Project acronym 4D-PET
Project Innovative PET scanner for dynamic imaging
Researcher (PI) José María BENLLOCH BAVIERA
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), LS7, ERC-2015-AdG
Summary The main objective of 4D-PET is to develop an innovative whole-body PET scanner based in a new detector concept that stores 3D position and time of every single gamma interaction with unprecedented resolution. The combination of scanner geometrical design and high timing resolution will enable developing a full sequence of all gamma-ray interactions inside the scanner, including Compton interactions, like in a 3D movie. 4D-PET fully exploits Time Of Flight (TOF) information to obtain a better image quality and to increase scanner sensitivity, through the inclusion in the image formation of all Compton events occurring inside the detector, which are always rejected in state-of-the-art PET scanners. The new PET design will radically improve state-of-the-art PET performance features, overcoming limitations of current PET technology and opening up new diagnostic venues and very valuable physiological information
Summary
The main objective of 4D-PET is to develop an innovative whole-body PET scanner based in a new detector concept that stores 3D position and time of every single gamma interaction with unprecedented resolution. The combination of scanner geometrical design and high timing resolution will enable developing a full sequence of all gamma-ray interactions inside the scanner, including Compton interactions, like in a 3D movie. 4D-PET fully exploits Time Of Flight (TOF) information to obtain a better image quality and to increase scanner sensitivity, through the inclusion in the image formation of all Compton events occurring inside the detector, which are always rejected in state-of-the-art PET scanners. The new PET design will radically improve state-of-the-art PET performance features, overcoming limitations of current PET technology and opening up new diagnostic venues and very valuable physiological information
Max ERC Funding
2 048 386 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym CATA-LUX
Project Light-Driven Asymmetric Organocatalysis
Researcher (PI) Paolo Melchiorre
Host Institution (HI) FUNDACIO PRIVADA INSTITUT CATALA D'INVESTIGACIO QUIMICA
Call Details Consolidator Grant (CoG), PE5, ERC-2015-CoG
Summary Visible light photocatalysis and metal-free organocatalytic processes are powerful strategies of modern chemical research with extraordinary potential for the sustainable preparation of organic molecules. However, these environmentally respectful approaches have to date remained largely unrelated. The proposed research seeks to merge these fields of molecule activation to redefine their synthetic potential.
Light-driven processes considerably enrich the modern synthetic repertoire, offering a potent way to build complex organic frameworks. In contrast, it is extremely challenging to develop asymmetric catalytic photoreactions that can create chiral molecules with a well-defined three-dimensional arrangement. By developing innovative methodologies to effectively address this issue, I will provide a novel reactivity framework for conceiving light-driven enantioselective organocatalytic processes.
I will translate the effective tools governing the success of ground state asymmetric organocatalysis into the realm of photochemical reactivity, exploiting the potential of key organocatalytic intermediates to directly participate in the photoexcitation of substrates. At the same time, the chiral organocatalyst will ensure effective stereochemical control. This single catalyst system, where stereoinduction and photoactivation merge in a sole organocatalyst, will serve for developing novel enantioselective photoreactions. In a complementary dual catalytic approach, the synergistic activities of an organocatalyst and a metal-free photosensitiser will combine to realise asymmetric variants of venerable photochemical processes, which have never before succumbed to a stereocontrolled approach.
This proposal challenges the current perception that photochemistry is too unselective to parallel the impressive levels of efficiency reached by the asymmetric catalysis of thermal reactions, expanding the way chemists think about making chiral molecules
Summary
Visible light photocatalysis and metal-free organocatalytic processes are powerful strategies of modern chemical research with extraordinary potential for the sustainable preparation of organic molecules. However, these environmentally respectful approaches have to date remained largely unrelated. The proposed research seeks to merge these fields of molecule activation to redefine their synthetic potential.
Light-driven processes considerably enrich the modern synthetic repertoire, offering a potent way to build complex organic frameworks. In contrast, it is extremely challenging to develop asymmetric catalytic photoreactions that can create chiral molecules with a well-defined three-dimensional arrangement. By developing innovative methodologies to effectively address this issue, I will provide a novel reactivity framework for conceiving light-driven enantioselective organocatalytic processes.
