Project acronym 3D-nanoMorph
Project Label-free 3D morphological nanoscopy for studying sub-cellular dynamics in live cancer cells with high spatio-temporal resolution
Researcher (PI) Krishna AGARWAL
Host Institution (HI) UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET
Call Details Starting Grant (StG), PE7, ERC-2018-STG
Summary Label-free optical nanoscopy, free from photobleaching and photochemical toxicity of fluorescence labels and yielding 3D morphological resolution of <50 nm, is the future of live cell imaging. 3D-nanoMorph breaks the diffraction barrier and shifts the paradigm in label-free nanoscopy, providing isotropic 3D resolution of <50 nm. To achieve this, 3D-nanoMorph performs non-linear inverse scattering for the first time in nanoscopy and decodes scattering between sub-cellular structures (organelles).
3D-nanoMorph innovatively devises complementary roles of light measurement system and computational nanoscopy algorithm. A novel illumination system and a novel light collection system together enable measurement of only the most relevant intensity component and create a fresh perspective about label-free measurements. A new computational nanoscopy approach employs non-linear inverse scattering. Harnessing non-linear inverse scattering for resolution enhancement in nanoscopy opens new possibilities in label-free 3D nanoscopy.
I will apply 3D-nanoMorph to study organelle degradation (autophagy) in live cancer cells over extended duration with high spatial and temporal resolution, presently limited by the lack of high-resolution label-free 3D morphological nanoscopy. Successful 3D mapping of nanoscale biological process of autophagy will open new avenues for cancer treatment and showcase 3D-nanoMorph for wider applications.
My cross-disciplinary expertise of 14 years spanning inverse problems, electromagnetism, optical microscopy, integrated optics and live cell nanoscopy paves path for successful implementation of 3D-nanoMorph.
Summary
Label-free optical nanoscopy, free from photobleaching and photochemical toxicity of fluorescence labels and yielding 3D morphological resolution of <50 nm, is the future of live cell imaging. 3D-nanoMorph breaks the diffraction barrier and shifts the paradigm in label-free nanoscopy, providing isotropic 3D resolution of <50 nm. To achieve this, 3D-nanoMorph performs non-linear inverse scattering for the first time in nanoscopy and decodes scattering between sub-cellular structures (organelles).
3D-nanoMorph innovatively devises complementary roles of light measurement system and computational nanoscopy algorithm. A novel illumination system and a novel light collection system together enable measurement of only the most relevant intensity component and create a fresh perspective about label-free measurements. A new computational nanoscopy approach employs non-linear inverse scattering. Harnessing non-linear inverse scattering for resolution enhancement in nanoscopy opens new possibilities in label-free 3D nanoscopy.
I will apply 3D-nanoMorph to study organelle degradation (autophagy) in live cancer cells over extended duration with high spatial and temporal resolution, presently limited by the lack of high-resolution label-free 3D morphological nanoscopy. Successful 3D mapping of nanoscale biological process of autophagy will open new avenues for cancer treatment and showcase 3D-nanoMorph for wider applications.
My cross-disciplinary expertise of 14 years spanning inverse problems, electromagnetism, optical microscopy, integrated optics and live cell nanoscopy paves path for successful implementation of 3D-nanoMorph.
Max ERC Funding
1 499 999 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym 5D-NanoTrack
Project Five-Dimensional Localization Microscopy for Sub-Cellular Dynamics
Researcher (PI) Yoav SHECHTMAN
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), PE7, ERC-2018-STG
Summary The sub-cellular processes that control the most critical aspects of life occur in three-dimensions (3D), and are intrinsically dynamic. While super-resolution microscopy has revolutionized cellular imaging in recent years, our current capability to observe the dynamics of life on the nanoscale is still extremely limited, due to inherent trade-offs between spatial, temporal and spectral resolution using existing approaches.
We propose to develop and demonstrate an optical microscopy methodology that would enable live sub-cellular observation in unprecedented detail. Making use of multicolor 3D point-spread-function (PSF) engineering, a technique I have recently developed, we will be able to simultaneously track multiple markers inside live cells, at high speed and in five-dimensions (3D, time, and color).
