Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet NeuroMag (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Machine learning applications based on artificial neural networks have undergone rapid progress in recent years. To improve the power efficiency over current hardware, alternative implementations of a critical part of artificial neural networks, the matrix-vector multiplier performing large-scale linear transformations, have been intensively researched. Recently, a matrix-vector multiplier based on the interference of optical waves has been proposed in combination with local adjustable electro-optic modulation of the refractive index to enable training. NeuroMag’s objective is to implement such an interference-based matrix-vector multiplier using spin waves (magnons). Magnetoelectric compound materials will be used to engineer scalable broadband transducers with high potential energy efficiency to generate, detect, and manipulate spin waves. Distinct advantages of such a spin wave implementation over a photonic one are (i) the full bidirectionality of the system since transducers can be operated both to excite as well as detect spin waves and (ii) the large tuning range of the phase velocity of spin waves (equivalent to the refractive index in photonics) by the magnetoelectric effect. Magnetoelectric transducers and low-damping Yttrium Iron Garnet magnetic media will be combined to nanofabricate a demonstrator device and study its matrix-vector multiplier operation. Using an interdisciplinary approach that combines materials science, physics, microwave engineering, and device nanofabrication, NeuroMag thus targets the ground-breaking proof-of-concept of a magnonic matrix-vector multiplier and its operation, paving the way towards magnonic artificial neural networks. The combination of learning through research and a comprehensive training plan, including both scientific and technological as well as soft skills, will strongly enhance the researcher profile of the applicant and provide a boost for his future scientific career.

Mots clés : spin waves, magnonics, neural networks, machine learning, nanoelectronics, wave based computing

Participants :
- IMEC (Belgique) — Coordinator, beneficiary, Recherche, subvention : 172800.0 €
Projet Liver ID3ntity (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Macrophages perform unique tissue-specific functions that are essential for the homeostasis of each organ. To perform these tissue-specific functions, each resident macrophage expresses a relatively unique gene expression profile controlled by specific transcription factors. Kupffer cells (KCs) are the biggest macrophage population of the body and represent 10% of all liver cells. The Guilliams lab recently reported that each KC projects an important part of its body across the liver endothelial cell barrier to be in close contact with hepatocytes. We have established that the transcription factor ID3 is highly expressed in murine KCs as compared to other macrophages, is highly preserved in KCs across 5 different species and is essential for controlling KC identity in vivo. We have recently reported that monocytes co-cultured with hepatocytes, but not with liver endothelial cells or liver fibroblasts, acquire strong ID3 expression, indicating that hepatocyte-derived signals induce ID3 expression. The objective of this proposal is to utilise ID3-expression in KCs to unravel the molecular mechanisms underlying the KC-Hepatocyte crosstalk. Since nothing is known about the hepatocyte-derived signals that induce ID3 expression in myeloid cells, I will utilize a genome-wide in vitro CRISPR screen to identify positive and negative regulators of the ID3 expression induced by hepatocytes. The result of this in vitro ID3-screen will then be combined with potential regulators predicted through epigenetic and ligand-receptor inference algorithms, to obtain our top candidates for genes involved in the liver KC-Hepatocyte crosstalk. Using cutting-edge technology combining direct guide-RNA capture with single-cell RNA sequencing, I will then perform a targeted in vivo CRISPR screen. Finally, I will knock-down the most interesting hits from this in vivo screen using CRE-Lox technology to understand the role of specific KC-Hepatocyte interactions in liver homeostasis and pathology.

Mots clés : cell cell interactions, tissue imprinting, tissue resident macrophages, macrophage niche, liver kupffer cells

