Project acronym BIOMOTIV
Project Why do we do what we do? Biological, psychological and computational bases of motivation
Researcher (PI) Mathias Pessiglione
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary We are largely unaware of our own motives. Understanding our motives can be reduced to knowing how we form goals and these goals translate into behavior. Goals can be defined as pleasurable situations that we particularly value and that we intend to reach. Recent investigation in the emerging field of neuro-economics has put forward a neuronal network constituting a brain valuation system (BVS). We wish to build a more comprehensive account of motivational processes, investigating not only valuation and choice but also effort (how much energy we would spend to attain a goal). More specifically, our aims are to better describe 1) how the brain assigns values to various objects and actions, 2) how values depend on parameters such as reward magnitude, probability, delay and cost, 3) how values are affected by social contexts, 4) how values are modified through learning and 5) how values influence the brain systems (perceptual, cognitive and motor) that underpin behavioral performance. To these aims, we would combine three approaches: 1) human cognitive neuroscience, which is central as we ultimately wish to understand ourselves, as well as human pathological conditions where motivation is either deficient (apathy) or out of control (compulsion), 2) primate neurophysiology, which is essential to describe information processing at the single-unit level and to derive causality by observing behavioral consequences of brain manipulations, 3) computational modeling, which is mandatory to link quantitatively the different descriptions levels (single-unit recordings, local field potentials, regional BOLD signal, vegetative manifestations and motor outputs). A bayesian framework will be developed to infer from experimental measures the subjects prior beliefs and value functions. We believe that our team, bringing together three complementary perspectives on motivation within a clinical environment, would represent a unique education and research center in Europe.
Summary
We are largely unaware of our own motives. Understanding our motives can be reduced to knowing how we form goals and these goals translate into behavior. Goals can be defined as pleasurable situations that we particularly value and that we intend to reach. Recent investigation in the emerging field of neuro-economics has put forward a neuronal network constituting a brain valuation system (BVS). We wish to build a more comprehensive account of motivational processes, investigating not only valuation and choice but also effort (how much energy we would spend to attain a goal). More specifically, our aims are to better describe 1) how the brain assigns values to various objects and actions, 2) how values depend on parameters such as reward magnitude, probability, delay and cost, 3) how values are affected by social contexts, 4) how values are modified through learning and 5) how values influence the brain systems (perceptual, cognitive and motor) that underpin behavioral performance. To these aims, we would combine three approaches: 1) human cognitive neuroscience, which is central as we ultimately wish to understand ourselves, as well as human pathological conditions where motivation is either deficient (apathy) or out of control (compulsion), 2) primate neurophysiology, which is essential to describe information processing at the single-unit level and to derive causality by observing behavioral consequences of brain manipulations, 3) computational modeling, which is mandatory to link quantitatively the different descriptions levels (single-unit recordings, local field potentials, regional BOLD signal, vegetative manifestations and motor outputs). A bayesian framework will be developed to infer from experimental measures the subjects prior beliefs and value functions. We believe that our team, bringing together three complementary perspectives on motivation within a clinical environment, would represent a unique education and research center in Europe.
Max ERC Funding
1 346 000 €
Duration
Start date: 2011-03-01, End date: 2016-08-31
Project acronym CBSCS
Project Physiology of the adult carotid body stem cell niche
Researcher (PI) Ricardo Pardal
Host Institution (HI) UNIVERSIDAD DE SEVILLA
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary The discovery of adult neural stem cells (NSCs) has broaden our view of the physiological plasticity of the nervous system,
and has opened new perspectives on the possibility of tissue regeneration and repair in the brain. NSCs reside in specialized
niches in the adult mammalian nervous system, where they are exposed to specific paracrine signals regulating their
behavior. These neural progenitors are generally in a quiescent state within their niche, and they activate their proliferation
depending on tissue regenerative and growth needs. Understanding the mechanisms by which NSCs enter and exit the
quiescent state is crucial for the comprehension of the physiology of the adult nervous system. In this project we will study
the behavior of a specific subpopulation of adult neural stem cells recently described by our group in the carotid body (CB).