Multicolor 3D PSF engineering holds the potential of being a uniquely powerful method for 5D tracking. However, it is not yet applicable to live-cell imaging, due to significant bottlenecks in optical engineering and signal processing, which we plan to overcome in this project. Importantly, we will also demonstrate the efficacy of our method using a challenging biological application: real-time visualization of chromatin dynamics - the spatiotemporal organization of DNA. This is a highly suitable problem due to its fundamental importance, its role in a variety of cellular processes, and the lack of appropriate tools for studying it.
The project is divided into 3 aims:
1. Technology development: diffractive-element design for multicolor 3D PSFs.
2. System design: volumetric tracking of dense emitters.
3. Live-cell measurements: chromatin dynamics.
Looking ahead, here we create the imaging tools that pave the way towards the holy grail of chromatin visualization: dynamic observation of the 3D positions of the ~3 billion DNA base-pairs in a live human cell. Beyond that, our results will be applicable to numerous 3D micro/nanoscale tracking applications.
Summary
The sub-cellular processes that control the most critical aspects of life occur in three-dimensions (3D), and are intrinsically dynamic. While super-resolution microscopy has revolutionized cellular imaging in recent years, our current capability to observe the dynamics of life on the nanoscale is still extremely limited, due to inherent trade-offs between spatial, temporal and spectral resolution using existing approaches.
We propose to develop and demonstrate an optical microscopy methodology that would enable live sub-cellular observation in unprecedented detail. Making use of multicolor 3D point-spread-function (PSF) engineering, a technique I have recently developed, we will be able to simultaneously track multiple markers inside live cells, at high speed and in five-dimensions (3D, time, and color).
Multicolor 3D PSF engineering holds the potential of being a uniquely powerful method for 5D tracking. However, it is not yet applicable to live-cell imaging, due to significant bottlenecks in optical engineering and signal processing, which we plan to overcome in this project. Importantly, we will also demonstrate the efficacy of our method using a challenging biological application: real-time visualization of chromatin dynamics - the spatiotemporal organization of DNA. This is a highly suitable problem due to its fundamental importance, its role in a variety of cellular processes, and the lack of appropriate tools for studying it.
The project is divided into 3 aims:
1. Technology development: diffractive-element design for multicolor 3D PSFs.
2. System design: volumetric tracking of dense emitters.
3. Live-cell measurements: chromatin dynamics.
Looking ahead, here we create the imaging tools that pave the way towards the holy grail of chromatin visualization: dynamic observation of the 3D positions of the ~3 billion DNA base-pairs in a live human cell. Beyond that, our results will be applicable to numerous 3D micro/nanoscale tracking applications.
Max ERC Funding
1 802 500 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym ABACUS
Project Ab-initio adiabatic-connection curves for density-functional analysis and construction
Researcher (PI) Trygve Ulf Helgaker
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Advanced Grant (AdG), PE4, ERC-2010-AdG_20100224
Summary Quantum chemistry provides two approaches to molecular electronic-structure calculations: the systematically refinable but expensive many-body wave-function methods and the inexpensive but not systematically refinable Kohn Sham method of density-functional theory (DFT). The accuracy of Kohn Sham calculations is determined by the quality of the exchange correlation functional, from which the effects of exchange and correlation among the electrons are extracted using the density rather than the wave function. However, the exact exchange correlation functional is unknown—instead, many approximate forms have been developed, by fitting to experimental data or by satisfying exact relations. Here, a new approach to density-functional analysis and construction is proposed: the Lieb variation principle, usually regarded as conceptually important but impracticable. By invoking the Lieb principle, it becomes possible to approach the development of approximate functionals in a novel manner, being directly guided by the behaviour of exact functional, accurately calculated for a wide variety of chemical systems. In particular, this principle will be used to calculate ab-initio adiabatic connection curves, studying the exchange correlation functional for a fixed density as the electronic interactions are turned on from zero to one. Pilot calculations have indicated the feasibility of this approach in simple cases—here, a comprehensive set of adiabatic-connection curves will be generated and utilized for calibration, construction, and analysis of density functionals, the objective being to produce improved functionals for Kohn Sham calculations by modelling or fitting such curves. The ABACUS approach will be particularly important in cases where little experimental information is available—for example, for understanding and modelling the behaviour of the exchange correlation functional in electromagnetic fields.
