Project acronym ANTILEAK
Project Development of antagonists of vascular leakage
Researcher (PI) Pipsa SAHARINEN
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Consolidator Grant (CoG), LS4, ERC-2017-COG
Summary Dysregulation of capillary permeability is a severe problem in critically ill patients, but the mechanisms involved are poorly understood. Further, there are no targeted therapies to stabilize leaky vessels in various common, potentially fatal diseases, such as systemic inflammation and sepsis, which affect millions of people annually. Although a multitude of signals that stimulate opening of endothelial cell-cell junctions leading to permeability have been characterized using cellular and in vivo models, approaches to reverse the harmful process of capillary leakage in disease conditions are yet to be identified. I propose to explore a novel autocrine endothelial permeability regulatory system as a potentially universal mechanism that antagonizes vascular stabilizing ques and sustains vascular leakage in inflammation. My group has identified inflammation-induced mechanisms that switch vascular stabilizing factors into molecules that destabilize vascular barriers, and identified tools to prevent the barrier disruption. Building on these discoveries, my group will use mouse genetics, structural biology and innovative, systematic antibody development coupled with gene editing and gene silencing technology, in order to elucidate mechanisms of vascular barrier breakdown and repair in systemic inflammation. The expected outcomes include insights into endothelial cell signaling and permeability regulation, and preclinical proof-of-concept antibodies to control endothelial activation and vascular leakage in systemic inflammation and sepsis models. Ultimately, the new knowledge and preclinical tools developed in this project may facilitate future development of targeted approaches against vascular leakage.
Summary
Dysregulation of capillary permeability is a severe problem in critically ill patients, but the mechanisms involved are poorly understood. Further, there are no targeted therapies to stabilize leaky vessels in various common, potentially fatal diseases, such as systemic inflammation and sepsis, which affect millions of people annually. Although a multitude of signals that stimulate opening of endothelial cell-cell junctions leading to permeability have been characterized using cellular and in vivo models, approaches to reverse the harmful process of capillary leakage in disease conditions are yet to be identified. I propose to explore a novel autocrine endothelial permeability regulatory system as a potentially universal mechanism that antagonizes vascular stabilizing ques and sustains vascular leakage in inflammation. My group has identified inflammation-induced mechanisms that switch vascular stabilizing factors into molecules that destabilize vascular barriers, and identified tools to prevent the barrier disruption. Building on these discoveries, my group will use mouse genetics, structural biology and innovative, systematic antibody development coupled with gene editing and gene silencing technology, in order to elucidate mechanisms of vascular barrier breakdown and repair in systemic inflammation. The expected outcomes include insights into endothelial cell signaling and permeability regulation, and preclinical proof-of-concept antibodies to control endothelial activation and vascular leakage in systemic inflammation and sepsis models. Ultimately, the new knowledge and preclinical tools developed in this project may facilitate future development of targeted approaches against vascular leakage.
Max ERC Funding
1 999 770 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym BHIVE
Project Bio-derived HIgh Value polymers through novel Enzyme function
Researcher (PI) Emma Rusi Master
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Consolidator Grant (CoG), LS9, ERC-2014-CoG
Summary Recent advances in systems-level study of cells and organisms have revealed the enormous potential to live more sustainably through better use of biological processes. Plants sustainably synthesize the most abundant and diverse materials on Earth. By applying recent advances in life science technology, we can better harness renewable plant resources and bioconversion processes, to develop environmentally and politically sustainable human enterprise and lifestyles. At the same time, the global market for high-value biochemicals and bioplastics from forest and agricultural sources is rapidly increasing, which presents new opportunities for forest and agricultural sectors.