This small organ constitutes the most important chemosensor of the peripheral nervous system and has neuronal glomus
cells responsible for the chemosensing, and glia-like sustentacular cells which were thought to have just a supportive role.
We recently described that these sustentacular cells are dormant stem cells able to activate their proliferation in response to a
physiological stimulus like hypoxia, and to differentiate into new glomus cells necessary for the adaptation of the organ.
Due to our precise experimental control of the activation and deactivation of the CB neurogenic niche, we believe the CB is
an ideal model to study fundamental questions about adult neural stem cell physiology and the interaction with the niche. We
propose to study the cellular and molecular mechanisms by which these carotid body stem cells enter and exit the quiescent
state, which will help us understand the physiology of adult neurogenic niches. Likewise, understanding this neurogenic
process will improve the efficacy of using glomus cells for cell therapy against neurological disease, and might help us
understand some neural tumors.
Summary
The discovery of adult neural stem cells (NSCs) has broaden our view of the physiological plasticity of the nervous system,
and has opened new perspectives on the possibility of tissue regeneration and repair in the brain. NSCs reside in specialized
niches in the adult mammalian nervous system, where they are exposed to specific paracrine signals regulating their
behavior. These neural progenitors are generally in a quiescent state within their niche, and they activate their proliferation
depending on tissue regenerative and growth needs. Understanding the mechanisms by which NSCs enter and exit the
quiescent state is crucial for the comprehension of the physiology of the adult nervous system. In this project we will study
the behavior of a specific subpopulation of adult neural stem cells recently described by our group in the carotid body (CB).
This small organ constitutes the most important chemosensor of the peripheral nervous system and has neuronal glomus
cells responsible for the chemosensing, and glia-like sustentacular cells which were thought to have just a supportive role.
We recently described that these sustentacular cells are dormant stem cells able to activate their proliferation in response to a
physiological stimulus like hypoxia, and to differentiate into new glomus cells necessary for the adaptation of the organ.
Due to our precise experimental control of the activation and deactivation of the CB neurogenic niche, we believe the CB is
an ideal model to study fundamental questions about adult neural stem cell physiology and the interaction with the niche. We
propose to study the cellular and molecular mechanisms by which these carotid body stem cells enter and exit the quiescent
state, which will help us understand the physiology of adult neurogenic niches. Likewise, understanding this neurogenic
process will improve the efficacy of using glomus cells for cell therapy against neurological disease, and might help us
understand some neural tumors.
Max ERC Funding
1 476 000 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym CLR SENSING NECROSIS
Project Immune Functions of Myeloid Syk-coupled C-type Lectin Receptors Sensing Necrosis
Researcher (PI) David Sancho Madrid
Host Institution (HI) CENTRO NACIONAL DE INVESTIGACIONESCARDIOVASCULARES CARLOS III (F.S.P.)
Call Details Starting Grant (StG), LS6, ERC-2010-StG_20091118
Summary Necrosis triggers an inflammatory response driven by macrophages that normally contributes to tissue repair but, under certain conditions, can induce a state of chronic inflammation that forms the basis of many diseases. In addition, dendritic cell (DC)-mediated presentation of antigens from necrotic cells can trigger adaptive immunity in infection-free situations, such as autoimmunity or therapy-induced tumour rejection. Recently, we and others have identified the myeloid C-type lectin receptors (CLRs) CLEC9A (DNGR-1), in DC, and Mincle, in macrophages, as receptors for necrotic cells that can signal via the Syk kinase. Previous studies on similar Syk-coupled CLRs showed that Dectin-1 and Dectin-2 can induce innate and adaptive immune responses. We thus hypothesise that recognition of cell death by myeloid Syk-coupled CLRs is at the root of immune pathologies associated with accumulation of dead cells. The overall objective of this proposal is to investigate necrosis sensing by myeloid cells as a trigger of immunity and to study the underlying molecular mechanisms. Our first goal is to characterise signalling and gene induction via CLEC9A as a model necrosis receptor in DCs. Second, we will investigate the role of myeloid Syk-coupled necrosis-sensing CLRs in animal models of atherosclerosis, lupus and immunity to chemotherapy-treated tumours. Our preliminary data suggest that additional receptors can couple necrosis recognition to the Syk pathway in DC; thus, our third aim is to identify novel myeloid Syk-coupled receptors for necrotic cells. Characterisation of the outcomes of sensing necrosis by myeloid Syk-coupled receptors and their effect on the proposed pathologies promises to identify new mechanisms and targets for the treatment of these diseases.