Summary
Quantum chemistry provides two approaches to molecular electronic-structure calculations: the systematically refinable but expensive many-body wave-function methods and the inexpensive but not systematically refinable Kohn Sham method of density-functional theory (DFT). The accuracy of Kohn Sham calculations is determined by the quality of the exchange correlation functional, from which the effects of exchange and correlation among the electrons are extracted using the density rather than the wave function. However, the exact exchange correlation functional is unknown—instead, many approximate forms have been developed, by fitting to experimental data or by satisfying exact relations. Here, a new approach to density-functional analysis and construction is proposed: the Lieb variation principle, usually regarded as conceptually important but impracticable. By invoking the Lieb principle, it becomes possible to approach the development of approximate functionals in a novel manner, being directly guided by the behaviour of exact functional, accurately calculated for a wide variety of chemical systems. In particular, this principle will be used to calculate ab-initio adiabatic connection curves, studying the exchange correlation functional for a fixed density as the electronic interactions are turned on from zero to one. Pilot calculations have indicated the feasibility of this approach in simple cases—here, a comprehensive set of adiabatic-connection curves will be generated and utilized for calibration, construction, and analysis of density functionals, the objective being to produce improved functionals for Kohn Sham calculations by modelling or fitting such curves. The ABACUS approach will be particularly important in cases where little experimental information is available—for example, for understanding and modelling the behaviour of the exchange correlation functional in electromagnetic fields.
Max ERC Funding
2 017 932 €
Duration
Start date: 2011-03-01, End date: 2016-02-29
Project acronym BeadsOnString
Project Beads on String Genomics: Experimental Toolbox for Unmasking Genetic / Epigenetic Variation in Genomic DNA and Chromatin
Researcher (PI) Yuval Ebenstein
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), PE4, ERC-2013-StG
Summary Next generation sequencing (NGS) is revolutionizing all fields of biological research but it fails to extract the full range of information associated with genetic material and is lacking in its ability to resolve variations between genomes. The high degree of genome variation exhibited both on the population level as well as between genetically “identical” cells (even in the same organ) makes genetic and epigenetic analysis on the single cell and single genome level a necessity.
Chromosomes may be conceptually represented as a linear one-dimensional barcode. However, in contrast to a traditional binary barcode approach that considers only two possible bits of information (1 & 0), I will use colour and molecular structure to expand the variety of information represented in the barcode. Like colourful beads threaded on a string, where each bead represents a distinct type of observable, I will label each type of genomic information with a different chemical moiety thus expanding the repertoire of information that can be simultaneously measured. A major effort in this proposal is invested in the development of unique chemistries to enable this labelling.
I specifically address three types of genomic variation: Variations in genomic layout (including DNA repeats, structural and copy number variations), variations in the patterns of chemical DNA modifications (such as methylation of cytosine bases) and variations in the chromatin composition (including nucleosome and transcription factor distributions). I will use physical extension of long DNA molecules on surfaces and in nanofluidic channels to reveal this information visually in the form of a linear, fluorescent “barcode” that is read-out by advanced imaging techniques. Similarly, DNA molecules will be threaded through a nanopore where the sequential position of “bulky” molecular groups attached to the DNA may be inferred from temporal modulation of an ionic current measured across the pore.
Summary
Next generation sequencing (NGS) is revolutionizing all fields of biological research but it fails to extract the full range of information associated with genetic material and is lacking in its ability to resolve variations between genomes. The high degree of genome variation exhibited both on the population level as well as between genetically “identical” cells (even in the same organ) makes genetic and epigenetic analysis on the single cell and single genome level a necessity.
