Project acronym BRAIN2BRAIN
Project Towards two-person neuroscience
Researcher (PI) Riitta Kyllikki Hari
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Advanced Grant (AdG), LS5, ERC-2008-AdG
Summary Humans interact with other people throughout their lives. This project aims to demonstrate that the complex social shaping of the human brain can be adequately tackled only by taking a leap from the conven-tional single-person neuroscience to two-person neuroscience. We will (1) develop a conceptual framework and experimental setups for two-person neuroscience, (2) apply time-sensitive methods for studies of two interacting persons, monitoring both brain and autonomic nervous activity to also cover the brain body connection, (3) use gaze as an index of subject s attention to simplify signal analysis in natural environments, and (4) apply insights from two-person neuroscience into disorders of social interaction. Brain activity will be recorded with millisecond-accurate whole-scalp (306-channel) magnetoencepha-lography (MEG), associated with EEG, and with the millimeter-accurate 3-tesla functional magnetic reso-nance imaging (fMRI). Heart rate, respiration, galvanic skin response, and pupil diameter inform about body function. A new psychophysiological interaction setting will be built, comprising a two-person eye-tracking system. Novel analysis methods will be developed to follow the interaction and possible synchronization of the two persons signals. This uncoventional approach crosses borders of neuroscience, social psychology, psychophysiology, psychiatry, medical imaging, and signal analysis, with intriguing connections to old philosophical questions, such as intersubjectivity and emphatic attunement. The results could open an unprecedented window into human human, instead of just brain brain, interactions, helping to understand also social disorders, such as autism and schizophrenia. Further applications include master apprentice and patient therapist relationships. Advancing from studies of single persons towards two-person neuroscience shows promise of a break-through in understanding the dynamic social shaping of human brain and mind.
Summary
Humans interact with other people throughout their lives. This project aims to demonstrate that the complex social shaping of the human brain can be adequately tackled only by taking a leap from the conven-tional single-person neuroscience to two-person neuroscience. We will (1) develop a conceptual framework and experimental setups for two-person neuroscience, (2) apply time-sensitive methods for studies of two interacting persons, monitoring both brain and autonomic nervous activity to also cover the brain body connection, (3) use gaze as an index of subject s attention to simplify signal analysis in natural environments, and (4) apply insights from two-person neuroscience into disorders of social interaction. Brain activity will be recorded with millisecond-accurate whole-scalp (306-channel) magnetoencepha-lography (MEG), associated with EEG, and with the millimeter-accurate 3-tesla functional magnetic reso-nance imaging (fMRI). Heart rate, respiration, galvanic skin response, and pupil diameter inform about body function. A new psychophysiological interaction setting will be built, comprising a two-person eye-tracking system. Novel analysis methods will be developed to follow the interaction and possible synchronization of the two persons signals. This uncoventional approach crosses borders of neuroscience, social psychology, psychophysiology, psychiatry, medical imaging, and signal analysis, with intriguing connections to old philosophical questions, such as intersubjectivity and emphatic attunement. The results could open an unprecedented window into human human, instead of just brain brain, interactions, helping to understand also social disorders, such as autism and schizophrenia. Further applications include master apprentice and patient therapist relationships. Advancing from studies of single persons towards two-person neuroscience shows promise of a break-through in understanding the dynamic social shaping of human brain and mind.
Max ERC Funding
2 489 643 €
Duration
Start date: 2009-01-01, End date: 2014-12-31
Project acronym BrainDrain
Project Translational implications of the discovery of brain-draining lymphatics
Researcher (PI) Kari ALITALO
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Advanced Grant (AdG), LS7, ERC-2016-ADG
Summary In 2010, 800 billion Euros was spent on brain diseases in Europe and the cost is expected to increase due to the aging population. – Here I propose to exploit our new discovery for research to alleviate this disease burden. In work selected by Nature Medicine among the top 10 ”Notable Advances” and by Science as one of the 10 ”Breakthroughs of the year” 2015, we discovered a meningeal lymphatic vascular system that serves brain homeostasis. We want to reassess current concepts about cerebrovascular dynamics, fluid drainage and cellular trafficking in physiological conditions, in Alzheimer’s disease mouse models and in human postmortem tissues. First, we will study the development and properties of meningeal lymphatics and how they are sustained during aging. We then want to analyse the clearance of macromolecules and protein aggregates in Alzheimer’s disease in mice that lack the newly discovered meningeal lymphatic drainage system. We will study if growth factor-mediated expansion of lymphatic vessels alleviates the parenchymal accumulation of neurotoxic amyloid beta and pathogenesis of Alzheimer’s disease and brain damage after traumatic brain injury. We will further analyse the role of lymphangiogenic growth factors and lymphatic vessels in brain solute clearance, immune cell trafficking and in a mouse model of multiple sclerosis. The meningeal lymphatics could be involved in a number of neurodegenerative and neuroinflammatory diseases of considerable human and socioeconomic burden. Several of our previous concepts have already been translated to clinical development and we aim to develop proof-of-principle therapeutic concepts in this project. I feel that we are just now in a unique position to advance frontline European translational biomedical research in this suddenly emerging field, which has received great attention worldwide.
