Project acronym 1st-principles-discs
Project A First Principles Approach to Accretion Discs
Researcher (PI) Martin Elias Pessah
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE9, ERC-2012-StG_20111012
Summary Most celestial bodies, from planets, to stars, to black holes; gain mass during their lives by means of an accretion disc. Understanding the physical processes that determine the rate at which matter accretes and energy is radiated in these discs is vital for unraveling the formation, evolution, and fate of almost every type of object in the Universe. Despite the fact that magnetic fields have been known to be crucial in accretion discs since the early 90’s, the majority of astrophysical questions that depend on the details of how disc accretion proceeds are still being addressed using the “standard” accretion disc model (developed in the early 70’s), where magnetic fields do not play an explicit role. This has prevented us from fully exploring the astrophysical consequences and observational signatures of realistic accretion disc models, leading to a profound disconnect between observations (usually interpreted with the standard paradigm) and modern accretion disc theory and numerical simulations (where magnetic turbulence is crucial). The goal of this proposal is to use several complementary approaches in order to finally move beyond the standard paradigm. This program has two main objectives: 1) Develop the theoretical framework to incorporate magnetic fields, and the ensuing turbulence, into self-consistent accretion disc models, and investigate their observational implications. 2) Investigate transport and radiative processes in collision-less disc regions, where non-thermal radiation originates, by employing a kinetic particle description of the plasma. In order to achieve these goals, we will use, and build upon, state-of-the-art magnetohydrodynamic and particle-in-cell codes in conjunction with theoretical modeling. This framework will make it possible to address fundamental questions on stellar and planet formation, binary systems with a compact object, and supermassive black hole feedback in a way that has no counterpart within the standard paradigm.
Summary
Most celestial bodies, from planets, to stars, to black holes; gain mass during their lives by means of an accretion disc. Understanding the physical processes that determine the rate at which matter accretes and energy is radiated in these discs is vital for unraveling the formation, evolution, and fate of almost every type of object in the Universe. Despite the fact that magnetic fields have been known to be crucial in accretion discs since the early 90’s, the majority of astrophysical questions that depend on the details of how disc accretion proceeds are still being addressed using the “standard” accretion disc model (developed in the early 70’s), where magnetic fields do not play an explicit role. This has prevented us from fully exploring the astrophysical consequences and observational signatures of realistic accretion disc models, leading to a profound disconnect between observations (usually interpreted with the standard paradigm) and modern accretion disc theory and numerical simulations (where magnetic turbulence is crucial). The goal of this proposal is to use several complementary approaches in order to finally move beyond the standard paradigm. This program has two main objectives: 1) Develop the theoretical framework to incorporate magnetic fields, and the ensuing turbulence, into self-consistent accretion disc models, and investigate their observational implications. 2) Investigate transport and radiative processes in collision-less disc regions, where non-thermal radiation originates, by employing a kinetic particle description of the plasma. In order to achieve these goals, we will use, and build upon, state-of-the-art magnetohydrodynamic and particle-in-cell codes in conjunction with theoretical modeling. This framework will make it possible to address fundamental questions on stellar and planet formation, binary systems with a compact object, and supermassive black hole feedback in a way that has no counterpart within the standard paradigm.
Max ERC Funding
1 793 697 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym 2DMATER
Project Controlled Synthesis of Two-Dimensional Nanomaterials for Energy Storage and Conversion
Researcher (PI) Xinliang Feng
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Call Details Starting Grant (StG), PE5, ERC-2012-StG_20111012
Summary "Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."
Summary
"Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-09-01, End date: 2017-08-31
Project acronym 2D–SYNETRA
Project Two-dimensional colloidal nanostructures - Synthesis and electrical transport
Researcher (PI) Christian Klinke
Host Institution (HI) UNIVERSITAET HAMBURG
Call Details Starting Grant (StG), PE4, ERC-2012-StG_20111012
Summary We propose to develop truly two-dimensional continuous materials and two-dimensional monolayer films composed of individual nanocrystals by the comparatively fast, inexpensive, and scalable colloidal synthesis method. The materials’ properties will be studied in detail, especially regarding their (photo-) electrical transport. This will allow developing new types of device structures, such as Coulomb blockade and field enhancement based transistors.
