Project acronym AEDNA
Project Amorphous and Evolutionary DNA Nanotechnology
Researcher (PI) Friedrich SIMMEL
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Advanced Grant (AdG), PE5, ERC-2015-AdG
Summary Amorphous and evolutionary DNA nanotechnology (AEDNA) explores novel conceptual directions and applications for DNA nanotechnology, which are based on intelligent, DNA-programmed soft hybrid materials, and the utilization of evolutionary principles for the optimization of nucleic acid nanocomponents.
Amorphous DNA nanotechnology first aims at the creation of cell-sized, DNA-programmed microgels – DNA cells – with sensor, computation, communication, and actuator functions. Interacting DNA cells will be arranged into chemical cell consortia and artificial tissues using microfluidics, micromanipulation and 3D bioprinting techniques. Spatially distributed chemical circuits will then be utilized to establish collective behaviors such as quorum sensing, pattern formation, and self-differentiation within these consortia and tissues. The approach will be further scaled up to produce multicomponent DNA gel compositions that become active and differentiate upon mixing.
In evolutionary nanotechnology, techniques derived from directed molecular evolution experiments will be applied to optimize the arrangement of functional nucleic acids on DNA and RNA nanoscaffolds. Compartmentalization and microfluidics will be utilized to screen for nucleic acid nanostructures capable of superstructure formation, and also for the development of ligand-sensitive components for molecular programming. An evolutionary approach will then be applied to amorphous DNA cells, resulting in DNA cell populations which contain individuals with different molecular identities.
The proposal will pave the way for the creation of macroscopic materials with DNA-programmed intelligence, resulting in novel applications for DNA nanotechnology and molecular programming in diverse fields such as environmental and biological sensing, biocatalysis, smart adaptive materials, and soft robotics.
Summary
Amorphous and evolutionary DNA nanotechnology (AEDNA) explores novel conceptual directions and applications for DNA nanotechnology, which are based on intelligent, DNA-programmed soft hybrid materials, and the utilization of evolutionary principles for the optimization of nucleic acid nanocomponents.
Amorphous DNA nanotechnology first aims at the creation of cell-sized, DNA-programmed microgels – DNA cells – with sensor, computation, communication, and actuator functions. Interacting DNA cells will be arranged into chemical cell consortia and artificial tissues using microfluidics, micromanipulation and 3D bioprinting techniques. Spatially distributed chemical circuits will then be utilized to establish collective behaviors such as quorum sensing, pattern formation, and self-differentiation within these consortia and tissues. The approach will be further scaled up to produce multicomponent DNA gel compositions that become active and differentiate upon mixing.
In evolutionary nanotechnology, techniques derived from directed molecular evolution experiments will be applied to optimize the arrangement of functional nucleic acids on DNA and RNA nanoscaffolds. Compartmentalization and microfluidics will be utilized to screen for nucleic acid nanostructures capable of superstructure formation, and also for the development of ligand-sensitive components for molecular programming. An evolutionary approach will then be applied to amorphous DNA cells, resulting in DNA cell populations which contain individuals with different molecular identities.
The proposal will pave the way for the creation of macroscopic materials with DNA-programmed intelligence, resulting in novel applications for DNA nanotechnology and molecular programming in diverse fields such as environmental and biological sensing, biocatalysis, smart adaptive materials, and soft robotics.
