Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : UVdynamicsProtection (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1971875.0 €

The human body takes different measures in order to protect itself against the results of UV exposure and its accompanied hazards, such as skin cancer. Despite extensive studies regarding the molecular regulation of the two main UV protection mechanisms, namely, the DNA repair system and the pigmentation system, a comprehensive theory that simultaneously accounts for the two systems is still missing. Hence, the ground-breaking goal of this proposal is to elucidate, for the first time, the dynamic control used to schedule and synchronize the UV protection subsystems. Since these two systems serve the same physiological purpose, but on different time scales (DNA repair takes minutes, while pigmentation lasts hours to days), I propose to take the novel approach of focusing on their timing as an opportunity to uncover their regulation. As a first step, we exposed human and mouse skin to UV and found that UV exposure at 48hr intervals resulted in higher skin pigmentation than did exposure at 24hr intervals, even after controlling for total UV dosage. Furthermore, we found that the expression level of the melanocyte central regulator, MITF, exhibits damped oscillatory behaviour during this 48hr interval. I therefore hypothesize that the dynamic behaviour of the central regulator dictates the UV–response timing of the two protection systems. In the proposed research, I will take a holistic approach and address this issue from three complementary perspectives: (1) transcriptional dynamics, (2) temporal effects on cellular output, and (3) DNA repair after UV. This will be achieved by utilizing and developing new experimental and analytical tools that will allow us to correlate the temporal behaviours of a wide set of molecular markers. Reaching our goals will provide a breakthrough in our understanding of skin protection from UV and the underlying mechanisms that control it. These findings may offer exciting new avenues for future skin cancer prevention.
Projet ERC : Breakborder (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : NKI-AVL
Type d'entité : Recherche
Financement ERC de l'entité : 2497000.0 €

The human genome carries genetic information in two distinct forms: Transcribed genes and regulatory DNA elements (rDEs). rDEs control the magnitude and pattern of gene expression, and are indispensable for organismal development and cellular homeostasis. Nevertheless, while large-scale functional genetic screens greatly advanced our knowledge in studying mammalian genes, such tools to study rDEs were lacking, impeding scientific progress. Interestingly, recent advance in genome editing technologies has not only expanded the available screening toolbox to examine genes, but also opened up novel opportunities in studying rDEs. We distinguish two types of rDEs: Transcriptional rDEs that recruit transcription factors to enhancers, and structural rDEs that maintain chromatin 3D structure to insulate transcriptional activities, a feature postulated to be essential for gene expression regulation by enhancers. Recently, we developed a CRISPR strategy to target enhancers. We showed its scalability and effectivity in identifying potential oncogenic and tumour-suppressive enhancers. Here, we will exploit this line of research and develop novel strategies to target structural rDEs (e.g. insulators). By setting up functional genetic screens, we will identify key players in cell proliferation, differentiation, and survival, which are related to cancer development, metastasis induction, and acquired therapy resistance. We will validate key insulators and decipher underlying mechanisms of action that control phenotypes. In a parallel approach, we will analyse whole genome sequencing datasets of cancer to identify and characterize genetic aberrations occurring in the identified regions. Altogether, the outlined research plan forms a natural extension of our successful functional approaches to study gene regulation. Our results will setup the foundation to better understand principles of chromatin architecture in gene expression regulation in development and cancer.

Mots-clés : non coding genome,chromatin architecture,functional genetic screens,cancer
Projet ERC : ExpoBiome (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Luxembourg — Pays : Luxembourg — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998620.0 €

