Project acronym ADDICTIONCIRCUITS
Project Drug addiction: molecular changes in reward and aversion circuits
Researcher (PI) Nils David Engblom
Host Institution (HI) LINKOPINGS UNIVERSITET
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary Our affective and motivational state is important for our decisions, actions and quality of life. Many pathological conditions affect this state. For example, addictive drugs are hyperactivating the reward system and trigger a strong motivation for continued drug intake, whereas many somatic and psychiatric diseases lead to an aversive state, characterized by loss of motivation. I will study specific neural circuits and mechanisms underlying reward and aversion, and how pathological signaling in these systems can trigger relapse in drug addiction.
Given the important role of the dopaminergic neurons in the midbrain for many aspects of reward signaling, I will study how synaptic plasticity in these cells, and in their target neurons in the striatum, contribute to relapse in drug seeking. I will also study the circuits underlying aversion. Little is known about these circuits, but my hypothesis is that an important component of aversion is signaled by a specific neuronal population in the brainstem parabrachial nucleus, projecting to the central amygdala. We will test this hypothesis and also determine how this aversion circuit contributes to the persistence of addiction and to relapse.
To dissect this complicated system, I am developing new genetic methods for manipulating and visualizing specific functional circuits in the mouse brain. My unique combination of state-of-the-art competence in transgenics and cutting edge knowledge in the anatomy and functional organization of the circuits behind reward and aversion should allow me to decode these systems, linking discrete circuits to behavior.
Collectively, the results will indicate how signals encoding aversion and reward are integrated to control addictive behavior and they may identify novel avenues for treatment of drug addiction as well as aversion-related symptoms affecting patients with chronic inflammatory conditions and cancer.
Summary
Our affective and motivational state is important for our decisions, actions and quality of life. Many pathological conditions affect this state. For example, addictive drugs are hyperactivating the reward system and trigger a strong motivation for continued drug intake, whereas many somatic and psychiatric diseases lead to an aversive state, characterized by loss of motivation. I will study specific neural circuits and mechanisms underlying reward and aversion, and how pathological signaling in these systems can trigger relapse in drug addiction.
Given the important role of the dopaminergic neurons in the midbrain for many aspects of reward signaling, I will study how synaptic plasticity in these cells, and in their target neurons in the striatum, contribute to relapse in drug seeking. I will also study the circuits underlying aversion. Little is known about these circuits, but my hypothesis is that an important component of aversion is signaled by a specific neuronal population in the brainstem parabrachial nucleus, projecting to the central amygdala. We will test this hypothesis and also determine how this aversion circuit contributes to the persistence of addiction and to relapse.
To dissect this complicated system, I am developing new genetic methods for manipulating and visualizing specific functional circuits in the mouse brain. My unique combination of state-of-the-art competence in transgenics and cutting edge knowledge in the anatomy and functional organization of the circuits behind reward and aversion should allow me to decode these systems, linking discrete circuits to behavior.
Collectively, the results will indicate how signals encoding aversion and reward are integrated to control addictive behavior and they may identify novel avenues for treatment of drug addiction as well as aversion-related symptoms affecting patients with chronic inflammatory conditions and cancer.
Max ERC Funding
1 500 000 €
Duration
Start date: 2010-10-01, End date: 2015-09-30
Project acronym AFRODITE
Project Advanced Fluid Research On Drag reduction In Turbulence Experiments
Researcher (PI) Jens Henrik Mikael Fransson
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Starting Grant (StG), PE8, ERC-2010-StG_20091028
Summary A hot topic in today's debate on global warming is drag reduction in aeronautics. The most beneficial concept for drag reduction is to maintain the major portion of the airfoil laminar. Estimations show that the potential drag reduction can be as much as 15%, which would give a significant reduction of NOx and CO emissions in the atmosphere considering that the number of aircraft take offs, only in the EU, is over 19 million per year. An important element for successful flow control, which can lead to a reduced aerodynamic drag, is enhanced physical understanding of the transition to turbulence process.
In previous wind tunnel measurements we have shown that roughness elements can be used to sensibly delay transition to turbulence. The result is revolutionary, since the common belief has been that surface roughness causes earlier transition and in turn increases the drag, and is a proof of concept of the passive control method per se. The beauty with a passive control technique is that no external energy has to be added to the flow system in order to perform the control, instead one uses the existing energy in the flow.