Summary
In 2010, 800 billion Euros was spent on brain diseases in Europe and the cost is expected to increase due to the aging population. – Here I propose to exploit our new discovery for research to alleviate this disease burden. In work selected by Nature Medicine among the top 10 ”Notable Advances” and by Science as one of the 10 ”Breakthroughs of the year” 2015, we discovered a meningeal lymphatic vascular system that serves brain homeostasis. We want to reassess current concepts about cerebrovascular dynamics, fluid drainage and cellular trafficking in physiological conditions, in Alzheimer’s disease mouse models and in human postmortem tissues. First, we will study the development and properties of meningeal lymphatics and how they are sustained during aging. We then want to analyse the clearance of macromolecules and protein aggregates in Alzheimer’s disease in mice that lack the newly discovered meningeal lymphatic drainage system. We will study if growth factor-mediated expansion of lymphatic vessels alleviates the parenchymal accumulation of neurotoxic amyloid beta and pathogenesis of Alzheimer’s disease and brain damage after traumatic brain injury. We will further analyse the role of lymphangiogenic growth factors and lymphatic vessels in brain solute clearance, immune cell trafficking and in a mouse model of multiple sclerosis. The meningeal lymphatics could be involved in a number of neurodegenerative and neuroinflammatory diseases of considerable human and socioeconomic burden. Several of our previous concepts have already been translated to clinical development and we aim to develop proof-of-principle therapeutic concepts in this project. I feel that we are just now in a unique position to advance frontline European translational biomedical research in this suddenly emerging field, which has received great attention worldwide.
Max ERC Funding
2 420 429 €
Duration
Start date: 2017-08-01, End date: 2022-07-31
Project acronym CHROMARRANGE
Project Programmed and unprogrammed genomic rearrangements during the evolution of yeast species
Researcher (PI) Kenneth Henry Wolfe
Host Institution (HI) UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Country Ireland
Call Details Advanced Grant (AdG), LS2, ERC-2010-AdG_20100317
Summary By detailed evolutionary comparisons among multiple sequenced yeast genomes, we have identified several unusual regions where our preliminary evidence suggests that previously unknown molecular biology phenomena, involving rearrangement of genomic DNA, are occurring. I now propose to use a combination of dry-lab and wet-lab experimental approaches to characterize these regions and phenomena further. One region is a 24-kb section of chromosome XIV that appears to undergo recurrent 'flip/flop' inversion between two isomers at a fairly high rate in five species as diverse as Saccharomyces cerevisiae and Naumovia castellii, leading to a 1:1 ratio of the two isomers in each species. We hypothesize that this region is the site of a programmed DNA rearrangement analogous to mating-type switching. We have also identified two new genes related to the mating-type switching endonuclease HO, but different from it, that are potentially involved in rearrangement processes though not necessarily the inversion described above. We will determine the sites of action of these endonucleases. Separately, we have found evidence for a process of recurrent deletion of DNA from regions flanking the mating-type (MAT) locus in all yeast species that are descended from the whole-genome duplication (WGD) event, causing continual transpositions of genes from beside MAT to other locations in the genome. In related computational work, we propose to investigate an hypothesis that evolutionary loss of the MATa2 transcriptional activator may have been the cause of the WGD event.