I will translate the effective tools governing the success of ground state asymmetric organocatalysis into the realm of photochemical reactivity, exploiting the potential of key organocatalytic intermediates to directly participate in the photoexcitation of substrates. At the same time, the chiral organocatalyst will ensure effective stereochemical control. This single catalyst system, where stereoinduction and photoactivation merge in a sole organocatalyst, will serve for developing novel enantioselective photoreactions. In a complementary dual catalytic approach, the synergistic activities of an organocatalyst and a metal-free photosensitiser will combine to realise asymmetric variants of venerable photochemical processes, which have never before succumbed to a stereocontrolled approach.
This proposal challenges the current perception that photochemistry is too unselective to parallel the impressive levels of efficiency reached by the asymmetric catalysis of thermal reactions, expanding the way chemists think about making chiral molecules
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym DYNAP
Project Dynamic Penetrating Peptide Adaptamers
Researcher (PI) Javier Montenegro Garcia
Host Institution (HI) UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary The aim of this proposal is to identify, at the molecular level, the minimal topological and structural motifs that govern the membrane translocation of short peptides. A covalent reversible bond strategy will be developed for the synthesis of self-adaptive penetrating peptides (adaptamers) for targeted delivery.
It is known that the recently developed therapeutic technologies (i.e. gene therapy, chemotherapy, hyperthermia, etc.) cannot reach their expected potential due to limitations in the current delivery strategies, which hinder the efficient targeting of the appropriate tissues, cells and organelles. Despite the enormous therapeutic potential of short penetrating peptides, these molecules suffer from drawbacks such as toxicity, instability to protease digestion and lack of specificity.
Dynamic covalent chemistry has significant synthetic advantages. In the proposed research, peptide scaffolds with clickable reversible groups (e.g. hydrazide) will be conjugated with collections of aldehydes to afford self-adaptive biomimetic transporters, whose secondary structure and penetrating properties will be systematically characterized by biophysical, cell-biology and pattern recognition techniques.
The versatility of dynamic supramolecular “peptide adaptamers” with precisely positioned protein ligands will be explored for multivalent specific recognition, protein transport, cell targeting of drugs and probes and membrane epitoping.
Additionally, we propose to synthesise dynamic and environmentally sensitive fluorescent probes for biocompatible membrane labelling and uptake signalling.
The resulting discoveries of this research will allow the formulation of novel transfecting reagents for gene therapy, selective platforms for drug-delivery and the development of dynamic fluorescent membrane probes. The potential results of this proposal will shake the fields of drug-delivery and non-viral gene transfection and will resolve the limitations of the current approaches.
Summary
The aim of this proposal is to identify, at the molecular level, the minimal topological and structural motifs that govern the membrane translocation of short peptides. A covalent reversible bond strategy will be developed for the synthesis of self-adaptive penetrating peptides (adaptamers) for targeted delivery.
It is known that the recently developed therapeutic technologies (i.e. gene therapy, chemotherapy, hyperthermia, etc.) cannot reach their expected potential due to limitations in the current delivery strategies, which hinder the efficient targeting of the appropriate tissues, cells and organelles. Despite the enormous therapeutic potential of short penetrating peptides, these molecules suffer from drawbacks such as toxicity, instability to protease digestion and lack of specificity.
Dynamic covalent chemistry has significant synthetic advantages. In the proposed research, peptide scaffolds with clickable reversible groups (e.g. hydrazide) will be conjugated with collections of aldehydes to afford self-adaptive biomimetic transporters, whose secondary structure and penetrating properties will be systematically characterized by biophysical, cell-biology and pattern recognition techniques.
The versatility of dynamic supramolecular “peptide adaptamers” with precisely positioned protein ligands will be explored for multivalent specific recognition, protein transport, cell targeting of drugs and probes and membrane epitoping.
Additionally, we propose to synthesise dynamic and environmentally sensitive fluorescent probes for biocompatible membrane labelling and uptake signalling.
The resulting discoveries of this research will allow the formulation of novel transfecting reagents for gene therapy, selective platforms for drug-delivery and the development of dynamic fluorescent membrane probes. The potential results of this proposal will shake the fields of drug-delivery and non-viral gene transfection and will resolve the limitations of the current approaches.
