Project acronym AMORE
Project A distributional MOdel of Reference to Entities
Researcher (PI) Gemma BOLEDA TORRENT
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Call Details Starting Grant (StG), SH4, ERC-2016-STG
Summary "When I asked my seven-year-old daughter ""Who is the boy in your class who was also new in school last year, like you?"", she instantly replied ""Daniel"", using the descriptive content in my utterance to identify an entity in the real world and refer to it. The ability to use language to refer to reality is crucial for humans, and yet it is very difficult to model. AMORE breaks new ground in Computational Linguistics, Linguistics, and Artificial Intelligence by developing a model of linguistic reference to entities implemented as a computational system that can learn its own representations from data.
This interdisciplinary project builds on two complementary semantic traditions: 1) Formal semantics, a symbolic approach that can delimit and track linguistic referents, but does not adequately match them with the descriptive content of linguistic expressions; 2) Distributional semantics, which can handle descriptive content but does not associate it to individuated referents. AMORE synthesizes the two approaches into a unified, scalable model of reference that operates with individuated referents and links them to referential expressions characterized by rich descriptive content. The model is a distributed (neural network) version of a formal semantic framework that is furthermore able to integrate perceptual (visual) and linguistic information about entities. We test it extensively in referential tasks that require matching noun phrases (“the Medicine student”, “the white cat”) with entity representations extracted from text and images.
AMORE advances our scientific understanding of language and its computational modeling, and contributes to the far-reaching debate between symbolic and distributed approaches to cognition with an integrative proposal. I am in a privileged position to carry out this integration, since I have contributed top research in both distributional and formal semantics.
"
Summary
"When I asked my seven-year-old daughter ""Who is the boy in your class who was also new in school last year, like you?"", she instantly replied ""Daniel"", using the descriptive content in my utterance to identify an entity in the real world and refer to it. The ability to use language to refer to reality is crucial for humans, and yet it is very difficult to model. AMORE breaks new ground in Computational Linguistics, Linguistics, and Artificial Intelligence by developing a model of linguistic reference to entities implemented as a computational system that can learn its own representations from data.
This interdisciplinary project builds on two complementary semantic traditions: 1) Formal semantics, a symbolic approach that can delimit and track linguistic referents, but does not adequately match them with the descriptive content of linguistic expressions; 2) Distributional semantics, which can handle descriptive content but does not associate it to individuated referents. AMORE synthesizes the two approaches into a unified, scalable model of reference that operates with individuated referents and links them to referential expressions characterized by rich descriptive content. The model is a distributed (neural network) version of a formal semantic framework that is furthermore able to integrate perceptual (visual) and linguistic information about entities. We test it extensively in referential tasks that require matching noun phrases (“the Medicine student”, “the white cat”) with entity representations extracted from text and images.
AMORE advances our scientific understanding of language and its computational modeling, and contributes to the far-reaching debate between symbolic and distributed approaches to cognition with an integrative proposal. I am in a privileged position to carry out this integration, since I have contributed top research in both distributional and formal semantics.
"
Max ERC Funding
1 499 805 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym APACHE
Project Atmospheric Pressure plAsma meets biomaterials for bone Cancer HEaling
Researcher (PI) Cristina CANAL BARNILS
Host Institution (HI) UNIVERSITAT POLITECNICA DE CATALUNYA
Call Details Starting Grant (StG), PE8, ERC-2016-STG
Summary Cold atmospheric pressure plasmas (APP) have been reported to selectively kill cancer cells without damaging the surrounding tissues. Studies have been conducted on a variety of cancer types but to the best of our knowledge not on any kind of bone cancer. Treatment options for bone cancer include surgery, chemotherapy, etc. and may involve the use of bone grafting biomaterials to replace the surgically removed bone.
APACHE brings a totally different and ground-breaking approach in the design of a novel therapy for bone cancer by taking advantage of the active species generated by APP in combination with biomaterials to deliver the active species locally in the diseased site. The feasibility of this approach is rooted in the evidence that the cellular effects of APP appear to strongly involve the suite of reactive species created by plasmas, which can be derived from a) direct treatment of the malignant cells by APP or b) indirect treatment of the liquid media by APP which is then put in contact with the cancer cells.