Summary
Necrosis triggers an inflammatory response driven by macrophages that normally contributes to tissue repair but, under certain conditions, can induce a state of chronic inflammation that forms the basis of many diseases. In addition, dendritic cell (DC)-mediated presentation of antigens from necrotic cells can trigger adaptive immunity in infection-free situations, such as autoimmunity or therapy-induced tumour rejection. Recently, we and others have identified the myeloid C-type lectin receptors (CLRs) CLEC9A (DNGR-1), in DC, and Mincle, in macrophages, as receptors for necrotic cells that can signal via the Syk kinase. Previous studies on similar Syk-coupled CLRs showed that Dectin-1 and Dectin-2 can induce innate and adaptive immune responses. We thus hypothesise that recognition of cell death by myeloid Syk-coupled CLRs is at the root of immune pathologies associated with accumulation of dead cells. The overall objective of this proposal is to investigate necrosis sensing by myeloid cells as a trigger of immunity and to study the underlying molecular mechanisms. Our first goal is to characterise signalling and gene induction via CLEC9A as a model necrosis receptor in DCs. Second, we will investigate the role of myeloid Syk-coupled necrosis-sensing CLRs in animal models of atherosclerosis, lupus and immunity to chemotherapy-treated tumours. Our preliminary data suggest that additional receptors can couple necrosis recognition to the Syk pathway in DC; thus, our third aim is to identify novel myeloid Syk-coupled receptors for necrotic cells. Characterisation of the outcomes of sensing necrosis by myeloid Syk-coupled receptors and their effect on the proposed pathologies promises to identify new mechanisms and targets for the treatment of these diseases.
Max ERC Funding
1 297 671 €
Duration
Start date: 2010-12-01, End date: 2016-08-31
Project acronym COMFUS
Project Computational Methods for Fusion Technology
Researcher (PI) Santiago Ignacio Badia Rodríguez
Host Institution (HI) CENTRE INTERNACIONAL DE METODES NUMERICS EN ENGINYERIA
Call Details Starting Grant (StG), PE8, ERC-2010-StG_20091028
Summary The simulation of multidisciplinary applications use very often a combination of heterogeneous and disjoint numerical techniques that are hard to put together by the user, and whose mathematical foundation is obscure. An example of this situation is the numerical modeling of the physical processes taking place in nuclear fusion reactors. This problem, which can be modeled by a set of partial differential equations, is extremely challenging. It involves (essentially) fluid mechanics, electromagnetics, thermal radiation and neutronics. The most common numerical approaches to each of these problems separately are very different and their coupling is a hard and inefficient task.
Our main objective in this proposal is to develop and analyze a unified numerical framework based on stabilized finite element methods based on multi-scale decompositions capable to simulate all the physical processes taking place in nuclear fusion technology. The project aims at giving a substantial contribution to the numerical approximation of every physical process as well as efficient coupling techniques for the multiphysics problems.
The development of the numerical formulations we propose and their application require mastering different physics, designing numerical approximations for these different physical problems, analyzing mathematically the resulting methods, implementing them in an efficient way in parallel platforms and understanding the results and drawing conclusions, both from a physical and from an engineering perspective. Advanced research in physical modeling, numerical approximations, mathematical analysis and computer implementation are the keys to meeting these objectives.
The successful implementation of the project will provide advanced numerical techniques for the simulation of the processes taking place in a fusion reactor. A deliverable product of the project will be a unified finite element software package that will be an extremely valuable tool.
Summary
The simulation of multidisciplinary applications use very often a combination of heterogeneous and disjoint numerical techniques that are hard to put together by the user, and whose mathematical foundation is obscure. An example of this situation is the numerical modeling of the physical processes taking place in nuclear fusion reactors. This problem, which can be modeled by a set of partial differential equations, is extremely challenging. It involves (essentially) fluid mechanics, electromagnetics, thermal radiation and neutronics. The most common numerical approaches to each of these problems separately are very different and their coupling is a hard and inefficient task.
