Project acronym 2F4BIODYN
Project Two-Field Nuclear Magnetic Resonance Spectroscopy for the Exploration of Biomolecular Dynamics
Researcher (PI) Fabien Ferrage
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE4, ERC-2011-StG_20101014
Summary The paradigm of the structure-function relationship in proteins is outdated. Biological macromolecules and supramolecular assemblies are highly dynamic objects. Evidence that their motions are of utmost importance to their functions is regularly identified. The understanding of the physical chemistry of biological processes at an atomic level has to rely not only on the description of structure but also on the characterization of molecular motions.
The investigation of protein motions will be undertaken with a very innovative methodological approach in nuclear magnetic resonance relaxation. In order to widen the ranges of frequencies at which local motions in proteins are probed, we will first use and develop new techniques for a prototype shuttle system for the measurement of relaxation at low fields on a high-field NMR spectrometer. Second, we will develop a novel system: a set of low-field NMR spectrometers designed as accessories for high-field spectrometers. Used in conjunction with the shuttle, this system will offer (i) the sensitivity and resolution (i.e. atomic level information) of a high-field spectrometer (ii) the access to low fields of a relaxometer and (iii) the ability to measure a wide variety of relaxation rates with high accuracy. This system will benefit from the latest technology in homogeneous permanent magnet development to allow a control of spin systems identical to that of a high-resolution probe. This new apparatus will open the way to the use of NMR relaxation at low fields for the refinement of protein motions at an atomic scale.
Applications of this novel approach will focus on the bright side of protein dynamics: (i) the largely unexplored dynamics of intrinsically disordered proteins, and (ii) domain motions in large proteins. In both cases, we will investigate a series of diverse protein systems with implications in development, cancer and immunity.
Summary
The paradigm of the structure-function relationship in proteins is outdated. Biological macromolecules and supramolecular assemblies are highly dynamic objects. Evidence that their motions are of utmost importance to their functions is regularly identified. The understanding of the physical chemistry of biological processes at an atomic level has to rely not only on the description of structure but also on the characterization of molecular motions.
The investigation of protein motions will be undertaken with a very innovative methodological approach in nuclear magnetic resonance relaxation. In order to widen the ranges of frequencies at which local motions in proteins are probed, we will first use and develop new techniques for a prototype shuttle system for the measurement of relaxation at low fields on a high-field NMR spectrometer. Second, we will develop a novel system: a set of low-field NMR spectrometers designed as accessories for high-field spectrometers. Used in conjunction with the shuttle, this system will offer (i) the sensitivity and resolution (i.e. atomic level information) of a high-field spectrometer (ii) the access to low fields of a relaxometer and (iii) the ability to measure a wide variety of relaxation rates with high accuracy. This system will benefit from the latest technology in homogeneous permanent magnet development to allow a control of spin systems identical to that of a high-resolution probe. This new apparatus will open the way to the use of NMR relaxation at low fields for the refinement of protein motions at an atomic scale.
Applications of this novel approach will focus on the bright side of protein dynamics: (i) the largely unexplored dynamics of intrinsically disordered proteins, and (ii) domain motions in large proteins. In both cases, we will investigate a series of diverse protein systems with implications in development, cancer and immunity.
Max ERC Funding
1 462 080 €
Duration
Start date: 2012-01-01, End date: 2017-12-31
Project acronym A-LIFE
Project The asymmetry of life: towards a unified view of the emergence of biological homochirality
Researcher (PI) Cornelia MEINERT
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE4, ERC-2018-STG
Summary What is responsible for the emergence of homochirality, the almost exclusive use of one enantiomer over its mirror image? And what led to the evolution of life’s homochiral biopolymers, DNA/RNA, proteins and lipids, where all the constituent monomers exhibit the same handedness?
Based on in-situ observations and laboratory studies, we propose that this handedness occurs when chiral biomolecules are synthesized asymmetrically through interaction with circularly polarized photons in interstellar space. The ultimate goal of this project will be to demonstrate how the diverse set of heterogeneous enantioenriched molecules, available from meteoritic impact, assembles into homochiral pre-biopolymers, by simulating the evolutionary stages on early Earth. My recent research has shown that the central chiral unit of RNA, ribose, forms readily under simulated comet conditions and this has provided valuable new insights into the accessibility of precursors of genetic material in interstellar environments. The significance of this project arises due to the current lack of experimental demonstration that amino acids, sugars and lipids can simultaneously and asymmetrically be synthesized by a universal physical selection process.