In APACHE we aim to investigate the fundamentals involved in the lethal effects of cold plasmas on bone cancer cells, and to develop improved bone cancer therapies. To achieve this we will take advantage of the highly reactive species generated by APP in the liquid media, which we will use in an incremental strategy: i) to investigate the effects of APP treated liquid on bone cancer cells, ii) to evaluate the potential of combining APP treated liquid in a hydrogel vehicle with/wo CaP biomaterials and iii) to ascertain the potential three directional interactions between APP reactive species in liquid medium with biomaterials and with chemotherapeutic drugs.
The methodological approach will involve an interdisciplinary team, dealing with plasma diagnostics in gas and liquid media; with cell biology and the effects of APP treated with bone tumor cells and its combination with biomaterials and/or with anticancer drugs.
Summary
Cold atmospheric pressure plasmas (APP) have been reported to selectively kill cancer cells without damaging the surrounding tissues. Studies have been conducted on a variety of cancer types but to the best of our knowledge not on any kind of bone cancer. Treatment options for bone cancer include surgery, chemotherapy, etc. and may involve the use of bone grafting biomaterials to replace the surgically removed bone.
APACHE brings a totally different and ground-breaking approach in the design of a novel therapy for bone cancer by taking advantage of the active species generated by APP in combination with biomaterials to deliver the active species locally in the diseased site. The feasibility of this approach is rooted in the evidence that the cellular effects of APP appear to strongly involve the suite of reactive species created by plasmas, which can be derived from a) direct treatment of the malignant cells by APP or b) indirect treatment of the liquid media by APP which is then put in contact with the cancer cells.
In APACHE we aim to investigate the fundamentals involved in the lethal effects of cold plasmas on bone cancer cells, and to develop improved bone cancer therapies. To achieve this we will take advantage of the highly reactive species generated by APP in the liquid media, which we will use in an incremental strategy: i) to investigate the effects of APP treated liquid on bone cancer cells, ii) to evaluate the potential of combining APP treated liquid in a hydrogel vehicle with/wo CaP biomaterials and iii) to ascertain the potential three directional interactions between APP reactive species in liquid medium with biomaterials and with chemotherapeutic drugs.
The methodological approach will involve an interdisciplinary team, dealing with plasma diagnostics in gas and liquid media; with cell biology and the effects of APP treated with bone tumor cells and its combination with biomaterials and/or with anticancer drugs.
Max ERC Funding
1 499 887 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym ARISYS
Project Engineering an artificial immune system with functional components assembled from prokaryotic parts and modules
Researcher (PI) Víctor De Lorenzo Prieto
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), LS9, ERC-2012-ADG_20120314
Summary The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.
Summary
The objective of this project is to overcome current limitations for antibody production that are inherent to the extant immune system of vertebrates. This will be done by creating an all-in-one artificial/synthetic counterpart based exclusively on prokaryotic parts, devices and modules. To this end, ARISYS will exploit design concepts, construction hierarchies and standardization notions that stem from contemporary Synthetic Biology for the assembly and validation of (what we believe is) the most complex artificial biological system ventured thus far. This all-bacterial immune-like system will not only simplify and make affordable the manipulations necessary for antibody generation, but will also permit the application of such binders by themselves or displayed on bacterial cells to biotechnological challenges well beyond therapeutic and health-related uses. The work plan involves the assembly and validation of autonomous functional modules for [i] displaying antibody/affibody (AB) scaffolds attached to the surface of bacterial cells, [ii] conditional diversification of target-binding sequences of the ABs, [iii] contact-dependent activation of gene expression, [iv] reversible bi-stable switches, and [v] clonal selection and amplification of improved binders. These modules composed of stand-alone parts and bearing well defined input/output functions, will be assembled in the genomic chassis of streamlined Escherichia coli and Pseudomonas putida strains. The resulting molecular network will make the ABs expressed and displayed on the cell surface to proceed spontaneously (or at the user's decision) through subsequent cycles of affinity and specificity maturation towards antigens or other targets presented to the bacterial population. In this way, a single, easy-to-handle (albeit heavily engineered) strain will govern all operations that are typically scattered in a multitude of separate methods and apparatuses for AB production.