Max ERC Funding
2 157 698 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym AGATM
Project A Global Anthropology of Transforming Marriage
Researcher (PI) Janet CARSTEN
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Country United Kingdom
Call Details Advanced Grant (AdG), SH5, ERC-2015-AdG
Summary This research will create a new theoretical vision of the importance of marriage as an agent of transformation in human sociality. Marriage globally is undergoing profound change, provoking intense debate and anxiety. These concerns refract wider instabilities in political, economic, and familial institutions. They signal the critical role of marriage in bringing together - and separating - intimate, personal, and familial life with wider state institutions. But we have little up to date comparative research or general theory of how marriage changes or the long-term significance of such change. Paradoxically, social scientific and public discourse emphasise the conservative and normative aspects of marriage. This underlines the need for a new theoretical frame that takes account of cultural and historical specificity to grasp the importance of marriage as both vehicle of and engine for transformation. AGATM overturns conventional understandings by viewing marriage as inherently transformative, indeed at the heart of social and cultural change. The research will investigate current transformations of marriage in two distinct senses. First, it will undertake an ethnographic investigation of new forms of marriage in selected sites in Europe, N. America, Asia, and Africa. Second, it will subject ‘marriage’ to a rigorous theoretical critique that will denaturalise marriage and reintegrate it into the new anthropology of kinship. Research on five complementary and contrastive sub-projects examining emerging forms of marriage in different locations will be structured through the themes of care, property, and ritual forms. The overarching analytic of temporality will frame the theoretical vision of the research and connect the themes. The resulting six monographs, journal articles, and exhibition will together revitalise the study of kinship by placing the moral, practical, political, and imaginative significance of marriage over time at its centre.
Summary
This research will create a new theoretical vision of the importance of marriage as an agent of transformation in human sociality. Marriage globally is undergoing profound change, provoking intense debate and anxiety. These concerns refract wider instabilities in political, economic, and familial institutions. They signal the critical role of marriage in bringing together - and separating - intimate, personal, and familial life with wider state institutions. But we have little up to date comparative research or general theory of how marriage changes or the long-term significance of such change. Paradoxically, social scientific and public discourse emphasise the conservative and normative aspects of marriage. This underlines the need for a new theoretical frame that takes account of cultural and historical specificity to grasp the importance of marriage as both vehicle of and engine for transformation. AGATM overturns conventional understandings by viewing marriage as inherently transformative, indeed at the heart of social and cultural change. The research will investigate current transformations of marriage in two distinct senses. First, it will undertake an ethnographic investigation of new forms of marriage in selected sites in Europe, N. America, Asia, and Africa. Second, it will subject ‘marriage’ to a rigorous theoretical critique that will denaturalise marriage and reintegrate it into the new anthropology of kinship. Research on five complementary and contrastive sub-projects examining emerging forms of marriage in different locations will be structured through the themes of care, property, and ritual forms. The overarching analytic of temporality will frame the theoretical vision of the research and connect the themes. The resulting six monographs, journal articles, and exhibition will together revitalise the study of kinship by placing the moral, practical, political, and imaginative significance of marriage over time at its centre.
Max ERC Funding
2 297 584 €
Duration
Start date: 2017-01-01, End date: 2022-06-30
Project acronym APEG
Project Algorithmic Performance Guarantees: Foundations and Applications
Researcher (PI) Susanne ALBERS
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Advanced Grant (AdG), PE6, ERC-2015-AdG
Summary Optimization problems are ubiquitous in computer science. Almost every problem involves the optimization of some objective function. However a major part of these problems cannot be solved to optimality. Therefore, algorithms that achieve provably good performance guarantees are of immense importance. Considerable progress has already been made, but great challenges remain: Some fundamental problems are not well understood. Moreover, for central problems arising in new applications, no solutions are known at all.
The goal of APEG is to significantly advance the state of the art on algorithmic performance guarantees. Specifically, the project has two missions: First, it will develop new algorithmic techniques, breaking new ground in the areas of online algorithms, approximations algorithms and algorithmic game theory. Second, it will apply these techniques to solve fundamental problems that are central in these algorithmic disciplines. APEG will attack long-standing open problems, some of which have been unresolved for several decades. Furthermore, it will formulate and investigate new algorithmic problems that arise in modern applications. The research agenda encompasses a broad spectrum of classical and timely topics including (a) resource allocation in computer systems, (b) data structuring, (c) graph problems, with relations to Internet advertising, (d) complex networks and (e) massively parallel systems. In addition to basic optimization objectives, the project will also study the new performance metric of energy minimization in computer systems.
Overall, APEG pursues cutting-edge algorithms research, focusing on both foundational problems and applications. Any progress promises to be a breakthrough or significant contribution.
