success of BioQ.
Summary
Many of the most remarkable contributions of modern science to society have arisen from interdisciplinary work of scientists enabling novel imaging and sensing technologies (NMR, X-ray diffraction, electron microscopy). BioQ will revolutionize the state of the art to create novel sensing technologies for the broad field of life sciences research that provide unprecedented access and insight into structure and function of individual bio-molecules under physiological conditions and apply these to the observation of biological processes down to the quantum level and with atomic resolution. At this level quantum properties are predicted to play an important role for the function of biological systems subject to environmental noise. BioQ will unravel the interplay of quantum coherent dynamics, molecular vibrations and environmental noise due to molecular vibrations in biological processes and design and carry out experimental tests of its predictions. BioQ will achieve new levels of understanding and control of biological systems, culminating in new ways to interface biological systems with quantum devices. To this end BioQ will exploit the ability of biological systems to arrange themselves into highly ordered structures to form novel hybrid materials of functionalized nano-diamonds that are capable of harnessing complex quantum dynamics at room temperature.
A deeper understanding of biological processes will open new roads towards drug design and bio-imaging. The elucidation of energy transport processes and dynamics may pave the way towards the design of more efficient light harvesting systems. Self-assembled hybrid bio-quantum devices provide a novel perspective towards quantum nanotechnology. The broad challenges that this ambitious programme present will be solved by an interdisciplinary team led by three PIs from experimental solid-state physics, theoretical quantum physics and bio-chemistry whose combination of expertise is essential for the success of BioQ.
Max ERC Funding
10 293 309 €
Duration
Start date: 2013-07-01, End date: 2019-06-30
Project acronym BrainPlay
Project The self-teaching brain
Researcher (PI) Michael BRECHT
Host Institution (HI) HUMBOLDT-UNIVERSITAET ZU BERLIN
Call Details Synergy Grants (SyG), SyG3LSb, ERC-2018-SyG
Summary Our goal is to uncover the learning algorithms that subserve biological intelligence and to discover how they are implemented in the brain. We take for granted that biological intelligence results from neural information processing, that neural information processing is based on the transmission of action potentials through synapses, and that learning is realized through synaptic plasticity. We are inspired by two key observations: Firstly, we know that biological learning unfolds in ways different from mainstream machine learning that relies on learning from large labeled datasets. Second, we discovered that the engagement of the brain during play can result in unexpected and profound cognitive benefits. This proposal describes an untravelled route to the learning algorithms of the brain that runs through the no-man’s-land between synaptic physiology, systems neuroscience, cognitive neuroscience, theoretical neuroscience and machine learning. Our approach focuses on the self-teaching abilities of the mammalian brain and covers and connects four major topics: (1) the objective functions that govern synaptic plasticity, (2) the teaching signals through which learning is steered, (3) behavioral mechanisms of self-teaching, in particular play behaviors, (4) the brain states that engage self-teaching behaviors, in particular the brain state of play. The BrainPlay grant will study self-teaching abilities from synapses to brains, from computational theory to action video games. As gaming has been shown to be highly beneficial for human brain function, we are intrigued by how little we know about what is going on in playing brains and how the brain state of play shapes learning. Engaging the latest theoretical and technological breakthroughs, BrainPlay will reach far beyond mainstream neuroscience and embrace and elucidate playfulness and self-teaching as important components of the brain's learning algorithms.