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 166320.0 €
Projet MacrophageEGR (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Macrophages play important roles in many aspects of immunity and therefore contribute to a diverse range of human inflammatory diseases, including atherosclerosis. The expression of macrophage genes is tightly controlled by regulatory DNA elements, such as enhancers. When macrophages are exposed to external stimuli, specific transcription factors affect enhancer activity, thereby impacting macrophage function in health and disease. I am investigating macrophage enhancer activation by interleukin-4 (IL-4). IL-4 is an important anti-inflammatory cytokine that suppresses macrophage activation and regulates immune responses during parasitic infections and allergies. I discovered that IL-4 activates the transcription factor Egr2 leading to specific IL-4-induced enhancer activation in macrophages. I surprisingly noticed that Egr1, while binding highly similar DNA motifs as Egr2, actually represses enhancer activity when macrophages are exposed to pro-inflammatory stimuli, indicating antagonistic effects of Egr1 and Egr2. By targeting transcriptional regulators, macrophages can be skewed to disease-favorable phenotypes. I here propose to investigate and target Egr1 and Egr2 in pro- and anti-inflammatory macrophage phenotypes in vitro and in disease. Aim 1: To elucidate the molecular mechanism resulting in differential outputs of Egr1 and Egr2 binding, I will study the transcription factor complexes in which Egr1/Egr2 function. Aim 2: To characterize the function of Egr1 and Egr2 in macrophages, I will study the effects of Egr1/Egr2 deletion in mouse and human macrophages. Aim 3: To study the roles of Egr1 and Egr2 in macrophage-driven diseases, I will delete Egr1/Egr2 in macrophages and assess the effect of deletion on atherosclerosis and endotoxemia. My proposed studies will reveal the role of macrophage Egr1 and Egr2 in disease and contribute to increased knowledge on how disease-associated signals regulate enhancer activity in disease-relevant cell types.

Mots clés : macrophage, enhancers, signal dependent transcription factors

Participants :
- Amsterdam University Medical Centers (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175572.48 €
Projet MADSEA (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

Madness is not only shaped by clinicians within the walls of asylums and psychiatric hospitals, but by ordinary people within communities. The non-material and material aspects of their lives, from belief and religiosity to physical environment, have driven individual and collective understanding, experiences and responses to mental difference and distress throughout history. Through shared cultures and experience, these community contexts can extend across the national and political boundaries which have dominated studies in the history of madness and psychiatry. MADSEA's primary objective is to develop an interdisciplinary methodology for the study of madness in these transnational community contexts, inclusive of the complex interaction of belief (religiosity) and materiality (environment) in the lives of ordinary sufferers. It uses early modern seafarers as a spatial, socio-cultural frame for its investigation, as their shared mobility and exposure to the dynamic effects of the ocean transcended borders and left a rich historical record of the action of religiosity and environment in their lives. Employing a microhistorical approach, MADSEA undertakes an in-depth comparative archival study of the meaning and societal impact of madness in the records of the eighteenth-century Danish-Norwegian and British navies. Blending qualitative and quantitative methods, it achieves three further objectives: establish how seafaring communities understood madness; gauge the degree mental difference and distress were stigmatised or tolerated; and evidence a trans-European seafaring community culture and response towards madness, to demonstrate how religiosity and environment, rather than national boundaries, shape mental illness. As such, MADSEA provides researchers with an empirical foundation and innovative methodological toolkit for accessing and analysing the experiences of ordinary people outside modern clinical settings, revitalising the history of madness 'from below'.

Mots clés : history of madness and psychiatry, maritime history, microhistory, eighteenth century, early modern

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet EstroGen (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Major depressive disorder afflicts ~16% of the population and is a leading cause of disability worldwide. Classical antidepressants take weeks-to-months for clinical efficacy and only a sub-population of patients responds to treatment, highlighting the need for the development of novel rapid-acting and effective pharmacotherapies. Hypogonadism, the decrease in the production of gonadal hormones occurring due to ageing or several other medical conditions, has been associated with an increased risk for development of mood disorders, including depression. Accumulating evidence suggests that epigenetic changes induced by stress or other environmental factors might also contribute to the development of depression; however, the reciprocal interactions between hypogonadism, stress, epigenetic modifications and depression has received limited attention. During this project, my in-depth knowledge in studying the role of gonadal hormones in the pathophysiology of mood disorders will be combined with expertise of the Host lab in assessing epigenetic mechanisms of disease, to identify novel associations between hypogonadism and epigenetic modifications underpinning and/or predicting susceptibility for depression development. In particular, EstroGen proposes an interdisciplinary approach to investigate the combinatorial effect of hypogonadism/stress on epigenome and their role in depression, using preclinical models. In addition, this project aims to identify hypogonadism-related epigenetic biomarkers to predict subsequent development of depression. Importantly, this fellowship will propel my academic career and help me become a scientific leader at the interface of epigenetics, gonadal hormones and mood disorders, by acting as a stepping stone towards securing future research funding and acquiring a tenure track position in Europe.

Mots clés : histone modifications, chromatin dynamics, gonadal hormones, hypogonadism, depression

Participants :
- University of Cyprus (Chypre) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 145941.12 €
Projet FEBRIS (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Malaria still claims more than 400,000 deaths every year, above all in children under 5. All symptoms are caused by the blood stage of the deadliest parasite species Plasmodium falciparum (Pf), which infects human red blood cells. Cerebral malaria (CM) is the most severe complication, with 20% mortality rate even after administration of fast-acting antimalarials, and is due to build-up of parasites in the brain microvasculature leading to vessel occlusion, blood-brain-barrier disruption, and brain swelling. Current knowledge of CM is based primarily on autopsy analysis, because of limitations of suitable animal models, where disease onset and progression cannot be studied. Additionally, different areas of the brain with distinctive vascular patterns show CM-specific lesions supporting the hypothesis of different regional microcirculations. In my project FEBRIS I will tackle, for the first time, human CM process in vitro models of white and grey matter, and basal ganglia, with cutting-edge bioengineering approaches. I will develop 3D microfluidic devices coated with endothelial cells mimicking vessel networks and physiological flow rates of these three regions of the brain. Numerical simulations will identify critical factors causing blood stagnation, predicting where and when a clog could form. Using this technology brings a unique angle to malaria research to systematically evaluate the unexplored effect of fever on molecular and biophysical mechanisms of Pf sequestration, and the concurrent vascular damage. The obtained findings will be validated with parasites from the field and brain samples from CM patients, examined with pioneer 3D autopsy imaging. This interdisciplinary approach, favoured by my host, aims to provide a holistic understanding of CM pathogenesis. The acquired knowledge could lead to new therapies to reduce fatality by malaria disease and, in a broader context, this innovative platform could be employed to study other neurovascular diseases.

Mots clés : malaria pathogenesis, plasmodium falciparum sequestration, brain vasculature, 3d microfluidics

Participants :
- European Molecular Biology Laboratory (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet MoroccoMasculinities (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Male juvenile delinquency as represented by self-styled tcharmils has been the focus of a moral panic in Morocco over the last years. The tcharmil subculture has gained visibility through a social-media propagated aesthetic that turns the stigma of social disqualification into a source of pride by extolling assertive masculinity, violence, and the transgression of social and religious norms. By adopting consumerist values that overlap with those of more privileged classes, and by frequenting the latter’s urban spaces of leisure, the tcharmil blur social boundaries. The resulting anxieties among the privileged has resulted in public campaigns and police crackdown. MoroccoMasculinities examines the construction of the masculinities of disadvantaged young men in order to understand how gender, class, space and ethnicity intersect in juvenile moral and cultural formations in today’s Morocco. On the one hand, studying the tcharmil subculture reveals how juvenile subjectivities are reshaped by the combined effect of urbanisation, the new media, and state policies interlinked with global systems of regulation such as neo-liberal reforms, restrictions on migratory movements, and the intensification of the struggle against the hashish economy. On the other hand, the study of state reactions to the same subculture allows to highlight changing patterns of criminalisation: the unprecedented emphasis on male delinquency possibly reflects a strategy of discursive de-politicisation of the threats to an established order faced with the challenges of the Arab Spring and its aftermaths.

Mots clés : morocco, youth, masculinities, gender relations, subculture, criminalisation, police work, social class, social change, disqualification, school, norms, middle east and north africa

Participants :
- University of Edinburgh (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet DRIVOME (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Mammalian behaviour is driven by instincts such as hunger, sex and aggression which are familiar to everyone from daily experience. Anomalies in these instincts cause disorders such as anorexia, excessive sexual drive and episodic dyscontrol syndrome, and potentially also psychologically difficult situations like marital infidelity. Neuronal circuits that drive these instincts reside in the hypothalamus where research is gaining pace rapidly. Recent work has uncovered hypothalamic neuronal populations in mouse, that can drive the following fundamental mammalian behaviours: feeding (Aponte et al., 2011, Betley et al., 2015), sex/aggression (Lee et al., 2014, Lin et al., 2011), sleep/wakefulness (Adamantidis et al., 2007, Jego et al., 2013) and parental behaviours (Marlin et al., 2015, Wu et al., 2014). Older work has demonstrated similar effects with cruder manipulations of the hypothalamus in several species. Classical work in ethology (Lorenz, 1981, Tinbergen, 1951) as well as newer anatomical insights (Swanson, 2000) have outlined hypotheses for how neuronal network architecture may guide the organization of instinctive behaviours into the coherent, adaptive, context-relevant displays evident throughout the animal kingdom. Modern techniques (opsins, genetically encoded calcium indicators, transgenic mice, multi photon imaging of deep brain structures and optrode recording) are now ripe for comprehensive cell-type specific probing of the hypothalamic networks in charge of fundamental drives and possibly emotions. We propose to use these methods to elucidate the intrahypothalamic wiring diagram (the connectome of drives, or 'DRIVOME') that can explain how instincts are orchestrated.

Mots clés : brain, hypothalamus, instinct, transgenic mice, patch clamp, optogenetics, in vivo recordings

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet IEOCCD (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Mammalian cells must round up to divide by remodeling their adhesions and their cytoskeleton to form a stiff actin cortex. Mitotic rounding provides the space necessary to develop a mitotic spindle to undergo symmetric chromosomal segregation. If mitotic rounding is impeded by physical confinement or preventing adhesion remodeling, defects in spindle assembly and chromosomal missegregation can lead to mitotic cell death. In cancer, the cells must divide in a challenging environment which can alter the way cells divide. Preliminary data show Ras- activated epithelial cells are able to round better compared to normal cells. This adaptation could protect the dividing cell from the physical environment and allow epithelial cancer cells to divide in the confines of the tumor and distant metastatic sites. Here, we aim to identify mechanisms that allow epithelial cancer cells to divide differently from that of normal epithelial cells. Potentially, this mechanism could be a powerful target if we are able to prevent cancer cell division without interfering with normal cell division. Preliminary data suggest Ras-ERK signalling could play a role in mitotic rounding of cancer cells. In this proposal, I will 1) investigate ERK signalling dynamics during mitotic progression, how it regulates mitotic rounding and effects on the following cell cycle 2) investigate how Ras-ERK signalling and the mechanism of cell division are affected by environment using microfabricated tools and 3) initiate oncogenic activation by over-expressing receptor tyrosine kinases commonly found over-expressed in cancer or constitutive activation of Ras/Raf and measure changes in Ras-ERK signalling and cell mechanics. By establishing a link between Ras-ERK signalling and mitotic progression, I will determine how oncogenesis affects Ras-ERK signalling dynamics and cell division to allow cancer cells to divide in a wide range of environments.

Mots clés : mitotic rounding cell division ras mapk erk microfabrication cancer microenvironment

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet IMMUNO-RQC (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Mammalian cells present a fingerprint of their proteome through the display of endogenous peptides on MHC-I complexes. This allows for CD8+ T cells to recognize and kill cells infected with viruses or other intracellular parasites, or cells accumulating aberrant proteins resulting from malignant transformation. The MHC-I peptides originate from protein degradation by the ubiquitin proteasome system, which is responsible for controlled protein turnover. This would mean that viral proteins, which are typically very stable, would escape monitoring. Nevertheless, cells are able to mount an MHC-I immune response minutes after viral infection. Most MHC-I presented peptides are therefore thought to originate from newly synthesized, defective ribosomal products (DRiPs), rather than proteins at the end of their lifespan. Although there is a growing body of evidence showing that antigen presentation is better correlated with protein synthesis rather than protein stability, characterization of the underlying cellular pathway is lacking. Recently, the E3 ubiquitin ligase Listerin has been shown to mark nascent polypeptides resulting from defective mRNAs for degradation. Here we test the hypothesis that this pathway contributes to the production of peptides for MHC-I loading. Our major aim is therefore to investigate the involvement of Listerin in antigen presentation, using 3 different approaches: I) proof-of-principle experiments analyzing the rate of MHC-I presentation of a model protein, comparing the efficiency of its presentation when expressed from an intact or defective mRNA, and when expressed in WT or Listerin knock-out cells; II) global characterization of the MHC-I peptidome of WT and Listerin knock-out cells using mass spectrometry; III) quantitative analysis of the fraction of newly-synthesized proteins undergoing the RQC pathway, and of its possible correlation with the MHC-I peptidome.

Mots clés : protein degradation, e3 ubiquitin ligase, ribosomal quality control, mhc i, antigen presentation

Participants :
- Max Planck Society (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 159460.8 €