Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ALTIBRAIN (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1373033.33 €

Cognitive decline is an urgent strategic treatment target to improve the lives of people with neuropsychiatric disorders and reduce associated societal costs but treatments with robust and long-lasting efficacy are essentially lacking. Neuroplasticity is pivotal for cognitive functions and its disruption is involved in cognitive decline. However, the mechanisms underlying long-lasting neuroplasticity are unknown, which impedes the discovery of effective treatments. To address this challenge, I have conducted multidisciplinary research over the past 15 years into the cognitive and neurobiological effects of erythropoietin (EPO), a body-own protein involved in neurodevelopment, neuroprotection and cognition. We discovered that upregulation of EPO in the brain by low ambient oxygen increased neuroplasticity and cognition in mice. Building on this discovery, ALTIBRAIN will test a novel model linking oxygen manipulation, increased brain EPO, neuroplasticity and cognition. Specifically, ALTIBRAIN will determine whether upregulation of brain EPO by low ambient oxygen is a novel mechanism of long-lasting neuroplasticity and increased cognitive functions. We will achieve this ambitious goal using a multidisciplinary translational research approach combining cutting-edge methods from neuropsychology, neuroimaging and neuroscience. In parallel studies in humans and mice, we will investigate whether 3-week intermittent low ambient oxygen combined with cognitive training induces expression of brain EPO sufficient to produce similar effects to those, which I found upon exogenous EPO treatment. We expect long-lasting increase in cognitive performance, hippocampal volume and function and in differentiation/maturation of neural progenitor cells and dendritic spines. The findings can lead to a breakthrough in the understanding of mechanisms underlying enduring neuroplasticity and a paradigm shift in treatment strategies targeting cognitive decline.

Mots-clés : multidisciplinary,translational research,neuroimaging,cognitive impairments,cognitive training
Projet ERC : CONTEXT (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999995.0 €

Many childhood leukaemias start to develop before birth due to accumulation of mutations during foetal development. Children with trisomy of chromosome 21 (Ts21), also known as Down's Syndrome (DS), have a 500-fold increased chance of developing acute megakaryoblastic leukaemia. It is well known that aneuploidy (an abnormal number of chromosomes) is often associated with leukaemia and is likely to be driving this increased incidence of blood malignancies in children with DS. However, the mechanisms that control differentiation of haematopoietic stem and progenitor cells (HSPCs) and patterns of mutation acquisition in these cells during early human development are not well understood. This study will provide novel insights into two important questions: i) what is the impact of aneuploidy on blood formation in the context of specific tissue and ii) how it affects mutation accumulation and clonal selection in HSPCs. Here I aim to reveal cellular and mutational processes active during human Ts21 foetal blood development by: 1) performing comprehensive single-cell transcriptomics and spatial transcriptomics analysis of human Ts21 and healthy foetal liver and bone marrow combined with single-cell in vitro differentiation assays and 2) generating a catalogue of all somatically-acquired mutations in hundreds of Ts21 foetal haematopoietic progenitors using whole genome sequencing. The approach I propose derives its power from the close integration of state-of-the-art experimental data generation and computational analysis using novel methods. By examining cell intrinsic vs extrinsic processes in Ts21 haematopoiesis as well as mutation accumulation in individual stem cells this study will provide unprecedented insight into the mechanisms by which cellular changes induced by aneuploidy affect and possibly drive leukaemia. A better understanding of early events in human development, in health and disease, will open new routes for diagnosing, monitoring and treating disease.

Mots-clés : human foetal haematopoiesis,blood stem cells,single cell transcriptomics,spatial transciptomics,aneuploidy
Projet ERC : ALPGEN (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999958.0 €

