Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet TRaMaSI (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Unlocking the mysteries surrounding nutrient fate within the human body has remained an enigmatic pursuit. Our organs and tissues crave specific nutrients, especially in physiological and pathological conditions. Yet, the intricate journey these nutrients embark upon within our bodies remains largely unclear. The aim of my ambitious project is thus to create an innovative chemical-spatial workflow capable of (1) providing the anatomical coordinates of nutrients of interest across tissues (and organs) and (2) understanding the biochemical route these nutrients undergo in the respective tissue areas of the target organ. For this, I will use a complementary approach relying on advanced techniques such as tracer metabolomics, mass spectrometry imaging (MSI) and Stimulated Raman spectroscopy (SRS). I will benchmark this technological platform onto a model of acute kidney injury (AKI) to identify and localize the predominant biochemical pathways. The amalgamation of SRS and MSI with tracer metabolomics is groundbreaking given the current technological landscape and provides an innovative and feasible solution to the posed challenge.

Mots clés : tracer metabolomics, nutrient mapping, kidney

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 191760.0 €
Projet InnBeMods (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The balance of risk-taking and avoidance is essential for survival. Across different stages of life an animal’s priorities shift, which is reflected in changing behavioral preferences both during adolescents, when typically more risks are taken to facilitate exploration, and parenting, when avoiding risk is prioritized to ensure the safety of their young. These behavioral changes are correlated with distinct changes in hormonal levels. In mice, recently weaned adolescents exhibit high levels of corticosterone while parenting mice have increased oxytocin. The principles of how these changing hormonal levels impact the processing of information in neural circuits is poorly understood. Visually evoked avoidance behaviors are triggered through circuits of the superior colliculus. Here I will uncover how changing hormonal levels act to influence the processing of visual stimuli arriving from the retina and the resulting behaviors (e.g. freezing or escape). I will determine how this circuitry is affected by hormonal changes occurring across different life stages and whether these changes explain the resulting changes in behavior. To accomplish this, I will measure changes in innate defensive behaviors at different life stages, then identify the underlying circuit mechanisms involved. My expertise in precise circuit dissection in the retina provides me with the ideal background to uncover the mechanisms underlying the hormonal modulation of circuits in the superior colliculus. Recent technological advancement in functional imaging and large-scale electrophysiology along with new understandings of cell types and pathways of the superior colliculus provide the appropriate opportunity to identify the local and global modulations of visual processing driving hormone dependent changes in innate defensive behaviors. Overall, this research will provide valuable insight into how hormonal fluctuations allow animals to adapt to their changing needs across different stages of life.

Mots clés : visual processing, superior colliculus, neural signaling, neuropixels

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 175920.0 €
Projet INTERCOM (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

It is common knowledge that an ethernet connection is safer than a wireless connection, and cellular organelles share this approach. To communicate directly among each other, organelles are thought to use Membrane Contact Sites (MCS), the “optical fibers” at the intracellular level. Organelles are in a prime position to sense and communicate stress signals due to their tight integration into the cell’s metabolic networks. Inter-organelle communication is thus crucial to pass on the message to coordinate cellular stress responses and maintain homeostasis. I hypothesise that MCS allow fast and efficient communication of stress signals between intracellular organelles (e.g. mitochondria and ER) to coordinate the cellular stress responses. However, the organelle tethering proteins, the stimuli driving MCS formation and the signalling molecules mediated through these MCS remain elusive in plants. In INTERCOM, I will characterise ER-mitochondria communication in response to stress in Arabidopsis thaliana. For that, I will leverage the host lab’s previously established ER-mitochondria communication model system and establish a proteomic screening setup to identify novel proteins involved in ER-mitochondria MCS in plants. In addition, I will develop a high-throughput platform to study inter-organelle interactions in vivo and to identify stimuli driving MCS dynamics. Finally, I will employ genetically encoded biosensors to pinpoint ROS and calcium inter-organelle signalling events. To reach my goal, I will combine my expertise in intracellular signalling and bioimaging with cutting-edge interactomics, live-cell imaging and high-content technologies available at the host institute. This innovative and interdisciplinary approach will allow me to shed light on plant inter-organelle communication, a field still in its infancy in plant biology with the potential to pave the path for the biotechnological engineering of plants more resilient to harmful environmental conditions.