Summary
By detailed evolutionary comparisons among multiple sequenced yeast genomes, we have identified several unusual regions where our preliminary evidence suggests that previously unknown molecular biology phenomena, involving rearrangement of genomic DNA, are occurring. I now propose to use a combination of dry-lab and wet-lab experimental approaches to characterize these regions and phenomena further. One region is a 24-kb section of chromosome XIV that appears to undergo recurrent 'flip/flop' inversion between two isomers at a fairly high rate in five species as diverse as Saccharomyces cerevisiae and Naumovia castellii, leading to a 1:1 ratio of the two isomers in each species. We hypothesize that this region is the site of a programmed DNA rearrangement analogous to mating-type switching. We have also identified two new genes related to the mating-type switching endonuclease HO, but different from it, that are potentially involved in rearrangement processes though not necessarily the inversion described above. We will determine the sites of action of these endonucleases. Separately, we have found evidence for a process of recurrent deletion of DNA from regions flanking the mating-type (MAT) locus in all yeast species that are descended from the whole-genome duplication (WGD) event, causing continual transpositions of genes from beside MAT to other locations in the genome. In related computational work, we propose to investigate an hypothesis that evolutionary loss of the MATa2 transcriptional activator may have been the cause of the WGD event.
Max ERC Funding
1 516 960 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym CleverGenes
Project Novel Gene Therapy Based on the Activation of Endogenous Genes for the Treatment of Ischemia - Concepts of endogenetherapy, release of promoter pausing, promoter-targeted ncRNAs and nuclear RNAi
Researcher (PI) Seppo Ylae-Herttuala
Host Institution (HI) ITA-SUOMEN YLIOPISTO
Country Finland
Call Details Advanced Grant (AdG), LS7, ERC-2014-ADG
Summary Background: Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) has great potential to become a novel, minimally invasive new treatment for a large number of patients with severe myocardial ischemia. However, this requires development of new technology. Advancing state-of-the-art: We propose a paradigm shift in gene therapy for chronic ischemia by activating endogenous VEGF-A,-B and -C genes and angiogenic transcription programs from the native promoters instead of gene transfer of exogenous cDNA to target tissues. We will develop a new platform technology (endogenetherapy) based on our novel concept of the release of promoter pausing and new promoter-targeted upregulating short hairpinRNAs, tissue-specific superenhancerRNAs activating specific transcription centers involving gene clusters in different chromosomal regions, small circularRNAs formed from self-splicing exons-introns that can be regulated with oligonucleotides and small molecules such as metabolites, nuclear RNAi vectors and specific CRISPR/gRNAmutatedCas9-VP16 technology with an ability to target integration into genomic safe harbor sites. After preclinical studies in mice and in a newly developed chronic cardiac ischemia model in pigs with special emphasis on the analysis of clinically relevant blood flow, metabolic and functional outcomes based on MRI, ultrasound, photoacoustic and PET imaging, the best construct will be taken to a phase I clinical study in patients with severe myocardial ischemia. Since endogenetherapy also involves epigenetic changes, which are reversible and long-lasting, we expect to efficiently activate natural angiogenic programs. Significance: If successful, this approach will begin a new era in gene therapy. Since there is a clear lack of technology capable of targeted upregulation of endogenous genes, the novel endogenetherapy approach may become widely applicable beyond cardiovascular diseases also in other areas of medicine and biomedical research.
Summary
Background: Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) has great potential to become a novel, minimally invasive new treatment for a large number of patients with severe myocardial ischemia. However, this requires development of new technology. Advancing state-of-the-art: We propose a paradigm shift in gene therapy for chronic ischemia by activating endogenous VEGF-A,-B and -C genes and angiogenic transcription programs from the native promoters instead of gene transfer of exogenous cDNA to target tissues. We will develop a new platform technology (endogenetherapy) based on our novel concept of the release of promoter pausing and new promoter-targeted upregulating short hairpinRNAs, tissue-specific superenhancerRNAs activating specific transcription centers involving gene clusters in different chromosomal regions, small circularRNAs formed from self-splicing exons-introns that can be regulated with oligonucleotides and small molecules such as metabolites, nuclear RNAi vectors and specific CRISPR/gRNAmutatedCas9-VP16 technology with an ability to target integration into genomic safe harbor sites. After preclinical studies in mice and in a newly developed chronic cardiac ischemia model in pigs with special emphasis on the analysis of clinically relevant blood flow, metabolic and functional outcomes based on MRI, ultrasound, photoacoustic and PET imaging, the best construct will be taken to a phase I clinical study in patients with severe myocardial ischemia. Since endogenetherapy also involves epigenetic changes, which are reversible and long-lasting, we expect to efficiently activate natural angiogenic programs. Significance: If successful, this approach will begin a new era in gene therapy. Since there is a clear lack of technology capable of targeted upregulation of endogenous genes, the novel endogenetherapy approach may become widely applicable beyond cardiovascular diseases also in other areas of medicine and biomedical research.