A synergistic methodology will be developed to build a unified theory for the origin of all chiral biological building blocks and their assembly into homochiral supramolecular entities. For the first time, advanced analyses of astrophysical-relevant samples, asymmetric photochemistry triggered by circularly polarized synchrotron and laser sources, and chiral amplification due to polymerization processes will be combined. Intermediates and autocatalytic reaction kinetics will be monitored and supported by quantum calculations to understand the underlying processes. A unified theory on the asymmetric formation and self-assembly of life’s biopolymers is groundbreaking and will impact the whole conceptual foundation of the origin of life.
Summary
What is responsible for the emergence of homochirality, the almost exclusive use of one enantiomer over its mirror image? And what led to the evolution of life’s homochiral biopolymers, DNA/RNA, proteins and lipids, where all the constituent monomers exhibit the same handedness?
Based on in-situ observations and laboratory studies, we propose that this handedness occurs when chiral biomolecules are synthesized asymmetrically through interaction with circularly polarized photons in interstellar space. The ultimate goal of this project will be to demonstrate how the diverse set of heterogeneous enantioenriched molecules, available from meteoritic impact, assembles into homochiral pre-biopolymers, by simulating the evolutionary stages on early Earth. My recent research has shown that the central chiral unit of RNA, ribose, forms readily under simulated comet conditions and this has provided valuable new insights into the accessibility of precursors of genetic material in interstellar environments. The significance of this project arises due to the current lack of experimental demonstration that amino acids, sugars and lipids can simultaneously and asymmetrically be synthesized by a universal physical selection process.
A synergistic methodology will be developed to build a unified theory for the origin of all chiral biological building blocks and their assembly into homochiral supramolecular entities. For the first time, advanced analyses of astrophysical-relevant samples, asymmetric photochemistry triggered by circularly polarized synchrotron and laser sources, and chiral amplification due to polymerization processes will be combined. Intermediates and autocatalytic reaction kinetics will be monitored and supported by quantum calculations to understand the underlying processes. A unified theory on the asymmetric formation and self-assembly of life’s biopolymers is groundbreaking and will impact the whole conceptual foundation of the origin of life.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym ABIOS
Project ABIOtic Synthesis of RNA: an investigation on how life started before biology existed
Researcher (PI) Guillaume STIRNEMANN
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE4, ERC-2017-STG
Summary The emergence of life is one of the most fascinating and yet largely unsolved questions in the natural sciences, and thus a significant challenge for scientists from many disciplines. There is growing evidence that ribonucleic acid (RNA) polymers, which are capable of genetic information storage and self-catalysis, were involved in the early forms of life. But despite recent progress, RNA synthesis without biological machineries is very challenging. The current project aims at understanding how to synthesize RNA in abiotic conditions. I will solve problems associated with three critical aspects of RNA formation that I will rationalize at a molecular level: (i) accumulation of precursors, (ii) formation of a chemical bond between RNA monomers, and (iii) tolerance for alternative backbone sugars or linkages. Because I will study problems ranging from the formation of chemical bonds up to the stability of large biopolymers, I propose an original computational multi-scale approach combining techniques that range from quantum calculations to large-scale all-atom simulations, employed together with efficient enhanced-sampling algorithms, forcefield improvement, cutting-edge analysis methods and model development.
My objectives are the following:
1 • To explain why the poorly-understood thermally-driven process of thermophoresis can contribute to the accumulation of dilute precursors.
2 • To understand why linking RNA monomers with phosphoester bonds is so difficult, to understand the molecular mechanism of possible catalysts and to suggest key improvements.
3 • To rationalize the molecular basis for RNA tolerance for alternative backbone sugars or linkages that have probably been incorporated in abiotic conditions.
This unique in-silico laboratory setup should significantly impact our comprehension of life’s origin by overcoming major obstacles to RNA abiotic formation, and in addition will reveal significant orthogonal outcomes for (bio)technological applications.