Max ERC Funding
1 492 525 €
Duration
Start date: 2016-02-01, End date: 2021-01-31
Project acronym FAT NKT
Project Targeting iNKT cell and adipocyte crosstalk for control of metabolism and body weight
Researcher (PI) Lydia Lynch
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Starting Grant (StG), LS6, ERC-2015-STG
Summary Obesity has reached epidemic proportions globally. At least 2.8 million people die each year as a result of being overweight or obese, the biggest burden being obesity-related diseases. It is now clear that inflammation is an underlying cause or contributor to many of these diseases, including type 2 diabetes, atherosclerosis, and cancer. Recognition that the immune system can regulate metabolic pathways has prompted a new way of thinking about diabetes and weight management. Despite much recent progress, most immunometabolic pathways, and how to target them, are currently unknown. One such pathway is the cross-talk between invariant natural killer (iNKT) cells and neighboring adipocytes. iNKT cells are the innate lipid-sensing arm of the immune system. Since our discovery that mammalian adipose tissue is enriched for iNKT cells, we have identified a critical role for iNKT cells in regulating adipose inflammation and body weight. The goal of this project is to use a multi-disciplinary approach to identify key signals and molecules used by iNKT cells to induce metabolic control and weight loss in obesity. Using immunological assays and multi-photon intravital microscopy, cells and pathways that control the unique regulatory functions of adipose iNKT cells will be identified and characterised. Novel lipid antigens in adipose tissue will be identified using a biochemical approach, perhaps explaining iNKT cell conservation in adipose depots, and providing safe tools for iNKT cell manipulation in vivo. Finally, using proteomics and whole body metabolic analysis in vivo, novel ‘weight-loss inducing’ factors produced by adipose iNKT cells will be identified. This ambitious and high impact project has the potential to yield major insights into immunometabolic interactions at steady state and in obesity. The ability to activate or induce adipose iNKT cells holds remarkable potential as an entirely new therapeutic direction for treating obesity and type 2 diabetes.
Summary
Obesity has reached epidemic proportions globally. At least 2.8 million people die each year as a result of being overweight or obese, the biggest burden being obesity-related diseases. It is now clear that inflammation is an underlying cause or contributor to many of these diseases, including type 2 diabetes, atherosclerosis, and cancer. Recognition that the immune system can regulate metabolic pathways has prompted a new way of thinking about diabetes and weight management. Despite much recent progress, most immunometabolic pathways, and how to target them, are currently unknown. One such pathway is the cross-talk between invariant natural killer (iNKT) cells and neighboring adipocytes. iNKT cells are the innate lipid-sensing arm of the immune system. Since our discovery that mammalian adipose tissue is enriched for iNKT cells, we have identified a critical role for iNKT cells in regulating adipose inflammation and body weight. The goal of this project is to use a multi-disciplinary approach to identify key signals and molecules used by iNKT cells to induce metabolic control and weight loss in obesity. Using immunological assays and multi-photon intravital microscopy, cells and pathways that control the unique regulatory functions of adipose iNKT cells will be identified and characterised. Novel lipid antigens in adipose tissue will be identified using a biochemical approach, perhaps explaining iNKT cell conservation in adipose depots, and providing safe tools for iNKT cell manipulation in vivo. Finally, using proteomics and whole body metabolic analysis in vivo, novel ‘weight-loss inducing’ factors produced by adipose iNKT cells will be identified. This ambitious and high impact project has the potential to yield major insights into immunometabolic interactions at steady state and in obesity. The ability to activate or induce adipose iNKT cells holds remarkable potential as an entirely new therapeutic direction for treating obesity and type 2 diabetes.
Max ERC Funding
1 804 052 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym FUTURE-PRINT
Project Tuneable 2D Nanosheet Networks for Printed Electronics
Researcher (PI) Jonathan Nesbitt COLEMAN
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Advanced Grant (AdG), PE5, ERC-2015-AdG
Summary In the future, even the most mundane objects will contain electronic circuitry allowing them to gather, process, display and transmit information. The resulting vast network, often called the Internet of Things, will revolutionise society. To realise this will require the ability to produce electronic circuitry extremely cheaply, often on unconventional substrates. This will be achieved through printed electronics, by the assembly of devices from solution (i.e. ink) using methods adapted from printing technology. However, while printed electronics has been advancing rapidly, the development of new, nano-materials-based inks is required for this area to meet its true potential.