The overall aim of BHIVE is to illuminate uncharted regions of genome and metagenome sequences to discover entirely new protein families that can be used to sustainably synthesize novel, high-value biomaterials from renewable plant resources. The approach will include three parallel research thrusts: 1) strategic analysis of transcriptome and metagenome sequences to identify proteins with entirely unknown function relevant to biomass (lignocellulose) transformation, 2) mapping of uncharted regions within phylogenetic trees of poorly characterized enzyme families with recognized potential to modify the chemistry and biophysical properties of plant polysaccharides, and 3) the design and development of novel enzyme screens to directly address the increasing limitations of existing assays to uncover entirely new protein functions. BHIVE will be unique in its undivided focus on characterizing lignocellulose-active proteins encoded by the 30-40% of un-annotated sequence, or genomic “dark matter”, typical of nearly all genome sequences. In this way, BHIVE tackles a key constraint to fully realizing the societal and environmental benefits of the genomics era.
Summary
Recent advances in systems-level study of cells and organisms have revealed the enormous potential to live more sustainably through better use of biological processes. Plants sustainably synthesize the most abundant and diverse materials on Earth. By applying recent advances in life science technology, we can better harness renewable plant resources and bioconversion processes, to develop environmentally and politically sustainable human enterprise and lifestyles. At the same time, the global market for high-value biochemicals and bioplastics from forest and agricultural sources is rapidly increasing, which presents new opportunities for forest and agricultural sectors.
The overall aim of BHIVE is to illuminate uncharted regions of genome and metagenome sequences to discover entirely new protein families that can be used to sustainably synthesize novel, high-value biomaterials from renewable plant resources. The approach will include three parallel research thrusts: 1) strategic analysis of transcriptome and metagenome sequences to identify proteins with entirely unknown function relevant to biomass (lignocellulose) transformation, 2) mapping of uncharted regions within phylogenetic trees of poorly characterized enzyme families with recognized potential to modify the chemistry and biophysical properties of plant polysaccharides, and 3) the design and development of novel enzyme screens to directly address the increasing limitations of existing assays to uncover entirely new protein functions. BHIVE will be unique in its undivided focus on characterizing lignocellulose-active proteins encoded by the 30-40% of un-annotated sequence, or genomic “dark matter”, typical of nearly all genome sequences. In this way, BHIVE tackles a key constraint to fully realizing the societal and environmental benefits of the genomics era.
Max ERC Funding
1 977 781 €
Duration
Start date: 2015-09-01, End date: 2020-12-31
Project acronym CapTherPV
Project Integration of Capacitor, Thermoelectric and PhotoVoltaic thin films for efficient energy conversion and storage
Researcher (PI) Isabel Maria Das Merces Ferreira
Host Institution (HI) NOVA ID FCT - ASSOCIACAO PARA A INOVACAO E DESENVOLVIMENTO DA FCT
Country Portugal
Call Details Consolidator Grant (CoG), PE8, ERC-2014-CoG
Summary The possibility of having a unique device that converts thermal and photonics energy into electrical energy and simultaneously stores it, is something dreamed by the PI since the beginning of her research career. To achieve that goal, this project aims to gather, in a single substrate, solar cells with up-conversion nanoparticles, thermoelectrics and graphene super-capacitor, all made of thin films. These three main components will be developed separately and integrated sequentially. The innovation proposed is not limited to the integration of components, but rely in ground-breaking concepts: 1) thermoelectric elements based on thin film (TE-TF) oxides; 2) plasmonic nanoparticles for up conversion of near infrared radiation to visible emission in solar cells; 3) graphene super-capacitors; 4) integration and optimization of all components in a single CapTherPV device. This ambitious project will bring new insights at large area, low cost and flexible energy harvesting and comes from an old idea of combining energy conversion and storage that has been pursued by the PI. She started her career in amorphous silicon thin film solar cells, later she started the development of thin film batteries and more recently started a research line in thermoelectric films. If approved, this project will give financial support to consolidate the research being carried out and will give independence to the PI in terms of resources and creative think. More importantly, will facilitate the concretization of the dream that has been pursued with hard work.
