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 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 CORTEXFOLDING
Project Understanding the development and function of cerebral cortex folding
Researcher (PI) Victor Borrell Franco
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Starting Grant (StG), LS5, ERC-2012-StG_20111109
Summary The mammalian cerebral cortex was subject to a dramatic expansion in surface area during evolution. This process is recapitulated during development and is accompanied by folding of the cortical sheet, which allows fitting a large cortical surface within a limited cranial volume. A loss of cortical folds is linked to severe intellectual impairment in humans, so cortical folding is believed to be crucial for brain function. However, developmental mechanisms responsible for cortical folding, and the influence of this on cortical function, remain largely unknown. The goal of this proposal is to understand the genetic and cellular mechanisms that control the developmental expansion and folding of the cerebral cortex, and what is the impact of these processes on its functional organization. Human studies have identified genes essential for the proper folding of the human cerebral cortex. Genetic manipulations in mice have unraveled specific functions for some of those genes in the development of the cerebral cortex. But because the mouse cerebral cortex does not fold naturally, the mechanisms of cortical expansion and folding in larger brains remain unknown. We will study these mechanisms on ferret, an ideal model with a naturally folded cerebral cortex. We will combine the advantages of ferrets with cell biology, genetics and next-generation transcriptomics, together with state-of-the-art in vivo, in vitro and in silico approaches, including in vivo imaging of functional columnar maps. The successful execution of this project will provide insights into developmental and genetic risk factors for anomalies in human cortical topology, and into mechanisms responsible for the early formation of cortical functional maps.
Summary
The mammalian cerebral cortex was subject to a dramatic expansion in surface area during evolution. This process is recapitulated during development and is accompanied by folding of the cortical sheet, which allows fitting a large cortical surface within a limited cranial volume. A loss of cortical folds is linked to severe intellectual impairment in humans, so cortical folding is believed to be crucial for brain function. However, developmental mechanisms responsible for cortical folding, and the influence of this on cortical function, remain largely unknown. The goal of this proposal is to understand the genetic and cellular mechanisms that control the developmental expansion and folding of the cerebral cortex, and what is the impact of these processes on its functional organization. Human studies have identified genes essential for the proper folding of the human cerebral cortex. Genetic manipulations in mice have unraveled specific functions for some of those genes in the development of the cerebral cortex. But because the mouse cerebral cortex does not fold naturally, the mechanisms of cortical expansion and folding in larger brains remain unknown. We will study these mechanisms on ferret, an ideal model with a naturally folded cerebral cortex. We will combine the advantages of ferrets with cell biology, genetics and next-generation transcriptomics, together with state-of-the-art in vivo, in vitro and in silico approaches, including in vivo imaging of functional columnar maps. The successful execution of this project will provide insights into developmental and genetic risk factors for anomalies in human cortical topology, and into mechanisms responsible for the early formation of cortical functional maps.
Max ERC Funding
1 701 116 €
Duration
Start date: 2013-01-01, End date: 2018-06-30
Project acronym CUMTAS
Project Customized Micro Total Analysis Systems to Study Human Phase I Metabolism
Researcher (PI) Tiina Marjukka Sikanen
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS9, ERC-2012-StG_20111109
Summary The goal of this project is to develop inexpensive, high-throughput technology to screen the thus far unexplored metabolic interactions between environmental and household chemicals and clinically relevant drugs. The main influential focus will be on human phase I metabolism (redox reactions) of common toxicants like agrochemicals and plasticizers. On the basis of their structural resemblance to pharmaceuticals and endogenous compounds, many of these chemicals are suspected to have critical effects on cytochrome P450 metabolism which is the main detoxification route of pharmaceuticals in man. However, with the current analytical instrumentation, screening of such large chemical pool would take several years, and new chemicals would be introduced faster than the old ones are screened. Thus, the main technological goal of this project is to develop novel, practically zero-cost analytical instruments that enable characterization of a compound’s metabolic profile at very high speed (<1 min/sample). This goal is achieved through miniaturization and high degree of integration of analytical instrumentation by microfabrication means, an approach often called lab(oratory)-on-a-chip. The microfabricated arrays are envisioned to incorporate all analytical key functions required (i.e., sample pretreatment, metabolic reaction, separation of the reaction products, detection) on a single chip. Thanks to the reduced dimensions, the amount of chemical waste and consumption of expensive reagents are significantly reduced. In this project, several different microfabrication techniques, from delicate cleanroom processes to extremely simple printing techniques, will be exploited to produce smart microfluidic designs and multifunctional surfaces. Towards the end of the project, more focus will be put on “printable microfluidics” which provides a truly low-cost approach for fabrication of highly customized microfluidic assays. Numerical modelling is also an integral part of the work.