We believe recent developments in liquid exfoliation of 2D nanosheets have given us the ideal family of materials to revolutionise electronic ink production. Liquid exfoliation can transform layered crystals into suspensions of nanosheets in very large quantities. In this way we can produce liquid-dispersed nanosheets of a wide range of types including conducting (e.g. graphene, MXenes, TiB2 etc), semiconducting (e.g. MoS2, WSe2, GaS, Black phosphorous etc), insulating (e.g. BN, talc) or electrochemically active (e.g. MoO3, Ni(OH)2, MnO2 etc). These nanosheets can be deposited from liquid to form porous networks of defined electronic type. While these networks have huge applications potential, a large amount of work must be done to translate them into working printed devices.
In this project, we will develop methods to transform large volume suspensions of exfoliated nanosheets into bespoke 2D inks with properties engineered for a range of specific printed device applications. We will learn to use this 2D ink to print patterned or large area 2D nanosheet networks with controlled structure, allowing us to tune the electrical properties of the network during printing. We will combine networks of different nanosheet types into complex heterostructures. This will allow us to print all device components (electrodes, active layers, dielectrics, energy storage layers) from one contiguous, multi-component network. In this way we will produce 2D network transistors, solar cells, displays and energy storage systems. FUTURE-PRINT will revolutionise electronic inks and will offer a new path forward for printed electronics.
Summary
In the future, even the most mundane objects will contain electronic circuitry allowing them to gather, process, display and transmit information. The resulting vast network, often called the Internet of Things, will revolutionise society. To realise this will require the ability to produce electronic circuitry extremely cheaply, often on unconventional substrates. This will be achieved through printed electronics, by the assembly of devices from solution (i.e. ink) using methods adapted from printing technology. However, while printed electronics has been advancing rapidly, the development of new, nano-materials-based inks is required for this area to meet its true potential.
We believe recent developments in liquid exfoliation of 2D nanosheets have given us the ideal family of materials to revolutionise electronic ink production. Liquid exfoliation can transform layered crystals into suspensions of nanosheets in very large quantities. In this way we can produce liquid-dispersed nanosheets of a wide range of types including conducting (e.g. graphene, MXenes, TiB2 etc), semiconducting (e.g. MoS2, WSe2, GaS, Black phosphorous etc), insulating (e.g. BN, talc) or electrochemically active (e.g. MoO3, Ni(OH)2, MnO2 etc). These nanosheets can be deposited from liquid to form porous networks of defined electronic type. While these networks have huge applications potential, a large amount of work must be done to translate them into working printed devices.
In this project, we will develop methods to transform large volume suspensions of exfoliated nanosheets into bespoke 2D inks with properties engineered for a range of specific printed device applications. We will learn to use this 2D ink to print patterned or large area 2D nanosheet networks with controlled structure, allowing us to tune the electrical properties of the network during printing. We will combine networks of different nanosheet types into complex heterostructures. This will allow us to print all device components (electrodes, active layers, dielectrics, energy storage layers) from one contiguous, multi-component network. In this way we will produce 2D network transistors, solar cells, displays and energy storage systems. FUTURE-PRINT will revolutionise electronic inks and will offer a new path forward for printed electronics.
Max ERC Funding
2 213 317 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym HurdlingOxoWall
Project Late First-Row Transition Metal-Oxo Complexes for C–H Bond Activation
Researcher (PI) Aidan McDonald
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary The chemical, pharmaceutical, and materials industries rely heavily upon chemicals from oil and natural gas feed-stocks (saturated hydrocarbons) that require considerable functionalisation prior to use. Catalytic oxidative functionalisation (e.g. CH4 + [O] + cat. → CH3OH), using first row transition metal catalysts, is potentially a sustainable, cheap, and green route to these high-commodity chemicals. However, catalytic oxidation remains a great modern challenge because such hydrocarbons contain remarkably strong inert C–H bonds that can only be activated with potent catalysts. We will take a Nature-inspired approach to designing and preparing powerful oxidation catalysts: we will interrogate the active oxidant, a metal-oxo (M=O) species, to guide our catalyst design. Specifically, we will prepare unprecedented Late first-row transition Metal-Oxo complexes (LM=O’s, LM = Co, Ni, Cu) that will activate the strongest of C–H bonds (e.g. CH4).