Our main objective in this proposal is to develop and analyze a unified numerical framework based on stabilized finite element methods based on multi-scale decompositions capable to simulate all the physical processes taking place in nuclear fusion technology. The project aims at giving a substantial contribution to the numerical approximation of every physical process as well as efficient coupling techniques for the multiphysics problems.
The development of the numerical formulations we propose and their application require mastering different physics, designing numerical approximations for these different physical problems, analyzing mathematically the resulting methods, implementing them in an efficient way in parallel platforms and understanding the results and drawing conclusions, both from a physical and from an engineering perspective. Advanced research in physical modeling, numerical approximations, mathematical analysis and computer implementation are the keys to meeting these objectives.
The successful implementation of the project will provide advanced numerical techniques for the simulation of the processes taking place in a fusion reactor. A deliverable product of the project will be a unified finite element software package that will be an extremely valuable tool.
Max ERC Funding
1 320 000 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym D-END
Project Telomeres: from the DNA end replication problem to the control of cell proliferation
Researcher (PI) Maria Teresa Teixeira Fernandes Bernardo
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS1, ERC-2010-StG_20091118
Summary Linear chromosomes of eukaryotes end with telomeres that ensure their stability. Because of the inability of semi-conservative DNA replication machinery to fully replicate DNA ends, telomeres require dedicated mechanisms to be duplicated and their length is eroded at each cell division. For this reason, telomeres constitute molecular clocks that determine cell proliferation potential in eukaryotes. Strikingly, we have shown recently that it is the shortest telomere in the cell that determines the onset of replicative senescence. This project aims a complete and detailed dissection of the in vivo DNA-end replication problem and the deep understanding of its impact for cell division capability. Specifically my goals are (1) the determination of the exact structures that result from the replication of DNA extremities, (2) the examination of the activities operating at the shortest telomere that triggers replicative senescence and (3) the investigation of the correspondence between telomere molecular structure and cell proliferation state at individual cell scale. To achieve this, I will undertake in Saccharomyces cerevisiae original and innovative single-molecule and single-cell approaches, that, in combination with genome-wide screens and sophisticated cellular settings, will allow to track and challenge a specified telomere of defined length. I anticipate that this work will lead to an in-depth understanding of how telomeres are replicated and how they enable the control of cell proliferation in eukaryotic cells, a matter at the intersection of the fundamentals of molecular genetics, cell biology of aging and oncology.
Summary
Linear chromosomes of eukaryotes end with telomeres that ensure their stability. Because of the inability of semi-conservative DNA replication machinery to fully replicate DNA ends, telomeres require dedicated mechanisms to be duplicated and their length is eroded at each cell division. For this reason, telomeres constitute molecular clocks that determine cell proliferation potential in eukaryotes. Strikingly, we have shown recently that it is the shortest telomere in the cell that determines the onset of replicative senescence. This project aims a complete and detailed dissection of the in vivo DNA-end replication problem and the deep understanding of its impact for cell division capability. Specifically my goals are (1) the determination of the exact structures that result from the replication of DNA extremities, (2) the examination of the activities operating at the shortest telomere that triggers replicative senescence and (3) the investigation of the correspondence between telomere molecular structure and cell proliferation state at individual cell scale. To achieve this, I will undertake in Saccharomyces cerevisiae original and innovative single-molecule and single-cell approaches, that, in combination with genome-wide screens and sophisticated cellular settings, will allow to track and challenge a specified telomere of defined length. I anticipate that this work will lead to an in-depth understanding of how telomeres are replicated and how they enable the control of cell proliferation in eukaryotic cells, a matter at the intersection of the fundamentals of molecular genetics, cell biology of aging and oncology.