Recently, we demonstrated the possibility to synthesize in a controlled manner truly two-dimensional colloidal nanostructures. We will investigate their formation mechanism, synthesize further materials as “nanosheets”, develop methodologies to tune their geometrical properties, and study their (photo-) electrical properties.
Furthermore, we will use the Langmuir-Blodgett method to deposit highly ordered monolayers of monodisperse nanoparticles. Such structures show interesting transport properties governed by Coulomb blockade effects known from individual nanoparticles. This leads to semiconductor-like behavior in metal nanoparticle films. The understanding of the electric transport in such “multi-tunnel devices” is still very limited. Thus, we will investigate this concept in detail and take it to its limits. Beside improvement of quality and exchange of material we will tune the nanoparticles’ size and shape in order to gain a deeper understanding of the electrical properties of supercrystallographic assemblies. Furthermore, we will develop device concepts for diode and transistor structures which take into account the novel properties of the low-dimensional assemblies.
Nanosheets and monolayers of nanoparticles truly follow the principle of building devices by the bottom-up approach and allow electric transport measurements in a 2D regime. Highly ordered nanomaterial systems possess easy and reliably to manipulate electronic properties what make them interesting for future (inexpensive) electronic devices.
Summary
We propose to develop truly two-dimensional continuous materials and two-dimensional monolayer films composed of individual nanocrystals by the comparatively fast, inexpensive, and scalable colloidal synthesis method. The materials’ properties will be studied in detail, especially regarding their (photo-) electrical transport. This will allow developing new types of device structures, such as Coulomb blockade and field enhancement based transistors.
Recently, we demonstrated the possibility to synthesize in a controlled manner truly two-dimensional colloidal nanostructures. We will investigate their formation mechanism, synthesize further materials as “nanosheets”, develop methodologies to tune their geometrical properties, and study their (photo-) electrical properties.
Furthermore, we will use the Langmuir-Blodgett method to deposit highly ordered monolayers of monodisperse nanoparticles. Such structures show interesting transport properties governed by Coulomb blockade effects known from individual nanoparticles. This leads to semiconductor-like behavior in metal nanoparticle films. The understanding of the electric transport in such “multi-tunnel devices” is still very limited. Thus, we will investigate this concept in detail and take it to its limits. Beside improvement of quality and exchange of material we will tune the nanoparticles’ size and shape in order to gain a deeper understanding of the electrical properties of supercrystallographic assemblies. Furthermore, we will develop device concepts for diode and transistor structures which take into account the novel properties of the low-dimensional assemblies.
Nanosheets and monolayers of nanoparticles truly follow the principle of building devices by the bottom-up approach and allow electric transport measurements in a 2D regime. Highly ordered nanomaterial systems possess easy and reliably to manipulate electronic properties what make them interesting for future (inexpensive) electronic devices.
Max ERC Funding
1 497 200 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym 2STEPPARKIN
Project A novel two-step model for neurodegeneration in Parkinson’s disease
Researcher (PI) Emi Nagoshi
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Starting Grant (StG), LS5, ERC-2012-StG_20111109
Summary Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Despite the advances in gene discovery associated with PD, the knowledge of the PD pathogenesis is largely limited to the involvement of these genes in the generic cell death pathways, and why degeneration is specific to DA neurons and why the degeneration is progressive remain enigmatic. Broad goal of our work is therefore to elucidate the mechanisms underlying specific and progressive DA neuron degeneration in PD. Our new Drosophila model of PD ⎯Fer2 gene loss-of-function mutation⎯ is unusually well suited to address these questions. Fer2 mutants exhibit specific and progressive death of brain DA neurons as well as severe locomotor defects and short life span. Strikingly, the death of DA neuron is initiated in a small cluster of Fer2-expressing DA neurons and subsequently propagates to Fer2-negative DA neurons. We therefore propose a novel two-step model of the neurodegeneration in PD: primary cell death occurs in a specific subset of dopamindegic neurons that are genetically defined, and subsequently the failure of the neuronal connectivity triggers and propagates secondary cell death to remaining DA neurons. In this research, we will test this hypothesis and investigate the underlying molecular mechanisms. This will be the first study to examine circuit-dependency in DA neuron degeneration. Our approach will use a combination of non-biased genomic techniques and candidate-based screening, in addition to the powerful Drosophila genetic toolbox. Furthermore, to test this hypothesis beyond the Drosophila model, we will establish new mouse models of PD that exhibit progressive DA neuron degeneration. Outcome of this research will likely revolutionize the understanding of PD pathogenesis and open an avenue toward the discovery of effective therapy strategies against PD.