In this project proposal, AFRODITE, we will take this passive control method to the next level by making it twofold, more persistent and more robust. Transition prevention is the goal rather than transition delay and the method will be extended to simultaneously control separation, which is another unwanted flow phenomenon especially during airplane take offs. AFRODITE will be a catalyst for innovative research, which will lead to a cleaner sky.
Summary
A hot topic in today's debate on global warming is drag reduction in aeronautics. The most beneficial concept for drag reduction is to maintain the major portion of the airfoil laminar. Estimations show that the potential drag reduction can be as much as 15%, which would give a significant reduction of NOx and CO emissions in the atmosphere considering that the number of aircraft take offs, only in the EU, is over 19 million per year. An important element for successful flow control, which can lead to a reduced aerodynamic drag, is enhanced physical understanding of the transition to turbulence process.
In previous wind tunnel measurements we have shown that roughness elements can be used to sensibly delay transition to turbulence. The result is revolutionary, since the common belief has been that surface roughness causes earlier transition and in turn increases the drag, and is a proof of concept of the passive control method per se. The beauty with a passive control technique is that no external energy has to be added to the flow system in order to perform the control, instead one uses the existing energy in the flow.
In this project proposal, AFRODITE, we will take this passive control method to the next level by making it twofold, more persistent and more robust. Transition prevention is the goal rather than transition delay and the method will be extended to simultaneously control separation, which is another unwanted flow phenomenon especially during airplane take offs. AFRODITE will be a catalyst for innovative research, which will lead to a cleaner sky.
Max ERC Funding
1 418 399 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym AGINGSEXDIFF
Project Aging Differently: Understanding Sex Differences in Reproductive, Demographic and Functional Senescence
Researcher (PI) Alexei Maklakov
Host Institution (HI) Uppsala University
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a
long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not
only in how long they live and when they start to senesce, but also in how they react to
environmental interventions aimed at prolonging their life span or decelerating the onset of aging.
Therefore, sex differences in life span and aging have important implications beyond the questions
posed by fundamental science. Both evolutionary reasons and medical implications of sex
differences in demographic, reproductive and physiological senescence are and will be crucial
targets of present and future research in the biology of aging. Here I propose a two-step approach
that can provide a significant breakthrough in our understanding of the biological basis of sex
differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific
mortality rate in sex differences in aging by developing a series of targeted experimental
evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I
address the role of intra-locus sexual conflict in the evolution of aging by combining novel
methodology from nutritional ecology – the Geometric Framework – with artificial selection
approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will
directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the
adaptive evolution of diet choice. By combining techniques from evolutionary biology and
nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to
the training of young scientists in this rapidly developing field.
Summary
Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a
long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not
only in how long they live and when they start to senesce, but also in how they react to
environmental interventions aimed at prolonging their life span or decelerating the onset of aging.
Therefore, sex differences in life span and aging have important implications beyond the questions
posed by fundamental science. Both evolutionary reasons and medical implications of sex
differences in demographic, reproductive and physiological senescence are and will be crucial
targets of present and future research in the biology of aging. Here I propose a two-step approach
that can provide a significant breakthrough in our understanding of the biological basis of sex
differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific
mortality rate in sex differences in aging by developing a series of targeted experimental
evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I
address the role of intra-locus sexual conflict in the evolution of aging by combining novel
methodology from nutritional ecology – the Geometric Framework – with artificial selection
approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will
directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the
adaptive evolution of diet choice. By combining techniques from evolutionary biology and
nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to
the training of young scientists in this rapidly developing field.
Max ERC Funding
1 391 904 €
Duration
Start date: 2010-12-01, End date: 2016-05-31
Project acronym BOTMED
Project Microrobotics and Nanomedicine
Researcher (PI) Bradley James Nelson
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE7, ERC-2010-AdG_20100224
Summary The introduction of minimally invasive surgery in the 1980’s created a paradigm shift in surgical procedures. Health care is now in a position to make a more dramatic leap by integrating newly developed wireless microrobotic technologies with nanomedicine to perform precisely targeted, localized endoluminal techniques. Devices capable of entering the human body through natural orifices or small incisions to deliver drugs, perform diagnostic procedures, and excise and repair tissue will be used. These new procedures will result in less trauma to the patient and faster recovery times, and will enable new therapies that have not yet been conceived. In order to realize this, many new technologies must be developed and synergistically integrated, and medical therapies for which the technology will prove successful must be aggressively pursued.
