Project acronym APES
Project Accuracy and precision for molecular solids
Researcher (PI) Jiri KLIMES
Host Institution (HI) UNIVERZITA KARLOVA
Call Details Starting Grant (StG), PE4, ERC-2017-STG
Summary The description of high pressure phases or polymorphism of molecular solids represents a significant scientific challenge both for experiment and theory. Theoretical methods that are currently used struggle to describe the tiny energy differences between different phases. It is the aim of this project to develop a scheme that would allow accurate and reliable predictions of the binding energies of molecular solids and of the energy differences between different phases.
To reach the required accuracy, we will combine the coupled cluster approach, widely used for reference quality calculations for molecules, with the random phase approximation (RPA) within periodic boundary conditions. As I have recently shown, RPA-based approaches are already some of the most accurate and practically usable methods for the description of extended systems. However, reliability is not only a question of accuracy. Reliable data need to be precise, that is, converged with the numerical parameters so that they are reproducible by other researchers.
Reproducibility is already a growing concern in the field. It is likely to become a considerable issue for highly accurate methods as the calculated energies have a stronger dependence on the simulation parameters such as the basis set size. Two main approaches will be explored to assure precision. First, we will develop the so-called asymptotic correction scheme to speed-up the convergence of the correlation energies with the basis set size. Second, we will directly compare the lattice energies from periodic and finite cluster based calculations. Both should yield identical answers, but if and how the agreement can be reached for general system is currently far from being understood for methods such as coupled cluster. Reliable data will allow us to answer some of the open questions regarding the stability of polymorphs and high pressure phases, such as the possibility of existence of high pressure ionic phases of water and ammonia.
Summary
The description of high pressure phases or polymorphism of molecular solids represents a significant scientific challenge both for experiment and theory. Theoretical methods that are currently used struggle to describe the tiny energy differences between different phases. It is the aim of this project to develop a scheme that would allow accurate and reliable predictions of the binding energies of molecular solids and of the energy differences between different phases.
To reach the required accuracy, we will combine the coupled cluster approach, widely used for reference quality calculations for molecules, with the random phase approximation (RPA) within periodic boundary conditions. As I have recently shown, RPA-based approaches are already some of the most accurate and practically usable methods for the description of extended systems. However, reliability is not only a question of accuracy. Reliable data need to be precise, that is, converged with the numerical parameters so that they are reproducible by other researchers.
Reproducibility is already a growing concern in the field. It is likely to become a considerable issue for highly accurate methods as the calculated energies have a stronger dependence on the simulation parameters such as the basis set size. Two main approaches will be explored to assure precision. First, we will develop the so-called asymptotic correction scheme to speed-up the convergence of the correlation energies with the basis set size. Second, we will directly compare the lattice energies from periodic and finite cluster based calculations. Both should yield identical answers, but if and how the agreement can be reached for general system is currently far from being understood for methods such as coupled cluster. Reliable data will allow us to answer some of the open questions regarding the stability of polymorphs and high pressure phases, such as the possibility of existence of high pressure ionic phases of water and ammonia.
Max ERC Funding
924 375 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym Cat-In-hAT
Project Catastrophic Interactions of Binary Stars and the Associated Transients
Researcher (PI) Ondrej PEJCHA
Host Institution (HI) UNIVERZITA KARLOVA
Call Details Starting Grant (StG), PE9, ERC-2018-STG
Summary "One of the crucial formation channels of compact object binaries, including sources of gravitational waves, critically depends on catastrophic binary interactions accompanied by the loss of mass, angular momentum, and energy (""common envelope"" evolution - CEE). Despite its importance, CEE is perhaps the least understood major phase of binary star evolution and progress in this area is urgently needed to interpret observations from the new facilities (gravitational wave detectors, time-domain surveys).
Recently, the dynamical phase of the CEE has been associated with a class of transient brightenings exhibiting slow expansion velocities and copious formation of dust and molecules (red transients - RT). A number of RT features, especially the long timescale of mass loss, challenge the existing CEE paradigm.
Motivated by RT, I will use a new variant of magnetohydrodynamics to comprehensively examine the 3D evolution of CEE from the moment when the mass loss commences to the remnant phase. I expect to resolve the long timescales observed in RT, characterize binary stability in 3D with detailed microphysics, illuminate the fundamental problem of how is orbital energy used to unbind the common envelope in a regime that was inaccessible before, and break new ground on the amplification of magnetic fields during CEE.
