Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MINTRAF (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Ministry of Health — Pays : Espagne — Rôle : PI
Acronyme de l'entité : MISAN
Type d'entité : Recherche
Financement ERC de l'entité : 2455167.0 €

Mitochondrial research has consistently yielded surprising discoveries, such as the presence of their own DNA, use of a distinct genetic code, and their role in apoptosis. Recently, the proposal of intracellular mitochondrial transfer (ICMT) in vivo has sparked considerable interest, as this process is believed to hold significant therapeutic potential. This has generated growing public and private economical and scientific effort aimed at exploring ICMT as a potential treatment for common and rare diseases (ischemic reperfusion injury in heart, brain, kidney, etc.; mitochondrial diseases; delay in aging among others). However, there are still significant lack of knowledge, particularly regarding the proposed cellular mechanism of action, with insufficient experimental validation. Additionally, there are no studies on the physiological consequences, modulation, and functional roles of ICTM. A largely overlooked aspect is that mitochondria contain their own DNA. Therefore, if biogenetically competent mtDNA is transmitted by ICTM, the recipient cell become genetically modified. Such phenomenon has so far only been demonstrated in cancer. Therefore, any treatment with mitochondria could be classified as a form of genetic therapy. MINTRAF will establish a new strategy to determine the existence, extent and physiological relevance of ICMT. It will also investigate the maintenance of mtDNA biogenetic competence and the context where this process occurs. To achieve this, we will exploit our unique conplastic and heteroplasmic animal models to: (1) determine the extent, relevance and physiological impact of intercellular mitochondrial transfer; (2) decipher the role of ICMT as signalling process in tumour context; and (3) assess the extent, relevance and physiological impact of the horizontal mtDNA transfer in medical interventions.

Mots-clés : mitochondria oxphos cardiovascular heteroplasmy heterozygosity allele selective expression allele imbalance
Projet ERC : COORDINATION (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Académie royale néerlandaise des arts et des sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 3163750.0 €

Self-organisation is a defining feature of living systems and entails complex interplay between multiple parameters across various spatio-temporal scales. Using pre-implantation mouse embryos as a model system, our studies revealed a principle of regulative development, in which feedback between cell fate, polarity and mechanics ensures robust control of embryo size, shape and pattern. However, as embryos undergo implantation, this self-organisation mechanism has to be integrated in its spatio-temporal context. In this project, we aim to understand how developmental mechanisms are coordinated in space and time. The peri-implantation mouse embryo is an attractive system in which to study this coordination, as it begins to interact with uterine tissues, marks a key transition in morphogenesis, cell cycle and growth, and exhibits a remarkable capacity for size regulation. We recently developed an ex vivo 3D culture, engineered uterus and light-sheet microscopy to recapitulate morphogenesis and embryo-uterus interactions, and analyse changes in cell shape, fate, polarity and mechanics. Using these new methods, we aim to mechanistically understand the transformation from blastocyst to egg cylinder as embryonic-extraembryonic tissues interact. We will use embryo size control as a paradigm to study the coordination of developmental programmes in space and time. At the cellular level, we will identify what triggers the transition from cleavage to proliferative cell cycle – mammalian mid-blastula transition. At the embryonic level, we aim to understand how animal size is sensed and changes the temporal progression of development. Finally, we will investigate the role of embryo-uterus interactions in embryo morphogenesis and positioning within the uterus. The bottom-up engineering approaches will be complemented by top-down intravital microscopy to monitor embryogenesis in utero. Together, this project will bring mammalian developmental biology into a new stage.

Mots-clés : self organisation,morphogenesis,pattern formation,size control,timing,mouse development,cell polarity,differentiation,microscopy,cell and tissue mechanics,modelling
Projet ERC : CENTROSHAPE (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Académie royale néerlandaise des arts et des sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