Mots clés : inter organelle communication plant membrane contact sites endoplasmic reticulum mitochondria protein protein interactions plant stress response

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 175920.0 €
Projet SpiLearn (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Animals adjust movement throughout their life to adapt to a changing environment and to learn new motor skills. The underlying mechanisms have been studied for decades, almost exclusively as a function of the brain. Interestingly, however, the spinal cord adapts and learns motor sequences without the brain, using only spinal sensory feedback. Therefore, the spinal cord must contain adequate neuronal circuitry for motor learning. This project aims to characterize brain-independent mechanisms of learning that take place within the spinal cord. With a complete thoracic transection, I will functionally isolate the lumbar spinal cord from the brain and enable hindlimb locomotion on a motorized treadmill with pharmacological stimulation. Using a skilled yet repetitive locomotor paradigm, I will identify cell-types indispensable for obstacle learning through circuit manipulation. Our preliminary data indicate that mice learn to avoid obstacles and improve their performance over weeks. We will test the integrity of this performance upon specific and acute inhibition of a selected neuronal population during the behavioral task. Furthermore, using in-vivo awake eletrophysiological recordings, I will characterize circuit dynamics that underlie motor learning capacity attributed to the spinal cord while mice perform the obstacle task. This project maximizes the synergies of the host lab’s expertise, i.e., kinematic analysis, circuit dissection, and the use of high-density Neuropixel probes, and my expertise in electrophysiological recordings in mouse spinal cord. In addition to implementing an innovative system of multichannel recordings of spinal circuits in behaving mice, knowledge gained from this project will enable linking cell-type specific activity profiles in the spinal cord to a motor learning behaviour for the first time. This link is an essential yet currently missing piece to understand how the spinal cord contributes to the acquisition of a new motor repertoire.

Mots clés : spinal cord, motor learning, behavior, electrophysiology, circuit dissection, locomotion

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 175920.0 €
Projet MicroSyn-MIND (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Microglia are immune cells that monitor our brain and degrade unhealthy neurons and excess synapses. In Alzheimer’s disease (AD) however, microglia excessively destroy synapses, marking them as enticing treatment targets. AD patients accumulate cortical Amyloid-beta (Aβ) plaques and neurofibrillary tau tangles, whilst losing neurons and synapses, and consequently: memory and cognition. Microglia are the brain’s immune cells, mediate neuroinflammation, continuously monitor their surrounding cells, and prune (eliminate) excess synapses during development. Interestingly, various AD risk genes are highly expressed in- or linked to- microglia, and while “activated” microglia can clear Aβ, they also degrade neurons and synapses. Our knowledge on microglia function mainly stems from rodent studies, which show microglia can target synapses via complement molecules or fractalkine, but we do not know exactly which proteins mediate this contact, how this translates to humans, and how this is affected in AD. I hypothesize that microglia use different cell surface proteins to interact with synapses in AD, compared to a healthy brain. By combining several cutting-edge technologies, I can now test this hypothesis in living, human microglia. I will transplant human iPSC-derived microglial progenitors into the cortex of healthy- and APPNLGF mice, to ensure the microglia develop a transcriptional- and morphological state like human in vivo microglia (expertise of the Mancuso lab). Using TurboID proximity labeling and quantitative high-resolution mass spectrometry, I will tag-, extract-, and identify the proteins at the microglia-synapse interaction site and determine how they differ from the AD mouse model (expertise of the De Wit lab). Given that abnormal microglial function is linked to various neurodegenerative diseases, my work will both provide valuable fundamental knowledge on microglial-synapse interactions and contribute to the development of new AD treatment targets.

