Project acronym 0MSPIN
Project Spintronics based on relativistic phenomena in systems with zero magnetic moment
Researcher (PI) Tomas Jungwirth
Host Institution (HI) FYZIKALNI USTAV AV CR V.V.I
Country Czechia
Call Details Advanced Grant (AdG), PE3, ERC-2010-AdG_20100224
Summary The 0MSPIN project consists of an extensive integrated theoretical, experimental and device development programme of research opening a radical new approach to spintronics. Spintronics has the potential to supersede existing storage and memory applications, and to provide alternatives to current CMOS technology. Ferromagnetic matels used in all current spintronics applications may make it impractical to realise the full potential of spintronics. Metals are unsuitable for transistor and information processing applications, for opto-electronics, or for high-density integration. The 0MSPIN project aims to remove the major road-block holding back the development of spintronics in a radical way: removing the ferromagnetic component from key active parts or from the whole of the spintronic devices. This approach is based on exploiting the combination of exchange and spin-orbit coupling phenomena and material systems with zero macroscopic moment. The goal of the 0MSPIN is to provide a new paradigm by which spintronics can enter the realms of conventional semiconductors in both fundamental condensed matter research and in information technologies. In the central part of the proposal, the research towards this goal is embedded within a materials science project whose aim is to introduce into physics and microelectronics an entirely new class of semiconductors. 0MSPIN seeks to exploit three classes of material systems: (1) Antiferromagnetic bi-metallic 3d-5d alloys (e.g. Mn2Au). (2) Antiferromagnetic I-II-V semiconductors (e.g. LiMnAs). (3) Non-magnetic spin-orbit coupled semiconductors with injected spin-polarized currents (e.g. 2D III-V structures). Proof of concept devices operating at high temperatures will be fabricated to show-case new functionalities offered by zero-moment systems for sensing and memory applications, information processing, and opto-electronics technologies.
Summary
The 0MSPIN project consists of an extensive integrated theoretical, experimental and device development programme of research opening a radical new approach to spintronics. Spintronics has the potential to supersede existing storage and memory applications, and to provide alternatives to current CMOS technology. Ferromagnetic matels used in all current spintronics applications may make it impractical to realise the full potential of spintronics. Metals are unsuitable for transistor and information processing applications, for opto-electronics, or for high-density integration. The 0MSPIN project aims to remove the major road-block holding back the development of spintronics in a radical way: removing the ferromagnetic component from key active parts or from the whole of the spintronic devices. This approach is based on exploiting the combination of exchange and spin-orbit coupling phenomena and material systems with zero macroscopic moment. The goal of the 0MSPIN is to provide a new paradigm by which spintronics can enter the realms of conventional semiconductors in both fundamental condensed matter research and in information technologies. In the central part of the proposal, the research towards this goal is embedded within a materials science project whose aim is to introduce into physics and microelectronics an entirely new class of semiconductors. 0MSPIN seeks to exploit three classes of material systems: (1) Antiferromagnetic bi-metallic 3d-5d alloys (e.g. Mn2Au). (2) Antiferromagnetic I-II-V semiconductors (e.g. LiMnAs). (3) Non-magnetic spin-orbit coupled semiconductors with injected spin-polarized currents (e.g. 2D III-V structures). Proof of concept devices operating at high temperatures will be fabricated to show-case new functionalities offered by zero-moment systems for sensing and memory applications, information processing, and opto-electronics technologies.
Max ERC Funding
1 938 000 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym 100 Archaic Genomes
Project Genome sequences from extinct hominins
Researcher (PI) Svante PaeaeBO
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Country Germany
Call Details Advanced Grant (AdG), LS2, ERC-2015-AdG
Summary Neandertals and Denisovans, an Asian group distantly related to Neandertals, are the closest evolutionary relatives of present-day humans. They are thus of direct relevance for understanding the origin of modern humans and how modern humans differ from their closest relatives. We will generate genome-wide data from a large number of Neandertal and Denisovan individuals from across their geographical and temporal range as well as from other extinct hominin groups which we may discover. This will be possible by automating highly sensitive approaches to ancient DNA extraction and DNA libraries construction that we have developed so that they can be applied to many specimens from many sites in order to identify those that contain retrievable DNA. Whenever possible we will sequence whole genomes and in other cases use DNA capture methods to generate high-quality data from representative parts of the genome. This will allow us to study the population history of Neandertals and Denisovans, elucidate how many times and where these extinct hominins contributed genes to present-day people, and the extent to which modern humans and archaic groups contributed genetically to Neandertals and Denisovans. By retrieving DNA from specimens that go back to the Middle Pleistocene we will furthermore shed light on the early history and origins of Neandertals and Denisovans.