Summary
The emergence of life is one of the most fascinating and yet largely unsolved questions in the natural sciences, and thus a significant challenge for scientists from many disciplines. There is growing evidence that ribonucleic acid (RNA) polymers, which are capable of genetic information storage and self-catalysis, were involved in the early forms of life. But despite recent progress, RNA synthesis without biological machineries is very challenging. The current project aims at understanding how to synthesize RNA in abiotic conditions. I will solve problems associated with three critical aspects of RNA formation that I will rationalize at a molecular level: (i) accumulation of precursors, (ii) formation of a chemical bond between RNA monomers, and (iii) tolerance for alternative backbone sugars or linkages. Because I will study problems ranging from the formation of chemical bonds up to the stability of large biopolymers, I propose an original computational multi-scale approach combining techniques that range from quantum calculations to large-scale all-atom simulations, employed together with efficient enhanced-sampling algorithms, forcefield improvement, cutting-edge analysis methods and model development.
My objectives are the following:
1 • To explain why the poorly-understood thermally-driven process of thermophoresis can contribute to the accumulation of dilute precursors.
2 • To understand why linking RNA monomers with phosphoester bonds is so difficult, to understand the molecular mechanism of possible catalysts and to suggest key improvements.
3 • To rationalize the molecular basis for RNA tolerance for alternative backbone sugars or linkages that have probably been incorporated in abiotic conditions.
This unique in-silico laboratory setup should significantly impact our comprehension of life’s origin by overcoming major obstacles to RNA abiotic formation, and in addition will reveal significant orthogonal outcomes for (bio)technological applications.
Max ERC Funding
1 497 031 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym ADAM
Project The Adaptive Auditory Mind
Researcher (PI) Shihab Shamma
Host Institution (HI) ECOLE NORMALE SUPERIEURE
Call Details Advanced Grant (AdG), SH4, ERC-2011-ADG_20110406
Summary Listening in realistic situations is an active process that engages perceptual and cognitive faculties, endowing speech with meaning, music with joy, and environmental sounds with emotion. Through hearing, humans and other animals navigate complex acoustic scenes, separate sound mixtures, and assess their behavioral relevance. These remarkable feats are currently beyond our understanding and exceed the capabilities of the most sophisticated audio engineering systems. The goal of the proposed research is to investigate experimentally a novel view of hearing, where active hearing emerges from a deep interplay between adaptive sensory processes and goal-directed cognition. Specifically, we shall explore the postulate that versatile perception is mediated by rapid-plasticity at the neuronal level. At the conjunction of sensory and cognitive processing, rapid-plasticity pervades all levels of auditory system, from the cochlea up to the auditory and prefrontal cortices. Exploiting fundamental statistical regularities of acoustics, it is what allows humans and other animal to deal so successfully with natural acoustic scenes where artificial systems fail. The project builds on the internationally recognized leadership of the PI in the fields of physiology and computational modeling, combined with the expertise of the Co-Investigator in psychophysics. Building on these highly complementary fields and several technical innovations, we hope to promote a novel view of auditory perception and cognition. We aim also to contribute significantly to translational research in the domain of signal processing for clinical hearing aids, given that many current limitations are not technological but rather conceptual. The project will finally result in the creation of laboratory facilities and an intellectual network unique in France and rare in all of Europe, combining cognitive, neural, and computational approaches to auditory neuroscience.
Summary
Listening in realistic situations is an active process that engages perceptual and cognitive faculties, endowing speech with meaning, music with joy, and environmental sounds with emotion. Through hearing, humans and other animals navigate complex acoustic scenes, separate sound mixtures, and assess their behavioral relevance. These remarkable feats are currently beyond our understanding and exceed the capabilities of the most sophisticated audio engineering systems. The goal of the proposed research is to investigate experimentally a novel view of hearing, where active hearing emerges from a deep interplay between adaptive sensory processes and goal-directed cognition. Specifically, we shall explore the postulate that versatile perception is mediated by rapid-plasticity at the neuronal level. At the conjunction of sensory and cognitive processing, rapid-plasticity pervades all levels of auditory system, from the cochlea up to the auditory and prefrontal cortices. Exploiting fundamental statistical regularities of acoustics, it is what allows humans and other animal to deal so successfully with natural acoustic scenes where artificial systems fail. The project builds on the internationally recognized leadership of the PI in the fields of physiology and computational modeling, combined with the expertise of the Co-Investigator in psychophysics. Building on these highly complementary fields and several technical innovations, we hope to promote a novel view of auditory perception and cognition. We aim also to contribute significantly to translational research in the domain of signal processing for clinical hearing aids, given that many current limitations are not technological but rather conceptual. The project will finally result in the creation of laboratory facilities and an intellectual network unique in France and rare in all of Europe, combining cognitive, neural, and computational approaches to auditory neuroscience.
Max ERC Funding
3 199 078 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym AGNES
Project ACTIVE AGEING – RESILIENCE AND EXTERNAL SUPPORT AS MODIFIERS OF THE DISABLEMENT OUTCOME
Researcher (PI) Taina Tuulikki RANTANEN
Host Institution (HI) JYVASKYLAN YLIOPISTO
Call Details Advanced Grant (AdG), SH3, ERC-2015-AdG
Summary The goals are 1. To develop a scale assessing the diversity of active ageing with four dimensions that are ability (what people can do), activity (what people do do), ambition (what are the valued activities that people want to do), and autonomy (how satisfied people are with the opportunity to do valued activities); 2. To examine health and physical and psychological functioning as the determinants and social and build environment, resilience and personal skills as modifiers of active ageing; 3. To develop a multicomponent sustainable intervention aiming to promote active ageing (methods: counselling, information technology, help from volunteers); 4. To test the feasibility and effectiveness on the intervention; and 5. To study cohort effects on the phenotypes on the pathway to active ageing.
“If You Can Measure It, You Can Change It.” Active ageing assessment needs conceptual progress, which I propose to do. A quantifiable scale will be developed that captures the diversity of active ageing stemming from the WHO definition of active ageing as the process of optimizing opportunities for health and participation in the society for all people in line with their needs, goals and capacities as they age. I will collect cross-sectional data (N=1000, ages 75, 80 and 85 years) and model the pathway to active ageing with state-of-the art statistical methods. By doing this I will create novel knowledge on preconditions for active ageing. The collected cohort data will be compared to a pre-existing cohort data that was collected 25 years ago to obtain knowledge about changes over time in functioning of older people. A randomized controlled trial (N=200) will be conducted to assess the effectiveness of the envisioned intervention promoting active ageing through participation. The project will regenerate ageing research by launching a novel scale, by training young scientists, by creating new concepts and theory development and by producing evidence for active ageing promotion
Summary
The goals are 1. To develop a scale assessing the diversity of active ageing with four dimensions that are ability (what people can do), activity (what people do do), ambition (what are the valued activities that people want to do), and autonomy (how satisfied people are with the opportunity to do valued activities); 2. To examine health and physical and psychological functioning as the determinants and social and build environment, resilience and personal skills as modifiers of active ageing; 3. To develop a multicomponent sustainable intervention aiming to promote active ageing (methods: counselling, information technology, help from volunteers); 4. To test the feasibility and effectiveness on the intervention; and 5. To study cohort effects on the phenotypes on the pathway to active ageing.
“If You Can Measure It, You Can Change It.” Active ageing assessment needs conceptual progress, which I propose to do. A quantifiable scale will be developed that captures the diversity of active ageing stemming from the WHO definition of active ageing as the process of optimizing opportunities for health and participation in the society for all people in line with their needs, goals and capacities as they age. I will collect cross-sectional data (N=1000, ages 75, 80 and 85 years) and model the pathway to active ageing with state-of-the art statistical methods. By doing this I will create novel knowledge on preconditions for active ageing. The collected cohort data will be compared to a pre-existing cohort data that was collected 25 years ago to obtain knowledge about changes over time in functioning of older people. A randomized controlled trial (N=200) will be conducted to assess the effectiveness of the envisioned intervention promoting active ageing through participation. The project will regenerate ageing research by launching a novel scale, by training young scientists, by creating new concepts and theory development and by producing evidence for active ageing promotion
Max ERC Funding
2 044 364 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym AMPERE
Project Accounting for Metallicity, Polarization of the Electrolyte, and Redox reactions in computational Electrochemistry
Researcher (PI) Mathieu Eric Salanne
Host Institution (HI) SORBONNE UNIVERSITE
Call Details Consolidator Grant (CoG), PE4, ERC-2017-COG
Summary Applied electrochemistry plays a key role in many technologies, such as batteries, fuel cells, supercapacitors or solar cells. It is therefore at the core of many research programs all over the world. Yet, fundamental electrochemical investigations remain scarce. In particular, electrochemistry is among the fields for which the gap between theory and experiment is the largest. From the computational point of view, there is no molecular dynamics (MD) software devoted to the simulation of electrochemical systems while other fields such as biochemistry (GROMACS) or material science (LAMMPS) have dedicated tools. This is due to the difficulty of accounting for complex effects arising from (i) the degree of metallicity of the electrode (i.e. from semimetals to perfect conductors), (ii) the mutual polarization occurring at the electrode/electrolyte interface and (iii) the redox reactivity through explicit electron transfers. Current understanding therefore relies on standard theories that derive from an inaccurate molecular-scale picture. My objective is to fill this gap by introducing a whole set of new methods for simulating electrochemical systems. They will be provided to the computational electrochemistry community as a cutting-edge MD software adapted to supercomputers. First applications will aim at the discovery of new electrolytes for energy storage. Here I will focus on (1) ‘‘water-in-salts’’ to understand why these revolutionary liquids enable much higher voltage than conventional solutions (2) redox reactions inside a nanoporous electrode to support the development of future capacitive energy storage devices. These selected applications are timely and rely on collaborations with leading experimental partners. The results are expected to shed an unprecedented light on the importance of polarization effects on the structure and the reactivity of electrode/electrolyte interfaces, establishing MD as a prominent tool for solving complex electrochemistry problems.
Summary
Applied electrochemistry plays a key role in many technologies, such as batteries, fuel cells, supercapacitors or solar cells. It is therefore at the core of many research programs all over the world. Yet, fundamental electrochemical investigations remain scarce. In particular, electrochemistry is among the fields for which the gap between theory and experiment is the largest. From the computational point of view, there is no molecular dynamics (MD) software devoted to the simulation of electrochemical systems while other fields such as biochemistry (GROMACS) or material science (LAMMPS) have dedicated tools. This is due to the difficulty of accounting for complex effects arising from (i) the degree of metallicity of the electrode (i.e. from semimetals to perfect conductors), (ii) the mutual polarization occurring at the electrode/electrolyte interface and (iii) the redox reactivity through explicit electron transfers. Current understanding therefore relies on standard theories that derive from an inaccurate molecular-scale picture. My objective is to fill this gap by introducing a whole set of new methods for simulating electrochemical systems. They will be provided to the computational electrochemistry community as a cutting-edge MD software adapted to supercomputers. First applications will aim at the discovery of new electrolytes for energy storage. Here I will focus on (1) ‘‘water-in-salts’’ to understand why these revolutionary liquids enable much higher voltage than conventional solutions (2) redox reactions inside a nanoporous electrode to support the development of future capacitive energy storage devices. These selected applications are timely and rely on collaborations with leading experimental partners. The results are expected to shed an unprecedented light on the importance of polarization effects on the structure and the reactivity of electrode/electrolyte interfaces, establishing MD as a prominent tool for solving complex electrochemistry problems.
Max ERC Funding
1 588 769 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym AQUARAMAN
Project Pipet Based Scanning Probe Microscopy Tip-Enhanced Raman Spectroscopy: A Novel Approach for TERS in Liquids
Researcher (PI) Aleix Garcia Guell
Host Institution (HI) ECOLE POLYTECHNIQUE
Call Details Starting Grant (StG), PE4, ERC-2016-STG
Summary Tip-enhanced Raman spectroscopy (TERS) is often described as the most powerful tool for optical characterization of surfaces and their proximities. It combines the intrinsic spatial resolution of scanning probe techniques (AFM or STM) with the chemical information content of vibrational Raman spectroscopy. Capable to reveal surface heterogeneity at the nanoscale, TERS is currently playing a fundamental role in the understanding of interfacial physicochemical processes in key areas of science and technology such as chemistry, biology and material science.
Unfortunately, the undeniable potential of TERS as a label-free tool for nanoscale chemical and structural characterization is, nowadays, limited to air and vacuum environments, with it failing to operate in a reliable and systematic manner in liquid. The reasons are more technical than fundamental, as what is hindering the application of TERS in water is, among other issues, the low stability of the probes and their consistency. Fields of science and technology where the presence of water/electrolyte is unavoidable, such as biology and electrochemistry, remain unexplored with this powerful technique.
We propose a revolutionary approach for TERS in liquids founded on the employment of pipet-based scanning probe microscopy techniques (pb-SPM) as an alternative to AFM and STM. The use of recent but well established pb-SPM brings the opportunity to develop unprecedented pipet-based TERS probes (beyond the classic and limited metallized solid probes from AFM and STM), together with the implementation of ingenious and innovative measures to enhance tip stability, sensitivity and reliability, unattainable with the current techniques.
We will be in possession of a unique nano-spectroscopy platform capable of experiments in liquids, to follow dynamic processes in-situ, addressing fundamental questions and bringing insight into interfacial phenomena spanning from materials science, physics, chemistry and biology.
Summary
Tip-enhanced Raman spectroscopy (TERS) is often described as the most powerful tool for optical characterization of surfaces and their proximities. It combines the intrinsic spatial resolution of scanning probe techniques (AFM or STM) with the chemical information content of vibrational Raman spectroscopy. Capable to reveal surface heterogeneity at the nanoscale, TERS is currently playing a fundamental role in the understanding of interfacial physicochemical processes in key areas of science and technology such as chemistry, biology and material science.
Unfortunately, the undeniable potential of TERS as a label-free tool for nanoscale chemical and structural characterization is, nowadays, limited to air and vacuum environments, with it failing to operate in a reliable and systematic manner in liquid. The reasons are more technical than fundamental, as what is hindering the application of TERS in water is, among other issues, the low stability of the probes and their consistency. Fields of science and technology where the presence of water/electrolyte is unavoidable, such as biology and electrochemistry, remain unexplored with this powerful technique.
We propose a revolutionary approach for TERS in liquids founded on the employment of pipet-based scanning probe microscopy techniques (pb-SPM) as an alternative to AFM and STM. The use of recent but well established pb-SPM brings the opportunity to develop unprecedented pipet-based TERS probes (beyond the classic and limited metallized solid probes from AFM and STM), together with the implementation of ingenious and innovative measures to enhance tip stability, sensitivity and reliability, unattainable with the current techniques.
We will be in possession of a unique nano-spectroscopy platform capable of experiments in liquids, to follow dynamic processes in-situ, addressing fundamental questions and bringing insight into interfacial phenomena spanning from materials science, physics, chemistry and biology.
Max ERC Funding
1 528 442 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym Babylearn
Project Neural mechanisms of learning in the infant brain : from Statistics to Rules and Symbols
Researcher (PI) Ghislaine, Marie-Therese, Aline DEHAENE-LAMBERTZ
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Advanced Grant (AdG), SH4, ERC-2015-AdG
Summary Infant is the most powerful learner: He learns in a few months to master language, complex social interactions, etc. Powerful statistical algorithms, simultaneously acting at the different levels of functional hierarchies have been proposed to explain learning. I propose here that two other elements are crucial. The first is the particular human cerebral architecture that constrains statistical computations. The second is the human’s ability to access a rich symbolic system. I have planned 6 work packages using the complementary information offered by non-invasive brain-imaging techniques (EEG, MRI and optical topography) to understand the neural bases of infant statistical computations and symbolic competence from 6 months of gestation up until the end of the first year of life.
WP1 studies from which preterm age, statistical inferences can be demonstrated using hierarchical auditory oddball paradigms.
WP2 investigates the consequences of a different pre-term environment (in-utero versus ex-utero) on the early statistical computations in the visual and auditory domains and their consequences on the ongoing brain activity along the first year of life.
WP3 explores the neural bases of how infants infer word meaning and word category, and in particular the role of the left perisylvian areas and of their particular connectivity.
WP4 questions infant symbolic competency. I propose several criteria (generalization, bidirectionality, use of algebraic rules and of logical operations) tested in successive experiments to clarify infant symbolic abilities during the first semester of life.
WP5-6 are transversal to WP1-4: WP5 uses MRI to obtain accurate functional localization and maturational markers correlated with functional results. In WP6, we develop new tools to combine and analyse multimodal brain images.
With this proposal, I hope to clarify the specificities of a neural functional architecture that are critical for human learning from the onset of cortical circuits.
Summary
Infant is the most powerful learner: He learns in a few months to master language, complex social interactions, etc. Powerful statistical algorithms, simultaneously acting at the different levels of functional hierarchies have been proposed to explain learning. I propose here that two other elements are crucial. The first is the particular human cerebral architecture that constrains statistical computations. The second is the human’s ability to access a rich symbolic system. I have planned 6 work packages using the complementary information offered by non-invasive brain-imaging techniques (EEG, MRI and optical topography) to understand the neural bases of infant statistical computations and symbolic competence from 6 months of gestation up until the end of the first year of life.
WP1 studies from which preterm age, statistical inferences can be demonstrated using hierarchical auditory oddball paradigms.
WP2 investigates the consequences of a different pre-term environment (in-utero versus ex-utero) on the early statistical computations in the visual and auditory domains and their consequences on the ongoing brain activity along the first year of life.