The prehistoric pile dwellings in and around the Alps constitute one of the most important archaeological archives of human prehistory. Dating from around 5000 to 500 BC, there are over 1000 known sites in the region, 111 of which are listed on UNESCO’s World Heritage List. The sites are mainly located under water, on lake shores, along rivers, or in wetlands, offering exceptional conditions for the preservation of organic materials like wood, plant remains, animal bones, artefacts, and even textiles. Because of their exceptional preservation, the archaeological remains from those sites give us a unique window into the lives of prehistoric people and the development of early agrarian societies in Central Europe. However, despite the rich material evidence from the settlements, we know relatively little about the people who lived there. This is because there are no burials directly associated with the lake settlements, which has precluded the study of ancient DNA, for example. Luckily, there are other sources of ancient DNA, including ancient “chewing gums” which provide a rich of ancient human and host-associated microbial DNA as we recently demonstrated. In this project we will sequence ancient DNA and other biomolecules from ancient “chewing gums” found at lake settlements in and around the Alps to shed new light on the lives of the Alpine communities that settled there between 5000 and 500 BC. With access to over 300 specimens from archaeological sites north and south of the Alps, we have the unique opportunity to study their interactions and the demographic and cultural changes that characterised the transition from the Neolithic to the Bronze Age in Central Europe. In addition, the project promises to offer new insights into peoples’ health and the composition of their oral microbiome, as well as their diet and subsistence strategies. Together, the proposed research will provide us with a richer understanding of the pile-dwelling communities of Central Europe.

Mots-clés : ancient dna,prehistory,neolithic,wetlands,population history,microbiome,evolution
Projet ERC : UNRAVEL (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

The growing number of classes of RNA therapeutics, including siRNA, mRNA and RNA components of the CRISPR/Cas9 machinery, hold the promise of providing new treatment possibilities for almost any disease. However, these interventions require delivery of therapeutic RNA to their final intracellular targets in diseased cells, and delivery efficiency by current RNA nanocarriers is unsatisfactory. Endogenous nanoparticles called extracellular vesicles (EVs) have emerged as promising novel RNA delivery systems, due to their intrinsic ability to transfer biological cargo between cells in a selective manner. In fact, with my ERC StG, I have shown that EVs outperform synthetic carriers in terms of RNA delivery efficiency. However, EVs are a heterogeneous population of vesicles that differ in their targeting and cargo delivery properties, which forms a hurdle for the design of EV-based delivery systems. As methods to separate EV subpopulations and study their characteristics individually are lacking, a fundamentally different approach to address this hurdle is necessary.  The aim of UNRAVEL is to reveal how variations in EV composition lead to specialized subpopulations with unique delivery features. Using this knowledge, I will develop the first biomimetic class of EV-inspired synthetic RNA delivery systems. I will pursue three objectives: 1) Identify EV subpopulations with unique targeting and RNA delivery properties using a novel EV barcoding strategy 2) Define these EV subpopulations in terms of unique surface properties, intracellular trafficking and cargo release 3) Apply this knowledge to improve synthetic RNA delivery systems by incorporating molecular features from EV subpopulations  This work will significantly advance our understanding of the natural targeting and RNA delivery mechanisms of EV subpopulations and may result in a new generation RNA delivery system based on EV mimetics. In turn, this will allow more widespread application of RNA therapeutics.

Mots-clés : exosomes,extracellular vesicles,rna therapeutics,drug delivery
Projet ERC : PLANTEX (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Foundation for Research and Technology Hellas — Pays : Grèce — Rôle : PI
Acronyme de l'entité : FORTH
Type d'entité : Recherche
Financement ERC de l'entité : 1908375.0 €

Heat waves threaten agriculture in the EU and worldwide. Exactly how we can protect our crops precisely and rapidly from heat is a lingering question with important implications for future food security. My aim with PLANTEX is to explore the potential of a rapid stress response that my lab has discovered and incorporate this knowledge into the design of new breeding strategies to improve crops. To bolster heat tolerance, I propose an innovative approach for the control of protein production networks by repurposing proteolytic pathways that control the dynamics of organelle-like assemblies known as condensates. My lab pioneers the study of proteolysis on the formation of condensates with unique properties that allow them to store functionally related proteins and RNAs. I dubbed the networks in these condensates that we discovered “coregulons”. These coregulons are responsible for undocumented rapid and synchronized stress responses, for example during heat, that depend on proteolysis. I hypothesize that the discovered condensates ensure an unappreciated rapid response to stress that is important for plant acclimation and that this knowledge can be exploited to engineer desirable traits in crops. In this project, I propose 1) to use our approaches to collect an extensive dataset of coregulons important for growth and environmental adaptation in the model organism Arabidopsis and the agricultural-relevant crop tomato, 2) to characterize novel mechanisms involving proteolysis of coregulons by refining and developing new approaches of protease-substrate capture, and 3) design and implement innovative strategies based on cutting-edge genetic approaches to improve the tolerance of tomato to heat waves. My objectives are ambitious but potentially game-changing by providing approaches that can help combat the escalating problem of food security and for our comprehension of how plants adapt to dynamic environments.