Summary
The possibility of having a unique device that converts thermal and photonics energy into electrical energy and simultaneously stores it, is something dreamed by the PI since the beginning of her research career. To achieve that goal, this project aims to gather, in a single substrate, solar cells with up-conversion nanoparticles, thermoelectrics and graphene super-capacitor, all made of thin films. These three main components will be developed separately and integrated sequentially. The innovation proposed is not limited to the integration of components, but rely in ground-breaking concepts: 1) thermoelectric elements based on thin film (TE-TF) oxides; 2) plasmonic nanoparticles for up conversion of near infrared radiation to visible emission in solar cells; 3) graphene super-capacitors; 4) integration and optimization of all components in a single CapTherPV device. This ambitious project will bring new insights at large area, low cost and flexible energy harvesting and comes from an old idea of combining energy conversion and storage that has been pursued by the PI. She started her career in amorphous silicon thin film solar cells, later she started the development of thin film batteries and more recently started a research line in thermoelectric films. If approved, this project will give financial support to consolidate the research being carried out and will give independence to the PI in terms of resources and creative think. More importantly, will facilitate the concretization of the dream that has been pursued with hard work.
Max ERC Funding
1 999 375 €
Duration
Start date: 2015-07-01, End date: 2021-09-30
Project acronym CATCH
Project Cross-dimensional Activation of Two-Dimensional Semiconductors for Photocatalytic Heterojunctions
Researcher (PI) Wei CAO
Host Institution (HI) OULUN YLIOPISTO
Country Finland
Call Details Consolidator Grant (CoG), PE8, ERC-2020-COG
Summary Spacetime defines existence and evolution of materials. A key path to human’s sustainability through materials innovation can hardly circumvent materials dimensionalities. Despite numerous studies in electrically distinct 2D semiconductors, the route to engage them in high-performance photocatalysts remains elusive. Herein, CATCH proposes a cross-dimensional activation strategy of 2D semiconductors to implement practical photocatalysis. It operates electronic structures of dimensionally paradoxical 2D semiconductors and spatially limited nD (n=0-2) guests, directs charge migration processes, mass-produces advanced catalysts and elucidates time-evolved catalysis. Synergic impacts crossing 2D-nD will lead to > 95%/hour rates for pollutant removal and >20% quantum efficiencies for H2 evolution under visible light. CATCH enumerates chemical coordination and writes reaction equations with sub-nanosecond precision.
CATCH employs density functional theory optimization and data mining prediction to select most probable heterojunctional peers from hetero/homo- dimensions. Through facile but efficient wet and dry synthesis, nanostructures will be bonded to basal planes or brinks of 2D slabs. CATCH benefits in-house techniques for product characterizations and refinements and emphasizes on cutting-edge in situ studies to unveil photocatalysis at advanced photon sources. Assisted with theoretical modelling, ambient and time-evolved experiments will illustrate photocatalytic dynamics and kinetics in mixed spacetime.
CATCH unites low-dimensional materials designs by counting physical and electronic merits from spacetime confinements. It metrologically elaborates photocatalysis in an elevated 2D+nD+t, alters passages of materials combinations crossing dimensions, and directs future photocatalyst designs. Standing on cross-dimensional materials innovation and photocatalysis study, CATCH breaks the deadlock of practical photocatalysis that eventually leads to sustainability.
Summary
Spacetime defines existence and evolution of materials. A key path to human’s sustainability through materials innovation can hardly circumvent materials dimensionalities. Despite numerous studies in electrically distinct 2D semiconductors, the route to engage them in high-performance photocatalysts remains elusive. Herein, CATCH proposes a cross-dimensional activation strategy of 2D semiconductors to implement practical photocatalysis. It operates electronic structures of dimensionally paradoxical 2D semiconductors and spatially limited nD (n=0-2) guests, directs charge migration processes, mass-produces advanced catalysts and elucidates time-evolved catalysis. Synergic impacts crossing 2D-nD will lead to > 95%/hour rates for pollutant removal and >20% quantum efficiencies for H2 evolution under visible light. CATCH enumerates chemical coordination and writes reaction equations with sub-nanosecond precision.
CATCH employs density functional theory optimization and data mining prediction to select most probable heterojunctional peers from hetero/homo- dimensions. Through facile but efficient wet and dry synthesis, nanostructures will be bonded to basal planes or brinks of 2D slabs. CATCH benefits in-house techniques for product characterizations and refinements and emphasizes on cutting-edge in situ studies to unveil photocatalysis at advanced photon sources. Assisted with theoretical modelling, ambient and time-evolved experiments will illustrate photocatalytic dynamics and kinetics in mixed spacetime.