I will establish RT as an entirely new probe of the CEE physics by comparing my detailed theoretical predictions of light curves from different viewing angles, spectra, line profiles, and polarimetric signatures with observations of RT. I will accomplish this by coupling multi-dimensional moving mesh hydrodynamics with radiation, dust formation, and chemical reactions. Finally, I will examine the physical processes in RT remnants on timescales of years to centuries after the outburst to connect RT with the proposed merger products and to identify them in time-domain surveys.
"
Summary
"One of the crucial formation channels of compact object binaries, including sources of gravitational waves, critically depends on catastrophic binary interactions accompanied by the loss of mass, angular momentum, and energy (""common envelope"" evolution - CEE). Despite its importance, CEE is perhaps the least understood major phase of binary star evolution and progress in this area is urgently needed to interpret observations from the new facilities (gravitational wave detectors, time-domain surveys).
Recently, the dynamical phase of the CEE has been associated with a class of transient brightenings exhibiting slow expansion velocities and copious formation of dust and molecules (red transients - RT). A number of RT features, especially the long timescale of mass loss, challenge the existing CEE paradigm.
Motivated by RT, I will use a new variant of magnetohydrodynamics to comprehensively examine the 3D evolution of CEE from the moment when the mass loss commences to the remnant phase. I expect to resolve the long timescales observed in RT, characterize binary stability in 3D with detailed microphysics, illuminate the fundamental problem of how is orbital energy used to unbind the common envelope in a regime that was inaccessible before, and break new ground on the amplification of magnetic fields during CEE.
I will establish RT as an entirely new probe of the CEE physics by comparing my detailed theoretical predictions of light curves from different viewing angles, spectra, line profiles, and polarimetric signatures with observations of RT. I will accomplish this by coupling multi-dimensional moving mesh hydrodynamics with radiation, dust formation, and chemical reactions. Finally, I will examine the physical processes in RT remnants on timescales of years to centuries after the outburst to connect RT with the proposed merger products and to identify them in time-domain surveys.
"
Max ERC Funding
1 243 219 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym dEMORY
Project Dissecting the Role of Dendrites in Memory
Researcher (PI) Panayiota Poirazi
Host Institution (HI) FOUNDATION FOR RESEARCH AND TECHNOLOGY HELLAS
Call Details Starting Grant (StG), LS5, ERC-2012-StG_20111109
Summary Understanding the rules and mechanisms underlying memory formation, storage and retrieval is a grand challenge in neuroscience. In light of cumulating evidence regarding non-linear dendritic events (dendritic-spikes, branch strength potentiation, temporal sequence detection etc) together with activity-dependent rewiring of the connection matrix, the classical notion of information storage via Hebbian-like changes in synaptic connections is inadequate. While more recent plasticity theories consider non-linear dendritic properties, a unifying theory of how dendrites are utilized to achieve memory coding, storing and/or retrieval is cruelly missing. Using computational models, we will simulate memory processes in three key brain regions: the hippocampus, the amygdala and the prefrontal cortex. Models will incorporate biologically constrained dendrites and state-of-the-art plasticity rules and will span different levels of abstraction, ranging from detailed biophysical single neurons and circuits to integrate-and-fire networks and abstract theoretical models. Our main goal is to dissect the role of dendrites in information processing and storage across the three different regions by systematically altering their anatomical, biophysical and plasticity properties. Findings will further our understanding of the fundamental computations supported by these structures and how these computations, reinforced by plasticity mechanisms, sub-serve memory formation and associated dysfunctions, thus opening new avenues for hypothesis driven experimentation and development of novel treatments for memory-related diseases. Identification of dendrites as the key processing units across brain regions and complexity levels will lay the foundations for a new era in computational and experimental neuroscience and serve as the basis for groundbreaking advances in the robotics and artificial intelligence fields while also having a large impact on the machine learning community.