Summary
Our goal is to uncover the learning algorithms that subserve biological intelligence and to discover how they are implemented in the brain. We take for granted that biological intelligence results from neural information processing, that neural information processing is based on the transmission of action potentials through synapses, and that learning is realized through synaptic plasticity. We are inspired by two key observations: Firstly, we know that biological learning unfolds in ways different from mainstream machine learning that relies on learning from large labeled datasets. Second, we discovered that the engagement of the brain during play can result in unexpected and profound cognitive benefits. This proposal describes an untravelled route to the learning algorithms of the brain that runs through the no-man’s-land between synaptic physiology, systems neuroscience, cognitive neuroscience, theoretical neuroscience and machine learning. Our approach focuses on the self-teaching abilities of the mammalian brain and covers and connects four major topics: (1) the objective functions that govern synaptic plasticity, (2) the teaching signals through which learning is steered, (3) behavioral mechanisms of self-teaching, in particular play behaviors, (4) the brain states that engage self-teaching behaviors, in particular the brain state of play. The BrainPlay grant will study self-teaching abilities from synapses to brains, from computational theory to action video games. As gaming has been shown to be highly beneficial for human brain function, we are intrigued by how little we know about what is going on in playing brains and how the brain state of play shapes learning. Engaging the latest theoretical and technological breakthroughs, BrainPlay will reach far beyond mainstream neuroscience and embrace and elucidate playfulness and self-teaching as important components of the brain's learning algorithms.
Max ERC Funding
9 781 250 €
Duration
Start date: 2019-08-01, End date: 2025-07-31
Project acronym DECODE
Project Decoding Context-Dependent Genetic Networks in vivo
Researcher (PI) Michael Boutros
Host Institution (HI) DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Call Details Synergy Grants (SyG), SyG3LSa, ERC-2018-SyG
Summary The evolutionary success of multicellular organisms is based on the division of labor between cells. While some of the molecular determinants for cell fate specification have been identified, a fundamental understanding of which genetic activities are required in each cell of a developing tissue is still outstanding. The DECODE project will develop and apply leading-edge system genetics methods to Arabidopsis and Drosophila, two major model systems from the plant and animal kingdoms to decode context-dependent genetic networks in vivo. To achieve this, DECODE will bring together experimental and theoretical groups with complementary expertise in model organism genetics and cellular phenotyping, single-cell genomics, statistics and computational biology. Building on our combined expertise, we will create functional genetic maps using conditional CRISPR/Cas9-based single- and higher order knockout perturbations in vivo combined with single-cell expression profiling and imaging. Coupled with powerful computational analysis, this project will not only define, predict and rigorously test the unique genetic repertoire of each cell, but also unravel how genetic networks adapt their topology and function across cell types and external stimuli. With more than thousand conditional knockouts, characterized by several million single-cell transcriptome profiles and high-resolution imaging this project will create the largest single-cell perturbation map in any model organism and will provide fundamental insights into the genetic architecture of complex tissues. Analyzing two tissues with divergent organization and regulatory repertoire will enable us to uncover general principles in the genetic circuits controlling context
dependent cell behavior. Consequently, we expect that the DECODE project in model organisms will lay the conceptual and methodological foundation for perturbation-based functional atlases in other tissues or species.
Summary
The evolutionary success of multicellular organisms is based on the division of labor between cells. While some of the molecular determinants for cell fate specification have been identified, a fundamental understanding of which genetic activities are required in each cell of a developing tissue is still outstanding. The DECODE project will develop and apply leading-edge system genetics methods to Arabidopsis and Drosophila, two major model systems from the plant and animal kingdoms to decode context-dependent genetic networks in vivo. To achieve this, DECODE will bring together experimental and theoretical groups with complementary expertise in model organism genetics and cellular phenotyping, single-cell genomics, statistics and computational biology. Building on our combined expertise, we will create functional genetic maps using conditional CRISPR/Cas9-based single- and higher order knockout perturbations in vivo combined with single-cell expression profiling and imaging. Coupled with powerful computational analysis, this project will not only define, predict and rigorously test the unique genetic repertoire of each cell, but also unravel how genetic networks adapt their topology and function across cell types and external stimuli. With more than thousand conditional knockouts, characterized by several million single-cell transcriptome profiles and high-resolution imaging this project will create the largest single-cell perturbation map in any model organism and will provide fundamental insights into the genetic architecture of complex tissues. Analyzing two tissues with divergent organization and regulatory repertoire will enable us to uncover general principles in the genetic circuits controlling context
dependent cell behavior. Consequently, we expect that the DECODE project in model organisms will lay the conceptual and methodological foundation for perturbation-based functional atlases in other tissues or species.