CATCH unites low-dimensional materials designs by counting physical and electronic merits from spacetime confinements. It metrologically elaborates photocatalysis in an elevated 2D+nD+t, alters passages of materials combinations crossing dimensions, and directs future photocatalyst designs. Standing on cross-dimensional materials innovation and photocatalysis study, CATCH breaks the deadlock of practical photocatalysis that eventually leads to sustainability.
Max ERC Funding
1 999 946 €
Duration
Start date: 2021-05-01, End date: 2026-04-30
Project acronym Des.solve
Project When solids become liquids: natural deep eutectic solvents for chemical process engineering
Researcher (PI) Ana Rita CRUZ DUARTE
Host Institution (HI) NOVA ID FCT - ASSOCIACAO PARA A INOVACAO E DESENVOLVIMENTO DA FCT
Country Portugal
Call Details Consolidator Grant (CoG), PE8, ERC-2016-COG
Summary Sugars, aminoacids or organic acids are typically solid at room temperature. Nonetheless when combined at a particular molar fraction they present a high melting point depression, becoming liquids at room temperature. These are called Natural Deep Eutectic Solvents – NADES. NADES are envisaged to play a major role on different chemical engineering processes in the future. Nonetheless, there is a significant lack of knowledge on fundamental and basic research on NADES, which is hindering their industrial applications. For this reason it is important to extend the knowledge on these systems, boosting their application development. NADES applications go beyond chemical or materials engineering and cover a wide range of fields from biocatalysis, extraction, electrochemistry, carbon dioxide capture or biomedical applications. Des.solve encompasses four major themes of research: 1 – Development of NADES and therapeutic deep eutectic solvents – THEDES; 2 – Characterization of the obtained mixtures and computer simulation of NADES/THEDES properties; 3 – Phase behaviour of binary/ternary systems NADES/THEDES + carbon dioxide and thermodynamic modelling 4 – Application development. Starting from the development of novel NADES/THEDES which, by different characterization techniques, will be deeply studied and characterized, the essential raw-materials will be produced for the subsequent research activities. The envisaged research involves modelling and molecular simulations. Des.solve will be deeply engaged in application development, particularly in extraction, biocatalysis and pharmaceutical/biomedical applications. The knowledge that will be created in this proposal is expected not only to have a major impact in the scientific community, but also in society, economy and industry.
Summary
Sugars, aminoacids or organic acids are typically solid at room temperature. Nonetheless when combined at a particular molar fraction they present a high melting point depression, becoming liquids at room temperature. These are called Natural Deep Eutectic Solvents – NADES. NADES are envisaged to play a major role on different chemical engineering processes in the future. Nonetheless, there is a significant lack of knowledge on fundamental and basic research on NADES, which is hindering their industrial applications. For this reason it is important to extend the knowledge on these systems, boosting their application development. NADES applications go beyond chemical or materials engineering and cover a wide range of fields from biocatalysis, extraction, electrochemistry, carbon dioxide capture or biomedical applications. Des.solve encompasses four major themes of research: 1 – Development of NADES and therapeutic deep eutectic solvents – THEDES; 2 – Characterization of the obtained mixtures and computer simulation of NADES/THEDES properties; 3 – Phase behaviour of binary/ternary systems NADES/THEDES + carbon dioxide and thermodynamic modelling 4 – Application development. Starting from the development of novel NADES/THEDES which, by different characterization techniques, will be deeply studied and characterized, the essential raw-materials will be produced for the subsequent research activities. The envisaged research involves modelling and molecular simulations. Des.solve will be deeply engaged in application development, particularly in extraction, biocatalysis and pharmaceutical/biomedical applications. The knowledge that will be created in this proposal is expected not only to have a major impact in the scientific community, but also in society, economy and industry.
