Project acronym AAMOT
Project Arithmetic of automorphic motives
Researcher (PI) Michael Harris
Host Institution (HI) INSTITUT DES HAUTES ETUDES SCIENTIFIQUES
Country France
Call Details Advanced Grant (AdG), PE1, ERC-2011-ADG_20110209
Summary The primary purpose of this project is to build on recent spectacular progress in the Langlands program to study the arithmetic properties of automorphic motives constructed in the cohomology of Shimura varieties. Because automorphic methods are available to study the L-functions of these motives, which include elliptic curves and certain families of Calabi-Yau varieties over totally real fields (possibly after base change), they represent the most accessible class of varieties for which one can hope to verify fundamental conjectures on special values of L-functions, including Deligne's conjecture and the Main Conjecture of Iwasawa theory. Immediate goals include the proof of irreducibility of automorphic Galois representations; the establishment of period relations for automorphic and potentially automorphic realizations of motives in the cohomology of distinct Shimura varieties; the construction of p-adic L-functions for these and related motives, notably adjoint and tensor product L-functions in p-adic families; and the geometrization of the p-adic and mod p Langlands program. All four goals, as well as the others mentioned in the body of the proposal, are interconnected; the final goal provides a bridge to related work in geometric representation theory, algebraic geometry, and mathematical physics.
Summary
The primary purpose of this project is to build on recent spectacular progress in the Langlands program to study the arithmetic properties of automorphic motives constructed in the cohomology of Shimura varieties. Because automorphic methods are available to study the L-functions of these motives, which include elliptic curves and certain families of Calabi-Yau varieties over totally real fields (possibly after base change), they represent the most accessible class of varieties for which one can hope to verify fundamental conjectures on special values of L-functions, including Deligne's conjecture and the Main Conjecture of Iwasawa theory. Immediate goals include the proof of irreducibility of automorphic Galois representations; the establishment of period relations for automorphic and potentially automorphic realizations of motives in the cohomology of distinct Shimura varieties; the construction of p-adic L-functions for these and related motives, notably adjoint and tensor product L-functions in p-adic families; and the geometrization of the p-adic and mod p Langlands program. All four goals, as well as the others mentioned in the body of the proposal, are interconnected; the final goal provides a bridge to related work in geometric representation theory, algebraic geometry, and mathematical physics.
Max ERC Funding
1 491 348 €
Duration
Start date: 2012-06-01, End date: 2018-05-31
Project acronym ACCOMPLI
Project Assembly and maintenance of a co-regulated chromosomal compartment
Researcher (PI) Peter Burkhard Becker
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Country Germany
Call Details Advanced Grant (AdG), LS2, ERC-2011-ADG_20110310
Summary "Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment.
The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation.
We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis.
Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."
Summary
"Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment.
The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation.
We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis.
Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."
Max ERC Funding
2 482 770 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym analysisdirac
Project The analysis of the Dirac operator: the hypoelliptic Laplacian and its applications
Researcher (PI) Jean-Michel Philippe Marie-Jose Bismut
Host Institution (HI) UNIVERSITE PARIS-SUD
Country France
Call Details Advanced Grant (AdG), PE1, ERC-2011-ADG_20110209
Summary This proposal is devoted to the applications of a new hypoelliptic Dirac operator,
whose analytic properties have been studied by Lebeau and myself. Its construction connects classical Hodge theory with the geodesic flow, and more generally any geometrically defined Hodge Laplacian with a dynamical system on the cotangent bundle. The proper description of this object can be given in analytic, index theoretic and probabilistic terms, which explains both its potential many applications, and also its complexity.
Summary
This proposal is devoted to the applications of a new hypoelliptic Dirac operator,
whose analytic properties have been studied by Lebeau and myself. Its construction connects classical Hodge theory with the geodesic flow, and more generally any geometrically defined Hodge Laplacian with a dynamical system on the cotangent bundle. The proper description of this object can be given in analytic, index theoretic and probabilistic terms, which explains both its potential many applications, and also its complexity.