This proposed project will result in the realization of animal trials in which wireless microrobotic devices will be used to investigate a variety of extremely delicate ophthalmic therapies. The therapies to be pursued include the delivery of tissue plasminogen activator (t-PA) to blocked retinal veins, the peeling of epiretinal membranes from the retina, and the development of diagnostic procedures based on mapping oxygen concentration at the vitreous-retina interface. With successful animal trials, a path to human trials and commercialization will follow. Clearly, many systems in the body have the potential to benefit from the endoluminal technologies that this project considers, including the digestive system, the circulatory system, the urinary system, the central nervous system, the respiratory system, the female reproductive system and even the fetus. Microrobotic retinal therapies will greatly illuminate the potential that the integration of microrobotics and nanomedicine holds for society, and greatly accelerate this trend in Europe.
Summary
The introduction of minimally invasive surgery in the 1980’s created a paradigm shift in surgical procedures. Health care is now in a position to make a more dramatic leap by integrating newly developed wireless microrobotic technologies with nanomedicine to perform precisely targeted, localized endoluminal techniques. Devices capable of entering the human body through natural orifices or small incisions to deliver drugs, perform diagnostic procedures, and excise and repair tissue will be used. These new procedures will result in less trauma to the patient and faster recovery times, and will enable new therapies that have not yet been conceived. In order to realize this, many new technologies must be developed and synergistically integrated, and medical therapies for which the technology will prove successful must be aggressively pursued.
This proposed project will result in the realization of animal trials in which wireless microrobotic devices will be used to investigate a variety of extremely delicate ophthalmic therapies. The therapies to be pursued include the delivery of tissue plasminogen activator (t-PA) to blocked retinal veins, the peeling of epiretinal membranes from the retina, and the development of diagnostic procedures based on mapping oxygen concentration at the vitreous-retina interface. With successful animal trials, a path to human trials and commercialization will follow. Clearly, many systems in the body have the potential to benefit from the endoluminal technologies that this project considers, including the digestive system, the circulatory system, the urinary system, the central nervous system, the respiratory system, the female reproductive system and even the fetus. Microrobotic retinal therapies will greatly illuminate the potential that the integration of microrobotics and nanomedicine holds for society, and greatly accelerate this trend in Europe.
Max ERC Funding
2 498 044 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym BRAINCELL
Project Charting the landscape of brain development by large-scale single-cell transcriptomics and phylogenetic lineage reconstruction
Researcher (PI) Sten Linnarsson
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary Embryogenesis is the temporal unfolding of cellular processes: proliferation, migration, differentiation, morphogenesis, apoptosis and functional specialization. These processes are well understood in specific tissues, and for specific cell types. Nevertheless, our systematic knowledge of the types of cells present in the developing and adult animal, and about their functional and lineage relationships, is limited. For example, there is no consensus on the number of cell types, and many important stem cells and progenitors remain to be discovered. Similarly, the lineage relationships between specific cell types are often poorly characterized. This is particularly true for the mammalian nervous system. We have developed (1) a reliable high-throghput method for sequencing all transcripts in 96 single cells at a time; and (2) a system for high-throughput phylogenetic lineage reconstruction. We now propose to characterize embryogenesis using a shotgun approach borrowed from genomics. Tissues will be dissected from multiple stages and dissociated to single cells. A total of 10,000 cells will be analyzed by RNA sequencing, revealing their functional cell type, their lineage relationships, and their current state (e.g. cell cycle phase). The novel approach proposed here will bring the powerful strategies pioneered in genomics into the field of developmental biology, including automation, digitization, and the random shotgun method. The data thus obtained will bring clarity to the concept of ‘cell type’; will provide a first catalog of mouse brain cell types with deep functional annotation; will provide markers for every cell type, including stem cells; and will serve as a basis for future comparative work, especially with human embryos.