Max ERC Funding
1 877 006 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym ECM_INK
Project Cells-self Extracellular Matrices-based Bioinks to create accurate 3D diseased skin tissue models
Researcher (PI) Alexandra Margarida PINTO MARQUES
Host Institution (HI) UNIVERSIDADE DO MINHO
Country Portugal
Call Details Consolidator Grant (CoG), PE8, ERC-2016-COG
Summary It has been recognized that growing cells within 3D structures reduces the gap between 2D in vitro cell cultures and native tissue physiology. This has been paving the way for the development of reliable 3D in vitro cell-based platforms with major impact in the reduction/elimination of animal experimentation, diseases modelling and drug development. So far, the many strategies that have been followed to bioengineer in vitro 3D human tissue models mostly rely on the random culture of cells within a 3D structure without reflecting the compositional and structural complexity of the native tissues. Recently proposed bioprinting technologies that allow accurate and high speed deposition of various cells and matrices at high resolution, have therefore great potential in the development of physiologically reliable 3D in vitro tissue models by recreating the different microenvironments/microfunctionalities found in each tissue. Nonetheless, among the components required for bioprinting, bioinks in particular have demanding requirements and much has still to be done regarding their intrinsic formulation to lead cell behaviour and support specific functionalities.
ECM_INK intends to tackle this issue by developing cells-self extracellular matrices-based bioinks to create accurate and pathophysiological relevant 3D in vitro diseased skin tissue models. The development of cell phenotype-driven bioinks will generate complex microenvironments comprising varied cell types within matrices that were specifically designed to attain a particular response from each one of those cell types. The use of cells from patients suffering from chronic, genetic and neoplastic skin diseases represents a major advantage that will be reflected in the accuracy and functionality of the respective 3D in vitro models. The ultimate confirmation of their potential will be complete after validation using animal-free approaches reinforcing the intrinsic relationship of ECM_INK with the 3Rs policy.
Summary
It has been recognized that growing cells within 3D structures reduces the gap between 2D in vitro cell cultures and native tissue physiology. This has been paving the way for the development of reliable 3D in vitro cell-based platforms with major impact in the reduction/elimination of animal experimentation, diseases modelling and drug development. So far, the many strategies that have been followed to bioengineer in vitro 3D human tissue models mostly rely on the random culture of cells within a 3D structure without reflecting the compositional and structural complexity of the native tissues. Recently proposed bioprinting technologies that allow accurate and high speed deposition of various cells and matrices at high resolution, have therefore great potential in the development of physiologically reliable 3D in vitro tissue models by recreating the different microenvironments/microfunctionalities found in each tissue. Nonetheless, among the components required for bioprinting, bioinks in particular have demanding requirements and much has still to be done regarding their intrinsic formulation to lead cell behaviour and support specific functionalities.
ECM_INK intends to tackle this issue by developing cells-self extracellular matrices-based bioinks to create accurate and pathophysiological relevant 3D in vitro diseased skin tissue models. The development of cell phenotype-driven bioinks will generate complex microenvironments comprising varied cell types within matrices that were specifically designed to attain a particular response from each one of those cell types. The use of cells from patients suffering from chronic, genetic and neoplastic skin diseases represents a major advantage that will be reflected in the accuracy and functionality of the respective 3D in vitro models. The ultimate confirmation of their potential will be complete after validation using animal-free approaches reinforcing the intrinsic relationship of ECM_INK with the 3Rs policy.
Max ERC Funding
1 998 939 €
Duration
Start date: 2017-05-01, End date: 2022-10-31
Project acronym ForceMorph
Project The integration of cell signalling and mechanical forces in vascular morphology
Researcher (PI) Cecilia Maria SAHLGREN
Host Institution (HI) ABO AKADEMI
Country Finland
Call Details Consolidator Grant (CoG), LS9, ERC-2017-COG
Summary Cardiovascular diseases represent the principal worldwide medical challenge of the 21st century (WHO), and new concepts to treat, predict and even prevent these diseases are needed. Structural remodelling of the vasculature in response to changes in blood flow is important to maintain mechanical homeostasis, and many diseases are related to defects in tissue morphology and mechanical imbalance. Signalling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via the Notch pathway regulates the morphology and structural remodelling of the arterial wall. Importantly, Notch offers handles for therapeutic control and thus opportunities for treatment of malformation and adaptation. However, we lack the essential understanding of how hemodynamic forces integrate with Notch signalling to rationally and responsibly target Notch in vascular therapies. The complexity of the problem requires new tools and an interdisciplinary approach. Our project integrates engineering, computational modelling, with cell biology and in vivo model systems to address the question. In vivo models will validate the in in vitro model systems to ensure that they are reproducible and reflect the reality. Through this integrated approach we will enable new therapeutic developments.