The centre of the iconic X-shape of human chromosomes is the centromere. It is an extensive locus of specialised chromatin that assembles the kinetochore machinery to connect chromosomes to spindle microtubules for their correct segregation during cell division. How these centromeres obtain three-dimensional (3D) structures that coordinate assembly of kinetochores and resist substantial microtubule-based pulling forces is unknown. We discovered that vertebrate chromosomes are naturally dicentric: their centromeres are two-domain (‘bipartite’) structures, irrespective of underlying DNA sequence or position along the chromosome. Bipartite centromeres assemble bipartite kinetochores that connect to double microtubule bundles, fundamentally altering our view on chromosome-spindle interactions. Chromosome segregation errors in cancer are marked by split centromeres, linking centromere structural integrity to chromosomal instability. Our findings raise many elementary questions about the molecular origins, the 3D structure and the functional consequences of a bipartite mitotic centromere. In CENTROSHAPE, we will integrate advanced imaging and sequencing technologies with state-of-the-art cell models of neocentromeres, inducible centromeres and cancer, to uncover: - How centromere bipartition originates and is maintained, - What 3D chromatin structure shapes the bipartite centromere, and - How destabilisation of bipartite centromeres predisposes to chromosomal instability and centromere damage. The results of CENTROSHAPE will illuminate a hitherto ‘dark’ region of vertebrate mitotic chromosomes – the 3D organisation of centromeres. They will inform on the mechanisms that create this highly specialised chromatin domain in dividing cells and contribute to our understanding of the origins of chromosomal copy number alterations in diseases such as cancer.

Mots-clés : centromere,mitosis,aneuploidy,genome architecture,chromatin
Projet ERC : TRACE (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
Entité participante : Académie royale néerlandaise des arts et des sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

TRACE aims to amplify grassroots forces in climate governance to spearhead systematic transformations and just transitions. It pushes for a paradigm shift in climate governance, with Southeast Asia as a key site to adaptation strategies. Through reframing and reconceptualization of climate adaptation as geographies of knowledge, culture, and agency, TRACE will develop groundbreaking transdisciplinary concepts, frameworks, research methodologies, and tools for knowledge co-creation, power co-production, and agency shaping in climate governance. TRACE centrally puts co-creation of knowledge, co-production of power and culture, and agency as key praxis in climate adaptation and climate governance. It highlights the need to decipher past knowledge on adaptation and connects these with present and future adaptation strategies through archival, oral history and ethnographic research. It looks at evolutionary pathways of local institutions, their institutional arrangements, and adaptation practices as key building blocks for holistic, inclusive, and just climate governance. TRACE unpacks the underlying plural knowledge systems (e.g. traditional local knowledge, technological interventions) that inform ever-changing adaptation practices of farmers’, foresters’ and fishermen’s families across spatio-temporal scales, and vice versa. Climate adaptation as geographies of knowledge, culture, and agency is contextually rooted in four distinct yet interrelated socio-ecological systems across Southeast Asia. This is a region with diverse socio-ecological systems and wide range of knowledge systems, where grassroots forces in climate governance are present and hold great potential for the formation of inter-scalar climate adaptation networks. These socio-ecological systems are: 1) upland cultivation in Laos; 2) irrigated agriculture in Indonesia; 3) forest conservation in the Thai-Myanmar borderlands; and 4) sea nomads’ fishing territories in the Philippines.
Projet ERC : scTranslatomics (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Académie royale néerlandaise des arts et des sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

In recent years novel single-cell sequencing methods have allowed an in-depth analysis of the diversity of cell types and states in a wide range of organisms. Due to the continuous optimization of experimental and computational methods by many research groups, it is now possible to sequence the transcriptomes of thousands to millions of individual cells. Albeit an exciting development, transcription only covers the first step in the central dogma. The second step, the process of translation, is currently much harder to explore in single cells. Building upon existing ribosome profiling protocols, our laboratory recently majorly increased the sensitivity of these assays allowing ribosome profiling in single cells. However, currently no methods exist to determine the translation efficiencies in single cells and to correlate translation efficiencies to tRNA levels and their modifications, RNA bound proteins, and m6A methylation of mRNA, all major regulatory mechanisms of translation. The overarching goal of this proposal is to develop several novel multi-omics approaches to quantify translation in single cells by integrating information on ribosome position along the transcript, tRNA expression levels, tRNA modifications, RNA-bound proteins, and the m6A methylation status of the transcript. These technologies will open novel avenues to start exploring translation and its regulatory mechanisms with single-cell resolution. Whereas major discoveries have been made during the last decade by exploring the genome, the epigenome, and the transcriptome using single-cell sequencing approaches, translation, the major second step in the central dogma, is still very much unexplored at the single-cell level. I hope that the tools, presented in this proposal will provide the community with methods to explore, and ultimately understand, how translation contributes to the astonishing heterogeneity among single cells.