Summary
Embryogenesis is the temporal unfolding of cellular processes: proliferation, migration, differentiation, morphogenesis, apoptosis and functional specialization. These processes are well understood in specific tissues, and for specific cell types. Nevertheless, our systematic knowledge of the types of cells present in the developing and adult animal, and about their functional and lineage relationships, is limited. For example, there is no consensus on the number of cell types, and many important stem cells and progenitors remain to be discovered. Similarly, the lineage relationships between specific cell types are often poorly characterized. This is particularly true for the mammalian nervous system. We have developed (1) a reliable high-throghput method for sequencing all transcripts in 96 single cells at a time; and (2) a system for high-throughput phylogenetic lineage reconstruction. We now propose to characterize embryogenesis using a shotgun approach borrowed from genomics. Tissues will be dissected from multiple stages and dissociated to single cells. A total of 10,000 cells will be analyzed by RNA sequencing, revealing their functional cell type, their lineage relationships, and their current state (e.g. cell cycle phase). The novel approach proposed here will bring the powerful strategies pioneered in genomics into the field of developmental biology, including automation, digitization, and the random shotgun method. The data thus obtained will bring clarity to the concept of ‘cell type’; will provide a first catalog of mouse brain cell types with deep functional annotation; will provide markers for every cell type, including stem cells; and will serve as a basis for future comparative work, especially with human embryos.
Max ERC Funding
1 496 032 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym CAT4ENSUS
Project Molecular Catalysts Made of Earth-Abundant Elements for Energy and Sustainability
Researcher (PI) Xile Hu
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE5, ERC-2010-StG_20091028
Summary Energy and sustainability are among the biggest challenges humanity faces this century. Catalysis is an indispensable component for many potential solutions, and fundamental research in catalysis is as urgent as ever. Here, we propose to build up an interdisciplinary research program in molecular catalysis to address the challenges of energy and sustainability. There are two specific aims: (I) bio-inspired sulfur-rich metal complexes as efficient and practical electrocatalysts for hydrogen production and CO2 reduction; (II) well-defined Fe complexes of chelating pincer ligands for chemo- and stereoselective organic synthesis. An important feature of the proposed catalysts is that they are made of earth-abundant and readily available elements such as Fe, Co, Ni, S, N, etc.
Design and synthesis of catalysts are the starting point and a key aspect of this project. A major inspiration comes from nature, where metallo-enzymes use readily available metals for fuel production and challenging reactions. Our accumulated knowledge and experience in spectroscopy, electrochemistry, reaction chemistry, mechanism, and catalysis will enable us to thoroughly study the synthetic catalysts and their applications towards the research targets. Furthermore, we will explore research territories such as electrode modification and fabrication, catalyst immobilization and attachment, and asymmetric catalysis.
The proposed research should not only result in new insights and knowledge in catalysis that are relevant to energy and sustainability, but also produce functional, scalable, and economically feasible catalysts for fuel production and organic synthesis. The program can contribute to excellence in European research.
Summary
Energy and sustainability are among the biggest challenges humanity faces this century. Catalysis is an indispensable component for many potential solutions, and fundamental research in catalysis is as urgent as ever. Here, we propose to build up an interdisciplinary research program in molecular catalysis to address the challenges of energy and sustainability. There are two specific aims: (I) bio-inspired sulfur-rich metal complexes as efficient and practical electrocatalysts for hydrogen production and CO2 reduction; (II) well-defined Fe complexes of chelating pincer ligands for chemo- and stereoselective organic synthesis. An important feature of the proposed catalysts is that they are made of earth-abundant and readily available elements such as Fe, Co, Ni, S, N, etc.
Design and synthesis of catalysts are the starting point and a key aspect of this project. A major inspiration comes from nature, where metallo-enzymes use readily available metals for fuel production and challenging reactions. Our accumulated knowledge and experience in spectroscopy, electrochemistry, reaction chemistry, mechanism, and catalysis will enable us to thoroughly study the synthetic catalysts and their applications towards the research targets. Furthermore, we will explore research territories such as electrode modification and fabrication, catalyst immobilization and attachment, and asymmetric catalysis.
The proposed research should not only result in new insights and knowledge in catalysis that are relevant to energy and sustainability, but also produce functional, scalable, and economically feasible catalysts for fuel production and organic synthesis. The program can contribute to excellence in European research.
Max ERC Funding
1 475 712 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym CELLTYPESANDCIRCUITS
Project Neural circuit function in the retina of mice and humans
Researcher (PI) Botond Roska
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (multitasking cell types), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform a single computation or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.
Summary
The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (multitasking cell types), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform a single computation or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.