Chromosomes may be conceptually represented as a linear one-dimensional barcode. However, in contrast to a traditional binary barcode approach that considers only two possible bits of information (1 & 0), I will use colour and molecular structure to expand the variety of information represented in the barcode. Like colourful beads threaded on a string, where each bead represents a distinct type of observable, I will label each type of genomic information with a different chemical moiety thus expanding the repertoire of information that can be simultaneously measured. A major effort in this proposal is invested in the development of unique chemistries to enable this labelling.
I specifically address three types of genomic variation: Variations in genomic layout (including DNA repeats, structural and copy number variations), variations in the patterns of chemical DNA modifications (such as methylation of cytosine bases) and variations in the chromatin composition (including nucleosome and transcription factor distributions). I will use physical extension of long DNA molecules on surfaces and in nanofluidic channels to reveal this information visually in the form of a linear, fluorescent “barcode” that is read-out by advanced imaging techniques. Similarly, DNA molecules will be threaded through a nanopore where the sequential position of “bulky” molecular groups attached to the DNA may be inferred from temporal modulation of an ionic current measured across the pore.
Max ERC Funding
1 627 600 €
Duration
Start date: 2013-10-01, End date: 2018-09-30
Project acronym BeyondtheElite
Project Beyond the Elite: Jewish Daily Life in Medieval Europe
Researcher (PI) Elisheva Baumgarten
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Consolidator Grant (CoG), SH6, ERC-2015-CoG
Summary The two fundamental challenges of this project are the integration of medieval Jewries and their histories within the framework of European history without undermining their distinct communal status and the creation of a history of everyday medieval Jewish life that includes those who were not part of the learned elite. The study will focus on the Jewish communities of northern Europe (roughly modern Germany, northern France and England) from 1100-1350. From the mid-thirteenth century these medieval Jewish communities were subject to growing persecution. The approaches proposed to access daily praxis seek to highlight tangible dimensions of religious life rather than the more common study of ideologies to date. This task is complex because the extant sources in Hebrew as well as those in Latin and vernacular were written by the learned elite and will require a broad survey of multiple textual and material sources.
Four main strands will be examined and combined:
1. An outline of the strata of Jewish society, better defining the elites and other groups.
2. A study of select communal and familial spaces such as the house, the synagogue, the market place have yet to be examined as social spaces.
3. Ritual and urban rhythms especially the annual cycle, connecting between Jewish and Christian environments.
4. Material culture, as objects were used by Jews and Christians alike.
Aspects of material culture, the physical environment and urban rhythms are often described as “neutral” yet will be mined to demonstrate how they exemplified difference while being simultaneously ubiquitous in local cultures. The deterioration of relations between Jews and Christians will provide a gauge for examining change during this period. The final stage of the project will include comparative case studies of other Jewish communities. I expect my findings will inform scholars of medieval culture at large and promote comparative methodologies for studying other minority ethnic groups
Summary
The two fundamental challenges of this project are the integration of medieval Jewries and their histories within the framework of European history without undermining their distinct communal status and the creation of a history of everyday medieval Jewish life that includes those who were not part of the learned elite. The study will focus on the Jewish communities of northern Europe (roughly modern Germany, northern France and England) from 1100-1350. From the mid-thirteenth century these medieval Jewish communities were subject to growing persecution. The approaches proposed to access daily praxis seek to highlight tangible dimensions of religious life rather than the more common study of ideologies to date. This task is complex because the extant sources in Hebrew as well as those in Latin and vernacular were written by the learned elite and will require a broad survey of multiple textual and material sources.
Four main strands will be examined and combined:
1. An outline of the strata of Jewish society, better defining the elites and other groups.
2. A study of select communal and familial spaces such as the house, the synagogue, the market place have yet to be examined as social spaces.