Max ERC Funding
10 625 000 €
Duration
Start date: 2019-07-01, End date: 2025-06-30
Project acronym IMPACT
Project imPACT – Privacy, Accountability, Compliance, and Trust
in Tomorrow’s Internet
Researcher (PI) Peter Druschel
Host Institution (HI) UNIVERSITAT DES SAARLANDES
Call Details Synergy Grants (SyG), SYG6, ERC-2013-SyG
Summary The Internet has evolved from a mere communication network used by tens of millions of users two
decades ago, to a global multimedia platform for communication, social networking, entertainment,
education, trade and political activism used by more than two billion users. This transformation has
brought tremendous benefits to society, but has also created entirely new threats to privacy, safety,
law enforcement, freedom of information and freedom of speech. In today’s Internet, principals are
amorphous, identities can be fluid, users participate and exchange information as peers, and data is
processed on global third-party platforms. Existing models and techniques for security and privacy,
which assume trusted infrastructure and well-defined policies, principals and roles, fail to fully address
this challenge.
The imPACT project addresses the challenge of providing privacy, accountability, compliance and
trust (PACT) in tomorrow’s Internet, using a cross-disciplinary and synergistic approach to understanding
and mastering the different roles, interactions and relationships of users and their joint effect on
the four PACT properties. The focus is on principles and methodologies that are relevant to the needs
of individual Internet users, have a strong potential to lead to practical solutions and address the fundamental
long-term needs of the future Internet. We take on this challenge with a team of researchers
from relevant subdisciplines within computer science, and with input from outside experts in law,
social sciences, economics and business. The team of PIs consists of international leaders in privacy
and security, experimental distributed systems, formal methods, program analysis and verification, and
database systems. By teaming up and committing ourselves to this joint research, we are in a unique
position to meet the grand challenge of unifying the PACT properties and laying a new foundation for
their holistic treatment.
Summary
The Internet has evolved from a mere communication network used by tens of millions of users two
decades ago, to a global multimedia platform for communication, social networking, entertainment,
education, trade and political activism used by more than two billion users. This transformation has
brought tremendous benefits to society, but has also created entirely new threats to privacy, safety,
law enforcement, freedom of information and freedom of speech. In today’s Internet, principals are
amorphous, identities can be fluid, users participate and exchange information as peers, and data is
processed on global third-party platforms. Existing models and techniques for security and privacy,
which assume trusted infrastructure and well-defined policies, principals and roles, fail to fully address
this challenge.
The imPACT project addresses the challenge of providing privacy, accountability, compliance and
trust (PACT) in tomorrow’s Internet, using a cross-disciplinary and synergistic approach to understanding
and mastering the different roles, interactions and relationships of users and their joint effect on
the four PACT properties. The focus is on principles and methodologies that are relevant to the needs
of individual Internet users, have a strong potential to lead to practical solutions and address the fundamental
long-term needs of the future Internet. We take on this challenge with a team of researchers
from relevant subdisciplines within computer science, and with input from outside experts in law,
social sciences, economics and business. The team of PIs consists of international leaders in privacy
and security, experimental distributed systems, formal methods, program analysis and verification, and
database systems. By teaming up and committing ourselves to this joint research, we are in a unique
position to meet the grand challenge of unifying the PACT properties and laying a new foundation for
their holistic treatment.
