Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet MultiOmicsTox (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

My project proposes to understand what genetic and functional genomic variation contribute to the process of adaptation and to the evolutionary fate of natural populations when confronted with modern threats, such as multi-generational exposure to a chemical pollutant in the environment. The current environmental health policies and regulatory decisions are based on ad hoc methods and do not reflect true population susceptibility. My solution is to apply multi-view machine learning, combined with quantitative genetics, to analyse a huge volume of multi-omics data to advance Precision Toxicology that brings greater certainty in the causal links between chemicals and their adverse effects. My project focuses on the multi-generational effect of pesticides in shaping genetic variation and the molecular evolutionary trajectory of Daphnia obtained from resurrected subpopulations from within dated lake sediments spanning 120 years. The adaptive phenotypes at different doses of pesticides were scored in common garden experiments and samples were taken to produce associated multi-omics data (genomes, transcriptomes, regulomes and metabolomes). I propose utilizing this data to meet the following two objectives:(1) To use quantitative genetics for the determination of genetic susceptibility of the subpopulation to pesticide exposure; (2) To identify the mechanisms and forms of evolution that result in adaptation, by integrating multi-omics data using multi-view machine learning. Expected outcomes of this work will (a) fill a gap in mechanistic understanding of the adaptive responses of natural populations, (b) identify segregating genetic variation within genomes that regulates the pace and magnitude of an adaptive response to chemical pollutants, and (c) discover putative biomarkers that estimate exposure-related genetic susceptibility of populations to the multi-generational harmful effects of chemicals for setting site-specific controls on chemical pollutants.

Mots clés : multi view learning, precision toxicology, resurrection ecology

Participants :
- University of Birmingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet Renaissance Idiocy (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

My project will consider several examples of natural or artificial fools, clowns, idiots portrayed in the literary production of England from 1500 to 1640 and will investigate how early modern notions of intellectual deficiency primarily in medicine but also in society shaped the creation of those same figures. My literary corpus will include not only dramatic texts but also jestbooks, which notably offer a wealth of information on real or fantastic fools of the time, and poetical works. Folly in the sense of lack of wit, rather than the loss of it – which is the definition of madness – will be my primary focus. While the theme of madness in connection with early modern literature has been explored at length, the same cannot be said for cognitive disability or lack of intelligence. The main reason for this is that only recently have a small number of scholars started to discuss and bring together historical, medical and legal notions of natural folly in the early modern period. In the past, remarkable attempts at historicizing natural folly have bordered into discourses on madness and analogue mental disorders thus blurring the difference between the two conditions, the same difference that Renaissance legislation actually sought to define. In the wake of very recent trends in disability studies, therefore, I will use legal but especially medical theories of foolishness and idiocy to explore the characters of my corpus and to highlight, on a scientific and social basis, their separate nature from those conceived of as lunatics. Furthermore, because the exploration of intellectual disability in my period of interest is relatively a new field, I expect to find in the fools of my corpus hints to theories or assumptions that have not been discussed yet.

Mots clés : idiocy, intellectual disability, intelligence, natural fools, clown, folly, renaissance, early modern, drama, jestbooks, medical humanities, madness, galen, shakespeare, robert armin

Participants :
- University of Sussex (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet Entropic DNA Sensors (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

My proposed program consists in a 2-year research activity at the forefront of bioengineering, aiming at the development of Entropically programmable DNA-based bioSensors for high-precision medicine (Entropic DNA Sensors). Biosensors have achieved a significant feat in bioanalytical chemistry and translational science: high-frequency, real-time and quantitative measurements of clinically relevant molecules in vitro, and in vivo. Despite their advantages, our ability to precisely control and regulate the binding activity of their bioreceptors (i.e., the recognition element) still represents a highly relevant bioengineering challenge and limitation. Indeed, the fully control of bioreceptor’s binding properties would allow the design of new biosensors with improved and predictable analytical performance. In Entropic DNA Sensors I propose a multidisciplinary, innovative, and versatile approach based on a purely naturally inspired entropic allostery mechanism which allows to finely tune the activity and the response of synthetic bioreceptors. Specifically, my goal is to further explore our ability to rationally design intrinsically disordered domains into classic DNA-based bioreceptors so as to improve their useful dynamic range. Then, I will adapt these intrinsically disordered bioreceptors into an electrochemical read-out modality that supports the real-time, multi-hour, high-frequency, calibration-free measurements of clinically relevant molecules (i.e., doxorubicin, glucose, phenylalanie) directly in complex biological fluids in vitro. Finally, I will test them in simulated clinical scenarios to demonstrate their ability to reach personalized medicine. To achieve this goal I will leverage my experience in In vivo biosensing and Point-of-care (PoC) testing technologies with the recognized expertise in Functional DNA nanotechnology and Synthetic biology of Prof. Francesco Ricci at University of Rome Tor Vergata (UNITOV-Rome, Italy).