Max ERC Funding
2 422 271 €
Duration
Start date: 2013-05-01, End date: 2019-04-30
Project acronym BacBio
Project Mechanistic and functional studies of Bacillus biofilms assembly on plants, and their impact in sustainable agriculture and food safety
Researcher (PI) Diego Francisco Romero Hinojosa
Host Institution (HI) UNIVERSIDAD DE MALAGA
Call Details Starting Grant (StG), LS9, ERC-2014-STG
Summary Sustainable agriculture is an ambitious concept conceived to improve productivity but minimizing side effects. Why the efficiency of a biocontrol agent is so variable? How can different therapies be efficiently exploited in a combined way to combat microbial diseases? These are questions that need investigation to convey with criteria of sustainability. What I present is an integral proposal aim to study the microbial ecology and specifically bacterial biofilms as a central axis of two differential but likely interconnected scenarios in plant health: i) the beneficial interaction of the biocontrol agent (BCA) Bacillus subtilis, and ii) the non-conventional interaction of the food-borne pathogen Bacillus cereus.
I will start working with B. subtilis, and reasons are: 1) Different isolates are promising BCAs and are commercialized for such purpose, 2) There exist vast information of the genetics circuitries that govern important aspects of B. subtilis physiology as antibiotic production, cell differentiation, and biofilm formation. In parallel I propose to study the way B. cereus, a food-borne pathogenic bacterium interacts with vegetables. I am planning to set up a multidisciplinary approach that will combine genetics, biochemistry, proteomics, cell biology and molecular biology to visualize how these bacterial population interacts, communicates with plants and other microorganisms, or how all these factors trigger or inhibit the developmental program ending in biofilm formation. I am also interested on knowing if structural components of the bacterial extracellular matrix (exopolysaccharides or amyloid proteins) are important for bacterial fitness. If this were the case, I will also investigate which external factors affect their expression and assembly in functional biofilms. The insights get on these studies are committed to impulse our knowledge on microbial ecology and their biotechnological applicability to sustainable agriculture and food safety.
Summary
Sustainable agriculture is an ambitious concept conceived to improve productivity but minimizing side effects. Why the efficiency of a biocontrol agent is so variable? How can different therapies be efficiently exploited in a combined way to combat microbial diseases? These are questions that need investigation to convey with criteria of sustainability. What I present is an integral proposal aim to study the microbial ecology and specifically bacterial biofilms as a central axis of two differential but likely interconnected scenarios in plant health: i) the beneficial interaction of the biocontrol agent (BCA) Bacillus subtilis, and ii) the non-conventional interaction of the food-borne pathogen Bacillus cereus.
I will start working with B. subtilis, and reasons are: 1) Different isolates are promising BCAs and are commercialized for such purpose, 2) There exist vast information of the genetics circuitries that govern important aspects of B. subtilis physiology as antibiotic production, cell differentiation, and biofilm formation. In parallel I propose to study the way B. cereus, a food-borne pathogenic bacterium interacts with vegetables. I am planning to set up a multidisciplinary approach that will combine genetics, biochemistry, proteomics, cell biology and molecular biology to visualize how these bacterial population interacts, communicates with plants and other microorganisms, or how all these factors trigger or inhibit the developmental program ending in biofilm formation. I am also interested on knowing if structural components of the bacterial extracellular matrix (exopolysaccharides or amyloid proteins) are important for bacterial fitness. If this were the case, I will also investigate which external factors affect their expression and assembly in functional biofilms. The insights get on these studies are committed to impulse our knowledge on microbial ecology and their biotechnological applicability to sustainable agriculture and food safety.