Max ERC Funding
9 257 000 €
Duration
Start date: 2015-02-01, End date: 2021-01-31
Project acronym IndiGene
Project Genetics of Individuality
Researcher (PI) Ewan Birney
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Call Details Synergy Grants (SyG), SyG3LSa, ERC-2018-SyG
Summary We propose to thoroughly investigate and characterise the sources of variation that results in varying phenotypes in a complex vertebrate. As well as characterising the genetic and environmental sources of variation, we will also investigate individual stochastic variation present even in fixed settings (both genetically and environmentally). To achieve this we will exploit the unique properties of Medaka fish, which can be fully inbred from the wild. We have already inbred and performed whole genome sequencing of a panel of 111 diverse Medaka fish from a single location; we propose to phenotype these fish in depth with high replication structure, ranging from organismal to molecular phenotypes. We will also phenotype entirely wild fish from the same source population as the panel with a subset of the phenotypes. We will analyse the data using state of the art methods to partition variation between genetic, environmental and stochastic components, and their interactions. We will integrate across both the different levels of phenotypic information across the cardiovascular system, and also across vertebrate phenotypes, in particular the extensive human phenotypes. By using genetic crosses and CRISPR-Cas9 techniques we will definitively prove specific interactions. We will host a “Research Hotel” for other phenotyping schemes to be applied to this panel, in particular from the Zebrafish community. This comprehensive and carefully replicated study will allow us to understand the opportunities and limitations of genetic stratification and personalised medicine in humans.
Summary
We propose to thoroughly investigate and characterise the sources of variation that results in varying phenotypes in a complex vertebrate. As well as characterising the genetic and environmental sources of variation, we will also investigate individual stochastic variation present even in fixed settings (both genetically and environmentally). To achieve this we will exploit the unique properties of Medaka fish, which can be fully inbred from the wild. We have already inbred and performed whole genome sequencing of a panel of 111 diverse Medaka fish from a single location; we propose to phenotype these fish in depth with high replication structure, ranging from organismal to molecular phenotypes. We will also phenotype entirely wild fish from the same source population as the panel with a subset of the phenotypes. We will analyse the data using state of the art methods to partition variation between genetic, environmental and stochastic components, and their interactions. We will integrate across both the different levels of phenotypic information across the cardiovascular system, and also across vertebrate phenotypes, in particular the extensive human phenotypes. By using genetic crosses and CRISPR-Cas9 techniques we will definitively prove specific interactions. We will host a “Research Hotel” for other phenotyping schemes to be applied to this panel, in particular from the Zebrafish community. This comprehensive and carefully replicated study will allow us to understand the opportunities and limitations of genetic stratification and personalised medicine in humans.
Max ERC Funding
6 272 613 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym PLAMORF
Project Plant Mobile RNAs: Function, Transport and Features
Researcher (PI) Friedrich KRAGLER
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Synergy Grants (SyG), SyG3LSa, ERC-2018-SyG
Summary An essential consequence of multi-cellularity is the need for intercellular and tissue wide communication. As seen with animals, higher plants coordinate metabolic and developmental processes via signals transferred to different body parts. Plants use a dual vascular system consisting of phloem and xylem for long-distance transfer of metabolites and signalling molecules. In contrast to circular systems in animals, transport in flowering plants occurs in the phloem via the cytoplasm of connected cells devoid of nuclei. In addition to small molecules, a remarkably large number of so-called mobile micro RNAs (miRNAs), messenger RNAs (mRNAs), and phloem RNA-binding proteins (RBPs) were identified in the phloem and in chimeric plants. Mobile RNAs and RBPs move through plasmodesmata into and through the phloem to distinct tissues. Thus, mobile RNAs represent an additional class of signalling molecules, raising important questions in the field of intercellular signalling. This project combines the expertise of three research groups in the fields of cell biology/macromolecular transport, mathematical modelling/bioinformatics and phloem function/protein biochemistry. It addresses the questions: How are mobile miRNAs and mRNAs selected for transport? Is this process specific and regulated by RBPs and motifs? What determines their destination? And importantly, how are these signals processed in the destination cells? To address these questions, we will develop predictive models, using novel single cell transcriptomics pipelines to establish cell-type specific RNA transport and motifs (WP1), and studying the structure, affinity, and functions of phloem RBPs to gain insights in the RNA delivery mechanism (WP2). We will combine the advantages of the agronomically important plant oilseed rape to identify phloem RNAs and RBPs with the well-established A. thaliana model that allows us to identify and test cell-specific transported RNA signals and RBPs in a time-efficient manner.