Max ERC Funding
1 112 400 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym Arctic Domus
Project Arctic Domestication: Emplacing Human-Animal Relationships in the Circumpolar North
Researcher (PI) David George Anderson
Host Institution (HI) THE UNIVERSITY COURT OF THE UNIVERSITY OF ABERDEEN
Country United Kingdom
Call Details Advanced Grant (AdG), SH2, ERC-2011-ADG_20110406
Summary This 6-year project aims to co-ordinate field research in each of these fields to elaborate a new model of emplaced human-animal relations evoking recent theoretical concerns of the definition of the person, the attribution of agency, and renewed attention to ‘built environments’. The project will work inductively from empirical observations in seven field sites across the circumpolar Arctic from the Russian Federation, to Fennoscandia, to Canada. The circumpolar Arctic originally provided many of the primary thought experiments for classic models of cultural evolution. It has now again become the focus of powerful debates over the balance between the protection of cultural heritage and the development of natural resources to fuel a future for industrial economies. The human-non-human relationships chosen for study cover the full range of theoretical and political discourse within the sciences today from primary encounters in domination to contemporary bio-technical innovations in farming. The team will transcend typical ‘existential’ models of domination between people and animals by describing complex social settings where more than one species interact with the cultural landscape. The team will also challenge existing definitions between wild and tame by instead examining what links these behaviour types together. Further, the team members will examine how domestication was never a sudden, fleeting intuition but rather a process wherein people and domesticates are sometimes closer and sometimes farther from each other. Finally, the research team, working within the above mentioned literatures, will develop a renewed model – a new way of describing – these relationships which does not necessarily rely upon metaphors of domination, competition, individual struggle, origins, or hybridity. The strength of the team, and the principle investigator, is their demonstrated ability to carry out fieldwork in this often difficult to access region.
Summary
This 6-year project aims to co-ordinate field research in each of these fields to elaborate a new model of emplaced human-animal relations evoking recent theoretical concerns of the definition of the person, the attribution of agency, and renewed attention to ‘built environments’. The project will work inductively from empirical observations in seven field sites across the circumpolar Arctic from the Russian Federation, to Fennoscandia, to Canada. The circumpolar Arctic originally provided many of the primary thought experiments for classic models of cultural evolution. It has now again become the focus of powerful debates over the balance between the protection of cultural heritage and the development of natural resources to fuel a future for industrial economies. The human-non-human relationships chosen for study cover the full range of theoretical and political discourse within the sciences today from primary encounters in domination to contemporary bio-technical innovations in farming. The team will transcend typical ‘existential’ models of domination between people and animals by describing complex social settings where more than one species interact with the cultural landscape. The team will also challenge existing definitions between wild and tame by instead examining what links these behaviour types together. Further, the team members will examine how domestication was never a sudden, fleeting intuition but rather a process wherein people and domesticates are sometimes closer and sometimes farther from each other. Finally, the research team, working within the above mentioned literatures, will develop a renewed model – a new way of describing – these relationships which does not necessarily rely upon metaphors of domination, competition, individual struggle, origins, or hybridity. The strength of the team, and the principle investigator, is their demonstrated ability to carry out fieldwork in this often difficult to access region.