Max ERC Funding
1 453 563 €
Duration
Start date: 2015-03-01, End date: 2021-02-28
Project acronym BILITERACY
Project Bi-literacy: Learning to read in L1 and in L2
Researcher (PI) Manuel Francisco Carreiras Valiña
Host Institution (HI) BCBL BASQUE CENTER ON COGNITION BRAIN AND LANGUAGE
Call Details Advanced Grant (AdG), SH4, ERC-2011-ADG_20110406
Summary Learning to read is probably one of the most exciting discoveries in our life. Using a longitudinal approach, the research proposed examines how the human brain responds to two major challenges: (a) the instantiation a complex cognitive function for which there is no genetic blueprint (learning to read in a first language, L1), and (b) the accommodation to new statistical regularities when learning to read in a second language (L2). The aim of the present research project is to identify the neural substrates of the reading process and its constituent cognitive components, with specific attention to individual differences and reading disabilities; as well as to investigate the relationship between specific cognitive functions and the changes in neural activity that take place in the course of learning to read in L1 and in L2. The project will employ a longitudinal design. We will recruit children before they learn to read in L1 and in L2 and track reading development with both cognitive and neuroimaging measures over 24 months. The findings from this project will provide a deeper understanding of (a) how general neurocognitive factors and language specific factors underlie individual differences – and reading disabilities– in reading acquisition in L1 and in L2; (b) how the neuro-cognitive circuitry changes and brain mechanisms synchronize while instantiating reading in L1 and in L2; (c) what the limitations and the extent of brain plasticity are in young readers. An interdisciplinary and multi-methodological approach is one of the keys to success of the present project, along with strong theory-driven investigation. By combining both we will generate breakthroughs to advance our understanding of how literacy in L1 and in L2 is acquired and mastered. The research proposed will also lay the foundations for more applied investigations of best practice in teaching reading in first and subsequent languages, and devising intervention methods for reading disabilities.
Summary
Learning to read is probably one of the most exciting discoveries in our life. Using a longitudinal approach, the research proposed examines how the human brain responds to two major challenges: (a) the instantiation a complex cognitive function for which there is no genetic blueprint (learning to read in a first language, L1), and (b) the accommodation to new statistical regularities when learning to read in a second language (L2). The aim of the present research project is to identify the neural substrates of the reading process and its constituent cognitive components, with specific attention to individual differences and reading disabilities; as well as to investigate the relationship between specific cognitive functions and the changes in neural activity that take place in the course of learning to read in L1 and in L2. The project will employ a longitudinal design. We will recruit children before they learn to read in L1 and in L2 and track reading development with both cognitive and neuroimaging measures over 24 months. The findings from this project will provide a deeper understanding of (a) how general neurocognitive factors and language specific factors underlie individual differences – and reading disabilities– in reading acquisition in L1 and in L2; (b) how the neuro-cognitive circuitry changes and brain mechanisms synchronize while instantiating reading in L1 and in L2; (c) what the limitations and the extent of brain plasticity are in young readers. An interdisciplinary and multi-methodological approach is one of the keys to success of the present project, along with strong theory-driven investigation. By combining both we will generate breakthroughs to advance our understanding of how literacy in L1 and in L2 is acquired and mastered. The research proposed will also lay the foundations for more applied investigations of best practice in teaching reading in first and subsequent languages, and devising intervention methods for reading disabilities.
Max ERC Funding
2 487 000 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym BIOCON
Project Biological origins of linguistic constraints
Researcher (PI) Juan Manuel Toro
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Call Details Starting Grant (StG), SH4, ERC-2012-StG_20111124
Summary The linguistic capacity to express and comprehend an unlimited number of ideas when combining a limited number of elements has only been observed in humans. Nevertheless, research has not fully identified the components of language that make it uniquely human and that allow infants to grasp the complexity of linguistic structure in an apparently effortless manner. Research on comparative cognition suggests humans and other species share powerful learning mechanisms and basic perceptual abilities we use for language processing. But humans display remarkable linguistic abilities that other animals do not possess. Understanding the interplay between general mechanisms shared across species and more specialized ones dedicated to the speech signal is at the heart of current debates in human language acquisition. This is a highly relevant issue for researchers in the fields of Psychology, Linguistics, Biology, Philosophy and Cognitive Neuroscience. By conducting experiments across several populations (human adults and infants) and species (human and nonhuman animals), and using a wide array of experimental techniques, the present proposal hopes to shed some light on the origins of shared biological constraints that guide more specialized mechanisms in the search for linguistic structure. More specifically, we hope to understand how general perceptual and cognitive mechanisms likely present in other animals constrain the way humans tackle the task of language acquisition. Our hypothesis is that differences between humans and other species are not the result of humans being able to process increasingly complex structures that are the hallmark of language. Rather, differences might be due to humans and other animals focusing on different cues present in the signal to extract relevant information. This research will hint at what is uniquely human and what is shared across different animals species.
