Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : TAU-NOW (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 639807.5 €

Alzheimer’s disease (AD) poses a major challenge, as 40 million people worldwide are diagnosed with AD and there is currently no cure. AD is characterized by Aβ plaques and tau neurofibrillary tangles. Recently, several phase III clinical trials targeting the Aβ pathway have failed to reach their primary endpoints. This stresses the need for diversification of the drug portfolio. Tau pathology is a promising drug target due to its strong associations with synaptic density, atrophy and cognition. I envision two treatment options to be potentially effective in halting or slowing AD: 1) preventing the spreading of pathological tau, and 2) boosting resilience against tau pathology. Both processes are currently insufficiently understood, especially in living humans. Since a few years, AD-specific tau pathology can be measured in vivo using PET. TAU-NOW uniquely utilizes longitudinal tau PET in conjunction with functional and structural MRI, biofluid and cognitive data, to investigate mechanisms of tau spread and resilience in humans. In WP1, I will test the hypothesis that tau predominantly spreads through functionally connected regions, by relating tau PET changes over time to the functional architecture of the brain. Next, molecular (CSF) and genetic (GWAS) drivers of tau spread will be identified. On top of that, I will assess whether functional disconnection in subjects who underwent epileptic surgery (i.e. unilateral medial temporal lobe resection or corpus callosotomy) leads to an asymmetric tau PET pattern decades later. In WP2, I will investigate the functional (fMRI), molecular and genetic modifiers that render individuals resilient to tau pathology. In WP3, I will examine the consequences of tau spreading and resilience for important clinical trial outcomes like cognitive and volumetric changes over time. Altogether, TAU-NOW will enhance our understanding of tau spreading and resilience and may ultimately identify novel leads for drug discovery against AD.

Mots-clés : alzheimer s disease,spreading,resilience,neuroimaging,cognition,genetics
Projet ERC : IMMUNOALZHEIMER (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Verona — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Alzheimer’s disease is the most common form of dementia affecting more than 35 million people worldwide and its prevalence is projected to nearly double every 20 years with tremendous social and economical impact on the society. There is no cure for Alzheimer's disease and current drugs only temporarily improve disease symptoms. Alzheimer's disease is characterized by a progressive deterioration of cognitive functions, and the neuropathological features include amyloid beta deposition, aggregates of hyperphosphorylated tau protein, and the loss of neurons in the central nervous system (CNS). Research efforts in the past decades have been focused on neurons and other CNS resident cells, but this "neurocentric" view has not resulted in disease-modifying therapies. Growing evidence suggests that inflammation mechanisms are involved in Alzheimer's disease and our team has recently shown an unexpected role for neutrophils in Alzheimer's disease, supporting the innovative idea that circulating leukocytes contribute to disease pathogenesis. The main goal of this project is to study the role of immune cells in animal models of Alzheimer's disease focusing on neutrophils and T cells. We will first study leukocyte-endothelial interactions in CNS microcirculation in intravital microscopy experiments. Leukocyte trafficking will be then studied inside the brain parenchyma by using two-photon microscopy, which will allow us to characterize leukocyte dynamic behaviour and the crosstalk between migrating leukocytes and CNS cells. The effect of therapeutic blockade of leukocyte-dependent inflammation mechanisms will be determined in animal models of Alzheimer's disease. Finally, the presence of immune cells will be studied on brain samples from Alzheimer's disease patients. Overall, IMMUNOALZHEIMER will generate fundamental knowledge to the understanding of the role of immune cells in neurodegeneration and will unveil novel therapeutic strategies to address Alzheimer’s disease.

Mots-clés : leukocyte trafficking,vascular inflammation,neutrophils,t cells,intravital microscopy,neuroinflammation,neuroimmunology,alzheimer s disease
Projet ERC : INCALO (Horizon 2020, appel 2018, Proof of concept grants)
Entité participante : Hasselt University — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149170.0 €