Max ERC Funding
2 497 830 €
Duration
Start date: 2012-07-01, End date: 2018-06-30
Project acronym B-INNATE
Project Innate signaling networks in B cell antibody production: new targets for vaccine development
Researcher (PI) Andrea Cerutti
Host Institution (HI) FUNDACIO INSTITUT MAR D INVESTIGACIONS MEDIQUES IMIM
Country Spain
Call Details Advanced Grant (AdG), LS6, ERC-2011-ADG_20110310
Summary The long-term goal of this proposal is to explore a novel immune pathway that involves an unexpected interplay between marginal zone (MZ) B cells and neutrophils. MZ B cells are strategically positioned at the interface between the immune system and the circulation and rapidly produce protective antibodies to blood-borne pathogens through a T cell-independent pathway that remains poorly understood. We recently found that the human spleen contains a novel subset of B cell helper neutrophils (NBH cells) with a phenotype and gene expression profile distinct from those of conventional circulating neutrophils (NC cells). In this proposal, we hypothesize that NC cells undergo splenic reprogramming into NBH cells through an IL-10-dependent pathway involving perifollicular sinusoidal endothelial cells. We contend that these unique endothelial cells release NC cell-attracting chemokines and IL-10 upon sensing blood-borne bacteria through Toll-like receptors. We also argue that IL-10 from sinusoidal endothelial cells stimulates NC cells to differentiate into NBH cells equipped with powerful MZ B cell-stimulating activity. The following three aims will be pursued. Aim 1 is to determine the mechanisms by which splenic sinusoidal endothelial cells induce reprogramming of NC cells into NBH cells upon sensing bacteria through Toll-like receptors. Aim 2 is to elucidate the mechanisms by which NBH cells induce IgM production, IgG and IgA class switching, and plasma cell differentiation in MZ B cells. Aim 3 is to evaluate the mechanisms by which NBH cells induce V(D)J gene somatic hypermutation and high-affinity antibody production in MZ B cells. These studies will uncover previously unknown facets of the immunological function of neutrophils by taking advantage of unique cells and tissues from patients with rare primary immunodeficiencies and by making use of selected mouse models. Results from these studies may also lead to the identification of novel vaccine strategies.
Summary
The long-term goal of this proposal is to explore a novel immune pathway that involves an unexpected interplay between marginal zone (MZ) B cells and neutrophils. MZ B cells are strategically positioned at the interface between the immune system and the circulation and rapidly produce protective antibodies to blood-borne pathogens through a T cell-independent pathway that remains poorly understood. We recently found that the human spleen contains a novel subset of B cell helper neutrophils (NBH cells) with a phenotype and gene expression profile distinct from those of conventional circulating neutrophils (NC cells). In this proposal, we hypothesize that NC cells undergo splenic reprogramming into NBH cells through an IL-10-dependent pathway involving perifollicular sinusoidal endothelial cells. We contend that these unique endothelial cells release NC cell-attracting chemokines and IL-10 upon sensing blood-borne bacteria through Toll-like receptors. We also argue that IL-10 from sinusoidal endothelial cells stimulates NC cells to differentiate into NBH cells equipped with powerful MZ B cell-stimulating activity. The following three aims will be pursued. Aim 1 is to determine the mechanisms by which splenic sinusoidal endothelial cells induce reprogramming of NC cells into NBH cells upon sensing bacteria through Toll-like receptors. Aim 2 is to elucidate the mechanisms by which NBH cells induce IgM production, IgG and IgA class switching, and plasma cell differentiation in MZ B cells. Aim 3 is to evaluate the mechanisms by which NBH cells induce V(D)J gene somatic hypermutation and high-affinity antibody production in MZ B cells. These studies will uncover previously unknown facets of the immunological function of neutrophils by taking advantage of unique cells and tissues from patients with rare primary immunodeficiencies and by making use of selected mouse models. Results from these studies may also lead to the identification of novel vaccine strategies.