3. Ritual and urban rhythms especially the annual cycle, connecting between Jewish and Christian environments.
4. Material culture, as objects were used by Jews and Christians alike.
Aspects of material culture, the physical environment and urban rhythms are often described as “neutral” yet will be mined to demonstrate how they exemplified difference while being simultaneously ubiquitous in local cultures. The deterioration of relations between Jews and Christians will provide a gauge for examining change during this period. The final stage of the project will include comparative case studies of other Jewish communities. I expect my findings will inform scholars of medieval culture at large and promote comparative methodologies for studying other minority ethnic groups
Max ERC Funding
1 941 688 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym BIVAQUM
Project Bivariational Approximations in Quantum Mechanics and Applications to Quantum Chemistry
Researcher (PI) Simen Kvaal
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Starting Grant (StG), PE4, ERC-2014-STG
Summary The standard variational principles (VPs) are cornerstones of quantum mechanics, and one can hardly overestimate their usefulness as tools for generating approximations to the time-independent and
time-dependent Schröodinger equations. The aim of the proposal is to study and apply a generalization of these, the bivariational principles (BIVPs), which arise naturally when one does not assume a priori that the system Hamiltonian is Hermitian. This unconventional approach may have transformative impact on development of ab initio methodology, both for electronic structure and dynamics.
The first objective is to establish the mathematical foundation for the BIVPs. This opens up a whole new axis of method development for ab initio approaches. For instance, it is a largely ignored fact that the popular traditional coupled cluster (TCC) method can be neatly formulated with the BIVPs, and TCC is both polynomially scaling with the number of electrons and size-consistent. No “variational” method enjoys these properties simultaneously, indeed this seems to be incompatible with the standard VPs.
Armed with the BIVPs, the project aims to develop new and understand existing ab initio methods. The second objective is thus a systematic multireference coupled cluster theory (MRCC) based on the BIVPs. This
is in itself a novel approach that carries large potential benefits and impact. The third and last objective is an implementation of a new coupled-cluster type method where the orbitals are bivariational
parameters. This gives a size-consistent hierarchy of approximations to multiconfiguration
Hartree--Fock.
The PI's broad contact with and background in scientific disciplines such as applied mathematics and nuclear physics in addition to quantum chemistry increases the feasibility of the project.
Summary
The standard variational principles (VPs) are cornerstones of quantum mechanics, and one can hardly overestimate their usefulness as tools for generating approximations to the time-independent and
time-dependent Schröodinger equations. The aim of the proposal is to study and apply a generalization of these, the bivariational principles (BIVPs), which arise naturally when one does not assume a priori that the system Hamiltonian is Hermitian. This unconventional approach may have transformative impact on development of ab initio methodology, both for electronic structure and dynamics.
The first objective is to establish the mathematical foundation for the BIVPs. This opens up a whole new axis of method development for ab initio approaches. For instance, it is a largely ignored fact that the popular traditional coupled cluster (TCC) method can be neatly formulated with the BIVPs, and TCC is both polynomially scaling with the number of electrons and size-consistent. No “variational” method enjoys these properties simultaneously, indeed this seems to be incompatible with the standard VPs.
Armed with the BIVPs, the project aims to develop new and understand existing ab initio methods. The second objective is thus a systematic multireference coupled cluster theory (MRCC) based on the BIVPs. This
is in itself a novel approach that carries large potential benefits and impact. The third and last objective is an implementation of a new coupled-cluster type method where the orbitals are bivariational
parameters. This gives a size-consistent hierarchy of approximations to multiconfiguration
Hartree--Fock.
The PI's broad contact with and background in scientific disciplines such as applied mathematics and nuclear physics in addition to quantum chemistry increases the feasibility of the project.