The human gut microbiome is a complex ecosystem, which contributes essential functions to human physiology. Changes to the microbiome are associated with several chronic diseases characterised by inflammation, including neurodegenerative and autoimmune diseases. Microbiome-derived effector molecules comprising nucleic acids, (poly)peptides and metabolites are present at high levels in the gut but have so far eluded systematic study. This gap in knowledge is limiting mechanistic understanding of the microbiome’s functional impact on chronic diseases such as Parkinson’s disease (PD) and rheumatoid arthritis (RA). Here, I will for the first time integrate a combination of advanced high-resolution methodologies to comprehensively identify the constituents of this molecular complex and their impact on the human immune system. First, I will perform a quantitative, integrated multi-omic analysis on microbiome samples collected from healthy individuals and patients with newly diagnosed PD or RA. I will integrate and analyse the data using a newly developed knowledge base. Using contextualised prior knowledge (ExpoBiome Map) and machine learning methods, I will identify microbial molecules associated with condition-specific immunophenotypes. Second, I will validate and track the biomarker signature during a model clinical intervention (therapeutic fasting) to predict treatment outcomes. Third, microbes and molecules will be screened in personalised HuMiX gut-on-chip models to identify novel anti-inflammatory compounds. By providing mechanistic insights into the molecular basis of human-microbiome interactions, the project will generate essential new knowledge about causal relationships between the gut microbiome and the immune system in health and disease. By facilitating the elucidation of currently unknown microbiome-derived molecules, it will identify new genes, proteins, metabolites and host pathways for the development of future diagnostic and therapeutic applications.

Mots-clés : chronic diseases,data integration,fasting,health,immune system,inflammation,microbiome,omics,organ on a chip,parkinson s disease,rheumatoid arthritis
Projet ERC : ADIPOR (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 1989518.0 €

The human kind is witnessing an escalation of obesity-related health problems such as cardiovascular diseases and type 2 diabetes. A recent groundbreaking study revealed adiponectin receptors (ADIPOR) as key targets for treating such obesity-related diseases. Indeed, the modulation of this integral membrane protein by small molecules agonists ameliorates diabetes and prolongs lifespan of genetically obese rodent model. Despite these exciting results and the importance of ADIPOR in human physiology, there is a complete lack of knowledge of ADIPOR mechanisms of action and pharmacology. This is mainly due to the challenges associated with the characterization of membrane protein structure and function. To fill this gap of knowledge and based on my extensive experience in membrane protein biology, I propose here to characterize the the proximal signaling pathways associated with ADIPOR activation as well as the molecular and structural mechanisms of ADIPOR activation. We will develop an innovative integrated strategy combining state-of-the-art molecular and structural pharmacology approaches including 1) molecular analyses of ADIPOR network of interaction using resonance energy transfer measurement in living cells and a proteomic analysis and 2) structural analyses of ADIPOR and signaling complexes using biophysics and X-ray crystallography. Our data will have a major impact on drug discovery for treating obesity-related diseases as it will enable the application of structure-based drug design and in silico screening for the molecular control of ADIPOR activity. The proposed high-risk endeavor of obtaining structural data on these atypical membrane signaling complexes is a new direction both for my career and for the field of adiponectin biology; the exceptionally high gain from these studies fully justifies the risks; the feasibility of this project is supported by my recent success in membrane protein pharmacology, biochemistry, biophysics and crystallography.
Projet ERC : CAPSID (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Vienna — Pays : Autriche — Rôle : PI
Acronyme de l'entité : Univie
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1992240.0 €

The human microbiome has been increasingly in the focus of research for its importance in human health and disease. Yet, the viruses (phages) infecting these microbiota have gained much less attention. The majority of phages reside integrated in the genomes of their microbial hosts as so called lysogenic prophages. Often, these prophages encode important toxins and other virulence related factors that, while they are beneficial to their microbial hosts, may be detrimental for the infected human. Prophages can be induced under certain conditions to resume a lytic lifestyle resulting in the production of virus particles and often in the destruction of the host cell. Frequently, however, phage induction also leads to increased production of virulence factors. In this project, we aim to uncover small molecules modulating phage induction. We will explore to what extent microbial metabolites of human microbiota act as native triggers or inhibitors of phage induction and shape the complex interspecies interactions in the microbiome. The corresponding phage inducing or dysregulating metabolites will be isolated to elucidate their chemical structure and unveil their molecular targets. We will develop chemical tools to dissect and interrogate the responsible mechanisms and finally develop customized synthetic modulators that allow us to achieve control over the activity of phage-microbe systems with specific medical relevance. The integrated approach of the CAPSID project will provide first comprehensive insights into the chemistry of microbe-phage interactions and allow to assess its role for infectious diseases and its potential for customized treatment of microbial pathogens.