Mots-clés : proteolysis,proteases
Projet ERC : CELICOIDS (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Université polytechnique de Catalogne — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998313.0 €

Chirality plays a fundamental role in natural sciences and pharmacology. The ability to detect chiral molecules relies heavily on inherently weak circularly polarized light-matter interactions. Such interactions are enhanced in the presence of chiral metamaterials, which exhibit extraordinary electromagnetic properties not observed in nature. To date, large and broadband circular dichroism in the UV-visible spectrum requires arrays of metallic nanohelices in order to combine internal and Bragg resonances. However, their fabrication relies on costly electron/ion beam lithography or physical vapor deposition, in which it is difficult and time-consuming to control nanoscale morphology over large areas. New types of helix metamaterials and engineering processes based on self-assembly concepts are absolutely necessary in order to be viable for future technologies. Nevertheless, self-assembled metamaterials with large, broadband and tunable chiroptical responses in the UV-visible region is a great challenge due to the required subwavelength feature sizes. To this end, the helicoidal morphologies of chiral liquid crystals provide the ideal platform for maximizing chiral light-matter interactions. The objective of CELICOIDS is to investigate the use of the chiral liquid crystal phases of cellulose nanocrystals with end-tethered polyoxyethylene analogues as templates for the fabrication of a new class of metamaterial, solid metallic nanohelicoids. A recent breakthrough that now makes this project possible is the discovery that such cellulose nanocrystal hybrids form chiral liquid crystal phases. As one of the very few researchers in the world with the combined expertise in cellulose chemistry, polymer grafting and colloidal assembly, I am the ideal candidate to achieve success. New functionalities are envisioned thereafter, applicable to future devices for invisibility cloaking, super-resolution imaging and chiral sensing, prompting a change in paradigm in metamaterials.

Mots-clés : liquid crystals,cellulose,self assembly,polymers
Projet ERC : SSE1K (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Bâle — Pays : Suisse — Rôle : Partner
Acronyme de l'entité : UniBasel
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 250000.0 €

In the Mediterranean in the first millennium CE, environmental and climatic changes have been identified as causes for significant short- and long-term societal and political processes and events, such as epidemics and the rise and fall of empires. However, the effects of environmental or climatic variation on humans are substantially more complex than a narrative of causation of major events, since culturally specific perceptions and interpretations of environmental or climatic variation can have significant social, religious or political implications.  SSE1K builds on state-of-the-art research but goes beyond it to ask novel, important questions about relationships between past societies and environmental / climatic fluctuation. The project will pioneer an approach which is both multi- and interdisciplinary, centring on these questions: How did humans experience and perceive environmental and climatic variation across the Mediterranean in the first millennium CE, and how did they respond both intellectually and socially to these changing conditions? SSE1K addresses issues which have been raised as significant challenges for collaborative study of climate change but have yet to be fully addressed: it will investigate how the circulation of knowledge and adaptability intersect with sustainability and resilience in pre-modern societies, and how human perceptions and ways of thinking shaped societal, political or religious responses to environmental / climatic change.  The project will integrate textual, archaeological and environmental evidence to investigate a large geographical area (the Mediterranean) at a scale which balances human lived experience and climate trends (the first millennium CE) over macro- and micro-levels. This integration is crucial in producing a holistic picture of past knowledge, resilience and sustainability, and will change the ways that scholars understand the relationships between past humans and environmental / climatic fluctuation.