Max ERC Funding
2 437 500 €
Duration
Start date: 2015-11-01, End date: 2021-04-30
Project acronym CODE
Project Condensation in designed systems
Researcher (PI) Paeivi Elina Toermae
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Advanced Grant (AdG), PE2, ERC-2013-ADG
Summary "Quantum coherent phenomena, especially marcoscopic quantum coherence, are among the most striking predictions of quantum mechanics. They have lead to remarkable applications such as lasers and modern optical technologies, and in the future, breakthroughs such as quantum information processing are envisioned. Macroscopic quantum coherence is manifested in Bose-Einstein condensation (BEC), superfluidity, and superconductivity, which have been observed in a variety of systems and continue to be at the front line of scientific research. Here my objective is to extend the realm of Bose-Einstein condensation into new conceptual and practical directions. I focus on the role of a hybrid character of the object that condenses and on the role of non-equilibrium in the BEC phenomenon. The work is mostly theoretical but has also an experimental part. I study two new types of hybrids, fundamentally different from each other. First, I consider pairing and superfluidity in a mixed geometry. Experimental realization of mixed geometries is becoming feasible in ultracold gases. Second, I explore the possibility of finding novel hybrids of light and matter excitations that may display condensation. By combining insight from these two cases, my goal is to understand how the hybrid and non-equilibrium nature can be exploited to design desirable properties, such as high critical temperatures. In particular, in case of the new light-matter hybrids, the goal is to provide realistic scenarios for, and also experimentally demonstrate, a room temperature BEC."
Summary
"Quantum coherent phenomena, especially marcoscopic quantum coherence, are among the most striking predictions of quantum mechanics. They have lead to remarkable applications such as lasers and modern optical technologies, and in the future, breakthroughs such as quantum information processing are envisioned. Macroscopic quantum coherence is manifested in Bose-Einstein condensation (BEC), superfluidity, and superconductivity, which have been observed in a variety of systems and continue to be at the front line of scientific research. Here my objective is to extend the realm of Bose-Einstein condensation into new conceptual and practical directions. I focus on the role of a hybrid character of the object that condenses and on the role of non-equilibrium in the BEC phenomenon. The work is mostly theoretical but has also an experimental part. I study two new types of hybrids, fundamentally different from each other. First, I consider pairing and superfluidity in a mixed geometry. Experimental realization of mixed geometries is becoming feasible in ultracold gases. Second, I explore the possibility of finding novel hybrids of light and matter excitations that may display condensation. By combining insight from these two cases, my goal is to understand how the hybrid and non-equilibrium nature can be exploited to design desirable properties, such as high critical temperatures. In particular, in case of the new light-matter hybrids, the goal is to provide realistic scenarios for, and also experimentally demonstrate, a room temperature BEC."
Max ERC Funding
1 559 608 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
Project acronym CODEKILLER
Project Killer plasmids as drivers of genetic code changes during yeast evolution
Researcher (PI) Kenneth WOLFE
Host Institution (HI) UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Country Ireland
Call Details Advanced Grant (AdG), LS8, ERC-2017-ADG
Summary The genetic code was established at a very early stage during the evolution of life on Earth and is nearly universal. In eukaryotic nuclear genes, the only known examples of a sense codon that underwent an evolutionary change of meaning, from one amino acid to another, occur in yeast species. The codon CUG is translated as Leu in the universal genetic code, but it has long been known to be translated as Ser in some Candida species. In recent work, we discovered that this switch is one of three parallel reassignments of CUG that occurred in three closely related clades of yeasts. CUG was reassigned once from Leu to Ala, and twice from Leu to Ser, in three separate events. The meaning of sense codons in the nuclear genetic code has otherwise remained completely stable during all of eukaryotic evolution, so why was CUG so unstable in yeasts? CODEKILLER will test a radical new hypothesis that the genetic code changes were caused by a killer toxin that specifically attacked the tRNA that translated CUG as Leu. The hypothesis implies that the reassignments of CUG were not driven by selection in favor of their effects on the proteome, as commonly assumed, but by selection against the existence of a particular tRNA. As well as searching for this killer toxin, we will study the detailed mechanism of genetic code change by engineering a reversal of a CUG-Ser species back to CUG-Leu translation, and investigate translation in some species that naturally contain both tRNA-Leu and tRNA-Ser molecules capable of decoding CUG.