Mots-clés : microbial metabolites,natural product analysis,chemical probes,phage induction
Projet ERC : HyDream (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Münster — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WWU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2495000.0 €

The hydrogenation of ketones and olefins is one of the oldest synthetically used transformations. The reaction is highly sustainable and its value has been acknowledged by two Nobel Prizes. In contrast, the hydrogenation of arenes is still underexplored due to the high kinetic barrier caused by aromaticity. However, the selective arene hydrogenation constitutes a dream reaction for use in an ideal synthesis: The transformation is straightforward, uses readily available substrates, and is able to build-up an astonishing amount of complexity, with the potential to form multiple defined sterocentres, in a single step. With our first paper on selective arene hydrogenation published in 2004, we became pioneers in this field and have continuously made important contributions using metal–carbene complexes. As a world-leader in this area and with expertise in several relevant fields of catalysis, we are perfectly suited to convert arene hydrogenation into a reliable and general transformation within the frame of this project. We will provide rapid access to sought-after motifs and consequently will enable breakthroughs in material and life sciences. Key to our success will be the design of strongly electron-donating carbene ligands and deep mechanistic understanding. Specifically, we will develop solutions for the problematic hydrogenation of heteroatom-substituted arenes, and heteroarenes. Utilising the soluble nature of a homogenous catalyst, we also envision applications in the hydrogenation of polymers, offering direct access to new materials. Furthermore, the use of syngas is expected to allow for the development of a merged hydrogenation-hydroformylation reaction to yield highly functionalised cyclohexanes in a single step from minimally functionalised arenes. Finally, we aim to develop chiral versions of our highly reactive metal–carbene catalyst to enable the previously unknown but highly desirable enantioselective hydrogenation of benzene derivatives.

Mots-clés : hydrogenation,enantioselective catalysis,chemoselective catalysis,photochemistry,c h activation,saturated  hetero cycles,functional molecules,polymers,drugs
Projet ERC : Secret-Cells (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Medical University of Vienna — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2422698.0 €

The hypothalamus is an essential interface among neuroendocrine, autonomic and somatomotor systems, allowing dynamic bodily adaptations to environmental cues via the orchestration of complex physiological processes. Hypothalamic nuclei exhibit unprecedented molecular, structural and functional diversity of neurons, reflecting the breadth of neuroendocrine output. To date, a significant portion of hypothalamic neurons remains unaccounted for given the lack of identity markers. For known hypothalamic neuron subtypes, their ability to undergo stimulus-dependent expressional switches challenge their neurotransmitter- and neuropeptide-based classifications. These gaps of knowledge limit conceptual advances on neuronal loci, dynamic synapse recruitment and network hierarchy for metabolic control, and the molecular origins of disease. We have established the single cell transcriptome landscape of the paraventricular nucleus including its magno- and parvocellular domains. We will use this template to reveal novel cell identities and cell-state switches upon acute stress. We describe >25 neuronal subtypes under stress-free conditions, surpassing the resolution of any prior approach. Thus, we will resolve neurotransmitter-neuropeptide relationships at the single neuron level, with a focus on corticotropin-releasing hormone (CRH), determine biophysical parameters of CRH co-release with a fast neurotransmitter, and decipher changes to afferent organization upon stress. A novel parvocellular subclass constitutively expresses secretagogin, a calcium-sensor, which is indispensable for CRH release. We will link secretagogin loss-of-function in CRH neurons to Addison’s disease (chronic adrenal insufficiency associated with insulin resistance). Moreover, we propose a (pro-)hormone-like role for secretagogin released from CRH neurons into the circulation. Overall, our work program will produce new understanding on cellular diversity and organizational rules in the hypothalamus.

Mots-clés : stress,exocytosis,hormonal axis,transcriptome analysis,systems neurobiology
Projet ERC : iMPACT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 775000.0 €

The iMPACT project focuses on the realization of a proton Computed Tomography (pCT) scanner capable of acquiring a target full 3D image with 1s exposure, therefore opening the way to the practical application of proton imaging technique in medical radiotherapy treatments. Such cutting-edge particles scanner combines innovative ideas devised for the future High Energy Physics experiments together with original developments in the microelectronic field to enable charged particles imaging at the GHz scale. In recent years the use of hadrons (1H and 12C ions) for cancer radiation treatment has become an established technique and many facilities are currently operational or under construction worldwide. To fully exploit the therapeutic advantages offered by hadron therapy, precise target (body) imaging for accurate beam delivery is decisive. pCT systems, currently in their R&D phase, provide the ultimate in low dose (< 2 mGy), 3D imaging for hadrons treatment guidance. Key components of a pCT system are the detectors used to track the protons and measure their residual energy. The iMPACT scanner, composed by a proprietary monolithic pixels tracking detector and an innovative achromatic calorimeter, will improve current pCT imaging speed by more than a factor 100, leading to potential recording times of about 1 second for a full 3D target image (compared to present ≈ 10 minutes). The iMPACT detector will also have higher spatial resolution (equal or better than 10 µm) and lower material budget (by a factor 10) respect to state of the art systems, further enhancing 3D imaging accuracy. Not least when considering actual industrial application, production costs will be far lower than existent systems, because all sensors will be designed with commercially available technologies, making it possible to move pCT from the academic research realm to that of viable medical equipment.