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Despite the advances in gene discovery associated with PD, the knowledge of the PD pathogenesis is largely limited to the involvement of these genes in the generic cell death pathways, and why degeneration is specific to DA neurons and why the degeneration is progressive remain enigmatic. Broad goal of our work is therefore to elucidate the mechanisms underlying specific and progressive DA neuron degeneration in PD. Our new Drosophila model of PD ⎯Fer2 gene loss-of-function mutation⎯ is unusually well suited to address these questions. Fer2 mutants exhibit specific and progressive death of brain DA neurons as well as severe locomotor defects and short life span. Strikingly, the death of DA neuron is initiated in a small cluster of Fer2-expressing DA neurons and subsequently propagates to Fer2-negative DA neurons. We therefore propose a novel two-step model of the neurodegeneration in PD: primary cell death occurs in a specific subset of dopamindegic neurons that are genetically defined, and subsequently the failure of the neuronal connectivity triggers and propagates secondary cell death to remaining DA neurons. In this research, we will test this hypothesis and investigate the underlying molecular mechanisms. This will be the first study to examine circuit-dependency in DA neuron degeneration. Our approach will use a combination of non-biased genomic techniques and candidate-based screening, in addition to the powerful Drosophila genetic toolbox. Furthermore, to test this hypothesis beyond the Drosophila model, we will establish new mouse models of PD that exhibit progressive DA neuron degeneration. Outcome of this research will likely revolutionize the understanding of PD pathogenesis and open an avenue toward the discovery of effective therapy strategies against PD.
Max ERC Funding
1 518 960 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
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
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 3D-QUEST
Project 3D-Quantum Integrated Optical Simulation
Researcher (PI) Fabio Sciarrino
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Call Details Starting Grant (StG), PE2, ERC-2012-StG_20111012
Summary "Quantum information was born from the merging of classical information and quantum physics. Its main objective consists of understanding the quantum nature of information and learning how to process it by using physical systems which operate by following quantum mechanics laws. Quantum simulation is a fundamental instrument to investigate phenomena of quantum systems dynamics, such as quantum transport, particle localizations and energy transfer, quantum-to-classical transition, and even quantum improved computation, all tasks that are hard to simulate with classical approaches. Within this framework integrated photonic circuits have a strong potential to realize quantum information processing by optical systems.
The aim of 3D-QUEST is to develop and implement quantum simulation by exploiting 3-dimensional integrated photonic circuits. 3D-QUEST is structured to demonstrate the potential of linear optics to implement a computational power beyond the one of a classical computer. Such ""hard-to-simulate"" scenario is disclosed when multiphoton-multimode platforms are realized. The 3D-QUEST research program will focus on three tasks of growing difficulty.
A-1. To simulate bosonic-fermionic dynamics with integrated optical systems acting on 2 photon entangled states.
A-2. To pave the way towards hard-to-simulate, scalable quantum linear optical circuits by investigating m-port interferometers acting on n-photon states with n>2.
A-3. To exploit 3-dimensional integrated structures for the observation of new quantum optical phenomena and for the quantum simulation of more complex scenarios.
3D-QUEST will exploit the potential of the femtosecond laser writing integrated waveguides. This technique will be adopted to realize 3-dimensional capabilities and high flexibility, bringing in this way the optical quantum simulation in to new regime."
Summary
"Quantum information was born from the merging of classical information and quantum physics. Its main objective consists of understanding the quantum nature of information and learning how to process it by using physical systems which operate by following quantum mechanics laws. Quantum simulation is a fundamental instrument to investigate phenomena of quantum systems dynamics, such as quantum transport, particle localizations and energy transfer, quantum-to-classical transition, and even quantum improved computation, all tasks that are hard to simulate with classical approaches. Within this framework integrated photonic circuits have a strong potential to realize quantum information processing by optical systems.