Summary
Neandertals and Denisovans, an Asian group distantly related to Neandertals, are the closest evolutionary relatives of present-day humans. They are thus of direct relevance for understanding the origin of modern humans and how modern humans differ from their closest relatives. We will generate genome-wide data from a large number of Neandertal and Denisovan individuals from across their geographical and temporal range as well as from other extinct hominin groups which we may discover. This will be possible by automating highly sensitive approaches to ancient DNA extraction and DNA libraries construction that we have developed so that they can be applied to many specimens from many sites in order to identify those that contain retrievable DNA. Whenever possible we will sequence whole genomes and in other cases use DNA capture methods to generate high-quality data from representative parts of the genome. This will allow us to study the population history of Neandertals and Denisovans, elucidate how many times and where these extinct hominins contributed genes to present-day people, and the extent to which modern humans and archaic groups contributed genetically to Neandertals and Denisovans. By retrieving DNA from specimens that go back to the Middle Pleistocene we will furthermore shed light on the early history and origins of Neandertals and Denisovans.
Max ERC Funding
2 350 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym 1stProposal
Project An alternative development of analytic number theory and applications
Researcher (PI) ANDREW Granville
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Country United Kingdom
Call Details Advanced Grant (AdG), PE1, ERC-2014-ADG
Summary The traditional (Riemann) approach to analytic number theory uses the zeros of zeta functions. This requires the associated multiplicative function, say f(n), to have special enough properties that the associated Dirichlet series may be analytically continued. In this proposal we continue to develop an approach which requires less of the multiplicative function, linking the original question with the mean value of f. Such techniques have been around for a long time but have generally been regarded as “ad hoc”. In this project we aim to show that one can develop a coherent approach to the whole subject, not only reproving all of the old results, but also many new ones that appear inaccessible to traditional methods.
Our first goal is to complete a monograph yielding a reworking of all the classical theory using these new methods and then to push forward in new directions. The most important is to extend these techniques to GL(n) L-functions, which we hope will now be feasible having found the correct framework in which to proceed. Since we rarely know how to analytically continue such L-functions this could be of great benefit to the subject.
We are developing the large sieve so that it can be used for individual moduli, and will determine a strong form of that. Also a new method to give asymptotics for mean values, when they are not too small.
We wish to incorporate techniques of analytic number theory into our theory, for example recent advances on mean values of Dirichlet polynomials. Also the recent breakthroughs on the sieve suggest strong links that need further exploration.
Additive combinatorics yields important results in many areas. There are strong analogies between its results, and those for multiplicative functions, especially in large value spectrum theory, and its applications. We hope to develop these further.
Much of this is joint work with K Soundararajan of Stanford University.
Summary
The traditional (Riemann) approach to analytic number theory uses the zeros of zeta functions. This requires the associated multiplicative function, say f(n), to have special enough properties that the associated Dirichlet series may be analytically continued. In this proposal we continue to develop an approach which requires less of the multiplicative function, linking the original question with the mean value of f. Such techniques have been around for a long time but have generally been regarded as “ad hoc”. In this project we aim to show that one can develop a coherent approach to the whole subject, not only reproving all of the old results, but also many new ones that appear inaccessible to traditional methods.
Our first goal is to complete a monograph yielding a reworking of all the classical theory using these new methods and then to push forward in new directions. The most important is to extend these techniques to GL(n) L-functions, which we hope will now be feasible having found the correct framework in which to proceed. Since we rarely know how to analytically continue such L-functions this could be of great benefit to the subject.