Max ERC Funding
1 498 504 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym DICIG
Project Dynamic Interplay between Eukaryotic Chromosomes: Impact on Genome Stability
Researcher (PI) Romain Nicolas André Koszul
Host Institution (HI) INSTITUT PASTEUR
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary The structure and role of the DNA molecule raise fascinating questions regarding its dynamics, i.e. not only the tri-dimensional reorganisation associated with functional events at short time-scale, but also the structural changes, i.e. rearrangements, that occur in the chromosome over generations. It is increasingly obvious that the physical properties of both the chromosomes and their environment the nucleoplasm, the nuclear periphery, cytoskeleton, etc. are playing important roles in the dynamic changes observed. For instance, we recently showed that chromosome movements during mid-prophase of meiosis in budding yeast result from a trans-acting force generated at the level of the global cytoskeleton network, suggesting that extranuclear mechanical trans-acting signals could also regulate chromosomal metabolism in other ways. Our objectives are to make important contributions to the understanding of the mechanical and functional interplay between the cytoskeleton, the nuclear periphery, and chromosomes through in vitro and in vivo interdisciplinary approaches. We will investigate three questions of fundamental importance: i) the potential transmission and function of mechanical forces from the cytoskeleton to chromatin during interphase, ii) the physical principles that govern chromosome reorganization under mechanical force in vitro, and iii) the global chromatin dynamics during the fundamental S phase and its impact on genome stability. We will use a combination of high-resolution imaging, micromanipulation, and high-throughput molecular techniques (chromosome conformation capture and ChIP-Seq) to reach our goals. Most of these studies will be performed in budding yeast, but will have repercussions in our understanding of higher eukaryotes metabolism.
Summary
The structure and role of the DNA molecule raise fascinating questions regarding its dynamics, i.e. not only the tri-dimensional reorganisation associated with functional events at short time-scale, but also the structural changes, i.e. rearrangements, that occur in the chromosome over generations. It is increasingly obvious that the physical properties of both the chromosomes and their environment the nucleoplasm, the nuclear periphery, cytoskeleton, etc. are playing important roles in the dynamic changes observed. For instance, we recently showed that chromosome movements during mid-prophase of meiosis in budding yeast result from a trans-acting force generated at the level of the global cytoskeleton network, suggesting that extranuclear mechanical trans-acting signals could also regulate chromosomal metabolism in other ways. Our objectives are to make important contributions to the understanding of the mechanical and functional interplay between the cytoskeleton, the nuclear periphery, and chromosomes through in vitro and in vivo interdisciplinary approaches. We will investigate three questions of fundamental importance: i) the potential transmission and function of mechanical forces from the cytoskeleton to chromatin during interphase, ii) the physical principles that govern chromosome reorganization under mechanical force in vitro, and iii) the global chromatin dynamics during the fundamental S phase and its impact on genome stability. We will use a combination of high-resolution imaging, micromanipulation, and high-throughput molecular techniques (chromosome conformation capture and ChIP-Seq) to reach our goals. Most of these studies will be performed in budding yeast, but will have repercussions in our understanding of higher eukaryotes metabolism.
Max ERC Funding
1 497 000 €
Duration
Start date: 2011-06-01, End date: 2017-05-31
Project acronym DOME
Project Dissecting a Novel Mechanism of Cell Motility
Researcher (PI) Tâm Mignot
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary Cell motility is essential for many biological processes, including development and pathogenesis. Thus, the
molecular mechanisms underlying this process have been intensively studied in many cell systems, for
example, leukocytes, amoeba and even bacteria. Intriguingly, bacteria are also able to move across solid
surfaces (gliding motility) like eukaryotic cells by a process that has remained largely mysterious. The
emergence of bacterial cell biology: the discovery that the bacterial cell also has a dynamic cytoskeleton and
specialized subcellular regions now provides new research angles to study the motility mechanism. Using
cell biology approaches, we previously suggested that the mechanism may be akin to acto-myosin-based
motility in eukaryotic cells and proposed that bacterial focal adhesion complexes also power locomotion. In
this project, we propose two complementary research axes to define both the mechanism and its spatial
regulation in the cell at molecular resolution.
Using the model motility bacterium Myxococcus xanthus, we first propose to develop a “toolbox” of
biophysical and cell biology assays to analyze the motility process. Specifically, we will construct a Traction
Force Microscopy assay designed to image the motility forces directly by live moving cells and use
microfluidics to quantitate the secretion of a mucus that may participate directly in the motility process.