This will be accomplished using a family of novel low coordinate ligands that will support LM=O’s. Due to their expected potent reactivity we will prepare LM=O’s under unique oxidatively robust, low-temperature conditions to ensure their stabilisation. The poorly understood factors (thermodynamics, metal, d-electron count) that control the reactivity of M=O’s will be thoroughly investigated. Based on these investigations LM=O reactivity will be manipulated and optimised. We expect LM=O’s will be significantly more reactive than any early transition metal-oxo’s (EM=O’s), because they will display a greater thermodynamic driving force for C–H activation. It is thus expected that LM=O’s will be capable of the activation of the strongest of C–H bonds (i.e. CH4). Driven by the knowledge acquired from these investigations, we will design and prepare the next generation of molecular oxidation catalysts - a family of late first-row transition metal compounds capable of catalysing hydrocarbon functionalisation under ambient conditions.
Summary
The chemical, pharmaceutical, and materials industries rely heavily upon chemicals from oil and natural gas feed-stocks (saturated hydrocarbons) that require considerable functionalisation prior to use. Catalytic oxidative functionalisation (e.g. CH4 + [O] + cat. → CH3OH), using first row transition metal catalysts, is potentially a sustainable, cheap, and green route to these high-commodity chemicals. However, catalytic oxidation remains a great modern challenge because such hydrocarbons contain remarkably strong inert C–H bonds that can only be activated with potent catalysts. We will take a Nature-inspired approach to designing and preparing powerful oxidation catalysts: we will interrogate the active oxidant, a metal-oxo (M=O) species, to guide our catalyst design. Specifically, we will prepare unprecedented Late first-row transition Metal-Oxo complexes (LM=O’s, LM = Co, Ni, Cu) that will activate the strongest of C–H bonds (e.g. CH4).
This will be accomplished using a family of novel low coordinate ligands that will support LM=O’s. Due to their expected potent reactivity we will prepare LM=O’s under unique oxidatively robust, low-temperature conditions to ensure their stabilisation. The poorly understood factors (thermodynamics, metal, d-electron count) that control the reactivity of M=O’s will be thoroughly investigated. Based on these investigations LM=O reactivity will be manipulated and optimised. We expect LM=O’s will be significantly more reactive than any early transition metal-oxo’s (EM=O’s), because they will display a greater thermodynamic driving force for C–H activation. It is thus expected that LM=O’s will be capable of the activation of the strongest of C–H bonds (i.e. CH4). Driven by the knowledge acquired from these investigations, we will design and prepare the next generation of molecular oxidation catalysts - a family of late first-row transition metal compounds capable of catalysing hydrocarbon functionalisation under ambient conditions.
Max ERC Funding
1 499 865 €
Duration
Start date: 2016-03-01, End date: 2021-02-28
Project acronym IDRICA
Project Improving Drought Resistance in Crops and Arabidopsis
Researcher (PI) Ana Isabel Caño Delgado
Host Institution (HI) CENTRE DE RECERCA EN AGRIGENOMICA CSIC-IRTA-UAB-UB
Call Details Consolidator Grant (CoG), LS9, ERC-2015-CoG
Summary Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.