Max ERC Funding
1 499 000 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym CEV
Project Coordination by Evaluations and Valuations:
Market Logic Inside and Outside the Economy
Researcher (PI) Jonas Patrik Aspers
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), SH2, ERC-2010-StG_20091209
Summary This project studies evaluation and valuation as ways of coordinating actors and resources. Valuation is the ascribing of value to people, organizations, things and events given that there is no standard of value. Evaluation is judging according to an already existing value-standard. Valuation and evaluation are ways of ranking and thus ordering of objects . Markets are examples of economic social formations in which valuations and evaluations are the foundation for the choices made. Valuation and evaluation are important means of coordination also outside of the economy, in competitions (e.g., sports), reviews (e.g., books), and auditing (e.g., of ethical conduct).
This project is motivated by evaluation and valuation as increasingly influential ways of coordinating social life. Choices based on evaluation have gradually replaced networks and hierarchies as the preferred coordination form, but processes of valuation or evaluation are not well-understood. The overarching research question of this project is: how do processes of coordination based on valuations function? By understanding these processes can we analyze the consequences of coordinated by the means of evaluation in different spheres of life. It is also the foundation for policy suggestions.
The proposed project uses theoretical insights about market elements in economics and sociology and on the relational sociological literature on social formations. Empirical sub-projects are designed to facilitate comparison, to establish validated conclusions and to promote theory development. This project opens up a new avenue of research of coordination based on valuation and evaluation. It will lead to the establishment a high quality research group located at the frontiers of social science.
Summary
This project studies evaluation and valuation as ways of coordinating actors and resources. Valuation is the ascribing of value to people, organizations, things and events given that there is no standard of value. Evaluation is judging according to an already existing value-standard. Valuation and evaluation are ways of ranking and thus ordering of objects . Markets are examples of economic social formations in which valuations and evaluations are the foundation for the choices made. Valuation and evaluation are important means of coordination also outside of the economy, in competitions (e.g., sports), reviews (e.g., books), and auditing (e.g., of ethical conduct).
This project is motivated by evaluation and valuation as increasingly influential ways of coordinating social life. Choices based on evaluation have gradually replaced networks and hierarchies as the preferred coordination form, but processes of valuation or evaluation are not well-understood. The overarching research question of this project is: how do processes of coordination based on valuations function? By understanding these processes can we analyze the consequences of coordinated by the means of evaluation in different spheres of life. It is also the foundation for policy suggestions.
The proposed project uses theoretical insights about market elements in economics and sociology and on the relational sociological literature on social formations. Empirical sub-projects are designed to facilitate comparison, to establish validated conclusions and to promote theory development. This project opens up a new avenue of research of coordination based on valuation and evaluation. It will lead to the establishment a high quality research group located at the frontiers of social science.
Max ERC Funding
1 476 251 €
Duration
Start date: 2011-03-01, End date: 2016-02-29
Project acronym CIRCATRANS
Project Control of mouse metabolism by circadian clock-coordinated mRNA translation
Researcher (PI) Frédéric Bruno Martin Gachon
Host Institution (HI) NESTEC SA
Call Details Starting Grant (StG), LS1, ERC-2010-StG_20091118
Summary The mammalian circadian clock plays a fundamental role in the liver by regulating fatty acid, glucose and xenobiotic metabolism. Impairment of this rhythm has been show to lead to diverse pathologies including metabolic syndrome. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. We have now collected evidence that post-transcriptional regulations play also an important role in this regulation. Particularly, recent results from our laboratory show that the circadian clock can synchronize mRNA translation in mouse liver through rhythmic activation of the Target Of Rapamycin Complex 1 (TORC1) with a 12-hours period. Based on this unexpected observation, we plan to identify the genes rhythmically translated in the mouse liver as well as the mechanisms involved in this translation. Indeed, our initial observations suggest a cap-independent translation during the day and a cap-dependent translation during the night. Identification of the different complexes involved in translation at this two different times and their correlation with the sequence, structure, and/or function of the translated genes will provide new insight into the action of the circadian clock on animal metabolism. In parallel, we will identify the signalling pathways involved in the rhythmic activation of TORC1 in mouse liver. Finally, we will study the consequences of a deregulated rhythmic translation in circadian clock-deficient mice on the metabolism and the longevity of these animals. Perturbations of the circadian clock have been linked to numerous pathologies, including obesity, type 2 diabetes and cancer. Our project on the importance of circadian clock-coordinated translation will likely reveal new findings in the field of regulation of animal metabolism by the circadian clock.