Max ERC Funding
2 214 035 €
Duration
Start date: 2012-04-01, End date: 2017-09-30
Project acronym BATESON
Project Dissecting genotype-phenotype relationships using high-throughput genomics and carefully selected study populations
Researcher (PI) Leif Andersson
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), LS2, ERC-2011-ADG_20110310
Summary A major aim in genome research is to reveal how genetic variation affects phenotypic variation. Here I propose to use high-throughput genomics (whole genome sequencing, transcriptome and epigenome analysis) to screen carefully selected study populations where the chances are particularly favourable to obtain novel insight into genotype-phenotype relationships. The ambition is to take discoveries all the way from phenotypic characterization to the identification of the genes and the actual genetic variant causing a phenotypic effect and to understanding the underlying functional mechanisms. The program will involve a fish (the Atlantic herring), a bird (the domestic chicken) and a mammal (the European rabbit). The Atlantic herring will be studied because it provides unique opportunities to study the genetics of adaptation in a natural population and because of the possibilities to revolutionize the fishery management of this economically important marine fish. We will generate a draft assembly of the herring genome and then perform whole genome resequencing of different populations to reveal the population structure and the loci underlying genetic adaptation. The European rabbit is an excellent model for studying the genetics of speciation due to the presence of two distinct subspecies on the Iberian Peninsula. The domestication of the rabbit is also particularly interesting because it is a recent event (about 1500 years ago) and it is well established that domestication happened from the wild rabbit population in southern France. Finally, the domestic chicken provides excellent opportunities for in depth functional studies since it is both a domestic animal harbouring a rich genetic diversity and an experimental organism.
(BATESON is the acronym for this proposal because Bateson (1902) pioneered the study of genotype-phenotype relationships in animals and used the chicken for this work.)
Summary
A major aim in genome research is to reveal how genetic variation affects phenotypic variation. Here I propose to use high-throughput genomics (whole genome sequencing, transcriptome and epigenome analysis) to screen carefully selected study populations where the chances are particularly favourable to obtain novel insight into genotype-phenotype relationships. The ambition is to take discoveries all the way from phenotypic characterization to the identification of the genes and the actual genetic variant causing a phenotypic effect and to understanding the underlying functional mechanisms. The program will involve a fish (the Atlantic herring), a bird (the domestic chicken) and a mammal (the European rabbit). The Atlantic herring will be studied because it provides unique opportunities to study the genetics of adaptation in a natural population and because of the possibilities to revolutionize the fishery management of this economically important marine fish. We will generate a draft assembly of the herring genome and then perform whole genome resequencing of different populations to reveal the population structure and the loci underlying genetic adaptation. The European rabbit is an excellent model for studying the genetics of speciation due to the presence of two distinct subspecies on the Iberian Peninsula. The domestication of the rabbit is also particularly interesting because it is a recent event (about 1500 years ago) and it is well established that domestication happened from the wild rabbit population in southern France. Finally, the domestic chicken provides excellent opportunities for in depth functional studies since it is both a domestic animal harbouring a rich genetic diversity and an experimental organism.
(BATESON is the acronym for this proposal because Bateson (1902) pioneered the study of genotype-phenotype relationships in animals and used the chicken for this work.)
Max ERC Funding
2 300 000 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym BayCellS
Project A Bayesian Framework for Cellular Structural Biology
Researcher (PI) Michael Nilges
Host Institution (HI) INSTITUT PASTEUR
Country France
Call Details Advanced Grant (AdG), LS1, ERC-2011-ADG_20110310
Summary The functioning of a single cell or organism is governed by the laws of chemistry and physics. The bridge from biology to chemistry and physics is provided by structural biology: to understand the functioning of a cell, it is necessary to know the atomic structure of macromolecular assemblies, which may contain hundreds of components. To characterise the structures of the increasingly large and often flexible complexes, high resolution structure determination (as was possible for example for the ribosome) will likely stay the exception, and multiple sources of structural data at multiple resolutions are employed. Integrating these data into one consistent picture poses particular difficulties, since data are much more sparse than in high resolution methods, and the data sets from heterogeneous sources are of highly different and unknown quality and may be mutually inconsistent, and that data are in general averaged over large ensembles and long times. Molecular modelling, a crucial element of any structure determination, plays an even more important role in these multi-scale and multi-technique approaches, not only to obtain structures from the data, but also to evaluate their reliability. This proposal is to develop a consistent framework for this highly complex data integration problem, principally based on Bayesian probability theory. Appropriate models for the major types data types used in hybrid approaches will be developed, as well as representations to include structural knowledge for the components of the complexes, at multiple scales. The new methods will be applied to a series of problems with increasing complexity, going from the determination of protein complexes with high resolution information, over low resolution structures based on protein-protein interaction data such as the nuclear pore, to the genome organisation in the nucleus.