Mots clés : structure switching receptors, intrinsically disordered domains, electrochemical biosensors, electrochemical dna sensors, reagentless biosensors, aptamers

Participants :
- University of Rome Tor Vergata (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183473.28 €
Projet ASB (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

My research focuses on the interrelated areas of scattering amplitudes, string theory, and M-theory. Following Witten’s development of twistor string theory, many powerful methods have been developed for computing amplitudes in both gauge and gravity theories. I plan to further develop these methods in order to obtain new insights into the mathematical structure of quantum field theory and string theory. For example, I will extend recent 1-loop calculations using the twistor Wilson loop of N=4 super-Yang-Mills (SYM) to higher loops in order to search for new mathematical structures like cluster polylogarithms. I also plan to make contact with integrability by analyzing the multi-Regge limit of the twistor Wilson loop and searching for integrable deformations which allow one to compute amplitudes using Bethe Ansatz techniques. It may be possible to extend these ideas beyond N=4 SYM using ambitwistor string theory, which was recently shown to give rise to tree-level formulae for 4d gauge and gravity amplitudes with any amount of supersymmetry (including the case of no supersymmetry), and provide new insight into the relation between BMS symmetry and soft limits. I plan to generalize ambitwistor string calculations to loop level, curved backgrounds, and massive particles. Finally, another important direction is to understand the basic objects of M-theory, known as M2-branes and M5-branes. Although a great deal of progress has been made for M2-branes, formulating the M5-brane theory remains very challenging. Progress has recently been made in formulating non-abelian 2-form gauge fields on a Euclidean spacetime lattice. I plan to incorporate supersymmetry and self-duality into this construction, and compare it with supergravity in AdS4 x S7.

Mots clés : scattering amplitudes, string theory, superconformal field theory, twistor theory, m theory

Participants :
- Universität Hamburg (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 159460.8 €
Projet SpaTime_AnTB (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is an intracellular pathogen that killed 1.6 million people in 2017. Despite its enormous relevance for TB treatment, how intracellular environments affect the response of Mtb to antibiotics remain poorly characterised. This gap in knowledge is mainly due to the lack of appropriate technologies that have precluded comprehensive understanding of the response of intracellular pathogens to antibiotics, critical to design rational interventions. Here, I propose to use cutting-edge imaging approaches to define: (i) Mtb responses towards specific host-subcellular microenvironments by single-cell live long-term imaging in infected human stem cell-derived macrophages (iPSDM); (ii) the dynamics of antibiotic-mediated killing mechanisms using mycobacterial fluorescent reporters and high resolution correlative microscopy and (iii) the spatial and metabolic features of the Mtb response to antibiotics in vivo using a TB mouse model. For this, I will capitalise on technologies developed in the host group to quantify Mtb localisation and replication at the single-cell level combined with correlative electron microscopy (CLEM and CLEIM) approaches. This project will challenge the current limits of high content imaging by combining iPSDM with micro-patterning technologies for single-cell analysis. This will allow the identification of Mtb responses to antibiotics in host cells and how different intracellular microenvironments impact this process in cellulo and in vivo. Together, this proposal has the potential to uncover novel mechanisms of action of antibiotics in human macrophages, opening new avenues for a deeper understanding of human TB treatment and facilitate the discovery of new antibiotics.