We are developing the large sieve so that it can be used for individual moduli, and will determine a strong form of that. Also a new method to give asymptotics for mean values, when they are not too small.
We wish to incorporate techniques of analytic number theory into our theory, for example recent advances on mean values of Dirichlet polynomials. Also the recent breakthroughs on the sieve suggest strong links that need further exploration.
Additive combinatorics yields important results in many areas. There are strong analogies between its results, and those for multiplicative functions, especially in large value spectrum theory, and its applications. We hope to develop these further.
Much of this is joint work with K Soundararajan of Stanford University.
Max ERC Funding
2 011 742 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym 2DHIBSA
Project Nanoscopic and Hierachical Materials via Living Crystallization-Driven Self-Assembly
Researcher (PI) Ian MANNERS
Host Institution (HI) UNIVERSITY OF BRISTOL
Country United Kingdom
Call Details Advanced Grant (AdG), PE5, ERC-2017-ADG
Summary A key synthetic challenge of widespread interest in chemical science involves the creation of well-defined 2D functional materials that exist on a length-scale of nanometers to microns. In this ambitious 5 year proposal we aim to tackle this issue by exploiting the unique opportunities made possible by recent developments with the living crystallization-driven self-assembly (CDSA) platform. Using this solution processing approach, amphiphilic block copolymers (BCPs) with crystallizable blocks, related amphiphiles, and polymers with charged end groups will be used to predictably construct monodisperse samples of tailored, functional soft matter-based 2D nanostructures with controlled shape, size, and spatially-defined chemistries. Many of the resulting nanostructures will also offer unprecedented opportunities as precursors to materials with hierarchical structures through further solution-based “bottom-up” assembly methods. In addition to fundamental studies, the proposed work also aims to make important impact in the cutting-edge fields of liquid crystals, interface stabilization, catalysis, supramolecular polymers, and hierarchical materials.
Summary
A key synthetic challenge of widespread interest in chemical science involves the creation of well-defined 2D functional materials that exist on a length-scale of nanometers to microns. In this ambitious 5 year proposal we aim to tackle this issue by exploiting the unique opportunities made possible by recent developments with the living crystallization-driven self-assembly (CDSA) platform. Using this solution processing approach, amphiphilic block copolymers (BCPs) with crystallizable blocks, related amphiphiles, and polymers with charged end groups will be used to predictably construct monodisperse samples of tailored, functional soft matter-based 2D nanostructures with controlled shape, size, and spatially-defined chemistries. Many of the resulting nanostructures will also offer unprecedented opportunities as precursors to materials with hierarchical structures through further solution-based “bottom-up” assembly methods. In addition to fundamental studies, the proposed work also aims to make important impact in the cutting-edge fields of liquid crystals, interface stabilization, catalysis, supramolecular polymers, and hierarchical materials.
Max ERC Funding
2 499 597 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym 2DNanoSpec
Project Nanoscale Vibrational Spectroscopy of Sensitive 2D Molecular Materials
Researcher (PI) Renato ZENOBI
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Advanced Grant (AdG), PE4, ERC-2016-ADG
Summary I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Summary
I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Max ERC Funding
2 311 696 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym 2G-CSAFE
Project Combustion of Sustainable Alternative Fuels for Engines used in aeronautics and automotives
Researcher (PI) Philippe Dagaut
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Advanced Grant (AdG), PE8, ERC-2011-ADG_20110209
Summary This project aims at promoting sustainable combustion technologies for transport via validation of advanced combustion kinetic models obtained using sophisticated new laboratory experiments, engines, and theoretical computations, breaking through the current frontier of knowledge. It will focus on the unexplored kinetics of ignition and combustion of 2nd generation (2G) biofuels and blends with conventional fuels, which should provide energy safety and sustainability to Europe. The motivation is that no accurate kinetic models are available for the ignition, oxidation and combustion of 2G-biofuels, and improved ignition control is needed for new compression ignition engines. Crucial information is missing: data from well characterised experiments on combustion-generated pollutants and data on key-intermediates for fuels ignition in new engines.
To provide that knowledge new well-instrumented complementary experiments and kinetic modelling will be used. Measurements of key-intermediates, stables species, and pollutants will be performed. New ignition control strategies will be designed, opening new technological horizons. Kinetic modelling will be used for rationalising the results. Due to the complexity of 2G-biofuels and their unusual composition, innovative surrogates will be designed. Kinetic models for surrogate fuels will be generalised for extension to other compounds. The experimental results, together with ab-initio and detailed modelling, will serve to characterise the kinetics of ignition, combustion, and pollutants formation of fuels including 2G biofuels, and provide relevant data and models.
This research is risky because this is (i) the 1st effort to measure radicals by reactor/CRDS coupling, (ii) the 1st effort to use a μ-channel reactor to build ignition databases for conventional and bio-fuels, (iii) the 1st effort to design and use controlled generation and injection of reactive species to control ignition/combustion in compression ignition engines
Summary
This project aims at promoting sustainable combustion technologies for transport via validation of advanced combustion kinetic models obtained using sophisticated new laboratory experiments, engines, and theoretical computations, breaking through the current frontier of knowledge. It will focus on the unexplored kinetics of ignition and combustion of 2nd generation (2G) biofuels and blends with conventional fuels, which should provide energy safety and sustainability to Europe. The motivation is that no accurate kinetic models are available for the ignition, oxidation and combustion of 2G-biofuels, and improved ignition control is needed for new compression ignition engines. Crucial information is missing: data from well characterised experiments on combustion-generated pollutants and data on key-intermediates for fuels ignition in new engines.
To provide that knowledge new well-instrumented complementary experiments and kinetic modelling will be used. Measurements of key-intermediates, stables species, and pollutants will be performed. New ignition control strategies will be designed, opening new technological horizons. Kinetic modelling will be used for rationalising the results. Due to the complexity of 2G-biofuels and their unusual composition, innovative surrogates will be designed. Kinetic models for surrogate fuels will be generalised for extension to other compounds. The experimental results, together with ab-initio and detailed modelling, will serve to characterise the kinetics of ignition, combustion, and pollutants formation of fuels including 2G biofuels, and provide relevant data and models.
This research is risky because this is (i) the 1st effort to measure radicals by reactor/CRDS coupling, (ii) the 1st effort to use a μ-channel reactor to build ignition databases for conventional and bio-fuels, (iii) the 1st effort to design and use controlled generation and injection of reactive species to control ignition/combustion in compression ignition engines
Max ERC Funding
2 498 450 €
Duration
Start date: 2011-12-01, End date: 2016-11-30
Project acronym 3-TOP
Project Exploring the physics of 3-dimensional topological insulators
Researcher (PI) Laurens Wigbolt Molenkamp
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Country Germany
Call Details Advanced Grant (AdG), PE3, ERC-2010-AdG_20100224
Summary Topological insulators constitute a novel class of materials where the topological details of the bulk band structure induce a robust surface state on the edges of the material. While transport data for 2-dimensional topological insulators have recently become available, experiments on their 3-dimensional counterparts are mainly limited to photoelectron spectroscopy. At the same time, a plethora of interesting novel physical phenomena have been predicted to occur in such systems.
In this proposal, we sketch an approach to tackle the transport and magnetic properties of the surface states in these materials. This starts with high quality layer growth, using molecular beam epitaxy, of bulk layers of HgTe, Bi2Se3 and Bi2Te3, which are the prime candidates to show the novel physics expected in this field. The existence of the relevant surface states will be assessed spectroscopically, but from there on research will focus on fabricating and characterizing nanostructures designed to elucidate the transport and magnetic properties of the topological surfaces using electrical, optical and scanning probe techniques. Apart from a general characterization of the Dirac band structure of the surface states, research will focus on the predicted magnetic monopole-like response of the system to an electrical test charge. In addition, much effort will be devoted to contacting the surface state with superconducting and magnetic top layers, with the final aim of demonstrating Majorana fermion behavior. As a final benefit, growth of thin high quality thin Bi2Se3 or Bi2Te3 layers could allow for a demonstration of the (2-dimensional) quantum spin Hall effect at room temperature - offering a road map to dissipation-less transport for the semiconductor industry.