Summary
The functioning of a single cell or organism is governed by the laws of chemistry and physics. The bridge from biology to chemistry and physics is provided by structural biology: to understand the functioning of a cell, it is necessary to know the atomic structure of macromolecular assemblies, which may contain hundreds of components. To characterise the structures of the increasingly large and often flexible complexes, high resolution structure determination (as was possible for example for the ribosome) will likely stay the exception, and multiple sources of structural data at multiple resolutions are employed. Integrating these data into one consistent picture poses particular difficulties, since data are much more sparse than in high resolution methods, and the data sets from heterogeneous sources are of highly different and unknown quality and may be mutually inconsistent, and that data are in general averaged over large ensembles and long times. Molecular modelling, a crucial element of any structure determination, plays an even more important role in these multi-scale and multi-technique approaches, not only to obtain structures from the data, but also to evaluate their reliability. This proposal is to develop a consistent framework for this highly complex data integration problem, principally based on Bayesian probability theory. Appropriate models for the major types data types used in hybrid approaches will be developed, as well as representations to include structural knowledge for the components of the complexes, at multiple scales. The new methods will be applied to a series of problems with increasing complexity, going from the determination of protein complexes with high resolution information, over low resolution structures based on protein-protein interaction data such as the nuclear pore, to the genome organisation in the nucleus.
Max ERC Funding
2 130 212 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym BBBARRIER
Project Mechanisms of regulation of the blood-brain barrier; towards opening and closing the barrier on demand
Researcher (PI) Bjoern Christer Betsholtz
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), LS4, ERC-2011-ADG_20110310
Summary In the bone-enclosed CNS, increased vascular permeability may cause life-threatening tissue swelling, and/or ischemia and inflammation which compromise tissue repair after trauma or stroke. The brain vasculature possesses several unique features collectively named the blood-brain barrier (BBB) in which passive permeability is almost completely abolished and replaced by a complex of specific transport mechanisms. The BBB is necessary to uphold the specific milieu necessary for neuronal function. Whereas breakdown of the BBB is part of many CNS diseases, including stroke, neuroinflammation, trauma and neurodegenerative disorders, its molecular mechanisms and consequences are unclear and debated. Conversely, the intact BBB is a huge obstacle for drug delivery to the brain. Research on the BBB therefore has two seemingly opposing aims: 1) to seal a damaged BBB and protect the brain from toxic blood products, and 2) to open the BBB “on demand” for drug delivery. A major problem in the BBB field has been the lack of in vivo animal models for molecular and functional studies. So far, available in vitro models are not recapitulating the in vivo BBB. Our recent work on mouse models lacking pericytes, a BBB-associated cell type, demonstrates a specific role for pericytes in the development and regulation of the mammalian BBB. These animal models are the first ones showing a general and significant BBB impairment in adulthood, and as such they provide a unique opportunity to address molecular mechanisms of BBB disruption in disease and in drug transport across the BBB. Importantly, the new models and tools that we have developed allow us to search for relevant druggable mechanisms and molecular targets in the BBB. The long-term goals of this proposal are to develop molecular strategies and tools to open and close the BBB “on demand” for drug delivery to the CNS, and to explore the importance and mechanisms of BBB dysfunction in neurodegenerative diseases and stroke.