The aim of 3D-QUEST is to develop and implement quantum simulation by exploiting 3-dimensional integrated photonic circuits. 3D-QUEST is structured to demonstrate the potential of linear optics to implement a computational power beyond the one of a classical computer. Such ""hard-to-simulate"" scenario is disclosed when multiphoton-multimode platforms are realized. The 3D-QUEST research program will focus on three tasks of growing difficulty.
A-1. To simulate bosonic-fermionic dynamics with integrated optical systems acting on 2 photon entangled states.
A-2. To pave the way towards hard-to-simulate, scalable quantum linear optical circuits by investigating m-port interferometers acting on n-photon states with n>2.
A-3. To exploit 3-dimensional integrated structures for the observation of new quantum optical phenomena and for the quantum simulation of more complex scenarios.
3D-QUEST will exploit the potential of the femtosecond laser writing integrated waveguides. This technique will be adopted to realize 3-dimensional capabilities and high flexibility, bringing in this way the optical quantum simulation in to new regime."
Max ERC Funding
1 474 800 €
Duration
Start date: 2012-08-01, End date: 2017-07-31
Project acronym 3Ps
Project 3Ps
Plastic-Antibodies, Plasmonics and Photovoltaic-Cells: on-site screening of cancer biomarkers made possible
Researcher (PI) Maria Goreti Ferreira Sales
Host Institution (HI) INSTITUTO SUPERIOR DE ENGENHARIA DO PORTO
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
Summary This project presents a new concept for the detection, diagnosis and monitoring of cancer biomarker patterns in point-of-care. The device under development will make use of the selectivity of the plastic antibodies as sensing materials and the interference they will play on the normal operation of a photovoltaic cell.
Plastic antibodies will be designed by surface imprinting procedures. Self-assembled monolayer and molecular imprinting techniques will be merged in this process because they allow the self-assembly of nanostructured materials on a “bottom-up” nanofabrication approach. A dye-sensitized solar cell will be used as photovoltaic cell. It includes a liquid interface in the cell circuit, which allows the introduction of the sample (also in liquid phase) without disturbing the normal cell operation. Furthermore, it works well with rather low cost materials and requires mild and easy processing conditions. The cell will be equipped with plasmonic structures to enhance light absorption and cell efficiency.
The device under development will be easily operated by any clinician or patient. It will require ambient light and a regular multimeter. Eye detection will be also tried out.
Summary
This project presents a new concept for the detection, diagnosis and monitoring of cancer biomarker patterns in point-of-care. The device under development will make use of the selectivity of the plastic antibodies as sensing materials and the interference they will play on the normal operation of a photovoltaic cell.
Plastic antibodies will be designed by surface imprinting procedures. Self-assembled monolayer and molecular imprinting techniques will be merged in this process because they allow the self-assembly of nanostructured materials on a “bottom-up” nanofabrication approach. A dye-sensitized solar cell will be used as photovoltaic cell. It includes a liquid interface in the cell circuit, which allows the introduction of the sample (also in liquid phase) without disturbing the normal cell operation. Furthermore, it works well with rather low cost materials and requires mild and easy processing conditions. The cell will be equipped with plasmonic structures to enhance light absorption and cell efficiency.
The device under development will be easily operated by any clinician or patient. It will require ambient light and a regular multimeter. Eye detection will be also tried out.
Max ERC Funding
998 584 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym 4TH-NU-AVENUE
Project Search for a fourth neutrino with a PBq anti-neutrino source
Researcher (PI) Thierry Michel René Lasserre
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Starting Grant (StG), PE2, ERC-2012-StG_20111012
Summary Several observed anomalies in neutrino oscillation data can be explained by a hypothetical fourth neutrino separated from the three standard neutrinos by a squared mass difference of a few eV2. This hypothesis can be tested with a PBq (ten kilocurie scale) 144Ce antineutrino beta-source deployed at the center of a large low background liquid scintillator detector, such like Borexino, KamLAND, and SNO+. In particular, the compact size of such a source could yield an energy-dependent oscillating pattern in event spatial distribution that would unambiguously determine neutrino mass differences and mixing angles.