Summary
Optimization problems are ubiquitous in computer science. Almost every problem involves the optimization of some objective function. However a major part of these problems cannot be solved to optimality. Therefore, algorithms that achieve provably good performance guarantees are of immense importance. Considerable progress has already been made, but great challenges remain: Some fundamental problems are not well understood. Moreover, for central problems arising in new applications, no solutions are known at all.
The goal of APEG is to significantly advance the state of the art on algorithmic performance guarantees. Specifically, the project has two missions: First, it will develop new algorithmic techniques, breaking new ground in the areas of online algorithms, approximations algorithms and algorithmic game theory. Second, it will apply these techniques to solve fundamental problems that are central in these algorithmic disciplines. APEG will attack long-standing open problems, some of which have been unresolved for several decades. Furthermore, it will formulate and investigate new algorithmic problems that arise in modern applications. The research agenda encompasses a broad spectrum of classical and timely topics including (a) resource allocation in computer systems, (b) data structuring, (c) graph problems, with relations to Internet advertising, (d) complex networks and (e) massively parallel systems. In addition to basic optimization objectives, the project will also study the new performance metric of energy minimization in computer systems.
Overall, APEG pursues cutting-edge algorithms research, focusing on both foundational problems and applications. Any progress promises to be a breakthrough or significant contribution.
Max ERC Funding
2 404 250 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym ARTISYM
Project Artificial endosymbiosis
Researcher (PI) Jan Van hest
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Country Netherlands
Call Details Advanced Grant (AdG), PE5, ERC-2015-AdG
Summary Living organisms have acquired new functionalities by uptake and integration of species to create symbiotic life-forms. This process of endosymbiosis has intrigued scientists over the years, albeit mostly from an evolution biology perspective. With the advance of chemical and synthetic biology, our ability to create molecular-life-like systems has increased tremendously, which enables us to build cell and organelle-like structures. However, these advances have not been taken to a level to study comprehensively if endosymbiosis can be applied to non-living systems or to integrate living with non-living matter. The aim of the research described in the ARTISYM proposal is to establish the field of artificial endosymbiosis. Two lines of research will be followed. First, we will incorporate artificial organelles in living cells to design hybrid cells with acquired functionality. This investigation is scientifically of great interest, as it will show us how to introduce novel compartmentalized pathways into living organisms. It also serves an important societal goal, as with these compartments dysfunctional cellular processes can be corrected. We will follow both a transient and a permanent approach. With the transient route biodegradable nanoreactors are introduced to supply living cells temporarily with novel function. Functionality is permanently introduced using genetic engineering to express protein-based nanoreactors in living cells, or via organelle transplantation of healthy mitochondria in diseased living cells. Secondly I aim to create artificial cells with the ability to perform endosymbiosis; the uptake and presence of artificial organelles in synthetic vesicles allows them to dynamically respond to their environment. Responses that are envisaged are shape changes, motility, and growth and division. Furthermore, the incorporation of natural organelles in liposomes provides biocatalytic cascades with the necessary cofactors to function in an artificial cell
Summary
Living organisms have acquired new functionalities by uptake and integration of species to create symbiotic life-forms. This process of endosymbiosis has intrigued scientists over the years, albeit mostly from an evolution biology perspective. With the advance of chemical and synthetic biology, our ability to create molecular-life-like systems has increased tremendously, which enables us to build cell and organelle-like structures. However, these advances have not been taken to a level to study comprehensively if endosymbiosis can be applied to non-living systems or to integrate living with non-living matter. The aim of the research described in the ARTISYM proposal is to establish the field of artificial endosymbiosis. Two lines of research will be followed. First, we will incorporate artificial organelles in living cells to design hybrid cells with acquired functionality. This investigation is scientifically of great interest, as it will show us how to introduce novel compartmentalized pathways into living organisms. It also serves an important societal goal, as with these compartments dysfunctional cellular processes can be