Summary
The goal of this project is to develop inexpensive, high-throughput technology to screen the thus far unexplored metabolic interactions between environmental and household chemicals and clinically relevant drugs. The main influential focus will be on human phase I metabolism (redox reactions) of common toxicants like agrochemicals and plasticizers. On the basis of their structural resemblance to pharmaceuticals and endogenous compounds, many of these chemicals are suspected to have critical effects on cytochrome P450 metabolism which is the main detoxification route of pharmaceuticals in man. However, with the current analytical instrumentation, screening of such large chemical pool would take several years, and new chemicals would be introduced faster than the old ones are screened. Thus, the main technological goal of this project is to develop novel, practically zero-cost analytical instruments that enable characterization of a compound’s metabolic profile at very high speed (<1 min/sample). This goal is achieved through miniaturization and high degree of integration of analytical instrumentation by microfabrication means, an approach often called lab(oratory)-on-a-chip. The microfabricated arrays are envisioned to incorporate all analytical key functions required (i.e., sample pretreatment, metabolic reaction, separation of the reaction products, detection) on a single chip. Thanks to the reduced dimensions, the amount of chemical waste and consumption of expensive reagents are significantly reduced. In this project, several different microfabrication techniques, from delicate cleanroom processes to extremely simple printing techniques, will be exploited to produce smart microfluidic designs and multifunctional surfaces. Towards the end of the project, more focus will be put on “printable microfluidics” which provides a truly low-cost approach for fabrication of highly customized microfluidic assays. Numerical modelling is also an integral part of the work.
Max ERC Funding
1 499 668 €
Duration
Start date: 2013-05-01, End date: 2019-02-28
Project acronym DYSTRUCTURE
Project The Dynamical and Structural Basis of Human Mind Complexity: Segregation and Integration of Information and Processing in the Brain
Researcher (PI) Gustavo Deco
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Call Details Advanced Grant (AdG), SH4, ERC-2011-ADG_20110406
Summary "Perceptions, memories, emotions, and everything that makes us human, demand the flexible integration of information represented and computed in a distributed manner. The human brain is structured into a large number of areas in which information and computation are highly segregated. Normal brain functions require the integration of functionally specialized but widely distributed brain areas. Furthermore, human behavior entails a flexible task- dependent interplay between different subsets of these brain areas in order to integrate them according to the corresponding goal-directed requirements. We contend that the functional and encoding roles of diverse neuronal populations across areas are subject to intra- and inter-cortical dynamics. More concretely, we hypothesize that coherent oscillations within frequency-specific large-scale networks and coherent structuring of the underlying fluctuations are crucial mechanisms for the flexible integration of distributed processing and interaction of representations.
The project aims to elucidate precisely the interplay and mutual entrainment between local brain area dynamics and global network dynamics and their breakdown in brain diseases. We wish to better understand how segregated distributed information and processing are integrated in a flexible and context-dependent way as required for goal-directed behavior. It will allow us to comprehend the mechanisms underlying brain functions by complementing structural and activation based analyses with dynamics. We expect to gain a full explanation of the mechanisms that mediate the interactions between global and local spatio-temporal patterns of activity revealed at many levels of observations (fMRI, EEG, MEG) in humans under task and resting conditions, complemented and further constrained by using more detailed characterization of brain dynamics via Local Field Potentials and neuronal recording in animals under task and resting conditions."
Summary
"Perceptions, memories, emotions, and everything that makes us human, demand the flexible integration of information represented and computed in a distributed manner. The human brain is structured into a large number of areas in which information and computation are highly segregated. Normal brain functions require the integration of functionally specialized but widely distributed brain areas. Furthermore, human behavior entails a flexible task- dependent interplay between different subsets of these brain areas in order to integrate them according to the corresponding goal-directed requirements. We contend that the functional and encoding roles of diverse neuronal populations across areas are subject to intra- and inter-cortical dynamics. More concretely, we hypothesize that coherent oscillations within frequency-specific large-scale networks and coherent structuring of the underlying fluctuations are crucial mechanisms for the flexible integration of distributed processing and interaction of representations.
The project aims to elucidate precisely the interplay and mutual entrainment between local brain area dynamics and global network dynamics and their breakdown in brain diseases. We wish to better understand how segregated distributed information and processing are integrated in a flexible and context-dependent way as required for goal-directed behavior. It will allow us to comprehend the mechanisms underlying brain functions by complementing structural and activation based analyses with dynamics. We expect to gain a full explanation of the mechanisms that mediate the interactions between global and local spatio-temporal patterns of activity revealed at many levels of observations (fMRI, EEG, MEG) in humans under task and resting conditions, complemented and further constrained by using more detailed characterization of brain dynamics via Local Field Potentials and neuronal recording in animals under task and resting conditions."
Max ERC Funding
2 467 530 €
Duration
Start date: 2012-07-01, End date: 2017-06-30
Project acronym EarlyDev
Project Brain networks for processing social signals of emotions: early development and the emergence of individual differences
Researcher (PI) Jukka Matias Leppänen
Host Institution (HI) TAMPEREEN YLIOPISTO
Call Details Starting Grant (StG), SH4, ERC-2011-StG_20101124
Summary Recent research has shown that genetic variations in central serotonin function are associated with biases in emotional information processing (heightened attention to signals of negative emotion) and that these biases contribute significantly to vulnerability to affective disorders. Here, we propose to examine a novel hypothesis that the biases in attention to emotional cues are ontogenetically primary, arise very early in development, and modulate an individual’s interaction with the environment during development. The four specific aims of the project are to 1) test the hypothesis that developmental processes resulting in increased functional connectivity of visual and emotion/attention-related neural systems (i.e., increased phase-synchrony of oscillatory activity) from 5 to 7 months of age are associated with the emergence of an overt attentional bias towards affectively salient facial expressions at 7 months of age, 2) use eye-tracking to ascertain that the attentional bias in 7-month-old infants reflects sensitivity to the emotional signal value of facial expressions instead of correlated non-emotional features, 3) test the hypothesis that increased serotonergic tone early in life (through genetic polymorphisms or exposure to serotonin enhancing drugs) is associated with reduced control of attention to affectively salient facial expressions and reduced temperamental emotion-regulation at 7, 24 and 48 months of age, and 4) examine the plasticity of the attentional bias towards emotional facial expressions in infancy, particularly whether the bias can be overridden by using positive reinforcers. The proposed studies will be the first to explicate the neural bases and nature of early-emerging cognitive deficits and biases that pose a risk for emotional dysfunction. As such, the results will be very important for developing intervention methods that benefit of the plasticity of the developing brain and skill formation to support healthy development.
Summary
Recent research has shown that genetic variations in central serotonin function are associated with biases in emotional information processing (heightened attention to signals of negative emotion) and that these biases contribute significantly to vulnerability to affective disorders. Here, we propose to examine a novel hypothesis that the biases in attention to emotional cues are ontogenetically primary, arise very early in development, and modulate an individual’s interaction with the environment during development. The four specific aims of the project are to 1) test the hypothesis that developmental processes resulting in increased functional connectivity of visual and emotion/attention-related neural systems (i.e., increased phase-synchrony of oscillatory activity) from 5 to 7 months of age are associated with the emergence of an overt attentional bias towards affectively salient facial expressions at 7 months of age, 2) use eye-tracking to ascertain that the attentional bias in 7-month-old infants reflects sensitivity to the emotional signal value of facial expressions instead of correlated non-emotional features, 3) test the hypothesis that increased serotonergic tone early in life (through genetic polymorphisms or exposure to serotonin enhancing drugs) is associated with reduced control of attention to affectively salient facial expressions and reduced temperamental emotion-regulation at 7, 24 and 48 months of age, and 4) examine the plasticity of the attentional bias towards emotional facial expressions in infancy, particularly whether the bias can be overridden by using positive reinforcers. The proposed studies will be the first to explicate the neural bases and nature of early-emerging cognitive deficits and biases that pose a risk for emotional dysfunction. As such, the results will be very important for developing intervention methods that benefit of the plasticity of the developing brain and skill formation to support healthy development.
Max ERC Funding
1 397 351 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym IPLASTICITY
Project Induction of juvenile-like plasticity in the adult brain
Researcher (PI) Eero Castrén
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Advanced Grant (AdG), LS5, ERC-2012-ADG_20120314
Summary Neuronal networks are tuned to optimally represent external and internal milieu through neuronal plasticity during critical periods of juvenile life. After the closure of the critical periods, plasticity is considered to be much more limited. In a series of landmark studies, we have shown that critical period-like plasticity can be reactivated in the adult mammalian brain by pharmacological treatment with the antidepressant fluoxetine. These ground-breaking studies establish a new principle, induced juvenile-like plasticity (iPlasticity) and define a new class of drugs, iPlastic drugs. For optimal results, iPlastic drug must be combined with physical or psychological rehabilitation, which guide the plastic networks and together allow better adaptation towards changing environment. iPlasticity may facilitate functional recovery after brain injury and underlie the enhanced efficacy of combined antidepressant treatment and psychotherapy.
We have uncovered iPlasticity as an exciting new concept and established experimental models to study the molecular, cellular and network level mechanisms underlying it. We will here focus on the role of neurotrophin BDNF, because our previous and unpublished work clearly shows that BDNF and its receptors TrkB and p75 are essential and sufficient for iPlasticity. We have found that a major developmental reorganization in TrkB signalling takes place coinciding with the end of critical periods, and its reversal may underlie iPlasticity. We will utilize our resources as a leading lab in BDNF effects in adult brain and through novel controlled transgenic models, genomics and proteomics, we will reveal the role of BDNF signalling through TrkB and p75 in brain maturation, iPlasticity and brain disorders. Understanding the neurobiological background of iPlasticity will be vital for iPlastic drug development and the numerous translational applications of iPlasticity clearly in sight.
Summary
Neuronal networks are tuned to optimally represent external and internal milieu through neuronal plasticity during critical periods of juvenile life. After the closure of the critical periods, plasticity is considered to be much more limited. In a series of landmark studies, we have shown that critical period-like plasticity can be reactivated in the adult mammalian brain by pharmacological treatment with the antidepressant fluoxetine. These ground-breaking studies establish a new principle, induced juvenile-like plasticity (iPlasticity) and define a new class of drugs, iPlastic drugs. For optimal results, iPlastic drug must be combined with physical or psychological rehabilitation, which guide the plastic networks and together allow better adaptation towards changing environment. iPlasticity may facilitate functional recovery after brain injury and underlie the enhanced efficacy of combined antidepressant treatment and psychotherapy.
We have uncovered iPlasticity as an exciting new concept and established experimental models to study the molecular, cellular and network level mechanisms underlying it. We will here focus on the role of neurotrophin BDNF, because our previous and unpublished work clearly shows that BDNF and its receptors TrkB and p75 are essential and sufficient for iPlasticity. We have found that a major developmental reorganization in TrkB signalling takes place coinciding with the end of critical periods, and its reversal may underlie iPlasticity. We will utilize our resources as a leading lab in BDNF effects in adult brain and through novel controlled transgenic models, genomics and proteomics, we will reveal the role of BDNF signalling through TrkB and p75 in brain maturation, iPlasticity and brain disorders. Understanding the neurobiological background of iPlasticity will be vital for iPlastic drug development and the numerous translational applications of iPlasticity clearly in sight.
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym LT-NRBS
Project Lab-in-a-tube and Nanorobotic biosensors
Researcher (PI) Samuel Sánchez Ordóñez
Host Institution (HI) FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
Call Details Starting Grant (StG), LS9, ERC-2012-StG_20111109
Summary The goal of this project is to develop new types of biosensors based on two different approaches: (i) a new bioanalytic microsystem platform for cell growth, manipulation and analysis using on-chip integrated microtubes and (ii) the use of synthetic self-propelled nanomotors for bioanalytical and biosensing applications. Based on the novel “Lab-in-a-tube” concept, we will design a multifunctional device for the capturing, growth and sensing of single cell behaviours inside “glass” microtubes to be employed for diverse biological applications. We will decorate the walls of the microtubes with proteins from the extracellular matrix enabling the long-term study of cellular changes such as mitosis time, spindle reorientation, DNA damage and cellular differentiation. These microtubes are fabricated by the well-established rolled-up nanotechnology developed in the host institution. Moreover, the multifunctionality of the “Lab-in-a-tube” platform will be extended by integrating different modules into a single microtubular unit, bringing up several applications such as optofluidics(bio)sensors, electrodes for electrochemical control and sensing, and magnetic biodetection.
At the IIN institute in IFW Dresden, we are pioneers on the fabrication of catalytic microjet engines (microbots) and their use for transporting different kinds of objects in vitro into a fluid. The remote controlled motion of these autonomous microbots and the transport of microobjects and cells to specific targets within lab-on-a-chip systems is possible. Their walls can be biofunctionalized with enzymes, antibodies or DNA, the catalytic microbots representing a novel and unique tool for biosensing, environmental and biomedical applications. Our next step is to use biocompatible fuels to propel these microbots with the final aim of transporting and delivering drugs in vivo.The separation of cancer cells, bacteria and other biomaterials to build up new tissues or to replace disease cells are also aimed.
Summary
The goal of this project is to develop new types of biosensors based on two different approaches: (i) a new bioanalytic microsystem platform for cell growth, manipulation and analysis using on-chip integrated microtubes and (ii) the use of synthetic self-propelled nanomotors for bioanalytical and biosensing applications. Based on the novel “Lab-in-a-tube” concept, we will design a multifunctional device for the capturing, growth and sensing of single cell behaviours inside “glass” microtubes to be employed for diverse biological applications. We will decorate the walls of the microtubes with proteins from the extracellular matrix enabling the long-term study of cellular changes such as mitosis time, spindle reorientation, DNA damage and cellular differentiation. These microtubes are fabricated by the well-established rolled-up nanotechnology developed in the host institution. Moreover, the multifunctionality of the “Lab-in-a-tube” platform will be extended by integrating different modules into a single microtubular unit, bringing up several applications such as optofluidics(bio)sensors, electrodes for electrochemical control and sensing, and magnetic biodetection.
At the IIN institute in IFW Dresden, we are pioneers on the fabrication of catalytic microjet engines (microbots) and their use for transporting different kinds of objects in vitro into a fluid. The remote controlled motion of these autonomous microbots and the transport of microobjects and cells to specific targets within lab-on-a-chip systems is possible. Their walls can be biofunctionalized with enzymes, antibodies or DNA, the catalytic microbots representing a novel and unique tool for biosensing, environmental and biomedical applications. Our next step is to use biocompatible fuels to propel these microbots with the final aim of transporting and delivering drugs in vivo.The separation of cancer cells, bacteria and other biomaterials to build up new tissues or to replace disease cells are also aimed.
Max ERC Funding
1 499 880 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym SEROTONINANDDISEASE
Project Dissecting the gene regulatory mechanisms that generate serotonergic neurons and their link to mental disorders
Researcher (PI) Nuria Flames Bonilla
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Starting Grant (StG), LS5, ERC-2011-StG_20101109
Summary Mental disorders constitute a human an economic burden for developed countries. Many mental disorders are linked to serotonin dysfunction, but the exact mechanism underlying these disorders is not well understood. Serotonin Related Mental Disorders (SRMD) are multigenic, making the identification of these mechanisms a difficult task. Understanding the molecular mechanisms that generate serotonergic neurons will provide us with the tools to identify mutations that could predispose to SRMD. In this grant we will use a multidisciplinary approach to dissect the transcriptional mechanisms that generate serotonergic neurons and use this knowledge to identify genetic links to SRMD. Serotonergic neurons are very ancient in evolution and enzymes and transporters responsible for the production of serotonin (serotonin pathway genes) are very well conserved in all metazoans. We would take advantage of this evolutionary conservation and use the genetic amenability of C. elegans to dissect the genetic mechanisms responsible for the generation of the serotonergic neurons. We will apply the lessons learned from C. elegans to unravel analogous mechanisms regulating mouse serotonergic differentiation. Our preliminary results show that the serotonergic pathway genes are co-regulated by the same factors and that this mechanism is evolutionary conserved. We will identify the cis-acting sequences (serotonergic motif) and trans-acting factors responsible for the activation of the serotonergic features, both in worms and mice. Finally, we will apply our knowledge on serotonergic differentiation to identify genetic association to SRMDs. Mutations in the serotonergic motif could lead to defects on the expression of the serotonergic genes, resulting in a dysfunctional serotonergic neuron. We will build a database of all human serotonergic motifs and look for mutations in these sites in SRMD patients. In summary, this grant will give us the tools to better understand and treat SRMD.
Summary
Mental disorders constitute a human an economic burden for developed countries. Many mental disorders are linked to serotonin dysfunction, but the exact mechanism underlying these disorders is not well understood. Serotonin Related Mental Disorders (SRMD) are multigenic, making the identification of these mechanisms a difficult task. Understanding the molecular mechanisms that generate serotonergic neurons will provide us with the tools to identify mutations that could predispose to SRMD. In this grant we will use a multidisciplinary approach to dissect the transcriptional mechanisms that generate serotonergic neurons and use this knowledge to identify genetic links to SRMD. Serotonergic neurons are very ancient in evolution and enzymes and transporters responsible for the production of serotonin (serotonin pathway genes) are very well conserved in all metazoans. We would take advantage of this evolutionary conservation and use the genetic amenability of C. elegans to dissect the genetic mechanisms responsible for the generation of the serotonergic neurons. We will apply the lessons learned from C. elegans to unravel analogous mechanisms regulating mouse serotonergic differentiation. Our preliminary results show that the serotonergic pathway genes are co-regulated by the same factors and that this mechanism is evolutionary conserved. We will identify the cis-acting sequences (serotonergic motif) and trans-acting factors responsible for the activation of the serotonergic features, both in worms and mice. Finally, we will apply our knowledge on serotonergic differentiation to identify genetic association to SRMDs. Mutations in the serotonergic motif could lead to defects on the expression of the serotonergic genes, resulting in a dysfunctional serotonergic neuron. We will build a database of all human serotonergic motifs and look for mutations in these sites in SRMD patients. In summary, this grant will give us the tools to better understand and treat SRMD.
Max ERC Funding
1 931 621 €
Duration
Start date: 2012-12-01, End date: 2018-11-30