These assays, combined with a newly developed laser trap system to visualize dynamic focal adhesions in
the cell envelope, will be instrumental not only to define new features of the motility process, but also to
study the function of novel motility genes which may encode the components of the elusive motility engine.
This way, we hope to establish the mechanism and structure function relationships within an entirely novel
motility machinery.
In a second part, we propose to investigate the mechanism that controls a polarity switch, allowing M.
xanthus cells to change their direction of movement. We have previously shown that dynamic motility
protein pole-to-pole oscillations convert the initial leading cell pole into the lagging pole. Here, we propose
that like in a eukaryotic cells, a bacterial counterpart of small GTPases of the Ras superfamily, MglA
controls the polarity cycle. To test this hypothesis, we will study both the MglA upstream regulation and the
MglA downstream effectors. We thus hope to establish a model of dynamic polarity control in a bacterial
Summary
Cell motility is essential for many biological processes, including development and pathogenesis. Thus, the
molecular mechanisms underlying this process have been intensively studied in many cell systems, for
example, leukocytes, amoeba and even bacteria. Intriguingly, bacteria are also able to move across solid
surfaces (gliding motility) like eukaryotic cells by a process that has remained largely mysterious. The
emergence of bacterial cell biology: the discovery that the bacterial cell also has a dynamic cytoskeleton and
specialized subcellular regions now provides new research angles to study the motility mechanism. Using
cell biology approaches, we previously suggested that the mechanism may be akin to acto-myosin-based
motility in eukaryotic cells and proposed that bacterial focal adhesion complexes also power locomotion. In
this project, we propose two complementary research axes to define both the mechanism and its spatial
regulation in the cell at molecular resolution.
Using the model motility bacterium Myxococcus xanthus, we first propose to develop a “toolbox” of
biophysical and cell biology assays to analyze the motility process. Specifically, we will construct a Traction
Force Microscopy assay designed to image the motility forces directly by live moving cells and use
microfluidics to quantitate the secretion of a mucus that may participate directly in the motility process.
These assays, combined with a newly developed laser trap system to visualize dynamic focal adhesions in
the cell envelope, will be instrumental not only to define new features of the motility process, but also to
study the function of novel motility genes which may encode the components of the elusive motility engine.
This way, we hope to establish the mechanism and structure function relationships within an entirely novel
motility machinery.
In a second part, we propose to investigate the mechanism that controls a polarity switch, allowing M.
xanthus cells to change their direction of movement. We have previously shown that dynamic motility
protein pole-to-pole oscillations convert the initial leading cell pole into the lagging pole. Here, we propose
that like in a eukaryotic cells, a bacterial counterpart of small GTPases of the Ras superfamily, MglA
controls the polarity cycle. To test this hypothesis, we will study both the MglA upstream regulation and the
MglA downstream effectors. We thus hope to establish a model of dynamic polarity control in a bacterial
Max ERC Funding
1 437 693 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym ENDOFOOD
Project Neurocircuitry of endocannabinoid regulation of food intake
Researcher (PI) Giovanni Marsicano
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary Few tasks executed by the brain hold greater survival and adaptive value than keeping us fed and in adequate nutritional state. The regulation of energy metabolism represents a prototypical homeostatic system, with the brain acting as the central coordinator. Any alteration of these mechanisms can lead to pathological states threatening the survival of the individual.
The main brain region regulating food intake behaviour is the hypothalamus. The endocannabinoid system (ECS), formed by cannabinoid receptors, their endogenous ligands (endocannabinoids) and the enzymatic machinery for the synthesis and degradation of endocannabinoids is centrally involved in the regulation of food intake.
This project aims at defining the mechanisms of the ECS-mediated control of food intake. We will reach the following goals:
1.We will generate advanced genetic tools allowing conditional deletion, rescue and overexpression of ECS elements. The integrated use of these tools will lead to the detailed mapping of the brain neurocircuitries where the ECS controls food intake.
2.We will provide strong evidence pointing to differential functions of the ECS in food intake, depending on the specific circuits activated.