Mots clés : microglia synapse neurodegeneration alzheimer turboid interactome protein crispr

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 191760.0 €
Projet GREBOS (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Air pollution is the biggest environmental health risk according to the EU and, it is responsible of several millions of premature deaths per year worldwide. In consequence, there is a growing demand for novel miniaturized, affordable, and reliable sensing devices able to detect pollutants at trace levels. The environmental monitoring market is estimated to grow at a CAGR of 4.1% to reach USD 17.10 billion by 2025. Within this market, the Air quality monitoring market size was valued at over 3.5B in 2018 and is expected to grow at a 7% CAGR. Noteworthy, through biogeochemical processes (i.e., acid rain) air pollutants released to the atmosphere can create a second pollution mechanism due to deposition in water surfaces, thereby increasing the potential threat to human health. Within this perspective, GREBOS lies in the development of a comprehensive sensing strategy employing innovative tailored functionalised borophene as a versatile nanomaterial for detecting trace levels of pollutants in both, water (SERS substrates) and air (chemoresistors) samples. This nanomaterial is at the forefront of research due to its superior and promising properties. In addition, borophene functionalisation with fluorine and phosphorous via low-energy ion irradiation will be studied for the first time, enabling novel studies about their changes in the electrical properties and surface chemistry. Besides, pollutants as nitrogen oxides and ammonia will be detected in both matrices below the threshold limit values established by the European Commission according to the Directive 2008/50/EC (air quality) and 98/83/EC (quality of the drinking water).

Mots clés : borophene, gas sensors, sers substrates, ion irradiation, electronic properties

Participants :
- Université de Mons (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191760.0 €
Projet Tau-Stick2Me (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The Tau protein during Alzheimer's disease (AD) becomes hyperphosphorylated, misfolds, and aggregates into neurofibrillary tangles (NFTs). Despite knowing the involvement of Tau in AD, the exact mechanism that drives Tau-mediated toxicity is largely unclear. Studying the Tau interactome is an excellent way to decipher the mechanism of Tau toxicity. Most interactome studies have primarily focused on Tau interactions related to NFTs, which represent the mature form of aggregated Tau. This emphasis has led to the overlooking of early-stage Tau interactions, mainly due to the lack of tools to access early Tau forms. My aim is to investigate the Tau interactome at these early stages, which are crucial in AD pathology. I hypothesize that extensive phosphorylation of Tau in the early stages of AD significantly alters its protein interaction network. This alteration contributes to Tau aggregation and subsequent toxicity in AD. To address this hypothesis, I will use an interdisciplinary approach to systematically identify interacting proteins associated with early Tau forms (non-phosphorylated, site-specifically phosphorylated, and hyperphosphorylated). I will use a protein semisynthesis technique to generate early Tau forms and employ affinity purification-mass spectrometry to identify the interactome associated with them from human brain tissue. Unique interacting proteins of Tau forms detected from the proteomic data, will be assessed in high-throughput Tau biosensor-based cellular screening to identify potential Tau aggregation modifiers. Finally, in vitro biophysical studies will be conducted to characterize the molecular interactions between Tau modifiers and Tau forms. The findings from this project will advance our mechanistic understanding of Tau phosphorylations in AD, elucidate the complex molecular interactions and pathways involved, and pave the way for the development of innovative therapeutic strategies targeting early Tau interactome.

Mots clés : alzheimer s disease, tau protein, interactome, hyperphosphorylation, protein semisynthesis

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 216240.0 €
Projet ZIREN (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Nucleic acids are potent inducers of an immune response. Nucleic acids normally exist in a right-handed conformation. However, during conditions of cellular stress, nucleic acids can also adopt an unusual, left-handed “Z-form”. These Z-nucleic acids, including Z-RNA and Z-DNA, are sensed by two proteins: ADAR1 and ZBP1. While ADAR1 binding to Z-nucleic acids prevents immune responses, activation of ZBP1 results in the activation of an innate immune response. It is clear, that ZBP1 has important functions in antiviral defence, cancer immunity and during autoinflammation, yet the mechanisms that govern its activation and which pathways downstream of ZBP1 are activated, is poorly understood. Additionally, a big hurdle currently preventing the molecular characterisation of ZBP1 signalling, is the lack of a selective ZBP1 agonist.  I hypothesise that understanding the molecular mechanisms regulating ZBP1 activation and its downstream signalling pathways is fundamental for the development of therapeutics targeting this pathway. To test this hypothesis, I will address three major knowledge gaps in ZBP1 biology: (i) by purification of active ZBP1 complexes followed by nanopore sequencing and through solid-phase nucleic acid synthesis, I will generate a bona fide ZBP1 agonist, (ii) I will validate the ZBP1 agonist in vivo by testing its adjuvanticity in a mouse vaccination model, and (iii) by using a small compound and a genome-wide CRISPR/Cas9 knockout approaches, I will identify upstream and downstream regulators of ZBP1 signalling. Together, my proposed research plan will contribute to understanding the activation mechanisms of ZBP1, as well as its regulatory factors laying the foundation for understanding human ZBP1-driven (patho)physiology and development of therapeutic intervention.

Mots clés : z nucleic acids, zbp1, z dna, z rna, cell death signalling, inflammation, apoptosis, necroptosis

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 200400.0 €
Projet iCON (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

In plants, the outermost epidermal cell layer is critical for protecting the entire plant against external threats such as rain, wind and pathogens. The plant epidermis is a complex tissue consisting of multiple cell types, all with different shapes, functions and developmental trajectories. Although studied in isolation, our understanding of how these cells interact to ensure tissue integrity is poor, but at present, the outermost jigsaw-puzzle-shaped pavement cells have emerged as key players. Recent findings in the host lab suggest that the diverse physical and/or mechanochemical nature of the cell wall is crucial for pavement cell-shape acquisition, and thus under influence of the underlying tissue layers. However, yet the identity of the putative signals derived from inner cell layers, defining the shape of epidermal cells and the integrity of the multilayered leaf tissue, remains to be explored. Hence, in iCON I will join the Robert (host) lab to disentangle the signaling networks and mechanical constraints of inner mesophyll cells that determine epidermal pavement cell shape and organogenesis of the leaf, using a suite of novel and multidisciplinary approaches in the model plant Arabidopsis thaliana. Specifically, I will acquire new skills in cutting-edge microscopy, cell biology and biomechanics to generate a high-resolution 3D map and uncover mechanical/physical cues, and leverage my expertise in transcriptomics, genetics and molecular biology to determine molecular components, together allowing me to decipher the overall mechanism via which mesophyll cells orchestrate pavement cell shape acquisition. Besides contributing new knowledge, iCON will allow me to expand my scientific expertise and gain key transferrable skills, boosting my strive to become a research leader. Ultimately, knowledge on how plants maintain tissue integrity can support the development of stress-resilient plants and thus contribute to a sustainable agriculture in a changing climate.

Mots clés : epidermal pavement cell, mesophyll cell, cell to cell communication, periclinal cell wall, mechanical cues, molecular signaling, stress resilient crop

Participants :
- Université suédoise des sciences agricoles (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 222727.68 €
Projet SAFEPCM (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Phase change materials (PCMs) has attracted much attention of researchers during the past two decades. However, current PCMs still have seriously potential problems on the fire safety mainly due to the flammability of the PCM substances. In this context, fire safe PCMs offer some advantages over conventional PCMs, leading to safe PCMs become very promising candidate for advanced energy saving field; but they still have a lot of challenges. In this project, aiming at solving some key scientific problems of PCMs and providing theoretical basis to the development of new generation fire safe PCM, based on the sophisticatedly structure design and fabrication the fellow will focus on the study of advanced (Sustainable, form-stable, and fire-safe) PCMs. The main objectives include: (1) To design and realize support materials for phase change materials with low cost, biomass source, good compatibility with organic PCM substances, uniform open pores, and convenience to realize large-scale preparation; (2) To design and prepare biobased phase change materials with fire safety, high thermal conductivity, and form stability: realize adjustable phase change temperature and ultra-high phase change enthalpy; (3) Develop the practical application of this new type of high-performance PCM in solar energy harvesting and storage, energy conservation and temperature regulation abilities; and (4) To expand the application of PLA, ionic liquid, other bio-based molecules (e.g., phytic acid, tannic acid, Chitosan, and Sodium alginate) in the new generation of PCMs. This proposal presents an interdisciplinary and innovative approach with great significance. These original ideas will bring us bran-new multi-functional and sustainable PCMs. It also provides a practical technical approach for the comprehensive design of PCMs.

Mots clés : energy storage, bio based, flame retardant

Participants :
- Université Aalto (Finlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 215534.4 €