The specific objectives of the project are to:
1) Study EC-VSMC signalling real time, at high resolution by a novel biomimetic 4D Artery-on-Chip that recapitulates the cell-composition, -organisation and hemodynamic forces of the physiological artery
2) Develop a computational model of the arterial wall that include the mechanosensitivity of Notch signalling to predict how the complex interactions affect arterial morphology and remodelling
3) Use in vivo animal models to elucidate how regulation of Notch signalling affects tissue morphology and remodelling in response to changes in hemodynamic conditions
Summary
Cardiovascular diseases represent the principal worldwide medical challenge of the 21st century (WHO), and new concepts to treat, predict and even prevent these diseases are needed. Structural remodelling of the vasculature in response to changes in blood flow is important to maintain mechanical homeostasis, and many diseases are related to defects in tissue morphology and mechanical imbalance. Signalling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via the Notch pathway regulates the morphology and structural remodelling of the arterial wall. Importantly, Notch offers handles for therapeutic control and thus opportunities for treatment of malformation and adaptation. However, we lack the essential understanding of how hemodynamic forces integrate with Notch signalling to rationally and responsibly target Notch in vascular therapies. The complexity of the problem requires new tools and an interdisciplinary approach. Our project integrates engineering, computational modelling, with cell biology and in vivo model systems to address the question. In vivo models will validate the in in vitro model systems to ensure that they are reproducible and reflect the reality. Through this integrated approach we will enable new therapeutic developments.
The specific objectives of the project are to:
1) Study EC-VSMC signalling real time, at high resolution by a novel biomimetic 4D Artery-on-Chip that recapitulates the cell-composition, -organisation and hemodynamic forces of the physiological artery
2) Develop a computational model of the arterial wall that include the mechanosensitivity of Notch signalling to predict how the complex interactions affect arterial morphology and remodelling
3) Use in vivo animal models to elucidate how regulation of Notch signalling affects tissue morphology and remodelling in response to changes in hemodynamic conditions
Max ERC Funding
1 919 599 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym FREEDLES
Project From needles to landscapes: a novel approach to scaling forest spectra
Researcher (PI) Miina Alina RAUTIAINEN
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Consolidator Grant (CoG), LS9, ERC-2017-COG
Summary Accounting for vegetation structure – clumping of foliage into shoots or crowns – is the largest remaining challenge in modelling scattered and absorbed radiation in complex vegetation canopies such as forests. Clumping controls the radiation regime of forest canopies, yet it is poorly quantified. Currently, the communities working with vegetation structure and optical measurements do not have a common understanding of the concept. The FREEDLES project sets out to develop a universal method for quantifying clumping of foliage in forests based on detailed 3D structure and spectral reflectance data. Clumping will be linked to photon recollision probability, an exciting new development in the field of photon transport modelling. Photon recollision probability will, in turn, be used to develop a spectral scaling algorithm which will connect the spectra of vegetation at all hierarchical levels from needles and leaves to crowns, stands and landscapes. The spectral scaling algorithm will be validated with detailed reference measurements in both laboratory and natural conditions, and applied to interpret forest variables from satellite images at different spatial resolutions. The proposed approach is contrary to many other lines of current development where more complexity is favoured in canopy radiation models. If successful, the approach will significantly improve estimates of absorbed and scattered radiation fields in forests and retrieval results of forest biophysical variables from satellite data. Future applications can also be expected in global radiation and carbon balance estimation and in chlorophyll fluorescence models for forests. Most importantly, the spectral scaling model will open new horizons for our scientific understanding of photon-vegetation interactions.