Max ERC Funding
1 499 572 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym BNYQ
Project Breaking the Nyquist Barrier: A New Paradigm in Data Conversion and Transmission
Researcher (PI) Yonina Eldar
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Consolidator Grant (CoG), PE7, ERC-2014-CoG
Summary Digital signal processing (DSP) is a revolutionary paradigm shift enabling processing of physical data in the digital domain where design and implementation are considerably simplified. However, state-of-the-art analog-to-digital convertors (ADCs) preclude high-rate wideband sampling and processing with low cost and energy consumption, presenting a major bottleneck. This is mostly due to a traditional assumption that sampling must be performed at the Nyquist rate, that is, twice the signal bandwidth. Modern applications including communications, medical imaging, radar and more use signals with high bandwidth, resulting in prohibitively large Nyquist rates.
Our ambitious goal is to introduce a paradigm shift in ADC design that will enable systems capable of low-rate, wideband sensing and low-rate DSP.
While DSP has a rich history in exploiting structure to reduce dimensionality and perform efficient parameter extraction, current ADCs do not exploit such knowledge.
We challenge current practice that separates the sampling stage from the processing stage and exploit structure in analog signals already in the ADC, to drastically reduce the sampling and processing rates.
Our preliminary data shows that this allows substantial savings in sampling and processing rates --- we show rate reduction of 1/28 in ultrasound imaging, and 1/30 in radar detection.
To achieve our overreaching goal we focus on three interconnected objectives -- developing the 1) theory 2) hardware and 3) applications of sub-Nyquist sampling.
Our methodology ties together two areas on the frontier of signal processing: compressed sensing (CS), focused on finite length vectors, and analog sampling. Our research plan also inherently relies on advances in several other important areas within signal processing and combines multi-disciplinary research at the intersection of signal processing, information theory, optimization, estimation theory and hardware design.
Summary
Digital signal processing (DSP) is a revolutionary paradigm shift enabling processing of physical data in the digital domain where design and implementation are considerably simplified. However, state-of-the-art analog-to-digital convertors (ADCs) preclude high-rate wideband sampling and processing with low cost and energy consumption, presenting a major bottleneck. This is mostly due to a traditional assumption that sampling must be performed at the Nyquist rate, that is, twice the signal bandwidth. Modern applications including communications, medical imaging, radar and more use signals with high bandwidth, resulting in prohibitively large Nyquist rates.
Our ambitious goal is to introduce a paradigm shift in ADC design that will enable systems capable of low-rate, wideband sensing and low-rate DSP.
While DSP has a rich history in exploiting structure to reduce dimensionality and perform efficient parameter extraction, current ADCs do not exploit such knowledge.
We challenge current practice that separates the sampling stage from the processing stage and exploit structure in analog signals already in the ADC, to drastically reduce the sampling and processing rates.
Our preliminary data shows that this allows substantial savings in sampling and processing rates --- we show rate reduction of 1/28 in ultrasound imaging, and 1/30 in radar detection.
To achieve our overreaching goal we focus on three interconnected objectives -- developing the 1) theory 2) hardware and 3) applications of sub-Nyquist sampling.
Our methodology ties together two areas on the frontier of signal processing: compressed sensing (CS), focused on finite length vectors, and analog sampling. Our research plan also inherently relies on advances in several other important areas within signal processing and combines multi-disciplinary research at the intersection of signal processing, information theory, optimization, estimation theory and hardware design.
Max ERC Funding
2 400 000 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym CartiLube
Project Lubricating Cartilage: exploring the relation between lubrication and gene-regulation to alleviate osteoarthritis
Researcher (PI) Jacob KLEIN
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), PE4, ERC-2016-ADG
Summary Can we exploit insights from the remarkably lubricated surfaces of articular cartilage, to create lubricants that may alleviate osteoarthritis (OA), the most widespread joint disease, affecting millions? These, succinctly, are the challenges of the present proposal. They are driven by our recent finding that lubrication of destabilised joints leads to changes in gene-regulation of the cartilage-embedded chondrocytes to protect against development of the disease. OA alleviation is known to arise through orthopedically suppressing shear-stresses on the cartilage, and a central premise of this project is that, by reducing friction at the articulating cartilage through suitable lubrication, we may achieve the same beneficial effect on the disease. The objectives of this project are to better understand the origins of cartilage boundary lubrication through examination of friction-reduction by its main molecular components, and exploit that understanding to create lubricants that, on intra-articular injection, will lubricate cartilage sufficiently well to achieve alleviation of OA via gene regulation. The project will examine, via both nanotribometric and macroscopic measurements, how the main molecular species implicated in cartilage lubrication, lipids, hyaluronan and lubricin, and their combinations, act together to form optimally lubricating boundary layers on model surfaces as well as on excised cartilage. Based on this, we shall develop suitable materials to lubricate cartilage in joints, using mouse models. Lubricants will further be optimized with respect to their retention in the joint and cartilage targeting, both in model studies and in vivo. The effect of the lubricants in regulating gene expression, in reducing pain and cartilage degradation, and in promoting stem-cell adhesion to the cartilage will be studied in a mouse model in which OA has been induced. Our results will have implications for treatment of a common, debilitating disease.