Summary
Topological insulators constitute a novel class of materials where the topological details of the bulk band structure induce a robust surface state on the edges of the material. While transport data for 2-dimensional topological insulators have recently become available, experiments on their 3-dimensional counterparts are mainly limited to photoelectron spectroscopy. At the same time, a plethora of interesting novel physical phenomena have been predicted to occur in such systems.
In this proposal, we sketch an approach to tackle the transport and magnetic properties of the surface states in these materials. This starts with high quality layer growth, using molecular beam epitaxy, of bulk layers of HgTe, Bi2Se3 and Bi2Te3, which are the prime candidates to show the novel physics expected in this field. The existence of the relevant surface states will be assessed spectroscopically, but from there on research will focus on fabricating and characterizing nanostructures designed to elucidate the transport and magnetic properties of the topological surfaces using electrical, optical and scanning probe techniques. Apart from a general characterization of the Dirac band structure of the surface states, research will focus on the predicted magnetic monopole-like response of the system to an electrical test charge. In addition, much effort will be devoted to contacting the surface state with superconducting and magnetic top layers, with the final aim of demonstrating Majorana fermion behavior. As a final benefit, growth of thin high quality thin Bi2Se3 or Bi2Te3 layers could allow for a demonstration of the (2-dimensional) quantum spin Hall effect at room temperature - offering a road map to dissipation-less transport for the semiconductor industry.
Max ERC Funding
2 419 590 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym 3D-E
Project 3D Engineered Environments for Regenerative Medicine
Researcher (PI) Ruth Elizabeth Cameron
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Advanced Grant (AdG), PE8, ERC-2012-ADG_20120216
Summary "This proposal develops a unified, underpinning technology to create novel, complex and biomimetic 3D environments for the control of tissue growth. As director of Cambridge Centre for Medical Materials, I have recently been approached by medical colleagues to help to solve important problems in the separate therapeutic areas of breast cancer, cardiac disease and blood disorders. In each case, the solution lies in complex 3D engineered environments for cell culture. These colleagues make it clear that existing 3D scaffolds fail to provide the required complex orientational and spatial anisotropy, and are limited in their ability to impart appropriate biochemical and mechanical cues.
I have a strong track record in this area. A particular success has been the use of a freeze drying technology to make collagen based porous implants for the cartilage-bone interface in the knee, which has now been commercialised. The novelty of this proposal lies in the broadening of the established scientific base of this technology to enable biomacromolecular structures with:
(A) controlled and complex pore orientation to mimic many normal multi-oriented tissue structures
(B) compositional and positional control to match varying local biochemical environments,
(C) the attachment of novel peptides designed to control cell behaviour, and
(D) mechanical control at both a local and macroscopic level to provide mechanical cues for cells.
These will be complemented by the development of
(E) robust characterisation methodologies for the structures created.
These advances will then be employed in each of the medical areas above.
This approach is highly interdisciplinary. Existing working relationships with experts in each medical field will guarantee expertise and licensed facilities in the required biological disciplines. Funds for this proposal would therefore establish a rich hub of mutually beneficial research and opportunities for cross-disciplinary sharing of expertise."
Summary
"This proposal develops a unified, underpinning technology to create novel, complex and biomimetic 3D environments for the control of tissue growth. As director of Cambridge Centre for Medical Materials, I have recently been approached by medical colleagues to help to solve important problems in the separate therapeutic areas of breast cancer, cardiac disease and blood disorders. In each case, the solution lies in complex 3D engineered environments for cell culture. These colleagues make it clear that existing 3D scaffolds fail to provide the required complex orientational and spatial anisotropy, and are limited in their ability to impart appropriate biochemical and mechanical cues.