Summary
An essential consequence of multi-cellularity is the need for intercellular and tissue wide communication. As seen with animals, higher plants coordinate metabolic and developmental processes via signals transferred to different body parts. Plants use a dual vascular system consisting of phloem and xylem for long-distance transfer of metabolites and signalling molecules. In contrast to circular systems in animals, transport in flowering plants occurs in the phloem via the cytoplasm of connected cells devoid of nuclei. In addition to small molecules, a remarkably large number of so-called mobile micro RNAs (miRNAs), messenger RNAs (mRNAs), and phloem RNA-binding proteins (RBPs) were identified in the phloem and in chimeric plants. Mobile RNAs and RBPs move through plasmodesmata into and through the phloem to distinct tissues. Thus, mobile RNAs represent an additional class of signalling molecules, raising important questions in the field of intercellular signalling. This project combines the expertise of three research groups in the fields of cell biology/macromolecular transport, mathematical modelling/bioinformatics and phloem function/protein biochemistry. It addresses the questions: How are mobile miRNAs and mRNAs selected for transport? Is this process specific and regulated by RBPs and motifs? What determines their destination? And importantly, how are these signals processed in the destination cells? To address these questions, we will develop predictive models, using novel single cell transcriptomics pipelines to establish cell-type specific RNA transport and motifs (WP1), and studying the structure, affinity, and functions of phloem RBPs to gain insights in the RNA delivery mechanism (WP2). We will combine the advantages of the agronomically important plant oilseed rape to identify phloem RNAs and RBPs with the well-established A. thaliana model that allows us to identify and test cell-specific transported RNA signals and RBPs in a time-efficient manner.
Max ERC Funding
6 134 102 €
Duration
Start date: 2019-04-01, End date: 2025-03-31
Project acronym PoInt
Project Principles of Integrin Mechanics and Adhesion
Researcher (PI) Reinhard Fässler
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Synergy Grants (SyG), SyG3LSa, ERC-2018-SyG
Summary Integrin-mediated adhesion to the extracellular matrix is a prerequisite for the development and homeostasis of multicellular organisms. A hallmark of integrins is that ligand binding requires an “integrin activation” step affecting the shape of the entire molecule is induced by the integrin tail- and actomyosin-binding adaptor proteins talin and kindlin. In a second step, integrins cluster and assemble a gigantic signaling hub, where they integrate biochemical and biophysical signals to achieve their functional output. Due to the lack of combined expertise and suitable technologies, the key steps of integrin activation are still largely unknown and the underlying physical principles still need to be identified. We propose a multifaceted approach combining quantitative single molecule measurements, reconstitution of minimal and cellular adhesion complexes as well as development of multicellular structures and organoids. We propose four aims. In our first aim we will unravel how forces are propagated through the talin-integrin tail bonds and how force-induced integrin shape changes affect signaling. In the second aim we will use novel force spectrometers to determine energy landscapes and the high-resolution structure of fibronectin-integrin complexes. In our third aim we will use in vitro model membranes to test how integrin tail-binding adaptors, cortical F-actin and specific domains of integrins induce integrin clustering. With our fourth aim we will unravel how integrins integrate chemical and biophysical signals during organ development. Using the proposed synergistic approach, we will decipher fundamental principles of cell adhesion biology. Furthermore, our research will result in a better understanding of the fundamental mechanisms regulating adhesion signaling that will allow us to develop strategies to curb adhesion functions without completely blocking integrins, thus limiting the enormous side effects of current interventions.