Summary
Can we exploit insights from the remarkably lubricated surfaces of articular cartilage, to create lubricants that may alleviate osteoarthritis (OA), the most widespread joint disease, affecting millions? These, succinctly, are the challenges of the present proposal. They are driven by our recent finding that lubrication of destabilised joints leads to changes in gene-regulation of the cartilage-embedded chondrocytes to protect against development of the disease. OA alleviation is known to arise through orthopedically suppressing shear-stresses on the cartilage, and a central premise of this project is that, by reducing friction at the articulating cartilage through suitable lubrication, we may achieve the same beneficial effect on the disease. The objectives of this project are to better understand the origins of cartilage boundary lubrication through examination of friction-reduction by its main molecular components, and exploit that understanding to create lubricants that, on intra-articular injection, will lubricate cartilage sufficiently well to achieve alleviation of OA via gene regulation. The project will examine, via both nanotribometric and macroscopic measurements, how the main molecular species implicated in cartilage lubrication, lipids, hyaluronan and lubricin, and their combinations, act together to form optimally lubricating boundary layers on model surfaces as well as on excised cartilage. Based on this, we shall develop suitable materials to lubricate cartilage in joints, using mouse models. Lubricants will further be optimized with respect to their retention in the joint and cartilage targeting, both in model studies and in vivo. The effect of the lubricants in regulating gene expression, in reducing pain and cartilage degradation, and in promoting stem-cell adhesion to the cartilage will be studied in a mouse model in which OA has been induced. Our results will have implications for treatment of a common, debilitating disease.
Max ERC Funding
2 499 944 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym CISS
Project Chiral Induced Spin Selectivity
Researcher (PI) Ron Naaman
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), PE4, ERC-2013-ADG
Summary The overall objective is to fully understand the Chiral Induced Spin Selectivity (CISS) effect, which was discovered recently. It was found that the transmission or conduction of electrons through chiral molecules is spin dependent. The CISS effect is a change in the pradigm that assumed that any spin manipulation requiers magnetic materials or materials with high spin-orbit coupling. These unexpected new findings open new possibilities for applying chiral molecules in spintronics applications and may provide new insights on electron transfer processes in Biology.
The specific goals of the proposed research are
(i) To establish the parameters that affect the magnitude of the CISS effect.
(ii) To demonstrate spintronics devices (memory and transistors) that are based on the CISS effect.
(iii) To investigate the role of CISS in electron transfer in biology related systems.
The experiments will be performed applying a combination of experimental methods including photoelectron spectroscopy, single molecule conduction, light-induced electron transfer, and spin specific conduction through magneto-electric devices.
The project has a potential to have very large impact on various fields from Physics to Biology. It will result in the establishment of chiral organic molecules as a new substrate for wide range of spintronics related applications including magnetic memory, and in determining whether spins play a role in electron transfer processes in biology.
Summary
The overall objective is to fully understand the Chiral Induced Spin Selectivity (CISS) effect, which was discovered recently. It was found that the transmission or conduction of electrons through chiral molecules is spin dependent. The CISS effect is a change in the pradigm that assumed that any spin manipulation requiers magnetic materials or materials with high spin-orbit coupling. These unexpected new findings open new possibilities for applying chiral molecules in spintronics applications and may provide new insights on electron transfer processes in Biology.