I have a strong track record in this area. A particular success has been the use of a freeze drying technology to make collagen based porous implants for the cartilage-bone interface in the knee, which has now been commercialised. The novelty of this proposal lies in the broadening of the established scientific base of this technology to enable biomacromolecular structures with:
(A) controlled and complex pore orientation to mimic many normal multi-oriented tissue structures
(B) compositional and positional control to match varying local biochemical environments,
(C) the attachment of novel peptides designed to control cell behaviour, and
(D) mechanical control at both a local and macroscopic level to provide mechanical cues for cells.
These will be complemented by the development of
(E) robust characterisation methodologies for the structures created.
These advances will then be employed in each of the medical areas above.
This approach is highly interdisciplinary. Existing working relationships with experts in each medical field will guarantee expertise and licensed facilities in the required biological disciplines. Funds for this proposal would therefore establish a rich hub of mutually beneficial research and opportunities for cross-disciplinary sharing of expertise."
Max ERC Funding
2 486 267 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym 3DBrainStrom
Project Brain metastases: Deciphering tumor-stroma interactions in three dimensions for the rational design of nanomedicines
Researcher (PI) Ronit Satchi Fainaro
Host Institution (HI) TEL AVIV UNIVERSITY
Country Israel
Call Details Advanced Grant (AdG), LS7, ERC-2018-ADG
Summary Brain metastases represent a major therapeutic challenge. Despite significant breakthroughs in targeted therapies, survival rates of patients with brain metastases remain poor. Nowadays, discovery, development and evaluation of new therapies are performed on human cancer cells grown in 2D on rigid plastic plates followed by in vivo testing in immunodeficient mice. These experimental settings are lacking and constitute a fundamental hurdle for the translation of preclinical discoveries into clinical practice. We propose to establish 3D-printed models of brain metastases (Aim 1), which include brain extracellular matrix, stroma and serum containing immune cells flowing in functional tumor vessels. Our unique models better capture the clinical physio-mechanical tissue properties, signaling pathways, hemodynamics and drug responsiveness. Using our 3D-printed models, we aim to develop two new fronts for identifying novel clinically-relevant molecular drivers (Aim 2) followed by the development of precision nanomedicines (Aim 3). We will exploit our vast experience in anticancer nanomedicines to design three therapeutic approaches that target various cellular compartments involved in brain metastases: 1) Prevention of brain metastatic colonization using targeted nano-vaccines, which elicit antitumor immune response; 2) Intervention of tumor-brain stroma cells crosstalk when brain micrometastases establish; 3) Regression of macrometastatic disease by selectively targeting tumor cells. These approaches will materialize using our libraries of polymeric nanocarriers that selectively accumulate in tumors.
This project will result in a paradigm shift by generating new preclinical cancer models that will bridge the translational gap in cancer therapeutics. The insights and tumor-stroma-targeted nanomedicines developed here will pave the way for prediction of patient outcome, revolutionizing our perception of tumor modelling and consequently the way we prevent and treat cancer.
Summary
Brain metastases represent a major therapeutic challenge. Despite significant breakthroughs in targeted therapies, survival rates of patients with brain metastases remain poor. Nowadays, discovery, development and evaluation of new therapies are performed on human cancer cells grown in 2D on rigid plastic plates followed by in vivo testing in immunodeficient mice. These experimental settings are lacking and constitute a fundamental hurdle for the translation of preclinical discoveries into clinical practice. We propose to establish 3D-printed models of brain metastases (Aim 1), which include brain extracellular matrix, stroma and serum containing immune cells flowing in functional tumor vessels. Our unique models better capture the clinical physio-mechanical tissue properties, signaling pathways, hemodynamics and drug responsiveness. Using our 3D-printed models, we aim to develop two new fronts for identifying novel clinically-relevant molecular drivers (Aim 2) followed by the development of precision nanomedicines (Aim 3). We will exploit our vast experience in anticancer nanomedicines to design three therapeutic approaches that target various cellular compartments involved in brain metastases: 1) Prevention of brain metastatic colonization using targeted nano-vaccines, which elicit antitumor immune response; 2) Intervention of tumor-brain stroma cells crosstalk when brain micrometastases establish; 3) Regression of macrometastatic disease by selectively targeting tumor cells. These approaches will materialize using our libraries of polymeric nanocarriers that selectively accumulate in tumors.