Summary
Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym MYELOMANEXT
Project Integrated next-generation flow cytometry and sequencing to uncover the pathway of curability in multiple myeloma
Researcher (PI) Bruno David Lourenço Paiva
Host Institution (HI) UNIVERSIDAD DE NAVARRA
Call Details Starting Grant (StG), LS7, ERC-2015-STG
Summary Multiple myeloma (MM) represents a unique model to investigate cancer stem cells (CSCs), circulating tumour cells (CTCs), and the mechanisms of malignant transformation and chemoresistance. Despite the substantial improvement in MM patients’ outcome, the vast majority of patients eventually relapse and the disease remains largely incurable. For those patients failing to achieve deep remissions, biologically targeted research on the ultra-chemoresistant minimal residual disease (MRD) clone may allow us to understand the cellular mechanisms driving chemoresistance, and design novel therapeutic to overcome; importantly, such effort should be equally performed on two additional key players: CSCs and CTCs. On the opposite side, it is unquestionable that a selected group of patients does experience long-term survival irrespectively of the depth of response achieved, but we fail to understand the mechanisms driving sustained disease control. Is it because of persistent residual benign clones? Is it because of immune surveillance? Here, we will integrate next-generation flow cytometry and sequencing to define i) the signature of CTCs and ultra-chemoresistant MRD cells, ii) the hierarchical place of putative CSCs, iii) the genomic landscape of benign vs. malignant clones; and iv) the role of immune surveillance to achieve functional cures. Hence, we will characterize for the first-time-ever the highly-professional subclones responsible for malignant transformation, disease dissemination, and dramatic relapses after optimal response to therapy. Noteworthy, the innovative approach of this scientific proposal strongly relies on the use and expertise of highly-sensitive next-generation flow cytometry, coupled with optimized DNA- and RNA-sequencing for low-cell-numbers, and prospective patient samples longitudinally available within the scope of well-controlled clinical trials. Herein, we believe that all requirements are met to conduct this ground-breaking research program.
Summary
Multiple myeloma (MM) represents a unique model to investigate cancer stem cells (CSCs), circulating tumour cells (CTCs), and the mechanisms of malignant transformation and chemoresistance. Despite the substantial improvement in MM patients’ outcome, the vast majority of patients eventually relapse and the disease remains largely incurable. For those patients failing to achieve deep remissions, biologically targeted research on the ultra-chemoresistant minimal residual disease (MRD) clone may allow us to understand the cellular mechanisms driving chemoresistance, and design novel therapeutic to overcome; importantly, such effort should be equally performed on two additional key players: CSCs and CTCs. On the opposite side, it is unquestionable that a selected group of patients does experience long-term survival irrespectively of the depth of response achieved, but we fail to understand the mechanisms driving sustained disease control. Is it because of persistent residual benign clones? Is it because of immune surveillance? Here, we will integrate next-generation flow cytometry and sequencing to define i) the signature of CTCs and ultra-chemoresistant MRD cells, ii) the hierarchical place of putative CSCs, iii) the genomic landscape of benign vs. malignant clones; and iv) the role of immune surveillance to achieve functional cures. Hence, we will characterize for the first-time-ever the highly-professional subclones responsible for malignant transformation, disease dissemination, and dramatic relapses after optimal response to therapy. Noteworthy, the innovative approach of this scientific proposal strongly relies on the use and expertise of highly-sensitive next-generation flow cytometry, coupled with optimized DNA- and RNA-sequencing for low-cell-numbers, and prospective patient samples longitudinally available within the scope of well-controlled clinical trials. Herein, we believe that all requirements are met to conduct this ground-breaking research program.
Max ERC Funding
1 468 606 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym NANOCOMP
Project Complex Dynamics of Clusters in High-Aspect Ratio Hollow Nanostructures:A Nanoscale Platform for High-Performance Computing
Researcher (PI) Maria del Carmen Gimenez Lopez
Host Institution (HI) UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary Practical aspects and understanding of frontier-computing concepts such as memcomputing (a brain-inspired computational paradigm), quantum computing and spintronics are hindered because of the lack of suitable nanostructured materials. The NANOCOMP project aims to develop a technology for the integration of nano-switches within the confined space of high-aspect ratio hollow carbon nanostructures, yielding a totally new class of hybrid metal-carbon nanomaterials with different dimensionality as model systems enabling the realisation of these computing schemes. This research will also pave the way for developing new energy-storage concepts. The main objectives are: 1) To develop protocols for successful transport and encapsulation of intact nano-switches within tubular carbon nanostructures (TCN); 2) To understand and control the effects of the confined nano-switches on the carbon nanocontainer (and vice versa); 3) To unravel and develop new methodologies for exploiting the functional properties of the confined nano-switches; 4) To fabricate nanodevices, novel 2D ordered arrays and highly-porous 3D networks for a variety of applications ranging from quantum processors to flexible spintronic devices and supercapacitors.