Ambient air pollution, including black carbon, entails a serious public health risk because of its carcinogenic potential and as climate pollutant. Inhalation of fossil fuel-derived particulate matter (PM) is associated with a wide range of non-pulmonary health effects. Based on the WHO report of 2015 the European health annual costs of air pollution have been estimated to US$ 1.6 trillion. Although recent studies strongly suggest that particle translocation in biological systems is biologically plausible, they do not prove that ambient fossil fuel-derived carbonaceous nanoparticles enter the human systemic circulation in real-life conditions. We developed a novel method to detect carbonaceous nanoparticles in the urine of healthy children. The ERC funded ENVIRONAGE project already made a strong case for promoting urinary carbon detection to practice by demonstrating its usefulness as individual long-term exposure marker. Taking advantage of white-light generation by carbonaceous nanoparticles under femtosecond pulsed laser illumination, we demonstrated the presence of these particles in urine and its relation with the external environmental air pollution (Saenen et al. Am J Respir & Crit Care Med, in press). This pioneering study is of innovative value, as it paved the way for a non-invasive assessment of long-term individual exposure to one of the most toxic air pollutants, black carbon, and will be useful in epidemiological investigations, biomonitoring studies as well as in occupational settings. The aim of the INCALO (INternal black CArbon LOading) project is to promote the output of the ENVIRONAGE project towards a process for facilitation and commercialization of internal markers of exposure to black carbon.

Mots-clés : biomonitoring,environmental epidemiology,exposomics,ambient air pollution
Projet ERC : preQFT (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Commissariat à l’énergie atomique et aux énergies alternatives — Pays : France — Rôle : PI
Acronyme de l'entité : CEA
Type d'entité : Recherche
Financement ERC de l'entité : 1299958.26 €

Ambitious Questions: * How does the relatively calm macroscopic universe survive and emerge from the violent quantum fluctuations of its underlying microphysics? * How do classical notions of space and time emerge from fundamental principles, and what governs their evolution? These questions are difficult to answer---perhaps impossible given current ideas and frameworks---but I believe a strategic path forward is to thoroughly understand the quantum predictions of our Yang-Mills and Gravity theories, and unambiguously identify their non-perturbative UV completions. The first step forward, and the goal of this project, is to move towards the trivialization of perturbative calculations. Consider the notion of failure-point calculations -- calculations that push modern methods and world-class technologies to their breaking-point. Such calculations, for their very success, engender the chance of cultivating and exploiting previously unappreciated structure. In doing so, such calculations advance the state of the art forward to some degree, dependent on the class of the problems and nature of the solution. With scattering amplitude calculations, we battle against (naive) combinatorial complexity as we go either higher in order of quantum correction ( loop order ), or higher in number of external particles scattering (multiplicity), so our advances must be revolutionary to lift us forward. Yet I and others have shown that the very complications of generalized gauge freedom promise a potential salvation at least as powerful as the complications that confront us. The potential reward is enormous, a rewriting of perturbative quantum field theory to make these principles manifest and calculation natural, an ambitious but now realistic goal. The path forward is optimized through strategic calculations.

Mots-clés : scattering amplitudes
Projet ERC : BIO-H-BORROW (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Manchester — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2337548.0 €

Amine containing compounds are ubiquitous in everyday life and find applications ranging from polymers to pharmaceuticals. The vast majority of amines are synthetic and manufactured on large scale which creates waste as well as requiring high temperatures and pressures. The increasing availability of biocatalysts, together with an understanding of how they can be used in organic synthesis (biocatalytic retrosynthesis), has stimulated chemists to consider new ways of making target molecules. In this context, the iterative construction of C-N bonds via biocatalytic hydrogen borrowing represents a powerful and unexplored way to synthesise a wide range of target amine molecules in an efficient manner. Hydrogen borrowing involves telescoping redox neutral reactions together using only catalytic amounts of hydrogen. In this project we will engineer the three key target biocatalysts (reductive aminase, amine dehydrogenase, alcohol dehydrogenase) required for biocatalytic hydrogen borrowing such that they possess the required regio-, chemo- and stereo-selectivity for practical application. Recently discovered reductive aminases (RedAms) and amine dehydrogenases (AmDHs) will be engineered for enantioselective coupling of alcohols (1o, 2o) with ammonia/amines (1o, 2o, 3o) under redox neutral conditions. Alcohol dehydrogenases will be engineered for low enantioselectivity. Hydrogen borrowing requires mutually compatible cofactors shared by two enzymes and in some cases will require redesign of cofactor specificity. Thereafter we shall develop conditions for the combined use of these biocatalysts under hydrogen borrowing conditions (catalytic NADH, NADPH), to enable the conversion of simple and sustainable feedstocks (alcohols) into amines using ammonia as the nitrogen source. The main deliverables of BIO-H-BORROW will be a set of novel engineered biocatalysts together with redox neutral cascades for the synthesis of amine products from inexpensive and renewable precursors.
Projet ERC : MANGO (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 1995523.0 €