The proposed program aims to perform the necessary research and developments to produce and deploy an intense antineutrino source in a large liquid scintillator detector. Our program will address the definition of the production process of the neutrino source as well as its experimental characterization, the detailed physics simulation of both signal and backgrounds, the complete design and the realization of the thick shielding, the preparation of the interfaces with the antineutrino detector, including the safety and security aspects.
Summary
Several observed anomalies in neutrino oscillation data can be explained by a hypothetical fourth neutrino separated from the three standard neutrinos by a squared mass difference of a few eV2. This hypothesis can be tested with a PBq (ten kilocurie scale) 144Ce antineutrino beta-source deployed at the center of a large low background liquid scintillator detector, such like Borexino, KamLAND, and SNO+. In particular, the compact size of such a source could yield an energy-dependent oscillating pattern in event spatial distribution that would unambiguously determine neutrino mass differences and mixing angles.
The proposed program aims to perform the necessary research and developments to produce and deploy an intense antineutrino source in a large liquid scintillator detector. Our program will address the definition of the production process of the neutrino source as well as its experimental characterization, the detailed physics simulation of both signal and backgrounds, the complete design and the realization of the thick shielding, the preparation of the interfaces with the antineutrino detector, including the safety and security aspects.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym 7TReImHo
Project 7kDa TSLP as a novel type of anti-inflammatory agent to re-establish immune homeostasis
Researcher (PI) Maria RESCIGNO
Host Institution (HI) ISTITUTO EUROPEO DI ONCOLOGIA SRL
Call Details Proof of Concept (PoC), PC1, ERC-2012-PoC
Summary Intestinal homeostasis is a complex event that relies on different interactions between the host and the commensal flora, also called microbiota. The microbiota is a source of gene products that are required for several functions linked to digestion and energy harvest, thus it has to be tolerated, but at the same time controlled. We have shown that the capacity to tolerate the microbiota is linked to a close interaction between epithelial cells, that are the first line of defence against luminal microorganisms, and specialized immune cells called dendritic cells, that acquire a tolerogenic phenotype and drive the development of T regulatory cells, capable to control the development of inflammatory responses to bacteria. We have identified several effectors mediating this control and focused on a cytokine called thymic stromal lymphopoietin (TSLP) that is released constitutively by epithelial cells and is strongly downregulated in inflammatory bowel disease (IBD). By contrast, in other inflammatory disorders like allergy or asthma, TSLP has been shown to be upregulated and to mediate disease.
This apparent controversy is solved when considering that TSLP comes in two different isoforms: a short (sTSLP) and a long (lTSLP). sTSLP has been completely neglected in the literature as most of the reagents do not distinguish it from lTSLP. Within the ERC project Dendroworld, we have generated all the tools to study the function of these two isoforms. We discovered that in IBD there is an inverse correlation between sTSLP and lTSLP. lTSLP is drastically upregulated by recruited immune cells, while sTSLP is downregulated in epithelial cells. Hence, we hypothesized and confirmed that the two isoforms had different activities, with the sTSLP being anti-inflammatory and lTSLP being inflammatory.
In this POC we propose scientific and commercialization activities to bring sTSLP to the market as a new class of anti-inflammatory drugs capable of re-establishing immune homeostasis.
Summary
Intestinal homeostasis is a complex event that relies on different interactions between the host and the commensal flora, also called microbiota. The microbiota is a source of gene products that are required for several functions linked to digestion and energy harvest, thus it has to be tolerated, but at the same time controlled. We have shown that the capacity to tolerate the microbiota is linked to a close interaction between epithelial cells, that are the first line of defence against luminal microorganisms, and specialized immune cells called dendritic cells, that acquire a tolerogenic phenotype and drive the development of T regulatory cells, capable to control the development of inflammatory responses to bacteria. We have identified several effectors mediating this control and focused on a cytokine called thymic stromal lymphopoietin (TSLP) that is released constitutively by epithelial cells and is strongly downregulated in inflammatory bowel disease (IBD). By contrast, in other inflammatory disorders like allergy or asthma, TSLP has been shown to be upregulated and to mediate disease.