Summary
Accounting for vegetation structure – clumping of foliage into shoots or crowns – is the largest remaining challenge in modelling scattered and absorbed radiation in complex vegetation canopies such as forests. Clumping controls the radiation regime of forest canopies, yet it is poorly quantified. Currently, the communities working with vegetation structure and optical measurements do not have a common understanding of the concept. The FREEDLES project sets out to develop a universal method for quantifying clumping of foliage in forests based on detailed 3D structure and spectral reflectance data. Clumping will be linked to photon recollision probability, an exciting new development in the field of photon transport modelling. Photon recollision probability will, in turn, be used to develop a spectral scaling algorithm which will connect the spectra of vegetation at all hierarchical levels from needles and leaves to crowns, stands and landscapes. The spectral scaling algorithm will be validated with detailed reference measurements in both laboratory and natural conditions, and applied to interpret forest variables from satellite images at different spatial resolutions. The proposed approach is contrary to many other lines of current development where more complexity is favoured in canopy radiation models. If successful, the approach will significantly improve estimates of absorbed and scattered radiation fields in forests and retrieval results of forest biophysical variables from satellite data. Future applications can also be expected in global radiation and carbon balance estimation and in chlorophyll fluorescence models for forests. Most importantly, the spectral scaling model will open new horizons for our scientific understanding of photon-vegetation interactions.
Max ERC Funding
1 963 590 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym IL7sigNETure
Project IL-7/IL-7R signaling networks in health and malignancy
Researcher (PI) Joao Pedro Taborda Barata
Host Institution (HI) INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Country Portugal
Call Details Consolidator Grant (CoG), LS4, ERC-2014-CoG
Summary Deregulation of signal transduction is a feature of tumor cells and signaling therapies are gaining importance in the growing arsenal against cancer. However, their full potential can only be achieved once we overcome the limited knowledge on how signaling networks are wired in cancer cells. Interleukin 7 (IL7) and its receptor (IL7R) are essential for normal T-cell development and function. However, they can also promote autoimmunity, chronic inflammation and cancer. We showed that patients with T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological cancer, can display IL7R gain-of-function mutations leading to downstream signaling activation and cell transformation. Despite the biological relevance of IL7 and IL7R, the characterization of their signaling effectors remains limited. Here, we propose to move from the single molecule/pathway-centered analysis that has characterized the research on IL7/IL7R signaling, into a ‘holistic’ view of the IL7/IL7R signaling landscape. To do so, we will employ a multidisciplinary strategy, in which data from complementary high throughput analyses, informing on different levels of regulation of the IL7/IL7R signaling network, will be integrated via a systems biology approach, and complemented by cell and molecular biology experimentation and state-of-the-art in vivo models. The knowledge we will generate should have a profound impact on the understanding of the fundamental mechanisms by which IL7/IL7R signaling promotes leukemia and reveal novel targets for fine-tuned therapeutic intervention in T-ALL. Moreover, the scope of insights gained should extend beyond leukemia. Our in-depth, systems-level characterization of IL7/IL7R signaling will constitute a platform with extraordinary potential to illuminate the molecular role of the IL7/IL7R axis in other cancers (e.g. breast and lung) and pathological settings where IL7 has been implicated, such as HIV infection, multiple sclerosis and rheumatoid arthritis.
Summary
Deregulation of signal transduction is a feature of tumor cells and signaling therapies are gaining importance in the growing arsenal against cancer. However, their full potential can only be achieved once we overcome the limited knowledge on how signaling networks are wired in cancer cells. Interleukin 7 (IL7) and its receptor (IL7R) are essential for normal T-cell development and function. However, they can also promote autoimmunity, chronic inflammation and cancer. We showed that patients with T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological cancer, can display IL7R gain-of-function mutations leading to downstream signaling activation and cell transformation. Despite the biological relevance of IL7 and IL7R, the characterization of their signaling effectors remains limited. Here, we propose to move from the single molecule/pathway-centered analysis that has characterized the research on IL7/IL7R signaling, into a ‘holistic’ view of the IL7/IL7R signaling landscape. To do so, we will employ a multidisciplinary strategy, in which data from complementary high throughput analyses, informing on different levels of regulation of the IL7/IL7R signaling network, will be integrated via a systems biology approach, and complemented by cell and molecular biology experimentation and state-of-the-art in vivo models. The knowledge we will generate should have a profound impact on the understanding of the fundamental mechanisms by which IL7/IL7R signaling promotes leukemia and reveal novel targets for fine-tuned therapeutic intervention in T-ALL. Moreover, the scope of insights gained should extend beyond leukemia. Our in-depth, systems-level characterization of IL7/IL7R signaling will constitute a platform with extraordinary potential to illuminate the molecular role of the IL7/IL7R axis in other cancers (e.g. breast and lung) and pathological settings where IL7 has been implicated, such as HIV infection, multiple sclerosis and rheumatoid arthritis.