Amyloid-like protein aggregation is a process of protein assembly via the formation of intermolecular β-structures by short aggregation prone sequence regions. This occurs as an unwanted side-reaction of impaired protein folding in disease, but also for the construction of natural nanomaterials. Aggregates appear to be strongly enriched in particular proteins, suggesting that the assembly process itself is specific, but the cross-seeding of the aggregation of one protein by aggregates of another protein has also been reported. The key question that I aim to address in this proposal is how the beta-interactions of the amino acids in the aggregate spine determine the trade-off between the specificity of aggregation versus cross-seeding. To this end, I will determine the energy difference between homotypic versus heterotypic interactions and how differences in sequence translate into energy gaps. Moreover, I will analyse the sequence variations of aggregation prone stretches in natural proteomes to understand the danger of widespread co-aggregation. To achieve these outcomes, I will study the interactions and cross-seeding of aggregating proteins and model peptides in vitro and in cells. I will extract the sequence and structural determinants of co-aggregation, and employ these to construct novel bioinformatics algorithm that can accurately predict co-aggregation and cross-seeding. I will use these to analyse co-aggregation cascades in natural proteomes looking for mechanisms that protect them from wide-spread cross-seeding. This work will have a significant impact on the understanding of the downstream effects of protein aggregates and may reveal co-aggregation networks in human diseases such as the major neurodegenerative diseases or cancer, potentially opening up new research lines on the mechanisms underlying these pathologies and thus identify targets for novel therapies.

Mots-clés : protein aggregation,amyloid,cross seeding,protein folding,prediction,protein sequence analysis,structural bio informatics
Projet ERC : MegaALS (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Karolinska Institutet — Pays : Suède — Rôle : PI
Acronyme de l'entité : KI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499196.0 €

Amyotrophic lateral sclerosis (ALS) is a rare but devastating neurodegenerative disorder that in lack of effective treatments leads to death within a few years of diagnosis. ALS is increasingly being recognized as a systemic disease affecting not only the central nervous system but also other physiological aspects. We hypothesize that there is a disease-specific interplay between metabolism, gut microbiome and adaptive immunity, which substantially contributes to the etiopathogenesis of ALS. The overarching aim of this project is therefore to explore such interplay, and to assess the effectiveness of a treatment regimen that specifically targets it. Using a population-based case-control study of ALS in Stockholm, I will first characterize the complex interactions between metabolism, microbiome, and immunity in ALS, through comprehensive proteomic, metagenomic and immune-response profiling. The specificity of these interactions will be tested in contrast to healthy individuals at high risk for ALS (siblings), individuals with similar environmental and lifestyle factors (spouses), and unrelated population-controls. I will then use an established ALS mouse model (SOD1G93A) to understand the usefulness of combining a high-caloric diet with a fecal microbiota transplant from healthy human donors in disease prevention and treatment. To better understand the underlying mechanisms, I will compare microbiome and immune-response profiles before and after the intervention. The proposed research is unique as it 1) combines innovative molecular platforms with a high-quality epidemiological study design, 2) uses a novel strategy of investigating multiple aspects of human physiology, and 3) offers a possibility to directly translate findings between human observational and animal experimental studies. The ultimate goal is to significantly advance our knowledge about ALS as a disease, and more importantly to identify novel and highly warranted preventive and therapeutic targets.