Summary
Understanding the rules and mechanisms underlying memory formation, storage and retrieval is a grand challenge in neuroscience. In light of cumulating evidence regarding non-linear dendritic events (dendritic-spikes, branch strength potentiation, temporal sequence detection etc) together with activity-dependent rewiring of the connection matrix, the classical notion of information storage via Hebbian-like changes in synaptic connections is inadequate. While more recent plasticity theories consider non-linear dendritic properties, a unifying theory of how dendrites are utilized to achieve memory coding, storing and/or retrieval is cruelly missing. Using computational models, we will simulate memory processes in three key brain regions: the hippocampus, the amygdala and the prefrontal cortex. Models will incorporate biologically constrained dendrites and state-of-the-art plasticity rules and will span different levels of abstraction, ranging from detailed biophysical single neurons and circuits to integrate-and-fire networks and abstract theoretical models. Our main goal is to dissect the role of dendrites in information processing and storage across the three different regions by systematically altering their anatomical, biophysical and plasticity properties. Findings will further our understanding of the fundamental computations supported by these structures and how these computations, reinforced by plasticity mechanisms, sub-serve memory formation and associated dysfunctions, thus opening new avenues for hypothesis driven experimentation and development of novel treatments for memory-related diseases. Identification of dendrites as the key processing units across brain regions and complexity levels will lay the foundations for a new era in computational and experimental neuroscience and serve as the basis for groundbreaking advances in the robotics and artificial intelligence fields while also having a large impact on the machine learning community.
Max ERC Funding
1 398 000 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym ISORI
Project Ion Spectroscopy of Reaction Intermediates
Researcher (PI) Jana Roithova
Host Institution (HI) UNIVERZITA KARLOVA
Call Details Starting Grant (StG), PE4, ERC-2010-StG_20091028
Summary Modern chemistry experiences a fast development of new reactions with dominance in organometallics and recently also organocatalysis. The massive synthetic progress however greatly foreruns mechanistic studies and the deeper insight is often rather limited. This large unexplored area accordingly challenges pioneering research and formulation of new concepts in chemistry. The present research project uses the most powerful tools of several research disciplines and aims towards the investigation of the elementary steps in organic reactions by means of mass spectrometry (MS) in combination with electrospray ionization (ESI) and quantum chemistry with a particular focus on ion spectroscopy.
The research will concentrate on elementary reactions in catalysis, e.g. the interaction of catalysts with substrates or bimolecular reactions of reactant/catalyst complexes. A major innovative contribution consists in applying ion spectroscopy for the structural characterization of reaction intermediates using a newly proposed tandem mass spectrometer with a cooled linear ion trap, which will allow two-photon experiments with IR and UV tunable lasers. The experiments will provide specific information about various intermediates and will help to disentangle even complicated mixtures or isomeric ions. In addition, an innovative experiment is designed, in which bimolecular reactivity of isobaric ions will be studied individually. Kinetics of selected reactions in solution will also be followed by ESI/MS. The combined efforts of these different approaches will provide a comprehensive understanding of the reaction mechanisms and will lead to the formulation of new general concepts in organic and organometallic reactivity.
Summary
Modern chemistry experiences a fast development of new reactions with dominance in organometallics and recently also organocatalysis. The massive synthetic progress however greatly foreruns mechanistic studies and the deeper insight is often rather limited. This large unexplored area accordingly challenges pioneering research and formulation of new concepts in chemistry. The present research project uses the most powerful tools of several research disciplines and aims towards the investigation of the elementary steps in organic reactions by means of mass spectrometry (MS) in combination with electrospray ionization (ESI) and quantum chemistry with a particular focus on ion spectroscopy.
The research will concentrate on elementary reactions in catalysis, e.g. the interaction of catalysts with substrates or bimolecular reactions of reactant/catalyst complexes. A major innovative contribution consists in applying ion spectroscopy for the structural characterization of reaction intermediates using a newly proposed tandem mass spectrometer with a cooled linear ion trap, which will allow two-photon experiments with IR and UV tunable lasers. The experiments will provide specific information about various intermediates and will help to disentangle even complicated mixtures or isomeric ions. In addition, an innovative experiment is designed, in which bimolecular reactivity of isobaric ions will be studied individually. Kinetics of selected reactions in solution will also be followed by ESI/MS. The combined efforts of these different approaches will provide a comprehensive understanding of the reaction mechanisms and will lead to the formulation of new general concepts in organic and organometallic reactivity.
Max ERC Funding
1 294 800 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym NEUROPHAGY
Project The Role of Autophagy in Synaptic Plasticity
Researcher (PI) Vassiliki NIKOLETOPOULOU
Host Institution (HI) IDRYMA TECHNOLOGIAS KAI EREVNAS
Call Details Starting Grant (StG), LS5, ERC-2016-STG
Summary Neuronal metabolism is emerging as an essential regulator of brain function and its deregulation is a common denominator in neurological disorders entailing intellectual disability and synapse dys-morphogenesis. The autophagy-lysosome system is the major catabolic pathway dedicated to the recycling not only of protein aggregates but also lipids, nucleic acids, polysaccharides and defective or superfluous organelles, among others.
Appreciation of the role of autophagic pathways in the healthy and diseased brain continues to expand, as accumulating evidence indicates that proper regulation of autophagy is indispensable for neuronal integrity. At the cellular level, several lines of evidence implicate autophagy in the regulation of synaptic plasticity. However, the synapse-specific substrates of autophagy remain elusive. Similarly, the synaptic defects arising from autophagy impairment have never been thus far systematically addressed, yet they translate into severe behavioural deficiencies, such as compromised memory and cognition, pertinent to disorders of intellectual disability.
The present proposal aims to determine how autophagy regulates synaptic plasticity and how its deregulation contributes to synaptic defects. In particular, the objectives aim to: 1) Monitor and characterize the presence of the autophagic machinery in pre- and post-synaptic sites. 2) Identify autophagic substrates residing in synapses and whose turnover via autophagy determines synaptic plasticity. 3) Characterize the synaptic defects and ensuing behavioural deficits arising from impaired autophagy in the hippocampus. 4) Use C. elegans as a model system to address the evolutionary conservation of the synaptic role of autophagy and perform forward genetic screens to reveal novel regulators of autophagy in synapses.
Summary
Neuronal metabolism is emerging as an essential regulator of brain function and its deregulation is a common denominator in neurological disorders entailing intellectual disability and synapse dys-morphogenesis. The autophagy-lysosome system is the major catabolic pathway dedicated to the recycling not only of protein aggregates but also lipids, nucleic acids, polysaccharides and defective or superfluous organelles, among others.
Appreciation of the role of autophagic pathways in the healthy and diseased brain continues to expand, as accumulating evidence indicates that proper regulation of autophagy is indispensable for neuronal integrity. At the cellular level, several lines of evidence implicate autophagy in the regulation of synaptic plasticity. However, the synapse-specific substrates of autophagy remain elusive. Similarly, the synaptic defects arising from autophagy impairment have never been thus far systematically addressed, yet they translate into severe behavioural deficiencies, such as compromised memory and cognition, pertinent to disorders of intellectual disability.
The present proposal aims to determine how autophagy regulates synaptic plasticity and how its deregulation contributes to synaptic defects. In particular, the objectives aim to: 1) Monitor and characterize the presence of the autophagic machinery in pre- and post-synaptic sites. 2) Identify autophagic substrates residing in synapses and whose turnover via autophagy determines synaptic plasticity. 3) Characterize the synaptic defects and ensuing behavioural deficits arising from impaired autophagy in the hippocampus. 4) Use C. elegans as a model system to address the evolutionary conservation of the synaptic role of autophagy and perform forward genetic screens to reveal novel regulators of autophagy in synapses.
Max ERC Funding
1 493 750 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym PICOSTRUCTURE
Project Structural studies of human picornaviruses
Researcher (PI) Pavel Plevka
Host Institution (HI) Masarykova univerzita
Call Details Starting Grant (StG), LS1, ERC-2013-StG
Summary Many picornaviruses are human pathogens that cause diseases varying in symptoms from common cold to life-threatening encephalitis. Currently there are no anti-picornavirus drugs approved for human use. We propose to study molecular structures of picornaviruses and their life cycle intermediates in order to identify new targets for anti-viral inhibitors and to lay the foundations for structure-based development of drugs against previously structurally uncharacterized picornaviruses.
We will use X-ray crystallography to determine virion structures of representative viruses from Parechovirus, Kobuvirus, Cardiovirus, and Cosavirus genera and Human Rhinovirus-C species. We will use cryo-electron microscopy to study picornavirus replication complexes in order to explain the mechanism of copy-choice recombination of picornavirus RNA genomes that leads to creation of new picornavirus species. We will determine whether picornavirus virions assemble from capsid protein protomers around the condensed genome or if the genome is packaged into a pre-formed empty capsid. Furthermore, we will investigate how picornaviruses initiate infection by analyzing genome release from virions and its translocation across lipid membrane.
A major innovation in our approach will be the use of focused ion beam micromachining for sample preparation that will allow us to study macromolecular complexes within infected mammalian cells by cryo-electron tomography. Our analysis of virion structure, cell entry, genome replication, and particle assembly will identify molecular details and mechanism of function of critical picornavirus life-cycle intermediates.
Summary
Many picornaviruses are human pathogens that cause diseases varying in symptoms from common cold to life-threatening encephalitis. Currently there are no anti-picornavirus drugs approved for human use. We propose to study molecular structures of picornaviruses and their life cycle intermediates in order to identify new targets for anti-viral inhibitors and to lay the foundations for structure-based development of drugs against previously structurally uncharacterized picornaviruses.
We will use X-ray crystallography to determine virion structures of representative viruses from Parechovirus, Kobuvirus, Cardiovirus, and Cosavirus genera and Human Rhinovirus-C species. We will use cryo-electron microscopy to study picornavirus replication complexes in order to explain the mechanism of copy-choice recombination of picornavirus RNA genomes that leads to creation of new picornavirus species. We will determine whether picornavirus virions assemble from capsid protein protomers around the condensed genome or if the genome is packaged into a pre-formed empty capsid. Furthermore, we will investigate how picornaviruses initiate infection by analyzing genome release from virions and its translocation across lipid membrane.
A major innovation in our approach will be the use of focused ion beam micromachining for sample preparation that will allow us to study macromolecular complexes within infected mammalian cells by cryo-electron tomography. Our analysis of virion structure, cell entry, genome replication, and particle assembly will identify molecular details and mechanism of function of critical picornavirus life-cycle intermediates.
Max ERC Funding
1 997 557 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym THz-FRaScan-ESR
Project THz Frequency Rapid Scan – Electron Spin Resonance spectroscopy for spin dynamics investigations of bulk and surface materials (THz-FRaScan-ESR)
Researcher (PI) Petr NEUGEBAUER
Host Institution (HI) VYSOKE UCENI TECHNICKE V BRNE
Call Details Starting Grant (StG), PE4, ERC-2016-STG
Summary Current high frequency electron spin resonance (HFESR) instruments suffer from the disadvantages of being limited to a single frequency and to tiny sample volumes. The study of spin dynamics at frequencies beyond a few hundred gigahertz is currently prohibitively difficult. These limitations are now preventing progress in dynamic nuclear polarization (DNP) and preclude the implementation of zero-field quantum computing. In order to revolutionize sensitivity in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) by means of DNP techniques allowing to watch in real time molecular interactions or even to monitor how sophisticated systems (ribosomes) work, the HFESR methods have to be substantially improved. I will develop a novel and worldwide unique technique called broadband terahertz frequency rapid scan (FRaScan) ESR. I intend to implement this method into a working prototype, which will seamlessly span the entire frequency range from 100 GHz to 1 THz, and allow spin dynamics investigation of large samples. This revolutionary new concept based on rapid frequency sweeps will remove all the restrictions and limitations of conventional HFESR methods used nowadays. It will enable for the first time multi-frequency studies of quantum coherence also in zero magnetic field. It will lead to substantial increases in sensitivity and concurrent decrease of measurement time, thus allowing more efficient use of resources. Finally, the method will allow identification of novel DNP signal enhancement agents, ultimately leading to a step change improvement of the MRI method. It will drastically shorten MRI scan times in hospitals, greatly enhancing patient comfort together with significantly better and precise diagnoses. The method will lead to zero field quantum computers with computation power which will be never reached with conventional technology. In summary it will lead to impacts far beyond the scientific community.