Summary
The genetic code was established at a very early stage during the evolution of life on Earth and is nearly universal. In eukaryotic nuclear genes, the only known examples of a sense codon that underwent an evolutionary change of meaning, from one amino acid to another, occur in yeast species. The codon CUG is translated as Leu in the universal genetic code, but it has long been known to be translated as Ser in some Candida species. In recent work, we discovered that this switch is one of three parallel reassignments of CUG that occurred in three closely related clades of yeasts. CUG was reassigned once from Leu to Ala, and twice from Leu to Ser, in three separate events. The meaning of sense codons in the nuclear genetic code has otherwise remained completely stable during all of eukaryotic evolution, so why was CUG so unstable in yeasts? CODEKILLER will test a radical new hypothesis that the genetic code changes were caused by a killer toxin that specifically attacked the tRNA that translated CUG as Leu. The hypothesis implies that the reassignments of CUG were not driven by selection in favor of their effects on the proteome, as commonly assumed, but by selection against the existence of a particular tRNA. As well as searching for this killer toxin, we will study the detailed mechanism of genetic code change by engineering a reversal of a CUG-Ser species back to CUG-Leu translation, and investigate translation in some species that naturally contain both tRNA-Leu and tRNA-Ser molecules capable of decoding CUG.
Max ERC Funding
2 368 356 €
Duration
Start date: 2018-10-01, End date: 2023-09-30
Project acronym COGNET
Project Cognitive Networks for Intelligent Materials and Devices
Researcher (PI) John Boland
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Country Ireland
Call Details Advanced Grant (AdG), PE5, ERC-2012-ADG_20120216
Summary "COGnitive NETwork (COGNET) is a new technology platform for materials, sensor and device design that exploits unique and hitherto unrecognised properties of random nanowire (NW) networks. These networks—comprised of metallic or semiconducting NWs connected to each other via junctions with controllably random property distributions—lead to new and unexpected levels of connectivity that are inherently scale dependent, creating opportunities for entirely new kinds of self-organised materials and devices. We propose to establish the ground rules for manipulating connectivity in NW networks. By choosing appropriate NWs and incorporating junctions with the approprate properties COGNET will enable the fabrication of (i) intelligent materials, (ii) neural networks and (iii) memory devices. Sequenced voltage pulse and back-gating techniques will in turn address and manipulate specific junctions or sets of junctions to demonstrate even higher density memory and in the case of neural networks, the possibility synaptic plasticity and self-learning."
Summary
"COGnitive NETwork (COGNET) is a new technology platform for materials, sensor and device design that exploits unique and hitherto unrecognised properties of random nanowire (NW) networks. These networks—comprised of metallic or semiconducting NWs connected to each other via junctions with controllably random property distributions—lead to new and unexpected levels of connectivity that are inherently scale dependent, creating opportunities for entirely new kinds of self-organised materials and devices. We propose to establish the ground rules for manipulating connectivity in NW networks. By choosing appropriate NWs and incorporating junctions with the approprate properties COGNET will enable the fabrication of (i) intelligent materials, (ii) neural networks and (iii) memory devices. Sequenced voltage pulse and back-gating techniques will in turn address and manipulate specific junctions or sets of junctions to demonstrate even higher density memory and in the case of neural networks, the possibility synaptic plasticity and self-learning."
Max ERC Funding
2 497 125 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym CROSSLOCATIONS
Project Crosslocations in the Mediterranean: rethinking the socio-cultural dynamics of relative positioning
Researcher (PI) Sarah Francesca Green
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Advanced Grant (AdG), SH5, ERC-2015-AdG
Summary The Mediterranean, a key socio-cultural, economic and political crossroads, has shifted its relative position recently, with profound effects for relations between the peoples associated with its diverse parts. Crosslocations is a groundbreaking theoretical approach that goes beyond current borders research to analyse the significance of the changes in relations between places and peoples that this involves. It does this through explaining shifts in the relative positioning of the Mediterranean’s many locations – i.e. the changing values of where people are rather than who they are. Approaches focusing on people’s identities, statecraft or networks do not provide a way to research how the relative value of ‘being somewhere in particular’ is changing and diversifying.
The approach builds on the idea that in socio-cultural terms, location is a form of political, social, economic, and technical relative positioning, involving diverse scales that calibrate relative values (here called ‘locating regimes’). This means locations are both multiple and historically variable, so different types of location may overlap in the same geographical space, particularly in crossroads regions such as the Mediterranean. The dynamics between them alter relations between places, significantly affecting people’s daily lives, including their life chances, wellbeing, environmental, social and political conditions and status.
The project will first research the locating regimes crossing the Mediterranean region (border regimes, infrastructures; digital technologies; fiscal, financial and trading systems; environmental policies; and social and religious structures); then intensively ethnographically study the socio-cultural dynamics of relative positioning that these regimes generate in selected parts of the Mediterranean region. Through explaining the dynamics of relative location, Crosslocations will transform our understanding of trans-local, socio-cultural relations and separations.
Summary
The Mediterranean, a key socio-cultural, economic and political crossroads, has shifted its relative position recently, with profound effects for relations between the peoples associated with its diverse parts. Crosslocations is a groundbreaking theoretical approach that goes beyond current borders research to analyse the significance of the changes in relations between places and peoples that this involves. It does this through explaining shifts in the relative positioning of the Mediterranean’s many locations – i.e. the changing values of where people are rather than who they are. Approaches focusing on people’s identities, statecraft or networks do not provide a way to research how the relative value of ‘being somewhere in particular’ is changing and diversifying.
The approach builds on the idea that in socio-cultural terms, location is a form of political, social, economic, and technical relative positioning, involving diverse scales that calibrate relative values (here called ‘locating regimes’). This means locations are both multiple and historically variable, so different types of location may overlap in the same geographical space, particularly in crossroads regions such as the Mediterranean. The dynamics between them alter relations between places, significantly affecting people’s daily lives, including their life chances, wellbeing, environmental, social and political conditions and status.
The project will first research the locating regimes crossing the Mediterranean region (border regimes, infrastructures; digital technologies; fiscal, financial and trading systems; environmental policies; and social and religious structures); then intensively ethnographically study the socio-cultural dynamics of relative positioning that these regimes generate in selected parts of the Mediterranean region. Through explaining the dynamics of relative location, Crosslocations will transform our understanding of trans-local, socio-cultural relations and separations.
Max ERC Funding
2 433 234 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym CROWDED-PRO-LIPIDS
Project Computational Perspective to Dynamical Protein-Lipid Complexes under Crowded Conditions
Researcher (PI) Ilpo Tapio Vattulainen
Host Institution (HI) TTY-SAATIO
Country Finland
Call Details Advanced Grant (AdG), PE3, ERC-2011-ADG_20110209
Summary "One of the great challenges is to understand how cellular functions emerge in cell membrane systems. Unlocking this mystery is the key to the vast majority of human diseases. The current view is based on a static picture where membrane proteins in protein-poor membranes interact with a few specific lipids, while in reality the situation is much more complicated. This ambitious project aims for a breakthrough by changing the present paradigm. The objective is to focus on the dynamical interplay between lipids and proteins under crowded conditions, paving the way for understanding the dynamics of lipid-protein complexes and their resulting functions. The objectives are outstanding and contain a high risk, with exceptional gain. The main goal is better understanding of the physical principles that give rise to cellular functions, with a strong impact to clarify the relevance of dynamical lipid-protein interactions in cellular processes related to health and disease. For this purpose, the grand themes chosen for this project are lipoproteins coupled to cardiovascular disease (“good” and “bad” cholesterol) and the function of especially cholesterol and glycolipids with membrane proteins. In order to meet these goals, the applicant employs state-of-the-art simulation techniques that comprise quantum-mechanical, classical atomistic and coarse-grained simulation methods to elucidate the complex biological phenomena associated with lipid-protein systems. The simulations cover atomistic and molecular details, over time scales from femtoseconds up to milliseconds. The theory & simulation group lead by PI comprises expertise in a truly cross- and multi-disciplinary manner, and it strongly collaborates with some of the leading experimental teams in biomedical sciences, cell biology, structural biology, and membrane biophysics."