Summary
Practical aspects and understanding of frontier-computing concepts such as memcomputing (a brain-inspired computational paradigm), quantum computing and spintronics are hindered because of the lack of suitable nanostructured materials. The NANOCOMP project aims to develop a technology for the integration of nano-switches within the confined space of high-aspect ratio hollow carbon nanostructures, yielding a totally new class of hybrid metal-carbon nanomaterials with different dimensionality as model systems enabling the realisation of these computing schemes. This research will also pave the way for developing new energy-storage concepts. The main objectives are: 1) To develop protocols for successful transport and encapsulation of intact nano-switches within tubular carbon nanostructures (TCN); 2) To understand and control the effects of the confined nano-switches on the carbon nanocontainer (and vice versa); 3) To unravel and develop new methodologies for exploiting the functional properties of the confined nano-switches; 4) To fabricate nanodevices, novel 2D ordered arrays and highly-porous 3D networks for a variety of applications ranging from quantum processors to flexible spintronic devices and supercapacitors.
Max ERC Funding
1 689 554 €
Duration
Start date: 2016-04-01, End date: 2022-01-31
Project acronym NANOGRAPHOUT
Project Design, synthesis, study and applications of distorted nanographenes
Researcher (PI) María Araceli González Campaña
Host Institution (HI) UNIVERSIDAD DE GRANADA
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary Graphene is considered a very promising material. Perfect samples of graphene without structural defects are extremely electrical and thermal conductive. However, defects usually appear during the production of graphene, modifying its thermal, electrical and mechanical properties. If we understand the influence of imperfections on the properties of graphene, we may tune its local electrical properties by controlling the presence of defects, leading to new organic semiconductor materials. We aim to embed seven- and higher membered rings into an otherwise planar NANOGRAPHene lattice as a new tool for the preparation of innovative materials for organic electronics. These defects would induce a curvature in the planar sheet distorting the structure OUT of the plane. NANOGRAPHOUT focuses on providing a general synthetic method for the construction of a variety of distorted nanographenes with good control on size, shape and the edges of the final compounds. Key synthetic steps include alkyne cyclotrimerization and cyclodehydrogenation reactions. By evaluating the morphology, optical and electronic properties and electron transport of synthesized nanographenes, we aim to establish the first comprehensive study clarifying the influence of defects on the properties of nanographenes. We will test electrical transport properties of selected compounds in organic thin-film field-effect transistors (OTFTs) laying the foundation for using distorted nanographenes as organic semiconductors based on pi-pi interactions. With the same bottom-up approach based on organic synthesis we intend to present nanographenes with helical chirality. Adding chiroptical response to the semiconductor properties of nanographenes will provide the new devices the added value of their potential application in photonics. As proof-of-concept, we plan to implement helically chiral distorted nanographenes as active layer in OTFTs and evaluate their use as elliptically polarized light emitters and detectors.
Summary
Graphene is considered a very promising material. Perfect samples of graphene without structural defects are extremely electrical and thermal conductive. However, defects usually appear during the production of graphene, modifying its thermal, electrical and mechanical properties. If we understand the influence of imperfections on the properties of graphene, we may tune its local electrical properties by controlling the presence of defects, leading to new organic semiconductor materials. We aim to embed seven- and higher membered rings into an otherwise planar NANOGRAPHene lattice as a new tool for the preparation of innovative materials for organic electronics. These defects would induce a curvature in the planar sheet distorting the structure OUT of the plane. NANOGRAPHOUT focuses on providing a general synthetic method for the construction of a variety of distorted nanographenes with good control on size, shape and the edges of the final compounds. Key synthetic steps include alkyne cyclotrimerization and cyclodehydrogenation reactions. By evaluating the morphology, optical and electronic properties and electron transport of synthesized nanographenes, we aim to establish the first comprehensive study clarifying the influence of defects on the properties of nanographenes. We will test electrical transport properties of selected compounds in organic thin-film field-effect transistors (OTFTs) laying the foundation for using distorted nanographenes as organic semiconductors based on pi-pi interactions. With the same bottom-up approach based on organic synthesis we intend to present nanographenes with helical chirality. Adding chiroptical response to the semiconductor properties of nanographenes will provide the new devices the added value of their potential application in photonics. As proof-of-concept, we plan to implement helically chiral distorted nanographenes as active layer in OTFTs and evaluate their use as elliptically polarized light emitters and detectors.
Max ERC Funding
1 492 675 €
Duration
Start date: 2016-04-01, End date: 2021-03-31