WP3 explores the neural bases of how infants infer word meaning and word category, and in particular the role of the left perisylvian areas and of their particular connectivity.
WP4 questions infant symbolic competency. I propose several criteria (generalization, bidirectionality, use of algebraic rules and of logical operations) tested in successive experiments to clarify infant symbolic abilities during the first semester of life.
WP5-6 are transversal to WP1-4: WP5 uses MRI to obtain accurate functional localization and maturational markers correlated with functional results. In WP6, we develop new tools to combine and analyse multimodal brain images.
With this proposal, I hope to clarify the specificities of a neural functional architecture that are critical for human learning from the onset of cortical circuits.
Max ERC Funding
2 554 924 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym BabyRhythm
Project Tuned to the Rhythm: How Prenatally and Postnatally Heard Speech Prosody Lays the Foundations for Language Learning
Researcher (PI) Judit Gervain
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), SH4, ERC-2017-COG
Summary The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved.
The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language.
The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.
Summary
The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved.
The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language.
The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.
Max ERC Funding
1 621 250 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym BIOFUNCTION
Project Self assembly into biofunctional molecules, translating instructions into function
Researcher (PI) Nicolas Winssinger
Host Institution (HI) UNIVERSITE DE STRASBOURG
Call Details Starting Grant (StG), PE4, ERC-2007-StG
Summary The overall objective of the proposal is to develop enabling chemical technologies to address two important problems in biology: detect in a nondestructive fashion gene expression or microRNA sequences in vivo and, secondly, study the role of multivalency and spatial organization in carbohydrate recognition. Both of these projects exploit the programmable pre-organization of peptide nucleic acid (PNA) to induce a chemical reaction in the first case or modulate a ligand-receptor interaction in the second case. For nucleic acid detection, a DNA or RNA fragment will be utilized to bring two PNA fragments bearing reactive functionalities in close proximity thereby promoting a reaction. Two types of reactions are proposed, the first one to release a fluorophore for imaging purposes and the second one to release a drug as an “intelligent” therapeutic. If affinities are programmed such that hybridization is reversible, the template can work catalytically leading to large amplifications. As a proof of concept, this method will be used to measure the transcription level of genes implicated in stem cell differentiation and detect mutations in oncogenes. For the purpose of studying multivalent carbohydrate ligand architectures, the challenge of chemical synthesis has been a limiting factor. A supramolecular approach is proposed herein where different arrangements of carbohydrates can be displayed in a well organized fashion by hybridizing PNA-tagged carbohydrates to DNA templates. This will be used not only to control the distance between multiple ligands or to create combinatorial arrangements of hetero ligands but also to access more complex architectures such as Hollyday junctions. The oligosaccharide units will be prepared using de novo organoctalytic reactions. This technology will be first applied to probe the recognition events between HIV and dendritic cells which promote HIV infection.
Summary
The overall objective of the proposal is to develop enabling chemical technologies to address two important problems in biology: detect in a nondestructive fashion gene expression or microRNA sequences in vivo and, secondly, study the role of multivalency and spatial organization in carbohydrate recognition. Both of these projects exploit the programmable pre-organization of peptide nucleic acid (PNA) to induce a chemical reaction in the first case or modulate a ligand-receptor interaction in the second case. For nucleic acid detection, a DNA or RNA fragment will be utilized to bring two PNA fragments bearing reactive functionalities in close proximity thereby promoting a reaction. Two types of reactions are proposed, the first one to release a fluorophore for imaging purposes and the second one to release a drug as an “intelligent” therapeutic. If affinities are programmed such that hybridization is reversible, the template can work catalytically leading to large amplifications. As a proof of concept, this method will be used to measure the transcription level of genes implicated in stem cell differentiation and detect mutations in oncogenes. For the purpose of studying multivalent carbohydrate ligand architectures, the challenge of chemical synthesis has been a limiting factor. A supramolecular approach is proposed herein where different arrangements of carbohydrates can be displayed in a well organized fashion by hybridizing PNA-tagged carbohydrates to DNA templates. This will be used not only to control the distance between multiple ligands or to create combinatorial arrangements of hetero ligands but also to access more complex architectures such as Hollyday junctions. The oligosaccharide units will be prepared using de novo organoctalytic reactions. This technology will be first applied to probe the recognition events between HIV and dendritic cells which promote HIV infection.
Max ERC Funding
1 249 980 €
Duration
Start date: 2008-07-01, End date: 2013-06-30