Summary
The linguistic capacity to express and comprehend an unlimited number of ideas when combining a limited number of elements has only been observed in humans. Nevertheless, research has not fully identified the components of language that make it uniquely human and that allow infants to grasp the complexity of linguistic structure in an apparently effortless manner. Research on comparative cognition suggests humans and other species share powerful learning mechanisms and basic perceptual abilities we use for language processing. But humans display remarkable linguistic abilities that other animals do not possess. Understanding the interplay between general mechanisms shared across species and more specialized ones dedicated to the speech signal is at the heart of current debates in human language acquisition. This is a highly relevant issue for researchers in the fields of Psychology, Linguistics, Biology, Philosophy and Cognitive Neuroscience. By conducting experiments across several populations (human adults and infants) and species (human and nonhuman animals), and using a wide array of experimental techniques, the present proposal hopes to shed some light on the origins of shared biological constraints that guide more specialized mechanisms in the search for linguistic structure. More specifically, we hope to understand how general perceptual and cognitive mechanisms likely present in other animals constrain the way humans tackle the task of language acquisition. Our hypothesis is that differences between humans and other species are not the result of humans being able to process increasingly complex structures that are the hallmark of language. Rather, differences might be due to humans and other animals focusing on different cues present in the signal to extract relevant information. This research will hint at what is uniquely human and what is shared across different animals species.
Max ERC Funding
1 305 973 €
Duration
Start date: 2013-01-01, End date: 2018-12-31
Project acronym BIOFORCE
Project Simultaneous multi-pathway engineering in crop plants through combinatorial genetic transformation: Creating nutritionally biofortified cereal grains for food security
Researcher (PI) Paul Christou
Host Institution (HI) UNIVERSIDAD DE LLEIDA
Call Details Advanced Grant (AdG), LS9, ERC-2008-AdG
Summary BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways
Summary
BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways
Max ERC Funding
2 290 046 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym BLOODCELLSCROSSTALK
Project The Crosstalk Between Red And White Blood Cells: The Case Of Fish
Researcher (PI) Maria del Mar Ortega-Villaizan Romo
Host Institution (HI) UNIVERSIDAD MIGUEL HERNANDEZ DE ELCHE
Call Details Starting Grant (StG), LS9, ERC-2014-STG
Summary Fish are the phylogenetically oldest vertebrate group with an immune system with clear similarities to the immune system of mammals. However, it is an actual matter of fact that the current knowledge of the fish immune system seems to lack the key piece to complete the puzzle.
In 1953 Nelson described a new role of human red blood cells (RBCs) which would go beyond the simple transport of O2 to the tissues. This new role, involved in the defence against microbes, described the antibody and complement-dependent binding of microbial immune complexes to RBCs. Regardless of the importance of this finding in the field of microbial infection, this phenomenon has been poorly evaluated. Just recently, a set of biological processes relevant to immunity have been described in the RBCs of a diverse group of organisms, which include: pathogen recognition, pathogen binding and clearance and cytokines production. Furthermore, it has been demonstrated that nucleated erythrocytes from fish and avian species develop specific responses to different pathogen associated molecular patterns and produce soluble factors that modulate leukocyte activity.
In the light of these pieces of evidences, and in an attempt to improve the knowledge of the immune mechanism(s) responsible for fish protection against viral infections, we raised the question: could nucleated fish erythrocytes be the key mediators of the antiviral responses? To answer this question we decided to focus our project on the evaluation of the crosstalk between red and white blood cells in the scenario of fish viral infections and prophylaxis. For that a working model composed of the rainbow trout and the viral haemorrhagic septicaemia virus (VHSV) was chosen, being the objectives of the project to evaluate: i) the implication trout RBCs (tRBCs) in the clearance of VHSV, and ii) the involvement of tRBCs in the blood transportation of the glycoprotein G of VHSV (GVHSV), the antigen encoded by the DNA vaccine.
Summary
Fish are the phylogenetically oldest vertebrate group with an immune system with clear similarities to the immune system of mammals. However, it is an actual matter of fact that the current knowledge of the fish immune system seems to lack the key piece to complete the puzzle.