Mots-clés : single cell sequencing,single cell multiomics,single cell ribosomal profiling,scribo seq,single cell translatomics
Projet ERC : CARgiver (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Conseil national de la recherche — Pays : Italie — Rôle : PI
Acronyme de l'entité : CNR
Type d'entité : Recherche
Financement ERC de l'entité : 2493000.0 €

Mounting evidence has defined the key role played by the immune system in exacerbating dopaminergic neuron loss in Parkinson’s disease (PD). Pathological alpha-Synuclein (αSYN) activates microglia and recruits inflamed T cells, creating a toxic environment that directly negatively impact on neurodegenerative processes. Blocking or attenuating neuroinflammation can have a strong therapeutic potential in PD, but systemic treatments are associated with immune system general suppression leading to severe and unacceptable side effects. Therefore, a therapeutic strategy for long-term and local immune suppression would minimize adverse effects and provide a long-sought disease-modifying treatment for PD. To achieve this goal, we have generated αSYN-specific CAR T regulatory cells (Tregs) that are activated and recruited only in the presence of toxic αSYN aggregates, suppressing immune activation. Herein, we will determine the therapeutic efficacy of mouse and human αSYN-CAR Tregs in conventional and humanized mice with virally-induced synucleinopathy. These experiments will determine the dose and infusion schedule that will achieve maximal neuroprotection and symptomatic rescue with none or minimal side effects. Moreover, innovative all-human neuroimmune organoids will be generated by assembling patient and isogenic iPSC-derived neural, astroglial and microglial cells together with freshly isolated T cells and αSYN-CAR Tregs. This model will recapitulate human-specific neuroinflammatory processes and validate the capacity of αSYN-CAR Tregs to interfere with them. Finally, we conceived αSYN-CAR Tregs as ideal cellular shuttles for the local delivery of therapeutic molecules and this concept will be explore to express αSYN anti-aggregating agents. This treatment is of potential benefit for the entire PD patient population at any given stage of the disease and pharmacological regimen, and with a straightforward clinical implementation path using an autologous cellular source.

Mots-clés : parkinson s disease,alpha synuclein,neurodegeneration
Projet ERC : EXPERIENCE (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université libre de Bruxelles — Pays : Belgique — Rôle : PI
Acronyme de l'entité : ULB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2303531.0 €

Why would we do anything at all if the doing was not doing something to us? In other words: What is consciousness good for? Here, reversing classical views according to which subjective experience is a mere epiphenomenon that affords no functional advantage, I propose that the core function of phenomenal experience is to enable subject-level valuation: “What it feels like” is endowed with intrinsic value. Thus, I argue that it is only in virtue of the fact that conscious agents experience things and care about those experiences that they are motivated to act in certain ways and that they prefer some states of affairs vs. others. Conscious experience functions as a mental currency of sorts that makes it possible for agents to compare vastly different states of affairs in a common subject-centred mental quality space — a feature that explains that consciousness is unified. While my previous work was focused on the how question of consciousness, here, I propose to focus on the even more challenging question of the why of consciousness. EXPERIENCE will address this issue by pursuing a rich interdisciplinary program rooted in integrative philosophy of mind and in innovative cognitive neuroscience methods applied to the interactions between affect and consciousness in perception and action. The project is articulated over four work packages, each addressing a specific claim: (1) Subjective experience has intrinsic value, (2) The phenomenal field is valenced, (3) All intentional action is motivated by subjective experience & (4) Subjective experience has functional effects. EXPERIENCE is high-risk, for the function of subjective experience is largely unexplored territory, and high-gain, for it promises to question entrenched distinctions and to move the scientific approach of conscious a step closer to what we all know: That subjective experience matters. In fact, in many respects, it is the only thing that matters, as without it, life would simply not be worth living.

Mots-clés : functions of consciousness,phenomenal experience,visual perception,affective neuroscience,decision making
Projet ERC : KITAB-Transform (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Université Northeastern — Pays : Etats-Unis — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 196601.81 €

The premodern Arabic textual tradition between 700 and 1800 is one of the most prolific in human history, with the number of surviving works surpassing the extant production of any other pre-print culture except perhaps imperial China or Sanskritic India. These texts can now be studied in completely new ways using pioneering digital technology that can identify textual units displaying what one scholar has termed ‘extended textual similarity’. This means not only word-for-word matching, which can be detected by existing techniques and has been computationally studied, but also textual overlap obscured by transformations such as paraphrase and translation. By identifying, documenting, and interpreting this kind of transformational reuse across thousands of Arabic books, KITAB-Transform’s team of eight historians, linguists and computer scientists will uncover hitherto obscured connections between texts and shed light on the writerly attitudes and practices that created the Arabic written tradition and continue to shape Islamicate societies’ reservoirs of memory today. The project relies on a vast corpus of digitised texts that continues to grow thanks to an OCR pipeline developed by team members. KITAB-Transform will produce interdisciplinary monographs and edited volumes, journal articles, blog posts, language models, and data sets, as well as a web application through which less technically inclined scholars can access and work with our data, supported by a robust outreach programme. Our work will make an important contribution to Arabic book history and help redress a significant imbalance in the development of large language models, which favour English and modern social media but are comparatively impoverished for historical languages.

Mots-clés : arabic,islamicate,historiography,cultural memory,digital humanities,text reuse
Projet ERC : GraWFTy (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Université Humboldt de Berlin — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2195121.0 €

This project will determine the gravitational waves emitted in the encounter of two black holes or neutron stars in our universe at highest-precision. The gravitational waves emerging from such violent mergers are now routinely detected at the LIGO-Virgo-KAGRA observatories since their discovery in 2016. With the presently planed third generation of observatories the experimental accuracy will dramatically increase. Theoretical predictions for the emitted waveforms at highest-precision are therefore needed in order to determine the source parameters, such as masses, spins and intrinsic parameters of the two compact objects. Obtaining these waveforms requires solving the extremely difficult field equations of Einstein’s gravity. Major obstacles are the inclusion of radiative and spin effects at high-precision, as well as access to the strong gravity regime. Together with my research group, I have recently devised a novel quantum formalism to attack this classical physics scenario – worldline quantum field theory – that is methodologically rooted in elementary particle physics. It is the leading formalism to compute observables in the gravitational scattering of spinning black holes and neutron stars. My goal is to extend the scope of worldline quantum field theory to include radiative, higher spin and tidal effects, that discriminate between black holes and neutron stars. Moreover, I will uncover a hidden supersymmetry in the scattering of two spinning black holes. Finally, by matching to curved space-times I will develop theoretical tools that apply to strong gravitational fields as they arise close to the merger. These are presently unreachable by analytical methods. Our results will set the basis to test Einstein’s theory of gravity in extreme regions, possibly uncovering deviations from known physics; to understand black-hole formation; and to uncover the nature of neutron stars.

Mots-clés : quantum field theory,gravity,effective field theory,gravitational waves,feynman diagrams,scattering amplitudes
Projet ERC : ULPIS (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Université de Rostock — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499000.0 €

Material science, quantum chemistry, electrical and quantum engineering in the 21st century focus on manipulating and harnessing the properties of matter at the level of atoms and electrons. Advancing these technological capabilities to their ultimate limit calls for novel imaging techniques that can allow us to peer into matter at the level of valence electrons and follow their dynamics in space (tens of picometers) and time (femtosecond to attoseconds). Here we propose the development and use of ultrafast picoscopy to attain this grand goal of ultrafast and microscopy sciences. Intense laser fields can drive the coherent motion of electrons inside crystals to emit high harmonics of the fundamental whose spectral characteristics embody critical information about the spatial arrangement of electrons and atoms in the sub-angstrom scale. By combining this capability with state-of-the-art laser pulses whose field waveform is confined to a fraction of a femtosecond (optical attosecond pulses), it should be possible to record movies of electrons in solids in picometer space and attosecond time scales. Ultrafast picoscopy aims at enabling the three-dimensional visualization of the chemical bond in condensed matter, the detailed visualization of structural changes in crystalline materials and the real-time tracking of atomic and electron motion in ordinary and correlated materials. We anticipate the technique and the results of this endeavour to yield benefits to a broad range of scientific disciplines ranging from physics and quantum chemistry to material science and information technology.

Mots-clés : attosecond physics,nonlinear optics,high harmonic generation in solids,strong field physics