The specific goals of the proposed research are
(i) To establish the parameters that affect the magnitude of the CISS effect.
(ii) To demonstrate spintronics devices (memory and transistors) that are based on the CISS effect.
(iii) To investigate the role of CISS in electron transfer in biology related systems.
The experiments will be performed applying a combination of experimental methods including photoelectron spectroscopy, single molecule conduction, light-induced electron transfer, and spin specific conduction through magneto-electric devices.
The project has a potential to have very large impact on various fields from Physics to Biology. It will result in the establishment of chiral organic molecules as a new substrate for wide range of spintronics related applications including magnetic memory, and in determining whether spins play a role in electron transfer processes in biology.
Max ERC Funding
2 499 998 €
Duration
Start date: 2013-10-01, End date: 2018-09-30
Project acronym CloudRadioNet
Project Cloud Wireless Networks: An Information Theoretic Framework
Researcher (PI) Shlomo Shamai Shitz
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Advanced Grant (AdG), PE7, ERC-2015-AdG
Summary This five years research proposal is focused on the development of novel information theoretic concepts and techniques and their usage, as to identify the ultimate communications limits and potential of different cloud radio network structures, in which the central signal processing is migrated to the cloud (remote central units), via fronthaul/backhaul infrastructure links. Moreover, it is also directed to introduce and study the optimal or close to optimal strategies for those systems that are to be motivated by the developed theory. We plan to address wireless networks, having future cellular technology in mind, but the basic tools and approaches to be built and researched are relevant to other communication networks as well. Cloud communication networks motivate novel information theoretic views, and perspectives that put backhaul/fronthaul connections in the center, thus deviating considerably from standard theoretical studies of communications links and networks, which are applied to this domain. Our approach accounts for the fact that in such networks information theoretic separation concepts are no longer optimal, hence isolating simple basic components of the network is essentially suboptimal. The proposed view incorporates, in a unified way, under the general cover of information theory: Multi-terminal distributed networks; Basic and timely concepts of distributed coding and communications; Network communications and primarily network coding, Index coding, as associated with interference alignment and caching; Information-Estimation relations and signal processing, addressing the impact of distributed channel state information directly; A variety of fundamental concepts in optimization and random matrix theories. This path provides a natural theoretical framework directed towards better understanding the potential and limitation of cloud networks on one hand and paves the way to innovative communications design principles on the other.
Summary
This five years research proposal is focused on the development of novel information theoretic concepts and techniques and their usage, as to identify the ultimate communications limits and potential of different cloud radio network structures, in which the central signal processing is migrated to the cloud (remote central units), via fronthaul/backhaul infrastructure links. Moreover, it is also directed to introduce and study the optimal or close to optimal strategies for those systems that are to be motivated by the developed theory. We plan to address wireless networks, having future cellular technology in mind, but the basic tools and approaches to be built and researched are relevant to other communication networks as well. Cloud communication networks motivate novel information theoretic views, and perspectives that put backhaul/fronthaul connections in the center, thus deviating considerably from standard theoretical studies of communications links and networks, which are applied to this domain. Our approach accounts for the fact that in such networks information theoretic separation concepts are no longer optimal, hence isolating simple basic components of the network is essentially suboptimal. The proposed view incorporates, in a unified way, under the general cover of information theory: Multi-terminal distributed networks; Basic and timely concepts of distributed coding and communications; Network communications and primarily network coding, Index coding, as associated with interference alignment and caching; Information-Estimation relations and signal processing, addressing the impact of distributed channel state information directly; A variety of fundamental concepts in optimization and random matrix theories. This path provides a natural theoretical framework directed towards better understanding the potential and limitation of cloud networks on one hand and paves the way to innovative communications design principles on the other.
Max ERC Funding
1 981 782 €
Duration
Start date: 2016-07-01, End date: 2021-06-30