Summary
Current high frequency electron spin resonance (HFESR) instruments suffer from the disadvantages of being limited to a single frequency and to tiny sample volumes. The study of spin dynamics at frequencies beyond a few hundred gigahertz is currently prohibitively difficult. These limitations are now preventing progress in dynamic nuclear polarization (DNP) and preclude the implementation of zero-field quantum computing. In order to revolutionize sensitivity in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) by means of DNP techniques allowing to watch in real time molecular interactions or even to monitor how sophisticated systems (ribosomes) work, the HFESR methods have to be substantially improved. I will develop a novel and worldwide unique technique called broadband terahertz frequency rapid scan (FRaScan) ESR. I intend to implement this method into a working prototype, which will seamlessly span the entire frequency range from 100 GHz to 1 THz, and allow spin dynamics investigation of large samples. This revolutionary new concept based on rapid frequency sweeps will remove all the restrictions and limitations of conventional HFESR methods used nowadays. It will enable for the first time multi-frequency studies of quantum coherence also in zero magnetic field. It will lead to substantial increases in sensitivity and concurrent decrease of measurement time, thus allowing more efficient use of resources. Finally, the method will allow identification of novel DNP signal enhancement agents, ultimately leading to a step change improvement of the MRI method. It will drastically shorten MRI scan times in hospitals, greatly enhancing patient comfort together with significantly better and precise diagnoses. The method will lead to zero field quantum computers with computation power which will be never reached with conventional technology. In summary it will lead to impacts far beyond the scientific community.
Max ERC Funding
1 999 874 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym TRANSARREST
Project Keeping gene expression in check: eliciting the role of transcription in the maintenance of genome integrity
Researcher (PI) Maria Fousteri
Host Institution (HI) BIOMEDICAL SCIENCES RESEARCH CENTER ALEXANDER FLEMING
Call Details Starting Grant (StG), LS1, ERC-2012-StG_20111109
Summary Genomic integrity is essential for accurate gene expression and epigenetic inheritance. On the other hand, a prolonged transcriptional arrest can challenge genome stability, contributing to genetic and epigenetic defects and the mechanisms of ageing and disease.
Here we aim to identify the molecular mechanisms that couple transcriptional arrest to chromatin alteration and repair. We wish to explore the idea that transcription suppresses cellular toxicity and preserves genetic and epigenetic inheritance.
Towards these goals our work will be focused on:
1. Deciphering the molecular events impinging on the manner cells respond when the progress of a transcribing RNA polymerase II is blocked.
2. Exploring a novel, so far unanticipated function of key players of the transcription-associated repair pathways, such as the Cockayne Syndrome (CS) proteins, not related to repair.
3. Understanding the role of transcription in chemotherapeutic-driven toxicity.
4. Investigating novel post-translational modifications of CS and determining their function.
These objectives will be addressed using advanced proteomics and genome wide technologies in combination with biochemical and cellular techniques in normal human cells and a large battery of patient-derived cell lines. Our rational is that better understanding of CS function will help reach our ultimate goal, which is to identify the regulatory cascades involved in the interplay between genomic stability and transcription. The novel key idea put forward in this proposal is that active transcription itself directly contributes to genome integrity. While the role of DNA damage-driven transcription blockage in promoting repair is well established, the protective role of active transcription in genome stability is entirely unexplored.
If successful, the proposed studies may help reveal the underlying causes of related disorders and explain their clinical features.
Summary
Genomic integrity is essential for accurate gene expression and epigenetic inheritance. On the other hand, a prolonged transcriptional arrest can challenge genome stability, contributing to genetic and epigenetic defects and the mechanisms of ageing and disease.
Here we aim to identify the molecular mechanisms that couple transcriptional arrest to chromatin alteration and repair. We wish to explore the idea that transcription suppresses cellular toxicity and preserves genetic and epigenetic inheritance.
Towards these goals our work will be focused on:
1. Deciphering the molecular events impinging on the manner cells respond when the progress of a transcribing RNA polymerase II is blocked.
2. Exploring a novel, so far unanticipated function of key players of the transcription-associated repair pathways, such as the Cockayne Syndrome (CS) proteins, not related to repair.
3. Understanding the role of transcription in chemotherapeutic-driven toxicity.
4. Investigating novel post-translational modifications of CS and determining their function.
These objectives will be addressed using advanced proteomics and genome wide technologies in combination with biochemical and cellular techniques in normal human cells and a large battery of patient-derived cell lines. Our rational is that better understanding of CS function will help reach our ultimate goal, which is to identify the regulatory cascades involved in the interplay between genomic stability and transcription. The novel key idea put forward in this proposal is that active transcription itself directly contributes to genome integrity. While the role of DNA damage-driven transcription blockage in promoting repair is well established, the protective role of active transcription in genome stability is entirely unexplored.
If successful, the proposed studies may help reveal the underlying causes of related disorders and explain their clinical features.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-11-01, End date: 2018-10-31
Project acronym TSuNAMI
Project Trans-Spin NanoArchitectures: from birth to functionalities in magnetic field
Researcher (PI) Jana KALBACOVA VEJPRAVOVA
Host Institution (HI) UNIVERZITA KARLOVA
Call Details Starting Grant (StG), PE4, ERC-2016-STG
Summary Control over electrons in molecules and periodic solids can be reached via manipulation of their internal quantum degrees of freedom. The most prominent and exploited case is the electronic spin accommodated in standalone spin units composed of 1 – 10^5 of spins. A challenging alternative to the spin is the binary quantum degree of freedom, termed pseudospin existing e.g. in two-dimensional semiconductors. The aim of the proposed research is to build prototypes of trans-spin nano-architectures composed of at least two divergent spin entities, the TSuNAMIes. The spin entities of interest correspond to single atomic spin embedded in spin crossover complexes (SCO), molecular spin of molecular magnets (SMM), superspins of single-domain magnetic nanoparticles (SuperS) and pseudospins in two-dimensional transition metal dichalcogenides (PseudoS). Ultimate goal of the project is to identify a profit from trans-spin cooperation between the different spin entities coexisting in a single TSuNAMI. Influence of external static and alternating magnetic fields on the elementary spin state, unit cell magnetic structure, long-range magnetic order, mesoscopic spin order, spin relaxations and pseudospin state mirrored in essential fingerprints of the spin units and their ensembles will be explored using macroscopic and microscopic in situ and ex situ probes, including Raman and Mössbauer spectroscopies in magnetic field. Within the proposed high-risk/high-gain trans-spin strategy, we thus expect: 1. Enhancement of magnetic anisotropy in SMM-SuperS with enormous impact on cancer therapy using magnetic fluid hyperthermia, 2. Control over SCO via coupling to giant classical spin giving rise to miniature ‘on-particle’ sensors, 3. Mutual visualization of electronic states in SCO-PseudoS pushing frontiers of nowadays pseudospintronics, and 4. Control over electronic states with nanometer resolution in SuperS-PseudoS giving rise to novel functionalization strategies of graphene successor.
Summary
Control over electrons in molecules and periodic solids can be reached via manipulation of their internal quantum degrees of freedom. The most prominent and exploited case is the electronic spin accommodated in standalone spin units composed of 1 – 10^5 of spins. A challenging alternative to the spin is the binary quantum degree of freedom, termed pseudospin existing e.g. in two-dimensional semiconductors. The aim of the proposed research is to build prototypes of trans-spin nano-architectures composed of at least two divergent spin entities, the TSuNAMIes. The spin entities of interest correspond to single atomic spin embedded in spin crossover complexes (SCO), molecular spin of molecular magnets (SMM), superspins of single-domain magnetic nanoparticles (SuperS) and pseudospins in two-dimensional transition metal dichalcogenides (PseudoS). Ultimate goal of the project is to identify a profit from trans-spin cooperation between the different spin entities coexisting in a single TSuNAMI. Influence of external static and alternating magnetic fields on the elementary spin state, unit cell magnetic structure, long-range magnetic order, mesoscopic spin order, spin relaxations and pseudospin state mirrored in essential fingerprints of the spin units and their ensembles will be explored using macroscopic and microscopic in situ and ex situ probes, including Raman and Mössbauer spectroscopies in magnetic field. Within the proposed high-risk/high-gain trans-spin strategy, we thus expect: 1. Enhancement of magnetic anisotropy in SMM-SuperS with enormous impact on cancer therapy using magnetic fluid hyperthermia, 2. Control over SCO via coupling to giant classical spin giving rise to miniature ‘on-particle’ sensors, 3. Mutual visualization of electronic states in SCO-PseudoS pushing frontiers of nowadays pseudospintronics, and 4. Control over electronic states with nanometer resolution in SuperS-PseudoS giving rise to novel functionalization strategies of graphene successor.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