Mots-clés : proton tomography,cmos pixel sensors
Projet ERC : OWidgets (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : University of Sussex — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149903.0 €

The idea for this proposal is to demonstrate the design of olfactory widgets (OWidgets) as a proof-of-concept implementation based on the semantic integration of smell to convey specific information to the user. We will showcase the meaningful design of OWidgets in two distinct markets. Widgets are well established as simple application extensions, integrated in a larger application and usually pre-installed on a device. Widgets allow quick access to information without requiring a user to open the application that manages this information. OWidgets will expand the existing range of widgets and provide users with a new non-existing layer of information delivery through smell, and consequently allow the creation of novel experiences in various application contexts.

Mots-clés : human computer interaction,smell as interaction modality
Projet ERC : LactaDiff (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
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 : 1999868.0 €

The idea has emerged that compartmentation of brain lactate, i.e. its distribution between different cell types and the extracellular space, plays a critical role in neurotransmission and brain plasticity. Dysregulations of lactate metabolism have also been reported in neurodegenerative diseases such as Alzheimer's disease. However, these notions remain challenged, and even fundamental mechanisms such as the astrocyte-to-neuron lactate shuttle, whereby astrocytes are supposed to export lactate to neurons to sustain neuronal energy needs, are still fiercely debated. This is largely due the lack of tools to evaluate cell-specific compartmentation of lactate in the living brain, in particular in Humans. In this project, we will develop new nuclear magnetic resonance spectroscopy techniques to non-invasively measure lactate diffusion, including in cortical regions. We will then take advantage of the unique ability of these methods to differentiate between metabolites diffusing in different environments, based on diffusion properties imposed by the microstructure, to quantify lactate in the extracellular space and, most importantly, in neurons and astrocytes. After validation in rodent models, these methods will be transposed on a clinical MRI system at ultra-high magnetic field, to gain unprecedented access to lactate compartmentation in the Human brain and its modifications during brain activity, plasticity, and in Alzheimer's disease. This will open a new research field for magnetic resonance spectroscopy in vivo.

Mots-clés : magnetic resonance spectroscopy,novel nmr sequences,diffusion,diffusion modeling,numerical simulations,lactate,brain metabolites,astrocyte,neuron,lactate shuttle,biomarkers,alzheimer
Projet ERC : MMP (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 147753.0 €

The idea that is presented is the commercialization of a multiparametric probe for monitoring in real time environmental variables in drilling boreholes which was designed and tested during the development of the ERC project IPBSL 250350 and able to perform in hostile environments (acidic pH, high concentration of oxidants, high pressure). The main difference between our prototype and the already existing commercial multiparametric probes is the number of measurable parameters, its control and transmission in real time to long distances and the flexibility to use different probes to obtain measurements at different depths of the borehole at the same time. The multiparametric probes already exiting in the market are restricted by the need to operate at low pressures, due mainly to the use of glass chemical sensors which have serious drawbacks such as the need of frequent maintenance, large size and limited range of operative pressures. To solve these problems we are using solid state sensors, ISFETs, carbon nanotubes and optical sensors which reduce the final size of the probe and extend the functioning period, increasing the range of scenarios in which can perform. The improvements that we plan to implement are the miniturization of the probe and improvement of its felxibility for its use in different areas of interest. Different experts from geophysical, geological, mining prospection, environment and space exploration have shown their interest in using our multiparametric adaptable probe. The plan of activities presented is affordable taking in consideration the experience of the proposing team.

Mots-clés : multiparametric probe,drilling boreholes,real time,physicochemical variables