Mots clés : macrophage, tuberculosis, antibiotic, imaging, live cell

Participants :
- The Francis Crick Institute (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 224933.76 €
Projet MRTFSen (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Myocardin-related transcription factors (MRTFs) are G-actin binding proteins which act as transcriptional co-activators Myocardin-related transcription factors (MRTFs) are G-actin binding proteins which act as transcriptional co-activators in association with the transcription factor SRF. MRTF-SRF target genes encode numerous proteins involved in actin dynamics, cell adhesion, migration and contractility. The subcellular localization of the MRTFs is controlled by actin binding which inhibits their nuclear import and promotes their nuclear export. Extracellular signals which activate Rho-family GTPases induce actin polymerization and G-actin depletion, which induces MRTF shuttling to the nucleus and transcriptional activation of MRTF-SRF target genes. The MRTF-SRF pathway activation via Rho plays an important role in cancer cell invasion and metastasis. In addition, in MRTF-SRF signalling inhibits cell senescence in hepatocarcinoma cells which present high Rho activity, but this has not been investigated in other cell types or cancer models. Cell senescence is a process of cell-cycle arrest which typically occurs in ageing, cancer, development or tissue repair, and can facilitate recruitment of immune cells. In the tumour microenvironment, senescent cells can direct events such as therapeutic resistance or metastasis that support malignant progression. In this project we will determine the molecular mechanisms by which MRTF-SRF signalling inhibits cell senescence in MEFs. We also aim to investigate the possibility for it to modulate melanoma progression in the BRafV600E mouse model, where senescence is an initial step prior tumour transformation. Increasing evidence suggests that anti- and pro-senescent therapies can be beneficial also in other pathologies, such as fibrosis, by limiting cell proliferation and allowing clearance of damaged cells. These studies have the potential to reveal new approaches to the modulation of senescence pathways for therapeutic benefit.

Mots clés : mrtf srf signalling, cell senesce, mechanotransduction, cell adhesion, melanoma, skin tumour, oncogene induced senescence, cell signalling

Participants :
- The Francis Crick Institute (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 224933.76 €
Projet OptoNMDA (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

NMDA receptors (NMDARs) form a class of receptors gated by glutamate, the major neurotransmitter in the mammalian brain. These receptors play fundamental roles in synaptic transmission and plasticity. They are also involved in numerous pathologies including stroke, mental retardation or schizophrenia. NMDARs are thus targets of strong therapeutic interest. NMDARs are tetramers usually composed of two GluN1 and two GluN2 subunits encoded by four different genes (GluN2A-D), resulting in a large number of receptor subtypes having distinct anatomical, biophysical, pharmacological and signalling properties. Understanding the functional role of these individual subtypes in the brain is of great importance to develop new strategies to counteract the deleterious effects of NMDAR dysregulation. However, tools allowing targeting of a specific population of NMDARs in a given neuronal circuit are currently lacking. The OptoNMDA research programme proposes the development of an innovative optical approach to selectively enhance the activity of NMDARs containing the GluN2B subunit (GluN2B-NMDARs) in ex vivo and in vivo preparations. This approach consists in developing photo-convertible polyamine derivatives that can reversibly isomerize between an inactive and active configuration with light to act on the GluN2B-NMDAR polyamine allosteric modulating site in a precise spatio-temporal manner (opto-allostery). I will study the physiological and potential therapeutic roles of these compounds by testing their effects on synaptic transmission and plasticity and on genetic models of NMDAR hypo-function. Compared to previous studies targeting orthosteric (competitive) sites, the opto-allostery approach will allow manipulation of NMDARs in a more specific and physiological manner. This project should thus provide critical novel information on NMDARs, and more generally, on the physiology and pathology of excitatory synapses.