Summary
In the bone-enclosed CNS, increased vascular permeability may cause life-threatening tissue swelling, and/or ischemia and inflammation which compromise tissue repair after trauma or stroke. The brain vasculature possesses several unique features collectively named the blood-brain barrier (BBB) in which passive permeability is almost completely abolished and replaced by a complex of specific transport mechanisms. The BBB is necessary to uphold the specific milieu necessary for neuronal function. Whereas breakdown of the BBB is part of many CNS diseases, including stroke, neuroinflammation, trauma and neurodegenerative disorders, its molecular mechanisms and consequences are unclear and debated. Conversely, the intact BBB is a huge obstacle for drug delivery to the brain. Research on the BBB therefore has two seemingly opposing aims: 1) to seal a damaged BBB and protect the brain from toxic blood products, and 2) to open the BBB “on demand” for drug delivery. A major problem in the BBB field has been the lack of in vivo animal models for molecular and functional studies. So far, available in vitro models are not recapitulating the in vivo BBB. Our recent work on mouse models lacking pericytes, a BBB-associated cell type, demonstrates a specific role for pericytes in the development and regulation of the mammalian BBB. These animal models are the first ones showing a general and significant BBB impairment in adulthood, and as such they provide a unique opportunity to address molecular mechanisms of BBB disruption in disease and in drug transport across the BBB. Importantly, the new models and tools that we have developed allow us to search for relevant druggable mechanisms and molecular targets in the BBB. The long-term goals of this proposal are to develop molecular strategies and tools to open and close the BBB “on demand” for drug delivery to the CNS, and to explore the importance and mechanisms of BBB dysfunction in neurodegenerative diseases and stroke.
Max ERC Funding
2 499 427 €
Duration
Start date: 2012-08-01, End date: 2017-07-31
Project acronym BLOWDISOL
Project "BLOW UP, DISPERSION AND SOLITONS"
Researcher (PI) Franck Merle
Host Institution (HI) UNIVERSITE DE CERGY-PONTOISE
Country France
Call Details Advanced Grant (AdG), PE1, ERC-2011-ADG_20110209
Summary "Many physical models involve nonlinear dispersive problems, like wave
or laser propagation, plasmas, ferromagnetism, etc. So far, the mathematical under-
standing of these equations is rather poor. In particular, we know little about the
detailed qualitative behavior of their solutions. Our point is that an apparent com-
plexity hides universal properties of these models; investigating and uncovering such
properties has started only recently. More than the equations themselves, these univer-
sal properties are essential for physical modelisation.
By considering several standard models such as the nonlinear Schrodinger, nonlinear
wave, generalized KdV equations and related geometric problems, the goal of this pro-
posal is to describe the generic global behavior of the solutions and the profiles which
emerge either for large time or by concentration due to strong nonlinear effects, if pos-
sible through a few relevant solutions (sometimes explicit solutions, like solitons). In
order to do this, we have to elaborate different mathematical tools depending on the
context and the specificity of the problems. Particular emphasis will be placed on
- large time asymptotics for global solutions, decomposition of generic solutions into
sums of decoupled solitons in non integrable situations,
- description of critical phenomenon for blow up in the Hamiltonian situation, stable
or generic behavior for blow up on critical dynamics, various relevant regularisations of
the problem,
- global existence for defocusing supercritical problems and blow up dynamics in the
focusing cases.
We believe that the PI and his team have the ability to tackle these problems at present.
The proposal will open whole fields of investigation in Partial Differential Equations in
the future, clarify and simplify our knowledge on the dynamical behavior of solutions
of these problems and provide Physicists some new insight on these models."
Summary
"Many physical models involve nonlinear dispersive problems, like wave
or laser propagation, plasmas, ferromagnetism, etc. So far, the mathematical under-
standing of these equations is rather poor. In particular, we know little about the
detailed qualitative behavior of their solutions. Our point is that an apparent com-
plexity hides universal properties of these models; investigating and uncovering such
properties has started only recently. More than the equations themselves, these univer-
sal properties are essential for physical modelisation.
By considering several standard models such as the nonlinear Schrodinger, nonlinear
wave, generalized KdV equations and related geometric problems, the goal of this pro-
posal is to describe the generic global behavior of the solutions and the profiles which
emerge either for large time or by concentration due to strong nonlinear effects, if pos-
sible through a few relevant solutions (sometimes explicit solutions, like solitons). In
order to do this, we have to elaborate different mathematical tools depending on the
context and the specificity of the problems. Particular emphasis will be placed on
- large time asymptotics for global solutions, decomposition of generic solutions into
sums of decoupled solitons in non integrable situations,
- description of critical phenomenon for blow up in the Hamiltonian situation, stable
or generic behavior for blow up on critical dynamics, various relevant regularisations of
the problem,
- global existence for defocusing supercritical problems and blow up dynamics in the
focusing cases.