In 1953 Nelson described a new role of human red blood cells (RBCs) which would go beyond the simple transport of O2 to the tissues. This new role, involved in the defence against microbes, described the antibody and complement-dependent binding of microbial immune complexes to RBCs. Regardless of the importance of this finding in the field of microbial infection, this phenomenon has been poorly evaluated. Just recently, a set of biological processes relevant to immunity have been described in the RBCs of a diverse group of organisms, which include: pathogen recognition, pathogen binding and clearance and cytokines production. Furthermore, it has been demonstrated that nucleated erythrocytes from fish and avian species develop specific responses to different pathogen associated molecular patterns and produce soluble factors that modulate leukocyte activity.
In the light of these pieces of evidences, and in an attempt to improve the knowledge of the immune mechanism(s) responsible for fish protection against viral infections, we raised the question: could nucleated fish erythrocytes be the key mediators of the antiviral responses? To answer this question we decided to focus our project on the evaluation of the crosstalk between red and white blood cells in the scenario of fish viral infections and prophylaxis. For that a working model composed of the rainbow trout and the viral haemorrhagic septicaemia virus (VHSV) was chosen, being the objectives of the project to evaluate: i) the implication trout RBCs (tRBCs) in the clearance of VHSV, and ii) the involvement of tRBCs in the blood transportation of the glycoprotein G of VHSV (GVHSV), the antigen encoded by the DNA vaccine.
Max ERC Funding
1 823 250 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym CADENCE
Project Catalytic Dual-Function Devices Against Cancer
Researcher (PI) Jesus Santamaria
Host Institution (HI) UNIVERSIDAD DE ZARAGOZA
Call Details Advanced Grant (AdG), PE8, ERC-2016-ADG
Summary Despite intense research efforts in almost every branch of the natural sciences, cancer continues to be one of the leading causes of death worldwide. It is thus remarkable that little or no therapeutic use has been made of a whole discipline, heterogeneous catalysis, which is noted for its specificity and for enabling chemical reactions in otherwise passive environments. At least in part, this could be attributed to practical difficulties: the selective delivery of a catalyst to a tumour and the remote activation of its catalytic function only after it has reached its target are highly challenging objectives. Only recently, the necessary tools to overcome these problems seem within reach.
CADENCE aims for a breakthrough in cancer therapy by developing a new therapeutic concept. The central hypothesis is that a growing tumour can be treated as a special type of reactor in which reaction conditions can be tailored to achieve two objectives: i) molecules essential to tumour growth are locally depleted and ii) toxic, short-lived products are generated in situ.
To implement this novel approach we will make use of core concepts of reactor engineering (kinetics, heat and mass transfer, catalyst design), as well as of ideas borrowed from other areas, mainly those of bio-orthogonal chemistry and controlled drug delivery. We will explore two different strategies (classical EPR effect and stem cells as Trojan Horses) to deliver optimized catalysts to the tumour. Once the catalysts have reached the tumour they will be remotely activated using near-infrared (NIR) light, that affords the highest penetration into body tissues.
This is an ambitious project, addressing all the key steps from catalyst design to in vivo studies. Given the novel perspective provided by CADENCE, even partial success in any of the approaches to be tested would have a significant impact on the therapeutic toolbox available to treat cancer.
Summary
Despite intense research efforts in almost every branch of the natural sciences, cancer continues to be one of the leading causes of death worldwide. It is thus remarkable that little or no therapeutic use has been made of a whole discipline, heterogeneous catalysis, which is noted for its specificity and for enabling chemical reactions in otherwise passive environments. At least in part, this could be attributed to practical difficulties: the selective delivery of a catalyst to a tumour and the remote activation of its catalytic function only after it has reached its target are highly challenging objectives. Only recently, the necessary tools to overcome these problems seem within reach.
CADENCE aims for a breakthrough in cancer therapy by developing a new therapeutic concept. The central hypothesis is that a growing tumour can be treated as a special type of reactor in which reaction conditions can be tailored to achieve two objectives: i) molecules essential to tumour growth are locally depleted and ii) toxic, short-lived products are generated in situ.
