Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : GLYCONOISE (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
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 : 432656.89 €

The surface of every living cell is covered with a dense matrix of glycans. Its particular composition and structure codes important messages in cell-cell communication, influencing development, differentiation, and immunological processes. The matrix is formed by highly complex biopolymers whose compositions vary from cell to cell, even between genetically identical cells. This gives rise to population noise in cell-cell communication. A second level of noise stems from glycans present on the same cell that disturb the decoding of the message by glycans binding receptors through competitive binding. Glycan-based communication is characterized by a high redundancy of both glycans and their receptors. Thus, noise and redundancy emerge as key properties of glycan-based cell-cell communication, but their extent and function are poorly understood. By adapting a transmitter-receiver model from communication sciences and combining it with state-of-the-art experimental techniques from biophysics and cell biology, we will address two fundamental questions: What is the role of the redundancy in glycan-based communication? How much ‚noise’ can it tolerate, before the message is lost? To do so, we first establish a simplified model system for glycan-based communication. Biophysical rate constants are determined for lectin-glycan interactions and expanded to glycosylated microparticles that trigger a biological response in lectin expressing receiver cells. Next, single cell glycomes are reconstructed from ultra-high dimensional flow cytometry data using lectin mixtures enabled by recent advancements in instrumentation and glycobioinformatics software. Glycomes accessible on single cell level allow replacing the microparticles with transmitter cells and employ a cell-cell interaction model. Our transmitter-receiver model is used to quantify the noise and reveals how redundancy provides robustness of messaging by cell surface glycans in cellular communication.
Projet ERC : WATCH (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : CO-PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 4243750.0 €

The survival of an organism depends on energy homeostasis, involving the control of neuroendocrine functions that integrate metabolic feedback and adapt the response of the organism to physiological demands. Tanycytes, specialized glial cells lining the floor of the third ventricle in the median eminence of the hypothalamus, act as linchpins of these processes, dynamically controlling the secretion of neuropeptides by hypothalamic neurons into the pituitary portal circulation and regulating blood-brain and blood-cerebrospinal fluid exchanges, both processes that depend on their morphological plasticity in response to the physiological state. In addition to their barrier properties, they actively shuttle circulating metabolic signals to hypothalamic neurons that control food intake. The overarching goal of WATCH is to synergistically employ state-of-the-art technologies in systems neuroscience, mouse genetics and bench-to-bedside research, to explore the role of these unique and versatile cells, providing new directions in biomarker research and new therapeutic approaches for a variety of disorders that impair well-aging. Our specific aims are: 1. Genetic dissection of the in vivo regulation, pathophysiological function and molecular markers of tanycytes classified according to their anatomical location. 2. Identification of novel heterogeneous, molecularly distinct tanycytes and associated endothelial cells and determining how these characteristics evolve under distinct physiological and pathological conditions. 3. Functional validation of newly classified subgroups of tanycytes and the specific modulation of the activity of these subgroups at the experimental level. 4. Exploration of the functional consequences of pharmacologically activating pathways required for the tanycytic shuttling of metabolic signals on their CSF levels of these factors, hypothalamic activity and cognition in animal models and patients with morbid obesity or age-related cognitive deficits.

Mots-clés : tanycytes,energy homeostasis,hypothalamo pituitary neuroedocrine axis,aging,neurodegenerative disorders,hypothalamus
Projet ERC : EVEREST (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : National University of Ireland — Pays : Irlande — Rôle : PI
Acronyme de l'entité : NUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499925.0 €

The therapeutic benefits of mesenchymal stem cells (MSCs), the state-of-the-art treatment for healing bone defects following trauma, resection of cancerous bone tumors, or metabolic bone diseases, has been attributed to their secreted factors. The regenerative potential of MSC-secreted extracellular vesicles (EVs), nanoparticles which deliver bioactive cargo (nucleic acids, proteins, and lipids) between cells, has recently been reported. The applicant will embark upon frontier research with the objective of progressing beyond the state-of-the-art, by harnessing the therapeutic effects of MSCs, but in a cutting-edge, cell-free manner, by developing high potency EV-based bone replacements. This objective will be addressed by firstly testing novel hypotheses to delineate how culture environments, specifically mechanical cues (substrate elasticity and 3D dynamic), hypoxia, and cell stress can modulate the cargo of EVs secreted by MSC. Size exclusion chromatography, which separates EVs from soluble proteins will be employed. Heterogeneity of EV cargo and functionality between human MSC donors will also be evaluated. Answering these hypotheses will permit the intelligent design of targeted EV therapies. The hypothesis that EV-functionalized constructs, fabricated by 3D-printing, will lead to controlled and sustained release of EVs and induce bone formation in vivo will best tested. Together, this will answer critical questions, namely the most favorable environment for collection of potent EVs for regenerative medicine, which secretome component (EV, soluble factors) is responsible for bone regeneration, and whether MSC cell therapy can be replaced by cell-free EVs. EVEREST will develop a platform for targeted EV delivery in ground-breaking, easy to transport and handle, ‘off-the-shelf’ anatomically correct constructs, which have the potential to reduce pain by elimination of bone or bone marrow harvest, and revolutionize the treatment of bone defects.