Mots-clés : environmental history environmental archaeology historical climatology history of science intellectual culture climatology and climate change
Projet ERC : EPISTAT (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université de Jyväskylä — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1970533.0 €

The distribution of fitness effects of mutations is vital to our understanding of rates and patterns of adaptation. Population genetics and mutation accumulation experiments have given us insight into the distribution of fitness effects of single mutations. However, mutations often interact with each other. This is called epistasis. The role of epistatic interactions in adaptation has remained controversial. Yet, the distribution of epistatic effects is as fundamental as distribution of mutational effects themselves. Without knowing the distribution of epistatic effects, we can’t calculate the average fitness effect of a given mutation across multiple genetic backgrounds. Moreover, if epistatic interactions tend to be positive or negative on average, this will have an important effect on evolutionary dynamics. Epistatic interactions are also known to play a role in speciation, but the proportion of mutations that exhibit incompatible interactions that can lead to speciation is unknown. I will investigate the properties of epistatic interactions among mutations with two complementary approaches. First, I will estimate the probability and distribution of effects of epistatic interactions among spontaneous mutations. I will cross mutation accumulation lines that I have developed for the fungus Neurospora crassa to produce a mapping population where spontaneous mutations are segregating, and use it to estimate the distribution of epistatic effects. Second, I will estimate the proportion of substitutions that cause reproductive incompatibilities between populations from the relationship between reproductive isolation and genetic divergence. This is achieved by an evolution experiment with fission yeast, with a design that will maximize the rate of genetic divergence with minimal change in mean phenotype. The elucidation of properties of epistatic interactions will be a major breakthrough for the field of evolutionary biology.

Mots-clés : quantitative genetics,experimental evolution,speciation
Projet ERC : ProteoKnot (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université de Jyväskylä — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999454.0 €

The most sophisticated functions of proteins emerge at the level of their tertiary structure and involve large amplitude conformational changes. In contrast, the functions of synthetic molecules are currently limited by our inability to control their structure beyond the level of static secondary structures. ProteoKnot seeks to address this limitation by introducing entanglements as a tool to control tertiary folding while maintaining the flexibility required to allow them to change conformation. The first objective of this project is to establish design principles to guide the construction of entangled tertiary folds. These principles will be tested with the assembly of multiply-stranded helices (WP1), entangled macromolecules (WP2) and polymers (WP3). The second objective is to introduce photoswitchable handles in these structures to enable remote control over their conformational states (WP4). Operating the transition from the traditional design of static secondary folds to the design of dynamic tertiary folds will unlock the possibility to engineer increasingly complex macromolecules with protein-like functions. These exquisite architectures feature tandem helical motifs and cavities, providing an avenue toward highly elaborated receptors and catalysts. To illustrate the great potential of entangled tertiary folds for future applications, our third objective will be to develop their use as multi-responsive switchable catalysts (WP5).

Mots-clés : molecular knots,molecular nanotopology,chiral catenanes,switchable catalysts
Projet ERC : MAGICWAVE (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Université de technologie de Delft — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU Delft
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999698.0 €

Spin waves are collective excitations of the spins in magnetic materials. They play a central role in the thermodynamics of magnets and are promising signal carriers in classical and quantum information devices. Spin waves offer non-reciprocal transport, low damping, microscale wavelengths at microwave frequencies, and strong interactions that enable signal conversion. As such, spin waves have raised the hopes of enabling information technology with functionalities and efficiencies beyond those provided by non-interacting particles. A key requirement is realizing efficient, low-damping spin-wave control. A potentially ground-breaking but virtually unexplored method is provided by superconductors. Superconductors have no electrical resistance, precluding damping by eddy currents, and a strong diamagnetism that enables stray-field control of the refractive index governing spin-wave transport. Moreover, superconductors are sensitive to electric currents, magnetic fields, temperature, and light, providing tunability. As such, superconductors provide unique opportunities for realizing low-damping, tunable spin-wave optical devices.  I propose to realize and locally study superconducting spin-wave optics. I will create spin-wave-optical devices - mirrors, waveguides, beamsplitters, and resonators – by harnessing the dissipationless superconducting diamagnetism. I will then demonstrate the power of superconductor-control by tuning the devices using electric currents, magnetic fields, temperature, and light. In addition, I propose to use superconductors to engineer spin-wave damping and enter new regimes of flat-band and topological transport. To locally study spin waves underneath superconductors, I will use magnetic imaging based on spins in diamond – a technique pioneered by my lab. The project thus aims to engineer and understand magnet-superconductor interaction, realize tunable low-damping spin-wave devices, and launch the field of superconducting spin-wave optics.

Mots-clés : nv centers,spin waves,superconductors,quantum sensing,diamond