Mots clés : optogenetics, nmda receptors, glutamate, ion channel, neurosciences, allostery, pharmacology, polyamines, synaptic transmission, synaptic plasticity

Participants :
- École normale supérieure PSL (France) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 69403.5 €
- Institut national de la santé et de la recherche médicale (France) — Coordinator, beneficiary, Recherche, subvention : 115672.5 €
Projet DNP-NMR (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

NMR (nuclear magnetic resonance) spectroscopy is limited by low sensitivity. Recently, it has been shown that a technique called DNP (dynamic nuclear polarization) can enhance solid-state NMR signals by orders of magnitude. DNP has enabled the determination of atomic-level structure in solids by accelerating complex multidimensional NMR experiments. However, only expert NMR spectroscopists apply DNP. This is because, DNP solid-state NMR requires highly specialized, large and expensive, dedicated equipment. Currently, DNP experiments are performed with high power microwave sources (gyrotrons) and low sample temperatures near 100 K. Gyrotrons and low-temperature control systems place a large demand on the building infrastructure and require expertise for routine operation. Additionally, a low sample temperature reduces the resolution of NMR spectra dramatically, which hinders the characterization of chemical structure. This project aims to develop methods that will simplify the application of DNP and enable its widespread utilization. We will develop methodology to perform DNP at high sample temperatures and low microwave powers, using compact microwave sources such as klystrons. Specifically, we will focus on the development of polarizing agents designed for low power and sample formulations that are optimized for high temperatures. Finally, we will perform liquid state Overhauser DNP at high temperatures and transfer the polarization to the surface of materials. The proposed advances will eliminate the need for a gyrotron and low-temperature equipment and therefore, will simplify the DNP experimental setup. This will enable the broad application of DNP to solve challenging problems in chemistry, materials science and biology that are inaccessible using conventional solid-state NMR.

Mots clés : dynamic nuclear polarizing, nuclear magnetic resonance, magic angle spinning, dnp radical development, dnp polarizing agents

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203149.44 €
Projet PCMNano (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Nano-fluids (fluid bases with a nano-particle suspension) and Phase Change Materials (PCM) provide innovative ways to handle the increased need for heat transfer and thermal efficiency. But information regarding the thermal properties (thermal conductivity, thermal diffusivity, enthalpy of transformation, enthalpy of fusion/melting, enthalpy of vaporization, specific heat, melting temperature, and crystallization temperature) of nano-fluids and PCMs is limited and antiquated. Therefore, is the purpose of this action to determine the thermal properties of a number of PCMs to then use as the base fluid for a number of nano-fluids. This will be done by measuring n-alkanes in both the solid and liquid phases using the transient hot wire and the differential scanning calorimetry (DSC) techniques. When possible, the obtained results will be compared with the scarcely available literature data. Lastly, the creation of a thermal properties prediction model for the nano-fluids will be attempted.

Mots clés : phase change materials, thermal properties, nanofluids, nano particles, fluid properties

Participants :
- Universidad Complutense de Madrid (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 158121.6 €
Projet FASTQUANTUM (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Physics
Statut du projet : CLOSED

Nanoscopic or microscopic structures with their physical properties strongly affected by confinement effects are called quantum structures. This proposal aims for the investigation of ultrafast dynamics in different kinds of quantum structures, namely, semiconductor nanocrystals and metal nano¬particles, their combination to complex nanohybrids, nanowires, nanosheets, as well as nanoemitters in optical cavities. The high-quality quantum structures have been fabricated and already optically investigated by the applicant and his co-workers. These successful experiments delivered important results, but they did not allow for the investigation of the dynamics on a time scale below several picoseconds. On this short time scale, however, multiexciton and exciton relaxation dynamics, phonon dynamics, trapping to surface or defect states, non-radiative recombination, or stimulated emission occur, all determining the optical properties of the quantum structures. It is proposed to perform ultrafast laser spectroscopy on these structures in the expert research group of Prof. Kambhampati at McGill University, Canada. Here, unique spectroscopic facilities exist to investigate the relevant dynamics. Two kinds of experiments will be performed, which will also train the applicant in cutting-edge ultrafast spectroscopy techniques. Firstly, state-resolved transient absorption measurements will directly access the ultrafast dynamics. Secondly, novel two-dimensional electronic spectroscopy will deliver insights into ultrafast coherent processes of the quantum structures. The understanding of the fundamental ultrafast processes will help to further improve the quantum structures and to further pave the way for their application in optical or opto-electric devices.

Mots clés : nanocrystals, nanoparticles, nanowires, microcavities, exciton dynamics, phonons, plasmons, trap states, blinking, transient absorption, two dimensional electronic spectroscopy

Participants :
- Universität Hamburg (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 164541.6 €
- McGill University (Canada) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €