Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The Distribution and Origin of Spatial Coding across the Brain (SpaceCode)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: United Kingdom
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Start date: 2022-03-01
End date: 2024-02-29
Duration (months): 24.0
Total project cost (EUR): 212933.76
EU funding (EUR): 212933.76
Participants: 1
Project status: SIGNED

This project will investigate the distribution and origin of spatial coding by recording from large populations of neurons across the brain, using next-generation electrodes developed by the host laboratory. Spatial navigation is a goal-directed task that animals perform daily, and its signals engage a variety of brain systems beyond classical navigational centers such as the hippocampus. I have three aims: (1) to characterize the distribution of spatial signals across the mouse brain, with a focus on sensory regions; (2) to understand how spatial signals interact with sensory signals; (3) to establish whether the spatial signals originate in the hippocampus. The experiments will be performed in mice that navigate virtual environments and will involve next-generation Neuropixels 2.0 probes, capable of recording from hundreds of neurons at a time. First, I will record activity from large populations of neurons across multiple brain regions during virtual navigation and define the interaction of sensory and spatial signals in sensory cortex. Then I will test whether the hippocampus is necessary for spatial coding in visual cortex by manipulating its activity with chemogenetics in transgenic mice. These experiments will provide the first large-scale view of spatial coding across the mouse brain, characterizing the distribution of spatial signals, their computational role, and their causal origin. I will perform these experiments in the Cortical Processing Laboratory at University College London, led by Professors Matteo Carandini and Kenneth Harris. I am confident I can further develop my skills as an independent researcher while answering exciting scientific questions. Professors Carandini and Harris are experts in conducting large-scale neuronal recordings in mice performing complex behavioral tasks as well as analytical techniques to process large data sets. I am experienced in systems neuroscience techniques and studying goal-directed behavior in mice.

Keywords: neuropixels,electrophysiology,spatial navigation,chemogenetics,vision,audition,virtual reality
Pathogen Oriented SNARE Trafficking for Immune Tailoring (POST-IT)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Molecules of Life: Biological Mechanisms, Structures and Functions
Panel description: Molecular biology, biochemistry, structural biology, molecular biophysics, synthetic and chemical biology, drug design, innovative methods and modelling
Countries involved: Netherlands
Call: ERC Consolidator Grant (ERC-2019-COG, 2019)
Start date: 2020-05-01
End date: 2025-04-30
Duration (months): 60.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: SIGNED

ImImmune clearance of infectious diseases requires correct T cell activation by macrophages and dendritic cells (DCs) that present peptides derived from ingested pathogens on major histocompatibility complexes (MHC). Yet, macrophages and DCs also ingest self-antigens present in healthy cells and their presentation might trigger autoimmune disease. Presentation of the minority of ingested pathogens is promoted by so-called phagosome-autonomous trafficking. Here, pathogen binding to Toll-like receptors in phagosomes triggers recruitment of proteases and transporters to these phagosomes, but not to other phagosomes present in the same cell, promoting specific presentation of pathogen-derived peptides. However, a molecular understanding of this pathogen-oriented phagosome-autonomous trafficking is lacking. The goal of this project is to determine how phagosome-autonomous pathogen recognition promotes presentation of pathogen-derived over harmless self-antigens. Based on my preliminary data and literature, I hypothesize that Toll-like receptor signaling triggers phosphorylation of multiple SNARE proteins at the phagosomal membrane. As SNARE phosphorylation can promote or prevent membrane fusion, this alters delivery of proteases and transporters to these phagosomes, which in turn promotes presentation of pathogen-derived peptides. Objective 1 is to determine how SNARE function is altered upon pathogen-recognition in phagosomes using my novel quantitative Förster resonance energy transfer-fluorescence lifetime imaging microscopy (FRET-FLIM)-based technique. Objective 2 is to address how Toll-like receptor-mediated SNARE phosphorylation affects phagosome-autonomous trafficking. Objective 3 is to resolve the functional roles of SNAREs in antigen presentation using a novel bio-orthogonal chemistry-based method. This study will explain the high sensitivity of the adaptive immune system for pathogens and could lead to better vaccinations and therapies for infectious diseases.

Keywords: phagocytosis,pathogen recognition,snare protein,macrophage,dendritic cell,phosphorylation
Measuring the Social Dimension of Culture (MESOC)

Framework: Horizon 2020 — Societal Challenges
Programme: Europe in a changing world - inclusive, innovative and reflective societies
Theme: Reflective societies - cultural heritage and European identity
Action type: Research and Innovation actions
Countries involved: Spain,Italy,Spain,Romania,Croatia,Greece,Belgium,France
Call: The societal value of culture and the impact of cultural policies in Europe (H2020-SC6-TRANSFORMATIONS-2019, 2019)
Start date: 2020-02-01
End date: 2023-05-31
Duration (months): 40.0
Total project cost (EUR): 2985937.5
EU funding (EUR): 2985937.5
Participants: 10
Project status: SIGNED

MESOC adapts and further develops a method for “transition based” impact assessment derived from a previous Unesco Chair publication, building a structural model of the Societal Dimension of Culture, as defined by one of the strategic objectives of the European Agenda. The model will be used in the project: - To define the perimeter of investigation of the societal value and impacts of cultural policies and practices, thus framing and guiding the collection of academic and institutional literature and the definition of a set of case studies relevant to the three crossover themes of a) Health and Wellbeing, 2) Urban and Territorial Renovation and 3) People’s Engagement and Participation; - As a theoretical lens to propose and validate, using the Delphi method, in collaboration with a large representation of key institutional, academic and professional actors, a long list of impact transmission variables and indicators reflecting the underlying approach (“theory of change”) of the surveyed case studies; - As an evaluative tool to assess the societal value and impacts of cultural policies and practices related to the three crossover themes, both diachronically and synchronically, within 10 European City pilots; - To propose a (tentative) set of statistical data sources (possibly including new ones that are practically and economically feasible) which could complement existing measures of the societal value and impacts of culture by adding its effects on personal well-being and health, citizens involvement and participation, urban identity and social cohesion. The ultimate, expected output of the project is a Free and Open Access, online service (named the MESOC Toolkit) that could be used by both researchers and practitioners (the latter including both policy makers and cultural operators from all over the EU) to measure the societal value and impacts of cultural policies and practices.

Keywords: cultural capabilities,transition variables and indicators,health and well being,urban and territorial renovation,people s engagement and participation
Impacts of Nanoparticles on microphytobenthic Biofilms and consequences on the Carbon cycle (NanoBioCar)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Environment and Geosciences
Countries involved: United Kingdom
Call: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2015, 2015)
Start date: 2016-09-01
End date: 2019-04-09
Duration (months): 24.0
Total project cost (EUR): 195454.8
EU funding (EUR): 195454.8
Participants: 1
Project status: CLOSED

Intertidal and shallow subtidal zones are key areas for biochemical transformations, and particularly they play a crucial zone in the carbon cycle. In soft-bottom areas, most primary production is performed by photosynthetic microorganisms organised in biofilms, and called microphytobenthos. The organic matter they produce is rapidly respired by bacteria or consumed by higher trophic levels. Together, microphytobenthos and bacteria realise most carbon transformation in these areas, and are therefore important groups to study in a view to understand carbon cycling in coastal zones. Coastal areas are currently under influence of numerous stressors linked to anthropogenic effects. The impacts of ‘well established’ pollutants, e.g. metals, oils, nitrogen, are fairly well understood; however there is now evidence that new compounds, products of advanced technology, have the potential to disrupt the environment. The aim of this project is to understand how a recently developed family of compounds, namely nanoparticles (NPs), influences the development of biofilms and their impact on the carbon cycle. NP concentrations are increasing dramatically in the environment, but their effect on organisms and ecosystems is currently poorly described. Yet, genotoxic and cytotoxic effects of NPs have been demonstrated, including on microorganisms. In this project, laboratory and field experiments will be performed to characterise the effects of NPs on microphytobenthos and bacteria, on their trophic interactions and on their roles in carbon and nutrient cycles. Two common types of NPs will be tested in a wide range of environmental conditions, to decipher in which conditions NPs are more or less harmful to organisms and processes. Such understanding will allow developing strategies to reduce the impacts of NPs and will be beneficial to environment and human well-being in EU and elsewhere.

Keywords: nanoparticles,biofilms,carbon cycle,coastal area,microphytobenthos,photosynthesis
Identification and Characterization of Cis-Regulatory Module Dysfunction in Rett Syndrome with ROQ-WACh (ROQ-WACh)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: Spain
Call: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2015, 2015)
Start date: 2016-03-01
End date: 2018-02-28
Duration (months): 24.0
Total project cost (EUR): 158121.6
EU funding (EUR): 158121.6
Participants: 1
Project status: CLOSED

Precise regulation of gene expression is achieved through the coordinated action of genomic cis-regulatory modules (CRMs). The identification of CRMs has long been a goal of functional genomics as CRM dysregulation can have devastating consequences for health and development such as autism. For example, mutations in the MeCP2 gene, which encodes protein that binds methylated DNA and regulates gene expression in neurons, results an Autism Spectrum Disorder termed Rett Syndrome. While thought to modulate CRM activity as a repressor, MeCP2’s function remains ambiguous and would benefit from a functional genomics characterization. To identify CRMs I recently developed a novel approach called FIREWACh. Here, I propose to utilize FIREWACh first to identify active CRMs within a homogenous population of neurons, identifying genomic loci of CRMs whose function may be compromised by MeCP2 mutations. I will adapt FIREWACh to allow the quantification of CRM output in a new method I propose to call ROQ-WACh (regulatory output quantification within accessible chromatin) by addition of barcodes to reporter mRNAs. This will allow high-throughput readout of CRM activity globally in vivo and will be broadly applicable to many biological fields. Lastly, I aim to combine the above approaches to quantify the changes in CRM output in response to pathological mutations in MeCP2. This Marie Sklodowska-Curie Action will allow me (the Experienced Researcher, Matthew Murtha) mobility to Spain to join the laboratory of Dr. Manel Esteller (Host Supervisor), renowned epigeneticist and expert in DNA-methylation biology to perform the research. Together the approaches and data generated by this MSCA action will provide key insights into the relationship between methylated DNA, precise control of gene expression, and high-order phenotypes such as cognitive behaviors.

Keywords: rett syndrome,mecp2,firewach,neurobiology,disease,mutations
EXtended Analysis of Circulating Tumour DNA to improve cancer management strategies (EXACT-dna)

Framework: Horizon 2020 — Industrial Leadership
Programme: Nanotechnologies, Advanced Materials, Advanced Manufacturing and Processing, and Biotechnology
Theme: Biotechnology
Action type: SME instrument
Countries involved: Sweden
Call: Dedicated support to biotechnology SMEs closing the gap from lab to market (H2020-SMEINST-1-2016-2017, 2017)
Start date: 2017-12-01
End date: 2018-05-31
Duration (months): 6.0
Total project cost (EUR): 71429.0
EU funding (EUR): 50000.0
Participants: 1
Project status: CLOSED

Through the EXACT-dna project, SAGA Diagnostics (SAGA Dx), intends to clinically validate and commercialize two distinct technologies, IBSAFE and KROMA, for the isolation, detection and quantification of cell-free circulating tumour DNA (ctDNA) in minimally invasive “liquid biopsies”. This revolutionary form of tumour genotyping and patient monitoring, based on the analysis of ctDNA and other tumour-specific biomarkers in body fluids such as blood samples, is one of five technologies that will disrupt healthcare by 2020 according to Forbes Magazine. SAGA Dx intends to take advantage of this business opportunity by further clinically validating their proprietary technologies which already have overwhelming superiority over competing methods due to four commercially- and technically-verified advantages that meet users’ needs: superior performance (a 100 to 5000-fold improvement in sensitivity), a faster turn-around time of 2-3 days (whereas competitors take 2-3 weeks), significantly lower production costs and wide applicability. IBSAFE™ is a patent-pending technology for exquisitely sensitive and specific quantification of gene mutations and other sequence variants in any DNA or RNA sample. KROMA™, on the other hand, is a proprietary technology for the detection and quantification of tumour-specific chromosomal rearrangements in circulating tumour DNA. SAGA Dx’s business model is based on generating revenue from the sales of laboratory services and ready-for-use diagnostic kits which are the primary focus of the Phase 2 project. The Phase 1 project will support this strategy by confirming the market feasibility of our technologies and define a road map for their continued clinical validation. The EXACT –dna project will play a significant role in strengthening the European presence in the rapidly growing global cancer liquid biopsy market.

Keywords: liquid biopsies,cell free circulating tumour dna ctdna,genomic methods,cancer management
Urban Adaptation to Extreme Heat Events (U-ADAPT)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Reintegration panel
Action type: Marie Skłodowska-Curie actions
Panel: Environment and Geosciences
Countries involved: Spain
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Start date: 2021-09-01
End date: 2023-08-31
Duration (months): 24.0
Total project cost (EUR): 160932.48
EU funding (EUR): 160932.48
Participants: 1
Project status: SIGNED

The U-ADAPT! project proposes a novel approach for the dynamic measuring of urban adaptation to extreme heat. Extreme Heat Events (EHE) are the deadliest weather- and climate-related hazard in Europe. In recent years, heat waves have overwhelmed the continent, and projections show an alarming increase in EHE risk driven by natural and socioeconomic factors . Mitigation, adaptation, and transformative strategies need immediate implementation, but the rate of adaptation and depth of the transformation are in question. Reports stress that the progress of adaptation in European cities is patchy, uncoordinated, and of varied quality. Cities are still implementing their first adaptive measures and developing ideas for monitoring and reporting adaptation strategies. However, concrete norms or indicators for adaptation monitoring are scarce. In the research sphere, adaptation has mostly been discussed in terms of adaptive capacity, rather than implementation, which is the focus of this proposal. Despite the efforts, there is still very little consensus as to what constitutes effective and adequate adaptation, and therefore little agreement about models and indicators to measure it. The scientific aim of U-ADAPT! is to advance and test a theoretical integrated framework to examine the actual implementation of adaptation strategies to the risk of EHE in urban areas of the European Union (EU), in the context of Disaster Risk Reduction (DRR) and Climate Change Adaptation (CCA). The ultimate societal goal is to develop a model to assist cities in their responsibility to provide a safe and sustainable environment. The output of this research will also empower citizens to audit the commitment of their cities to EHE risk reduction and evaluate measures to reduce short- and long-term negative impacts of heat.

Keywords: adaptation,resilience,extreme heat events
Dynamic interplay between DNA methylation, histone modifications and super enhancer activity in normal T cells and during malignant T cell transformation (EpiTALL)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Physiology in Health, Disease and Ageing
Panel description: Organ and tissue physiology, comparative physiology, physiology of ageing, pathophysiology, interorgan and tissue communication, endocrinology, nutrition, metabolism, interaction with the microbiome, non-communicable diseases including cancer (and except disorders of the nervous system and immunity-related diseases)
Countries involved: Belgium
Call: ERC Starting Grant (ERC-2014-STG, 2014)
Start date: 2015-07-01
End date: 2020-06-30
Duration (months): 60.0
Total project cost (EUR): 958750.0
EU funding (EUR): 958750.0
Participants: 1
Project status: CLOSED

Dynamic interplay between histone modifications and DNA methylation defines the chromatin structure of the humane genome and serves as a conceptual framework to understand transcriptional regulation in normal development and human disease. The ultimate goal of this research proposal is to study the chromatin architecture during normal and malignant T cell differentiation in order to define how DNA methylation drives oncogenic gene expression as a novel concept in cancer research. T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric and 25% of adult ALL cases and was originally identified as a highly aggressive tumor entity. T-ALL therapy has been intensified leading to gradual improvements in survival. However, 20% of pediatric and 50% of adult T-ALL cases still relapse and ultimately die because of refractory disease. Research efforts have unravelled the complex genetic basis of T-ALL but failed to identify new promising targets for precision therapy. Recent studies have identified a subset of T-ALLs whose transcriptional programs resemble those of early T-cell progenitors (ETPs), myeloid precursors and hematopoietic stem cells. Importantly, these so-called ETP-ALLs are characterized by early treatment failure and an extremely poor prognosis. The unique ETP-ALL gene expression signature suggests that the epigenomic landscape in ETP-ALL is markedly different as compared to other genetic subtypes of human T-ALL. My project aims to identify genome-wide patterns of DNA methylation and histone modifications in genetic subtypes of human T-ALL as a basis for elucidating how DNA methylation drives the expression of critical oncogenes in the context of poor prognostic ETP-ALL. Given that these ETP-ALL patients completely fail current chemotherapy treatment, tackling this completely novel aspect of ETP-ALL genetics will yield new targets for therapeutic intervention in this aggressive haematological malignancy.
The Function of Hippocampal and Cortical Memory Replay in Humans (REPLAY)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: The Human Mind and Its Complexity
Panel description: Cognitive science, psychology, linguistics, theoretical philosophy
Countries involved: Germany,Germany,United Kingdom,United Kingdom
Call: ERC Starting Grant (ERC-2019-STG, 2019)
Start date: 2020-04-01
End date: 2026-09-30
Duration (months): 78.0
Total project cost (EUR): 1416506.0
EU funding (EUR): 1132116.0
Participants: 4
Project status: SIGNED

How does the brain use past experiences to shape future actions? Over two decades ago, research in rodents has made a remarkable discovery that may provide key answers to this fundamental question. Researchers found that while rats were sleeping, activity in their hippocampus seemingly retraced the animals’ previous trajectories in a maze, only much faster than in real time. This phenomenon, known as replay, has become a major focus of neuroscientists and even artificial intelligence researchers over the past decades. The resulting research demonstrated that replay is prevalent during wakeful resting, related to memory, planning and reward processing, and shares similarities with machine learning algorithms. These findings suggest that replay may be a fundamental mechanism behind memory consolidation and the computation of optimal behavior. Yet, despite the significance of this phenomenon, little is known about replay in the human brain. The major reason for the lack of knowledge are difficulties to measure fast neural processes non-invasively in the human hippocampus. The main goal of the proposed research is to overcome these obstacles, and to provide deeper insights into replay in humans. To achieve this, we will use a novel fMRI analysis method that tests whether the transitions between successive fMRI patterns during rest or sleep exhibit non-random relations to the temporal structure of previous experiences. Using this approach, the proposed research will provide insights into four cognitive and computational aspects of replay in the human brain: (1) the coordination of hippocampal replay with activity in other brain areas, (2) the effects of reward and planning on content and direction of replay, (3) the role of replay during sleep and its relation to sleep spindles, and (4) its role in age-related memory decline. In combination, insights gained from this research promise to greatly enhance our understanding of how memories guide adaptive behavior in humans.

Keywords: cognitive neuroscience,cognitive computational neuroscience,fmri,decision making