corrected. We will follow both a transient and a permanent approach. With the transient route biodegradable nanoreactors are introduced to supply living cells temporarily with novel function. Functionality is permanently introduced using genetic engineering to express protein-based nanoreactors in living cells, or via organelle transplantation of healthy mitochondria in diseased living cells. Secondly I aim to create artificial cells with the ability to perform endosymbiosis; the uptake and presence of artificial organelles in synthetic vesicles allows them to dynamically respond to their environment. Responses that are envisaged are shape changes, motility, and growth and division. Furthermore, the incorporation of natural organelles in liposomes provides biocatalytic cascades with the necessary cofactors to function in an artificial cell
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym Babylearn
Project Neural mechanisms of learning in the infant brain : from Statistics to Rules and Symbols
Researcher (PI) Ghislaine, Marie-Therese, Aline DEHAENE-LAMBERTZ
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Country France
Call Details Advanced Grant (AdG), SH4, ERC-2015-AdG
Summary Infant is the most powerful learner: He learns in a few months to master language, complex social interactions, etc. Powerful statistical algorithms, simultaneously acting at the different levels of functional hierarchies have been proposed to explain learning. I propose here that two other elements are crucial. The first is the particular human cerebral architecture that constrains statistical computations. The second is the human’s ability to access a rich symbolic system. I have planned 6 work packages using the complementary information offered by non-invasive brain-imaging techniques (EEG, MRI and optical topography) to understand the neural bases of infant statistical computations and symbolic competence from 6 months of gestation up until the end of the first year of life.
WP1 studies from which preterm age, statistical inferences can be demonstrated using hierarchical auditory oddball paradigms.
WP2 investigates the consequences of a different pre-term environment (in-utero versus ex-utero) on the early statistical computations in the visual and auditory domains and their consequences on the ongoing brain activity along the first year of life.
WP3 explores the neural bases of how infants infer word meaning and word category, and in particular the role of the left perisylvian areas and of their particular connectivity.
WP4 questions infant symbolic competency. I propose several criteria (generalization, bidirectionality, use of algebraic rules and of logical operations) tested in successive experiments to clarify infant symbolic abilities during the first semester of life.
WP5-6 are transversal to WP1-4: WP5 uses MRI to obtain accurate functional localization and maturational markers correlated with functional results. In WP6, we develop new tools to combine and analyse multimodal brain images.
With this proposal, I hope to clarify the specificities of a neural functional architecture that are critical for human learning from the onset of cortical circuits.
Summary
Infant is the most powerful learner: He learns in a few months to master language, complex social interactions, etc. Powerful statistical algorithms, simultaneously acting at the different levels of functional hierarchies have been proposed to explain learning. I propose here that two other elements are crucial. The first is the particular human cerebral architecture that constrains statistical computations. The second is the human’s ability to access a rich symbolic system. I have planned 6 work packages using the complementary information offered by non-invasive brain-imaging techniques (EEG, MRI and optical topography) to understand the neural bases of infant statistical computations and symbolic competence from 6 months of gestation up until the end of the first year of life.
WP1 studies from which preterm age, statistical inferences can be demonstrated using hierarchical auditory oddball paradigms.
WP2 investigates the consequences of a different pre-term environment (in-utero versus ex-utero) on the early statistical computations in the visual and auditory domains and their consequences on the ongoing brain activity along the first year of life.
WP3 explores the neural bases of how infants infer word meaning and word category, and in particular the role of the left perisylvian areas and of their particular connectivity.
WP4 questions infant symbolic competency. I propose several criteria (generalization, bidirectionality, use of algebraic rules and of logical operations) tested in successive experiments to clarify infant symbolic abilities during the first semester of life.
WP5-6 are transversal to WP1-4: WP5 uses MRI to obtain accurate functional localization and maturational markers correlated with functional results. In WP6, we develop new tools to combine and analyse multimodal brain images.
With this proposal, I hope to clarify the specificities of a neural functional architecture that are critical for human learning from the onset of cortical circuits.
Max ERC Funding
2 554 924 €
Duration
Start date: 2016-09-01, End date: 2022-02-28
Project acronym BABYRHYTHM
Project Oscillatory Rhythmic Entrainment and the Foundations of Language Acquisition
Researcher (PI) Usha Claire GOSWAMI
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Advanced Grant (AdG), SH4, ERC-2015-AdG
Summary Half of “late talkers”, infants who are not yet speaking by 2 years of age, will go on to develop language impairments. Currently, we have no reliable means of identifying these infants. Here we combine our developmental approach to phonology (psycholinguistic grain size theory), to the neural mechanisms underlying speech encoding (temporal sampling [TS] theory) and our work on the developmental importance of the speech amplitude envelope (AE) to open a new research front in the foundations of language acquisition. Recent adult research confirms our decade-long focus on the importance of sensitivity to AE ‘rise time’ in children’s language development, showing that rise times (‘auditory edges’) re-set the endogenous cortical oscillations that encode speech. Accordingly, we now apply our in-house state-of-the-art methods for measuring oscillatory rhythmic entrainment in children along with our recent theoretical and behavioural advances concerning AE processing to infant studies. Our core aim is to use the TS theoretical perspective and analysis methods to generate robust early neural and behavioural markers of phonological and morphological development: TS for infants. We have published the first-ever studies of oscillatory entrainment to speech rhythm by children and we have developed methods for technically-challenging EEG speech envelope reconstruction. We now apply these innovative methods to infant language learning and infant-directed speech. Using our cutting-edge EEG methods, we will deliver a novel and innovative road map for charting early language acquisition from a rhythmic entrainment perspective. Our recent 5-year study of rise time sensitivity in infants confirms the feasibility of a TS approach. As our focus is on prosody, syllable stress and syllable processing, our methods will apply across European languages.
Summary
Half of “late talkers”, infants who are not yet speaking by 2 years of age, will go on to develop language impairments. Currently, we have no reliable means of identifying these infants. Here we combine our developmental approach to phonology (psycholinguistic grain size theory), to the neural mechanisms underlying speech encoding (temporal sampling [TS] theory) and our work on the developmental importance of the speech amplitude envelope (AE) to open a new research front in the foundations of language acquisition. Recent adult research confirms our decade-long focus on the importance of sensitivity to AE ‘rise time’ in children’s language development, showing that rise times (‘auditory edges’) re-set the endogenous cortical oscillations that encode speech. Accordingly, we now apply our in-house state-of-the-art methods for measuring oscillatory rhythmic entrainment in children along with our recent theoretical and behavioural advances concerning AE processing to infant studies. Our core aim is to use the TS theoretical perspective and analysis methods to generate robust early neural and behavioural markers of phonological and morphological development: TS for infants. We have published the first-ever studies of oscillatory entrainment to speech rhythm by children and we have developed methods for technically-challenging EEG speech envelope reconstruction. We now apply these innovative methods to infant language learning and infant-directed speech. Using our cutting-edge EEG methods, we will deliver a novel and innovative road map for charting early language acquisition from a rhythmic entrainment perspective. Our recent 5-year study of rise time sensitivity in infants confirms the feasibility of a TS approach. As our focus is on prosody, syllable stress and syllable processing, our methods will apply across European languages.
Max ERC Funding
2 614 275 €
Duration
Start date: 2016-09-01, End date: 2022-08-31
Project acronym BARRIERS
Project The evolution of barriers to gene exchange
Researcher (PI) Roger BUTLIN
Host Institution (HI) THE UNIVERSITY OF SHEFFIELD
Country United Kingdom
Call Details Advanced Grant (AdG), LS8, ERC-2015-AdG
Summary Speciation is a central process in evolution that involves the origin of barriers to gene flow between populations. Species are typically isolated by several barriers and assembly of multiple barriers separating the same populations seems to be critical to the evolution of strong reproductive isolation. Barriers resulting from direct selection can become coincident through a process of coupling while reinforcement can add barrier traits that are not under direct selection. In the presence of gene flow, these processes are opposed by recombination. While recent research using the latest sequencing technologies has provided much increased knowledge of patterns of differentiation and the genetic basis of local adaptation, it has so far added little to understanding of the coupling and reinforcement processes.
In this project, I will focus on the accumulation of barriers to gene exchange and the processes underlying increasing reproductive isolation. I will use the power of natural contact zones, combined with novel manipulative experiments, to separate the processes that underlie patterns of differentiation and introgression. The Littorina saxatilis model system allows me to do this with both local replication and a contrast between distinct spatial contexts on a larger geographic scale. I will use modelling to determine how processes interact and to investigate the conditions most likely to promote coupling and reinforcement. Overall, the project will provide major new insights into the speciation process, particularly revealing the requirements for progress towards complete reproductive isolation.
Summary
Speciation is a central process in evolution that involves the origin of barriers to gene flow between populations. Species are typically isolated by several barriers and assembly of multiple barriers separating the same populations seems to be critical to the evolution of strong reproductive isolation. Barriers resulting from direct selection can become coincident through a process of coupling while reinforcement can add barrier traits that are not under direct selection. In the presence of gene flow, these processes are opposed by recombination. While recent research using the latest sequencing technologies has provided much increased knowledge of patterns of differentiation and the genetic basis of local adaptation, it has so far added little to understanding of the coupling and reinforcement processes.
In this project, I will focus on the accumulation of barriers to gene exchange and the processes underlying increasing reproductive isolation. I will use the power of natural contact zones, combined with novel manipulative experiments, to separate the processes that underlie patterns of differentiation and introgression. The Littorina saxatilis model system allows me to do this with both local replication and a contrast between distinct spatial contexts on a larger geographic scale. I will use modelling to determine how processes interact and to investigate the conditions most likely to promote coupling and reinforcement. Overall, the project will provide major new insights into the speciation process, particularly revealing the requirements for progress towards complete reproductive isolation.
Max ERC Funding
2 499 927 €
Duration
Start date: 2016-09-01, End date: 2022-02-28
Project acronym BISON
Project Bio-Inspired Self-Assembled Supramolecular Organic Nanostructures
Researcher (PI) Ehud Gazit
Host Institution (HI) TEL AVIV UNIVERSITY
Country Israel
Call Details Advanced Grant (AdG), LS9, ERC-2015-AdG
Summary Peptide building blocks serve as very attractive bio-inspired elements in nanotechnology owing to their controlled self-assembly, inherent biocompatibility, chemical versatility, biological recognition abilities and facile synthesis. We have demonstrated the ability of remarkably simple aromatic peptides to form well-ordered nanostructures of exceptional physical properties. By taking inspiration from the minimal recognition modules used by nature to mediate coordinated processes of self-assembly, we have developed building blocks that form well-ordered nanostructures. The compact design of the building blocks, and therefore, the unique structural organization, resulted in metallic-like Young's modulus, blue luminescence due to quantum confinement, and notable piezoelectric properties. The goal of this proposal is to develop two new fronts for bio-inspired building block repertoire along with co-assembly to provide new avenues for organic nanotechnology. This will combine our vast experience in the assembly of aromatic peptides together with additional structural modules from nature. The new entities will be developed by exploiting the design principles of small aromatic building blocks to arrive at the smallest possible module that form super helical assembly based on the coiled coil motifs and establishing peptide nucleic acids based systems to combine the worlds of peptide and DNA nanotechnologies. The proposed research will combine extensive design and synthesis effort to provide a very diverse collection of novel buildings blocks and determination of their self-assembly process, followed by broad chemical, physical, and biological characterization of the nanostructures. Furthermore, effort will be made to establish supramolecular co-polymer systems to extend the morphological control of the assembly process. The result of the project will be a large and defined collection of novel chemical entities that will help reshape the field of bioorganic nanotechnology.
Summary
Peptide building blocks serve as very attractive bio-inspired elements in nanotechnology owing to their controlled self-assembly, inherent biocompatibility, chemical versatility, biological recognition abilities and facile synthesis. We have demonstrated the ability of remarkably simple aromatic peptides to form well-ordered nanostructures of exceptional physical properties. By taking inspiration from the minimal recognition modules used by nature to mediate coordinated processes of self-assembly, we have developed building blocks that form well-ordered nanostructures. The compact design of the building blocks, and therefore, the unique structural organization, resulted in metallic-like Young's modulus, blue luminescence due to quantum confinement, and notable piezoelectric properties. The goal of this proposal is to develop two new fronts for bio-inspired building block repertoire along with co-assembly to provide new avenues for organic nanotechnology. This will combine our vast experience in the assembly of aromatic peptides together with additional structural modules from nature. The new entities will be developed by exploiting the design principles of small aromatic building blocks to arrive at the smallest possible module that form super helical assembly based on the coiled coil motifs and establishing peptide nucleic acids based systems to combine the worlds of peptide and DNA nanotechnologies. The proposed research will combine extensive design and synthesis effort to provide a very diverse collection of novel buildings blocks and determination of their self-assembly process, followed by broad chemical, physical, and biological characterization of the nanostructures. Furthermore, effort will be made to establish supramolecular co-polymer systems to extend the morphological control of the assembly process. The result of the project will be a large and defined collection of novel chemical entities that will help reshape the field of bioorganic nanotechnology.
Max ERC Funding
3 003 125 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym BYPASSWITHOUTSURGERY
Project Reaching the effects of gastric bypass on diabetes and obesity without surgery
Researcher (PI) Jens Juul Holst
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Advanced Grant (AdG), LS4, ERC-2015-AdG
Summary Gastric bypass surgery results in massive weight loss and diabetes remission. The effect is superior to intensive medical treatment, showing that there are mechanisms within the body that can cure diabetes and obesity. Revealing the nature of these mechanisms could lead to new, cost-efficient, similarly effective, non-invasive treatments of these conditions. The hypothesis is that hyper-secretion of a number of gut hormones mediates the effect of surgery, as indicated by a series of our recent studies, demonstrating that hypersecretion of GLP-1, a hormone discovered in my laboratory and basis for the antidiabetic medication of millions of patients, is essential for the improved insulin secretion and glucose tolerance. But what are the mechanisms behind the up to 30-fold elevations in secretion of these hormones following surgery? Constantly with a translational scope, all elements involved in these responses will be addressed in this project, from detailed analysis of food items responsible for hormone secretion, to identification of the responsible regions of the gut, and to the molecular mechanisms leading to hypersecretion. Novel approaches for studies of human gut hormone secreting cells, including specific expression analysis, are combined with our advanced and unique isolated perfused gut preparations, the only tool that can provide physiologically relevant results with a translational potential regarding regulation of hormone secretion in the gut. This will lead to further groundbreaking experimental attempts to mimic and engage the identified mechanisms, creating similar hypersecretion and obtaining similar improvements as the operations in patients with obesity and diabetes. Based on our profound knowledge of gut hormone biology accumulated through decades of intensive and successful research and our successful elucidation of the antidiabetic actions of gastric bypass surgery, we are in a unique position to reach this ambitious goal.
Summary
Gastric bypass surgery results in massive weight loss and diabetes remission. The effect is superior to intensive medical treatment, showing that there are mechanisms within the body that can cure diabetes and obesity. Revealing the nature of these mechanisms could lead to new, cost-efficient, similarly effective, non-invasive treatments of these conditions. The hypothesis is that hyper-secretion of a number of gut hormones mediates the effect of surgery, as indicated by a series of our recent studies, demonstrating that hypersecretion of GLP-1, a hormone discovered in my laboratory and basis for the antidiabetic medication of millions of patients, is essential for the improved insulin secretion and glucose tolerance. But what are the mechanisms behind the up to 30-fold elevations in secretion of these hormones following surgery? Constantly with a translational scope, all elements involved in these responses will be addressed in this project, from detailed analysis of food items responsible for hormone secretion, to identification of the responsible regions of the gut, and to the molecular mechanisms leading to hypersecretion. Novel approaches for studies of human gut hormone secreting cells, including specific expression analysis, are combined with our advanced and unique isolated perfused gut preparations, the only tool that can provide physiologically relevant results with a translational potential regarding regulation of hormone secretion in the gut. This will lead to further groundbreaking experimental attempts to mimic and engage the identified mechanisms, creating similar hypersecretion and obtaining similar improvements as the operations in patients with obesity and diabetes. Based on our profound knowledge of gut hormone biology accumulated through decades of intensive and successful research and our successful elucidation of the antidiabetic actions of gastric bypass surgery, we are in a unique position to reach this ambitious goal.