Summary
Integrin-mediated adhesion to the extracellular matrix is a prerequisite for the development and homeostasis of multicellular organisms. A hallmark of integrins is that ligand binding requires an “integrin activation” step affecting the shape of the entire molecule is induced by the integrin tail- and actomyosin-binding adaptor proteins talin and kindlin. In a second step, integrins cluster and assemble a gigantic signaling hub, where they integrate biochemical and biophysical signals to achieve their functional output. Due to the lack of combined expertise and suitable technologies, the key steps of integrin activation are still largely unknown and the underlying physical principles still need to be identified. We propose a multifaceted approach combining quantitative single molecule measurements, reconstitution of minimal and cellular adhesion complexes as well as development of multicellular structures and organoids. We propose four aims. In our first aim we will unravel how forces are propagated through the talin-integrin tail bonds and how force-induced integrin shape changes affect signaling. In the second aim we will use novel force spectrometers to determine energy landscapes and the high-resolution structure of fibronectin-integrin complexes. In our third aim we will use in vitro model membranes to test how integrin tail-binding adaptors, cortical F-actin and specific domains of integrins induce integrin clustering. With our fourth aim we will unravel how integrins integrate chemical and biophysical signals during organ development. Using the proposed synergistic approach, we will decipher fundamental principles of cell adhesion biology. Furthermore, our research will result in a better understanding of the fundamental mechanisms regulating adhesion signaling that will allow us to develop strategies to curb adhesion functions without completely blocking integrins, thus limiting the enormous side effects of current interventions.
Max ERC Funding
7 217 200 €
Duration
Start date: 2019-04-01, End date: 2025-03-31
Project acronym Q-MAC
Project Frontiers in Quantum Materials Control
Researcher (PI) Jean-Marc Serge Thierry Triscone
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Synergy Grants (SyG), SYG6, ERC-2012-SyG
Summary The overarching goal of the present proposal is to exploit materials design, coherent optical methods and multiple theoretical approaches to deterministically control ordered states of strongly correlated electron materials, also referred to as “quantum” or “complex” materials. The underlying ideas can be applied to vast number of problems in materials physics, but the stated goal is that of optimizing superconductivity at higher temperatures than achieved so far, possibly even at room temperature. The proposal starts from research strands that follow challenging but well-establish paths, such as the use of complex-oxide heterostructures and strain engineering at interfaces to modulate the electronic properties. In a second class of investigations, coherent optical control of lattice dynamics with strong field THz transients is proposed to “anneal” the competing order quenching superconductivity. This builds on our recent discovery of light-induced transient superconductivity in high temperature cuprates, a remarkable process not yet understood or optimized. We will use a combination of femtosecond optical and x-ray experiments with Free Electron Lasers, together with time dependent real-materials simulations. Perhaps the most ambitious goal will be to develop laser-cooling techniques to reduce quantum phase fluctuations between planes of cuprate superconductors. Finally, we propose to use static and dynamic techniques to engineer new phases of condensed matter, for example by engineering new materials with a single band crossing the Fermi level, to optimize superconductivity. A unique combination of complementary expertise, from materials design, to coherent and ultrafast optical and x-ray physics, with materials and quantum optics theory, will be key in making true progress in these areas.
Summary
The overarching goal of the present proposal is to exploit materials design, coherent optical methods and multiple theoretical approaches to deterministically control ordered states of strongly correlated electron materials, also referred to as “quantum” or “complex” materials. The underlying ideas can be applied to vast number of problems in materials physics, but the stated goal is that of optimizing superconductivity at higher temperatures than achieved so far, possibly even at room temperature. The proposal starts from research strands that follow challenging but well-establish paths, such as the use of complex-oxide heterostructures and strain engineering at interfaces to modulate the electronic properties. In a second class of investigations, coherent optical control of lattice dynamics with strong field THz transients is proposed to “anneal” the competing order quenching superconductivity. This builds on our recent discovery of light-induced transient superconductivity in high temperature cuprates, a remarkable process not yet understood or optimized. We will use a combination of femtosecond optical and x-ray experiments with Free Electron Lasers, together with time dependent real-materials simulations. Perhaps the most ambitious goal will be to develop laser-cooling techniques to reduce quantum phase fluctuations between planes of cuprate superconductors. Finally, we propose to use static and dynamic techniques to engineer new phases of condensed matter, for example by engineering new materials with a single band crossing the Fermi level, to optimize superconductivity. A unique combination of complementary expertise, from materials design, to coherent and ultrafast optical and x-ray physics, with materials and quantum optics theory, will be key in making true progress in these areas.
Max ERC Funding
9 966 873 €
Duration
Start date: 2013-10-01, End date: 2019-09-30