3.We will determine which endocannabinoid(s) are involved in specific aspects of food intake.
4.We will detail the electrophysiological impact of the ECS on the hypothalamic neuronal network regulating food intake.
5.We will identify novel biochemical mechanisms, linking the ECS to hypothalamic neuronal activity, mitochondrial functions and regulation of food intake.
This project has the ambitious aim to explore new scientific avenues and to provide “in depth” knowledge on the neuronal mechanisms regulating ingestive behaviour in mammals. The results of this project will pave the way to novel lines of research for the physiology and pharmacology of the ECS in the control of energy balance.
Summary
Few tasks executed by the brain hold greater survival and adaptive value than keeping us fed and in adequate nutritional state. The regulation of energy metabolism represents a prototypical homeostatic system, with the brain acting as the central coordinator. Any alteration of these mechanisms can lead to pathological states threatening the survival of the individual.
The main brain region regulating food intake behaviour is the hypothalamus. The endocannabinoid system (ECS), formed by cannabinoid receptors, their endogenous ligands (endocannabinoids) and the enzymatic machinery for the synthesis and degradation of endocannabinoids is centrally involved in the regulation of food intake.
This project aims at defining the mechanisms of the ECS-mediated control of food intake. We will reach the following goals:
1.We will generate advanced genetic tools allowing conditional deletion, rescue and overexpression of ECS elements. The integrated use of these tools will lead to the detailed mapping of the brain neurocircuitries where the ECS controls food intake.
2.We will provide strong evidence pointing to differential functions of the ECS in food intake, depending on the specific circuits activated.
3.We will determine which endocannabinoid(s) are involved in specific aspects of food intake.
4.We will detail the electrophysiological impact of the ECS on the hypothalamic neuronal network regulating food intake.
5.We will identify novel biochemical mechanisms, linking the ECS to hypothalamic neuronal activity, mitochondrial functions and regulation of food intake.
This project has the ambitious aim to explore new scientific avenues and to provide “in depth” knowledge on the neuronal mechanisms regulating ingestive behaviour in mammals. The results of this project will pave the way to novel lines of research for the physiology and pharmacology of the ECS in the control of energy balance.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-02-01, End date: 2016-01-31
Project acronym ENDOSEXDET
Project The impact of endosymbionts on the evolution of host sex determination mechanisms
Researcher (PI) Richard Cordaux
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary Appreciation of endosymbiosis, a type of symbiosis in which a microbial partner lives within its host cells, as an important source of evolutionary novelty has developed relatively recently. In this proposal, we investigate a fundamental evolutionary process influenced by bacterial endosymbionts: the mechanisms of sex determination of their eukaryotic hosts.
In animals, the most common system of sex determination is genetic. It can also be affected by inherited bacterial endosymbionts. However, very few systems have been analyzed and there is no extensive empirical evidence of how endosymbionts can shape host sex-determining systems. In the isopod crustacean Armadillidium vulgare, genetic sex determination follows female heterogamety. However, many A. vulgare populations harbour Wolbachia bacterial endosymbionts which can invert genetic males into phenotypic functional females.
Other sex-determining factors have been identified in A. vulgare: a feminizing f element which may be a Wolbachia genome fragment carrying feminization information inserted into the host nuclear genome, and a masculinizing gene which can restore the male sex in the presence of the f element, as a result of a genetic conflict. Thus, sex determination mechanisms in A. vulgare seem to be largely driven by Wolbachia endosymbionts. However, the molecular genetic basis and evolutionary history of all these sex-determining factors is unknown.
The A. vulgare/Wolbachia model provides a unique opportunity for directly investigating the impact of endosymbionts on the evolution of host sex determination mechanisms at the molecular genetic level. We will address this issue using the latest developments of molecular genetics technologies, such as next-generation DNA sequencing and high throughput genotyping.
Summary
Appreciation of endosymbiosis, a type of symbiosis in which a microbial partner lives within its host cells, as an important source of evolutionary novelty has developed relatively recently. In this proposal, we investigate a fundamental evolutionary process influenced by bacterial endosymbionts: the mechanisms of sex determination of their eukaryotic hosts.