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym C.NAPSE
Project TOWARDS A COMPREHENSIVE ANALYSIS OF EXTRACELLULAR SCAFFOLDING AT THE SYNAPSE
Researcher (PI) Jean-Louis BESSEREAU
Host Institution (HI) UNIVERSITE LYON 1 CLAUDE BERNARD
Country France
Call Details Advanced Grant (AdG), LS5, ERC-2015-AdG
Summary Synaptic scaffolding molecules control the localization and the abundance of neurotransmitter receptors at the synapse, a key parameter to shape synaptic transfer function. Most characterized synaptic scaffolds are intracellular, yet a growing number of secreted proteins appear to organize the synapse from the outside of the cell. We recently demonstrated in C. elegans that an evolutionarily conserved protein secreted by motoneurons specifies the excitatory versus inhibitory identity of the postsynaptic domains at neuromuscular synapses. We propose to use this system as a genetically tractable paradigm to perform a comprehensive characterization of this unforeseen synaptic organization.
Specifically, this project will pursue 4 complementary aims:
1) Identify and characterize a comprehensive set of genes that organize and control the formation and maintenance of these scaffolds through a series of genetic screens based on the direct visualization of fluorescent acetylcholine and GABA receptors in living animals.
2) Solve the spatial synaptic organization of these scaffolds at a nanoscale resolution using super-resolutive and correlative light and electron microscopy, and analyze their dynamic behavior in vivo by implementing Single Particle Tracking imaging in living worms.
3) Decipher the role of the synaptomatrix in the organization of synaptic extracellular scaffolds and evaluate its functional contribution at the physiological and molecular levels using a candidate gene strategy and innovative imaging.
4) Analyze the formation and decline of these scaffolds at the lifetime scale and evaluate the role of synaptic activity and aging in these processes by taking advantage of the possibility to follow identified synapses over the entire life of C. elegans.
Using powerful genetics in combination with cutting-edge in vivo imaging and electrophysiology, we anticipate to identify new genes and new mechanisms at work to regulate normal and pathological synaptic function.
Summary
Synaptic scaffolding molecules control the localization and the abundance of neurotransmitter receptors at the synapse, a key parameter to shape synaptic transfer function. Most characterized synaptic scaffolds are intracellular, yet a growing number of secreted proteins appear to organize the synapse from the outside of the cell. We recently demonstrated in C. elegans that an evolutionarily conserved protein secreted by motoneurons specifies the excitatory versus inhibitory identity of the postsynaptic domains at neuromuscular synapses. We propose to use this system as a genetically tractable paradigm to perform a comprehensive characterization of this unforeseen synaptic organization.
Specifically, this project will pursue 4 complementary aims:
1) Identify and characterize a comprehensive set of genes that organize and control the formation and maintenance of these scaffolds through a series of genetic screens based on the direct visualization of fluorescent acetylcholine and GABA receptors in living animals.
2) Solve the spatial synaptic organization of these scaffolds at a nanoscale resolution using super-resolutive and correlative light and electron microscopy, and analyze their dynamic behavior in vivo by implementing Single Particle Tracking imaging in living worms.
3) Decipher the role of the synaptomatrix in the organization of synaptic extracellular scaffolds and evaluate its functional contribution at the physiological and molecular levels using a candidate gene strategy and innovative imaging.
4) Analyze the formation and decline of these scaffolds at the lifetime scale and evaluate the role of synaptic activity and aging in these processes by taking advantage of the possibility to follow identified synapses over the entire life of C. elegans.
Using powerful genetics in combination with cutting-edge in vivo imaging and electrophysiology, we anticipate to identify new genes and new mechanisms at work to regulate normal and pathological synaptic function.
Max ERC Funding
2 492 750 €
Duration
Start date: 2016-10-01, End date: 2022-09-30