This apparent controversy is solved when considering that TSLP comes in two different isoforms: a short (sTSLP) and a long (lTSLP). sTSLP has been completely neglected in the literature as most of the reagents do not distinguish it from lTSLP. Within the ERC project Dendroworld, we have generated all the tools to study the function of these two isoforms. We discovered that in IBD there is an inverse correlation between sTSLP and lTSLP. lTSLP is drastically upregulated by recruited immune cells, while sTSLP is downregulated in epithelial cells. Hence, we hypothesized and confirmed that the two isoforms had different activities, with the sTSLP being anti-inflammatory and lTSLP being inflammatory.
In this POC we propose scientific and commercialization activities to bring sTSLP to the market as a new class of anti-inflammatory drugs capable of re-establishing immune homeostasis.
Max ERC Funding
146 917 €
Duration
Start date: 2013-07-01, End date: 2014-06-30
Project acronym A2F2
Project Beyond Biopolymers: Protein-Sized Aromatic Amide Functional Foldamers
Researcher (PI) Ivan Huc
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), PE5, ERC-2012-ADG_20120216
Summary Nature has evolved ultimate chemical functions based on controlling and altering conformation of its molecular machinery. Prominent examples include enzyme catalysis and information storage/duplication in nucleic acids. These achievements are based on large and complex yet remarkably defined structures obtained through folding of polymeric chains and a subtle interplay of non-covalent forces. Nature uses a limited set of building blocks – e.g. twenty amino-acids and four nucleobases – with specific abilities to impart well-defined folds. In the last decade, chemists have discovered foldamers: non-natural oligomers and polymers also prone to adopt folded structures. The emergence of foldamers has far reaching implications. A new major long term prospect is open to chemistry: the de novo synthesis of artificial objects resembling biopolymers in terms of their size, complexity, and efficiency at achieving defined functions, yet having chemical structures beyond the reach of biopolymers amenable to new properties and functions. The PI of this project has shown internationally recognized leadership in the development of a class of foldamers, aromatic oligoamides, whose features arguably make them the most suitable candidates to systematically explore what folded structures beyond biopolymers give access to. This project aims at developing methods to allow the routine fabrication of 20-40 units long aromatic oligoamide foldamers (6-15 kDa) designed to fold into artificial molecular containers having engineerable cavities and surfaces for molecular recognition of organic substrates, in particular large peptides and saccharides, polymers, and proteins. The methodology rests on modelling based design, multistep organic synthesis of heterocyclic monomers and their assembly into long sequences, structural elucidation using, among other techniques, x-ray crystallography, and the physico-chemical characterization of molecular recognition events.
Summary
Nature has evolved ultimate chemical functions based on controlling and altering conformation of its molecular machinery. Prominent examples include enzyme catalysis and information storage/duplication in nucleic acids. These achievements are based on large and complex yet remarkably defined structures obtained through folding of polymeric chains and a subtle interplay of non-covalent forces. Nature uses a limited set of building blocks – e.g. twenty amino-acids and four nucleobases – with specific abilities to impart well-defined folds. In the last decade, chemists have discovered foldamers: non-natural oligomers and polymers also prone to adopt folded structures. The emergence of foldamers has far reaching implications. A new major long term prospect is open to chemistry: the de novo synthesis of artificial objects resembling biopolymers in terms of their size, complexity, and efficiency at achieving defined functions, yet having chemical structures beyond the reach of biopolymers amenable to new properties and functions. The PI of this project has shown internationally recognized leadership in the development of a class of foldamers, aromatic oligoamides, whose features arguably make them the most suitable candidates to systematically explore what folded structures beyond biopolymers give access to. This project aims at developing methods to allow the routine fabrication of 20-40 units long aromatic oligoamide foldamers (6-15 kDa) designed to fold into artificial molecular containers having engineerable cavities and surfaces for molecular recognition of organic substrates, in particular large peptides and saccharides, polymers, and proteins. The methodology rests on modelling based design, multistep organic synthesis of heterocyclic monomers and their assembly into long sequences, structural elucidation using, among other techniques, x-ray crystallography, and the physico-chemical characterization of molecular recognition events.
Max ERC Funding
2 496 216 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