In animals, the most common system of sex determination is genetic. It can also be affected by inherited bacterial endosymbionts. However, very few systems have been analyzed and there is no extensive empirical evidence of how endosymbionts can shape host sex-determining systems. In the isopod crustacean Armadillidium vulgare, genetic sex determination follows female heterogamety. However, many A. vulgare populations harbour Wolbachia bacterial endosymbionts which can invert genetic males into phenotypic functional females.
Other sex-determining factors have been identified in A. vulgare: a feminizing f element which may be a Wolbachia genome fragment carrying feminization information inserted into the host nuclear genome, and a masculinizing gene which can restore the male sex in the presence of the f element, as a result of a genetic conflict. Thus, sex determination mechanisms in A. vulgare seem to be largely driven by Wolbachia endosymbionts. However, the molecular genetic basis and evolutionary history of all these sex-determining factors is unknown.
The A. vulgare/Wolbachia model provides a unique opportunity for directly investigating the impact of endosymbionts on the evolution of host sex determination mechanisms at the molecular genetic level. We will address this issue using the latest developments of molecular genetics technologies, such as next-generation DNA sequencing and high throughput genotyping.
Max ERC Funding
1 403 285 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym FLINT
Project Finite-Length Information Theory
Researcher (PI) Albert Guillen I Fabregas
Host Institution (HI) UNIVERSIDAD POMPEU FABRA
Call Details Starting Grant (StG), PE7, ERC-2010-StG_20091028
Summary Shannon's Information Theory establishes the fundamental limits of information processing systems. A concept that is hidden in the mathematical proofs most of the Information Theory literature, is that in order to achieve the fundamental limits we need sequences of infinite duration. Practical information processing systems have strict limitations in terms of length, induced by system constraints on delay and complexity. The vast majority of the Information Theory literature ignores these constraints and theoretical studies that provide a finite-length treatment of information processing are hence urgently needed. When finite-lengths are employed, asymptotic techniques (laws of large numbers, large deviations) cannot be invoked and new techniques must be sought. A fundamental understanding of the impact of finite-lengths is crucial to harvesting the potential gains in practice. This project is aimed at contributing towards the ambitious goal of providing a unified framework for the study of finite-length Information Theory. The approach in this project will be based on information-spectrum combined with tight bounding techniques. A comprehensive study of finite-length information theory will represent a major step forward in Information Theory, with the potential to provide new tools and techniques to solve open problems in multiple disciplines. This unconventional and challenging treatment of Information Theory will advance the area and will contribute to disciplines where Information Theory is relevant. Therefore, the results of this project will be of benefit to areas such as communication theory, probability theory, statistics, physics, computer science, mathematics, economics, bioinformatics and computational neuroscience.
Summary
Shannon's Information Theory establishes the fundamental limits of information processing systems. A concept that is hidden in the mathematical proofs most of the Information Theory literature, is that in order to achieve the fundamental limits we need sequences of infinite duration. Practical information processing systems have strict limitations in terms of length, induced by system constraints on delay and complexity. The vast majority of the Information Theory literature ignores these constraints and theoretical studies that provide a finite-length treatment of information processing are hence urgently needed. When finite-lengths are employed, asymptotic techniques (laws of large numbers, large deviations) cannot be invoked and new techniques must be sought. A fundamental understanding of the impact of finite-lengths is crucial to harvesting the potential gains in practice. This project is aimed at contributing towards the ambitious goal of providing a unified framework for the study of finite-length Information Theory. The approach in this project will be based on information-spectrum combined with tight bounding techniques. A comprehensive study of finite-length information theory will represent a major step forward in Information Theory, with the potential to provide new tools and techniques to solve open problems in multiple disciplines. This unconventional and challenging treatment of Information Theory will advance the area and will contribute to disciplines where Information Theory is relevant. Therefore, the results of this project will be of benefit to areas such as communication theory, probability theory, statistics, physics, computer science, mathematics, economics, bioinformatics and computational neuroscience.
Max ERC Funding
1 303 606 €
Duration
Start date: 2011-08-01, End date: 2017-07-31