To implement this novel approach we will make use of core concepts of reactor engineering (kinetics, heat and mass transfer, catalyst design), as well as of ideas borrowed from other areas, mainly those of bio-orthogonal chemistry and controlled drug delivery. We will explore two different strategies (classical EPR effect and stem cells as Trojan Horses) to deliver optimized catalysts to the tumour. Once the catalysts have reached the tumour they will be remotely activated using near-infrared (NIR) light, that affords the highest penetration into body tissues.
This is an ambitious project, addressing all the key steps from catalyst design to in vivo studies. Given the novel perspective provided by CADENCE, even partial success in any of the approaches to be tested would have a significant impact on the therapeutic toolbox available to treat cancer.
Max ERC Funding
2 483 136 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym CAMBAT
Project Calcium and magnesium metal anode based batteries
Researcher (PI) Alexandre PONROUCH
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Starting Grant (StG), PE8, ERC-2016-STG
Summary Li-ion battery is ubiquitous and has emerged as the major contender to power electric vehicles, yet Li-ion is slowly but surely reaching its limits and controversial debates on lithium supply cannot be ignored. New sustainable battery chemistries must be developed and the most appealing alternatives are to use Ca or Mg metal anodes which would bring a breakthrough in terms of energy density relying on much more abundant elements. Since Mg and Ca do not appear to be plagued by dendrite formation like Li, metal anodes could thus safely be used. While standard electrolytes forming stable passivation layers at the electrode/electrolyte interfaces enabled the success of the Li-ion technology, the migration of divalent cations through a passivation layer was thought to be impossible. Thus, all research efforts to date have been devoted to the formulation of electrolytes that do not form such layer. This approach comes with complex electrolyte, highly corrosive and with narrow electrochemical stability window leading to incompatibility with high voltage cathodes thus penalizing energy density.
The applicant demonstrated that calcium can be reversibly plated and stripped through a stable passivation layer when transport properties within the electrolyte are tuned (decreasing ion pair formation). CAMBAT aims at developing new electrolytes forming stable passivation layers and allowing the migration of Ca2+ and Mg2+. Such a dramatic shift in the methodology would allow considering a completely new family of electrolytes enabling the evaluation of high voltage cathode materials that cannot be tested in the electrolytes available nowadays. 1Ah prototype cells will be assembled as proof of concept, targets for energy density and cost being ca. 300 Wh/kg and 250 $/kWh, respectively, thus doubling the energy density while dividing by at least a factor of 2 the price when compared to state of the art Li-ion batteries and having the potential for being SAFER (absence of dendrite).
Summary
Li-ion battery is ubiquitous and has emerged as the major contender to power electric vehicles, yet Li-ion is slowly but surely reaching its limits and controversial debates on lithium supply cannot be ignored. New sustainable battery chemistries must be developed and the most appealing alternatives are to use Ca or Mg metal anodes which would bring a breakthrough in terms of energy density relying on much more abundant elements. Since Mg and Ca do not appear to be plagued by dendrite formation like Li, metal anodes could thus safely be used. While standard electrolytes forming stable passivation layers at the electrode/electrolyte interfaces enabled the success of the Li-ion technology, the migration of divalent cations through a passivation layer was thought to be impossible. Thus, all research efforts to date have been devoted to the formulation of electrolytes that do not form such layer. This approach comes with complex electrolyte, highly corrosive and with narrow electrochemical stability window leading to incompatibility with high voltage cathodes thus penalizing energy density.
The applicant demonstrated that calcium can be reversibly plated and stripped through a stable passivation layer when transport properties within the electrolyte are tuned (decreasing ion pair formation). CAMBAT aims at developing new electrolytes forming stable passivation layers and allowing the migration of Ca2+ and Mg2+. Such a dramatic shift in the methodology would allow considering a completely new family of electrolytes enabling the evaluation of high voltage cathode materials that cannot be tested in the electrolytes available nowadays. 1Ah prototype cells will be assembled as proof of concept, targets for energy density and cost being ca. 300 Wh/kg and 250 $/kWh, respectively, thus doubling the energy density while dividing by at least a factor of 2 the price when compared to state of the art Li-ion batteries and having the potential for being SAFER (absence of dendrite).
Max ERC Funding
1 688 705 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