Mots-clés : amyotrophic lateral sclerosis,metabolism,gut microbiome,adaptive immunity,case control study,molecular epidemiology,transgenic model,fecal microbiota transplant,translational research
Projet ERC : MRI4DEEG (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Delft University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU Delft
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 12500.0 €

An EEG calibration toolkit for monitoring rehabilitation of stroke patients EEG records electric potential differences from electrodes attached to the human skin. Since it is a brain imaging technique that provides a direct measure of neural activity, it is an ideal device to monitor stroke rehabilitation. For instance, the amplitude of an EEG response to a fixed external stimulus on the wrist could act as a biomarker quantifying the number of active cells in the primary somatosensory cortex. In this way, an EEG system could work as a simple monitoring device rendering direct feedback to healthcare workers on the success of the applied therapeutic strategy. This would greatly help to select the most optimal therapy for the individual patient. However, with the current state of the art a direct comparison between EEG amplitudes of different subjects is not possible because these amplitudes are strongly affected by inter individual skull variations. In this PoC project a calibration step is proposed to reduce these influences on the EEG biomarker. We will develop a software toolkit, allowing to execute the required calibration step with a minimum of patient burden. We foresee that the prototype delivered by the end of the project can be developed into a commercial accessory EEG software device that can be provided to end users for relatively small add-on price. Best practices of EEG calibration will be disseminated by publications, presentations at conferences, a special workshop and business development activities.

Mots-clés : head models,conductivity,stroke
Projet ERC : HYPERION (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1759732.5 €

An emerging class of materials called hybrid perovskites is poised to revolutionise how power is both produced and consumed by enabling the production of highly-efficient, tunable solar photovoltaics (PV) and light-emitting diodes (LEDs) at exceptionally low cost. Although the efficiencies of perovskite devices are rising fast, both PV and LEDs fall short of out-performing current technology and reaching their theoretical performance limits. To achieve their full potential, parasitic non-radiative losses and bandgap instabilities from ionic segregation must be fundamentally understood and eliminated. HYPERION will address these issues by i) elucidating the origins of non-radiative decay and ion segregation in films and devices, ii) devising means to eliminate these processes, and iii) implementing optimised materials into boundary-pushing PV and LED devices. This will be achieved through a groundbreaking hierarchical analysis of the perovskite structures that not only characterises thin films and interfaces, but also the sub-units that comprise them, including grain-to-grain and sub-granular properties. The optoelectronic behaviour on these scales will be simultaneously correlated with local structural and chemical properties. HYPERION will use this fundamental understanding to eliminate non-radiative losses and ionic segregation on all scales through passivation treatments and compositional control. Addressing these knowledge gaps in the operation of perovskites will produce fundamental semiconductor science discoveries as well as illuminate routes to yield optimised and functional perovskites across the broad bandgap range 1.2–3.0 eV. These will be used to demonstrate all-perovskite tandem PV devices with efficiency exceeding crystalline silicon (26%), and white light LEDs with efficacies surpassing fluorescent light (50 lm/W). The work will realise the promise of perovskite technology as a versatile and scalable energy solution to secure a sustainable future.

Mots-clés : photovoltaics,light emitting diodes,metal halide perovskites
Projet ERC : PregnantBrain (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1494393.0 €

An expectant mother’s brain undergoes dramatic structural remodeling during pregnancy. These changes are thought to be elicited by hormones, orchestrating the behavioural and physiological adaptations necessary for infant care. Despite the scale of these effects, we know little about the neural mechanisms by which pregnancy affects the brain. Recent methodological advances now offer the exciting opportunity to address these questions. This project will use a multidisciplinary approach to uncover the molecular, cellular and circuit-level mechanisms of pregnancy hormone action in a mouse model. We will first focus on which aspects of parenting, feeding and aggression are affected by pregnancy – and over which time course these behavioural adaptations occur. This will provide important clues about the nature of underlying neural plasticity mechanisms. Next, we will determine which nodes of the circuits controlling these behaviours are sensitive to pregnancy hormones. This will then allow us to address the functional consequences of pregnancy at the network level, using in vivo calcium imaging approaches. Finally, we will study the biophysical and cellular mechanisms underlying pregnancy hormone action in genetically defined neurons, through a combination of electrophysiology and transcriptomic profiling. By integrating these complementary lines of evidence, we aim to obtain a mechanistic understanding of the neural adaptations occurring during pregnancy. I believe that these innovative studies will generate novel and highly generalizable insights into how physiological states shape information processing in the brain.

Mots-clés : neural circuits,hormones,pregnancy,parental behaviour,neuromodulation,neural plasticity,physiological state,internal state,feeding,aggression