We believe that the PI and his team have the ability to tackle these problems at present.
The proposal will open whole fields of investigation in Partial Differential Equations in
the future, clarify and simplify our knowledge on the dynamical behavior of solutions
of these problems and provide Physicists some new insight on these models."
Max ERC Funding
2 079 798 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym BRAINEVODEVO
Project A Neuron Type Atlas of the Annelid Brain: Development and Evolution of Chemosensory-Motor Circuits
Researcher (PI) Detlev Arendt
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Country Germany
Call Details Advanced Grant (AdG), LS3, ERC-2011-ADG_20110310
Summary Neural circuits, composed of interconnected neurons, represent the basic unit of the nervous system. One way to understand the highly complex arrangement of cross-talking, serial and parallel circuits is to resolve its developmental and evolutionary emergence. The rationale of the research proposal presented here is to elucidate the complex circuitry of the vertebrate and insect forebrain by comparison to the much simpler and evolutionary ancient “connectome” of the marine annelid Platynereis dumerilii. We will build a unique resource, the Platynereis Neuron Type Atlas, combining, for the first time, neuronal morphologies, axonal projections, cellular expression profiling and developmental lineage for an entire bilaterian brain. We will focus on five days old larvae when most adult neuron types are already present in small number and large part of the axonal scaffold in place.
Building on the Neuron Type Atlas, the second part of the proposal envisages the functional dissection of the Platynereis chemosensory-motor forebrain circuits. A newly developed microfluidics behavioural assay system, together with a cell-based GPCR screening will identify partaking neurons. Zinc finger nuclease-mediated knockout of circuit-specific transcription factors as identified from the Atlas will reveal circuit-specific gene regulatory networks, downstream effector genes and functional characteristics. Laser ablation of GFP-labeled single neurons and axonal connections will yield further insight into the function of circuit components and subcircuits. Given the ancient nature of the Platynereis brain, this research is expected to reveal a simple, developmental and evolutionary “blueprint” for the olfactory circuits in mice and flies and to shed new light on the evolution of information processing in glomeruli and higher-level integration in sensory-associative brain centres.
Summary
Neural circuits, composed of interconnected neurons, represent the basic unit of the nervous system. One way to understand the highly complex arrangement of cross-talking, serial and parallel circuits is to resolve its developmental and evolutionary emergence. The rationale of the research proposal presented here is to elucidate the complex circuitry of the vertebrate and insect forebrain by comparison to the much simpler and evolutionary ancient “connectome” of the marine annelid Platynereis dumerilii. We will build a unique resource, the Platynereis Neuron Type Atlas, combining, for the first time, neuronal morphologies, axonal projections, cellular expression profiling and developmental lineage for an entire bilaterian brain. We will focus on five days old larvae when most adult neuron types are already present in small number and large part of the axonal scaffold in place.
Building on the Neuron Type Atlas, the second part of the proposal envisages the functional dissection of the Platynereis chemosensory-motor forebrain circuits. A newly developed microfluidics behavioural assay system, together with a cell-based GPCR screening will identify partaking neurons. Zinc finger nuclease-mediated knockout of circuit-specific transcription factors as identified from the Atlas will reveal circuit-specific gene regulatory networks, downstream effector genes and functional characteristics. Laser ablation of GFP-labeled single neurons and axonal connections will yield further insight into the function of circuit components and subcircuits. Given the ancient nature of the Platynereis brain, this research is expected to reveal a simple, developmental and evolutionary “blueprint” for the olfactory circuits in mice and flies and to shed new light on the evolution of information processing in glomeruli and higher-level integration in sensory-associative brain centres.
Max ERC Funding
2 489 048 €
Duration
Start date: 2012-03-01, End date: 2017-02-28