Summary
The mammalian circadian clock plays a fundamental role in the liver by regulating fatty acid, glucose and xenobiotic metabolism. Impairment of this rhythm has been show to lead to diverse pathologies including metabolic syndrome. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. We have now collected evidence that post-transcriptional regulations play also an important role in this regulation. Particularly, recent results from our laboratory show that the circadian clock can synchronize mRNA translation in mouse liver through rhythmic activation of the Target Of Rapamycin Complex 1 (TORC1) with a 12-hours period. Based on this unexpected observation, we plan to identify the genes rhythmically translated in the mouse liver as well as the mechanisms involved in this translation. Indeed, our initial observations suggest a cap-independent translation during the day and a cap-dependent translation during the night. Identification of the different complexes involved in translation at this two different times and their correlation with the sequence, structure, and/or function of the translated genes will provide new insight into the action of the circadian clock on animal metabolism. In parallel, we will identify the signalling pathways involved in the rhythmic activation of TORC1 in mouse liver. Finally, we will study the consequences of a deregulated rhythmic translation in circadian clock-deficient mice on the metabolism and the longevity of these animals. Perturbations of the circadian clock have been linked to numerous pathologies, including obesity, type 2 diabetes and cancer. Our project on the importance of circadian clock-coordinated translation will likely reveal new findings in the field of regulation of animal metabolism by the circadian clock.
Max ERC Funding
1 475 831 €
Duration
Start date: 2011-03-01, End date: 2016-02-29
Project acronym COMCOM
Project Communication and Computation - Two Sides of One Tapestry
Researcher (PI) Michael Christoph Gastpar
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE7, ERC-2010-StG_20091028
Summary Networks have been studied in depth for several decades, but one aspect has received little attention: Interference. Most networks use clever algorithms to avoid interference, and this strategy has proved effective for traditional supply-chain or wired communication networks. However, the emergence of wireless networks revealed that simply avoiding interference leads to significant performance loss. A wealth of cooperative communication strategies have recently been developed to address this issue. Two fundamental roadblocks are emerging: First, it is ultimately unclear how to integrate cooperative techniques into the larger fabric of networks (short of case-by-case redesigns); and second, the lack of source/channel separation in networks (i.e., more bits do not imply better end-to-end signal quality) calls for ever more specialized cooperative techniques.
This proposal advocates a new understanding of interference as computation: Interference garbles together inputs to produce an output. This can be thought of as a certain computation, perhaps subject to noise or other stochastic effects. The proposed work will develop strategies that permit to exploit this computational potential. Building on these ``computation codes,'' an enhanced physical layer is proposed: Rather than only forwarding bits, the revised physical layer can also forward functions from several transmitting nodes to a receiver, much more efficiently than the full information. Near-seamless integration into the fabric of existing network architectures is thus possible, providing a solution for the first roadblock. In response to the second roadblock, computation codes suggest new computational primitives as fundamental currencies of information.
Summary
Networks have been studied in depth for several decades, but one aspect has received little attention: Interference. Most networks use clever algorithms to avoid interference, and this strategy has proved effective for traditional supply-chain or wired communication networks. However, the emergence of wireless networks revealed that simply avoiding interference leads to significant performance loss. A wealth of cooperative communication strategies have recently been developed to address this issue. Two fundamental roadblocks are emerging: First, it is ultimately unclear how to integrate cooperative techniques into the larger fabric of networks (short of case-by-case redesigns); and second, the lack of source/channel separation in networks (i.e., more bits do not imply better end-to-end signal quality) calls for ever more specialized cooperative techniques.
This proposal advocates a new understanding of interference as computation: Interference garbles together inputs to produce an output. This can be thought of as a certain computation, perhaps subject to noise or other stochastic effects. The proposed work will develop strategies that permit to exploit this computational potential. Building on these ``computation codes,'' an enhanced physical layer is proposed: Rather than only forwarding bits, the revised physical layer can also forward functions from several transmitting nodes to a receiver, much more efficiently than the full information. Near-seamless integration into the fabric of existing network architectures is thus possible, providing a solution for the first roadblock. In response to the second roadblock, computation codes suggest new computational primitives as fundamental currencies of information.
Max ERC Funding
1 776 473 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