This project will result in a paradigm shift by generating new preclinical cancer models that will bridge the translational gap in cancer therapeutics. The insights and tumor-stroma-targeted nanomedicines developed here will pave the way for prediction of patient outcome, revolutionizing our perception of tumor modelling and consequently the way we prevent and treat cancer.
Max ERC Funding
2 353 125 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym 3DEpi
Project Transgenerational epigenetic inheritance of chromatin states : the role of Polycomb and 3D chromosome architecture
Researcher (PI) Giacomo CAVALLI
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Advanced Grant (AdG), LS2, ERC-2017-ADG
Summary Epigenetic inheritance entails transmission of phenotypic traits not encoded in the DNA sequence and, in the most extreme case, Transgenerational Epigenetic Inheritance (TEI) involves transmission of memory through multiple generations. Very little is known on the mechanisms governing TEI and this is the subject of the present proposal. By transiently enhancing long-range chromatin interactions, we recently established isogenic Drosophila epilines that carry stable alternative epialleles, defined by differential levels of the Polycomb-dependent H3K27me3 mark. Furthermore, we extended our paradigm to natural phenotypes. These are ideal systems to study the role of Polycomb group (PcG) proteins and other components in regulating nuclear organization and epigenetic inheritance of chromatin states. The present project conjugates genetics, epigenomics, imaging and molecular biology to reach three critical aims.
Aim 1: Analysis of the molecular mechanisms regulating Polycomb-mediated TEI. We will identify the DNA, protein and RNA components that trigger and maintain transgenerational chromatin inheritance as well as their mechanisms of action.
Aim 2: Role of 3D genome organization in the regulation of TEI. We will analyze the developmental dynamics of TEI-inducing long-range chromatin interactions, identify chromatin components mediating 3D chromatin contacts and characterize their function in the TEI process.
Aim 3: Identification of a broader role of TEI during development. TEI might reflect a normal role of PcG components in the transmission of parental chromatin onto the next embryonic generation. We will explore this possibility by establishing other TEI paradigms and by relating TEI to the normal PcG function in these systems and in normal development.
This research program will unravel the biological significance and the molecular underpinnings of TEI and lead the way towards establishing this area of research into a consolidated scientific discipline.
Summary
Epigenetic inheritance entails transmission of phenotypic traits not encoded in the DNA sequence and, in the most extreme case, Transgenerational Epigenetic Inheritance (TEI) involves transmission of memory through multiple generations. Very little is known on the mechanisms governing TEI and this is the subject of the present proposal. By transiently enhancing long-range chromatin interactions, we recently established isogenic Drosophila epilines that carry stable alternative epialleles, defined by differential levels of the Polycomb-dependent H3K27me3 mark. Furthermore, we extended our paradigm to natural phenotypes. These are ideal systems to study the role of Polycomb group (PcG) proteins and other components in regulating nuclear organization and epigenetic inheritance of chromatin states. The present project conjugates genetics, epigenomics, imaging and molecular biology to reach three critical aims.
Aim 1: Analysis of the molecular mechanisms regulating Polycomb-mediated TEI. We will identify the DNA, protein and RNA components that trigger and maintain transgenerational chromatin inheritance as well as their mechanisms of action.
Aim 2: Role of 3D genome organization in the regulation of TEI. We will analyze the developmental dynamics of TEI-inducing long-range chromatin interactions, identify chromatin components mediating 3D chromatin contacts and characterize their function in the TEI process.
Aim 3: Identification of a broader role of TEI during development. TEI might reflect a normal role of PcG components in the transmission of parental chromatin onto the next embryonic generation. We will explore this possibility by establishing other TEI paradigms and by relating TEI to the normal PcG function in these systems and in normal development.
This research program will unravel the biological significance and the molecular underpinnings of TEI and lead the way towards establishing this area of research into a consolidated scientific discipline.
Max ERC Funding
2 500 000 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