Summary
"One of the great challenges is to understand how cellular functions emerge in cell membrane systems. Unlocking this mystery is the key to the vast majority of human diseases. The current view is based on a static picture where membrane proteins in protein-poor membranes interact with a few specific lipids, while in reality the situation is much more complicated. This ambitious project aims for a breakthrough by changing the present paradigm. The objective is to focus on the dynamical interplay between lipids and proteins under crowded conditions, paving the way for understanding the dynamics of lipid-protein complexes and their resulting functions. The objectives are outstanding and contain a high risk, with exceptional gain. The main goal is better understanding of the physical principles that give rise to cellular functions, with a strong impact to clarify the relevance of dynamical lipid-protein interactions in cellular processes related to health and disease. For this purpose, the grand themes chosen for this project are lipoproteins coupled to cardiovascular disease (“good” and “bad” cholesterol) and the function of especially cholesterol and glycolipids with membrane proteins. In order to meet these goals, the applicant employs state-of-the-art simulation techniques that comprise quantum-mechanical, classical atomistic and coarse-grained simulation methods to elucidate the complex biological phenomena associated with lipid-protein systems. The simulations cover atomistic and molecular details, over time scales from femtoseconds up to milliseconds. The theory & simulation group lead by PI comprises expertise in a truly cross- and multi-disciplinary manner, and it strongly collaborates with some of the leading experimental teams in biomedical sciences, cell biology, structural biology, and membrane biophysics."
Max ERC Funding
1 920 334 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym DEVHEALTH
Project UNDERSTANDING HEALTH ACROSS THE LIFECOURSE:
AN INTEGRATED DEVELOPMENTAL APPROACH
Researcher (PI) James Joseph Heckman
Host Institution (HI) UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Country Ireland
Call Details Advanced Grant (AdG), SH1, ERC-2010-AdG_20100407
Summary This proposal seeks support for a research group led by James Heckman of the Geary Institute at University College Dublin to produce an integrated developmental approach to health that studies the origins and the evolution of health inequalities over the lifecourse and across generations, and the role played by cognition, personality, genes, and environments. Major experimental and nonexperimental international datasets will be analyzed. A practical guide to implementing related policy will be produced. We will build a science of human development that draws on, extends, and unites research on the biology and epidemiology of health disparities with medical economics and the economics of skill formation. The goal is to develop an integrated framework to jointly model the economic, social and biological mechanisms that produce the evolution and the intergenerational transmission of health and of the capabilities that foster health. The following tasks will be undertaken: (1) We will quantify the importance of early-life conditions in explaining the existence of health disparities across the lifecourse. (2) We will understand how health inequalities are transmitted across generations. (3) We will assess the health benefits from early childhood interventions. (4) We will examine the role of genes and environments in the aetiology and evolution of disease. (5) We will analyze how health inequalities emerge and evolve across the lifecourse. (6) We will give biological foundations to both our models and the health measures we will use. The proposed research will investigate causal channels for promoting health. It will compare the relative effectiveness of interventions at various stages of the life cycle and the benefits and costs of later remediation if early adversity is not adequately eliminated. It will guide the design of current and prospective experimental and longitudinal studies and policy formulation, and will train young scholars in frontier methods of research
Summary
This proposal seeks support for a research group led by James Heckman of the Geary Institute at University College Dublin to produce an integrated developmental approach to health that studies the origins and the evolution of health inequalities over the lifecourse and across generations, and the role played by cognition, personality, genes, and environments. Major experimental and nonexperimental international datasets will be analyzed. A practical guide to implementing related policy will be produced. We will build a science of human development that draws on, extends, and unites research on the biology and epidemiology of health disparities with medical economics and the economics of skill formation. The goal is to develop an integrated framework to jointly model the economic, social and biological mechanisms that produce the evolution and the intergenerational transmission of health and of the capabilities that foster health. The following tasks will be undertaken: (1) We will quantify the importance of early-life conditions in explaining the existence of health disparities across the lifecourse. (2) We will understand how health inequalities are transmitted across generations. (3) We will assess the health benefits from early childhood interventions. (4) We will examine the role of genes and environments in the aetiology and evolution of disease. (5) We will analyze how health inequalities emerge and evolve across the lifecourse. (6) We will give biological foundations to both our models and the health measures we will use. The proposed research will investigate causal channels for promoting health. It will compare the relative effectiveness of interventions at various stages of the life cycle and the benefits and costs of later remediation if early adversity is not adequately eliminated. It will guide the design of current and prospective experimental and longitudinal studies and policy formulation, and will train young scholars in frontier methods of research
Max ERC Funding
2 505 222 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