Max ERC Funding
1 988 125 €
Duration
Start date: 2015-09-01, End date: 2021-08-31
Project acronym iPROTECTION
Project Molecular mechanisms of induced protection against sepsis by DNA damage responses
Researcher (PI) Luis Filipe Ferreira Moita
Host Institution (HI) FUNDACAO CALOUSTE GULBENKIAN
Country Portugal
Call Details Consolidator Grant (CoG), LS4, ERC-2014-CoG
Summary Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options outside of infection control and organ support measures. Based on our recent discovery that anthracycline drugs prevent organ failure without affecting the bacterial burden in a model of severe sepsis, we propose that strategies aimed at target organ protection have extraordinary potential for the treatment of sepsis and possibly for other inflammation-driven conditions. However, the mechanisms of organ protection and disease tolerance are either unknown or poorly characterized.
The central goal of the current proposal is to identify and characterize novel cytoprotective mechanisms, with a focus on DNA damage response dependent protection activated by anthracyclines as a window into stress-induced genetic programs conferring disease tolerance. To that end, we will carry out a combination of candidate and unbiased approaches for the in vivo identification of ATM-dependent and independent mechanisms of tissue protection. We will validate the leading candidates through adenovirus-mediated delivery of constructs for overexpression (gain-of-function) or shRNA for gene silencing (loss-of-function) to the lung, based on our recent finding that rescuing this organ is essential and perhaps sufficient in anthracycline-induced protection against severe sepsis. The candidates showing the most promise will be characterized using a combination of in vitro and in vivo genetic, biochemical, cell biological and physiological methods.
The results arising from the current proposal are likely not only to inspire the design of transformative therapies for sepsis but also to open a completely new field of opportunity to molecularly understand core surveillance mechanisms of basic cellular processes with a critical role in the homeostasis of organ function and whose activation can ultimately promote quality of life during aging and increase lifespan.
Summary
Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options outside of infection control and organ support measures. Based on our recent discovery that anthracycline drugs prevent organ failure without affecting the bacterial burden in a model of severe sepsis, we propose that strategies aimed at target organ protection have extraordinary potential for the treatment of sepsis and possibly for other inflammation-driven conditions. However, the mechanisms of organ protection and disease tolerance are either unknown or poorly characterized.
The central goal of the current proposal is to identify and characterize novel cytoprotective mechanisms, with a focus on DNA damage response dependent protection activated by anthracyclines as a window into stress-induced genetic programs conferring disease tolerance. To that end, we will carry out a combination of candidate and unbiased approaches for the in vivo identification of ATM-dependent and independent mechanisms of tissue protection. We will validate the leading candidates through adenovirus-mediated delivery of constructs for overexpression (gain-of-function) or shRNA for gene silencing (loss-of-function) to the lung, based on our recent finding that rescuing this organ is essential and perhaps sufficient in anthracycline-induced protection against severe sepsis. The candidates showing the most promise will be characterized using a combination of in vitro and in vivo genetic, biochemical, cell biological and physiological methods.
The results arising from the current proposal are likely not only to inspire the design of transformative therapies for sepsis but also to open a completely new field of opportunity to molecularly understand core surveillance mechanisms of basic cellular processes with a critical role in the homeostasis of organ function and whose activation can ultimately promote quality of life during aging and increase lifespan.
Max ERC Funding
1 985 375 €
Duration
Start date: 2015-10-01, End date: 2021-03-31