Mots-clés : regenerative medicine,bone regeneration,extracellular vesicles,tissue engineering,bioengineering,3d printing
Projet ERC : SMOOTH (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Euro-Mediterranean Center for Climate Change — Pays : Italie — Rôle : Partner
Acronyme de l'entité : CMCC
Type d'entité : Recherche
Financement ERC de l'entité : 369368.75 €

The threat of climate change calls for a rapid transition to a low-carbon society. Aligning the financial system with climate stability is a crucial prerequisite for achieving decarbonisation while preserving economic prosperity and societal welfare. However, we currently lack a comprehensive understanding of how the institutional and behavioural features of financial systems may affect the speed and shape of the low-carbon transition. Additionally, the coevolving socioeconomic, financial and environmental repercussions of such a large-scale societal transformation have not yet been systematically analysed. The SMOOTH project will lay the foundations of an innovative macro-financial analytical framework to provide essential insights on the links between financial systems and decarbonisation dynamics. Methodologically, I will introduce a breakthrough by linking macroeconomic analysis with an original evidence-based representation of investment decisions based on forward-looking expectations of transition pathways. In the course of five years, this integrated modelling framework will enable the first comprehensive assessment of the transition financial drivers and obstacles, and their implications for growth, financial stability, employment, private/public debt and functional distribution, with a focus on Europe. Building on this knowledge, a harmonised set of policies aimed at achieving a rapid and smooth transition can be designed. I will go beyond the current state of the art by integrating the analysis of fiscal policies with monetary policies and financial regulation, and investigating their institutional requirements and implications. SMOOTH will create a new interdisciplinary field of research integrating elements from macroeconomic modelling, climate economics, behavioural finance, socio-technical transition theory and political science, lifting the analytical power of transition modelling to a new level and opening up novel avenues for future research.

Mots-clés : low carbon transition,decarbonisation pathways,sustainable finance,climate related financial risks,stranded assets,macroeconomic modelling,expectations,behavioural finance,planning horizon,investment decisions,central banking,financial regulation,policy design,political economy
Projet ERC : FuncDis3D (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
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 : 1997425.0 €

The three-dimensional organization of the genome inside the nucleus (3DG) is crucial for gene regulation. Although the fundamental building blocks of the 3DG have been identified, how they contribute to gene regulation is incompletely understood. In recent years my lab has started to functionally dissect the 3DG in order to understand the effects on gene expression. The current proposal intends to expand this work and aims to i) broaden the array of proteins that are known organize the 3DG, ii) determine how loss of these proteins affects the 3DG and iii) elucidate how this influences gene expression. The key to this is to induce changes in the 3DG by acute protein depletion and measuring changes over time. We have preliminary data showing that by depleting regulators of the 3DG we can induce changes within a few hours. We will deplete a range of proteins in pluripotent and differentiated cells to determine their contribution to 3DG organization. Simultaneous characterization of the epigenome and transcriptome will allow us to determine the sequence of changes. In addition, we will perform Thousands of Reporters Integrated in Parallel (TRIP) after perturbation of the 3DG. TRIP reporters all have the same minimal promoter that acts as a sensor for promoter-enhancer (mis)-communication. By combining TRIP with 4C we can measure the changes in the reporter-enhancer interaction landscape. Our data will generate fundamental insight into the parameters that govern the interactions between promoters and regulatory elements, within the context of the 3DG, and their effects on gene expression. Furthermore, it allows us to determine the temporal order of changes in the 3DG, the epigenome and gene expression, which is essential for the establishment of cause-and-effect relationships. Collectively, our data will lead to a better appreciation of how distal and proximal regulatory regions cooperate to establish cell-type specific gene expression programs.

Mots-clés : 3d genome,acute protein depletion,hi c
Projet ERC : M3M (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

The topic of this proposal is mobile 3D modeling. Building on top of 4DVideo results published at the latest International Conference on Computer Vision (ICCV2013), the goal of this proposal is to explore the commercial potential of enabling mobile 3D scanning with smart phones. Our algorithms allow to perform accurate 3D modeling from images at interactive rates on a smart phone (without requiring any additional sensors or a live data connection). Our solution can greatly expand the range of applications requiring 3D models (e.g. 3D printing) and enable completely new applications to be developed which would rely on anytime, anywhere scanning capabilities. The goal of this project is to adapt and explore potential commercialization of our solution in the particular case of face reconstruction. Potential applications would be in the area of 3D authentication, 3D printing or medical diagnosis. This proposal addresses both engineering improvements that are required to reach market maturity, as well as business aspects of the commercialization including intellectual property protection and market consolidation.

Mots-clés : 3d scanning,3d reconstruction,mobile computer vision
Projet ERC : TarMyc (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Würzburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497905.0 €

The transcription factor Myc plays a central role in tumourigenesis but was deemed undruggable due to it being an essential protein. However, recent proof-of-principle studies in mice using a dominant negative allele of Myc demonstrated the dependency of established tumours on Myc function and showed that mice tolerated Myc inhibition to a degree that allowed tumour regression. In line with these observations my group found Myc to regulate distinct sets of genes at low, physiological and high, oncogenic levels, because promoters differ in their affinity for Myc. This notion implies the compelling possibility to specifically target the oncogenic functions of Myc. TarMyc aims to address four key questions required to bring this new concept from bench to bedside. Firstly, TarMyc will estimate the therapeutic window of Myc inhibition in vivo by expressing shRNAs against Myc in mice with established solid tumours. Secondly, TarMyc aims to identify in vivo Myc target genes crucial for tumourigenesis. Thirdly, this proposal aims to elucidate the role of Myc’s differential promoter affinity in untransformed cells. Analysis of published gene expression datasets revealed Myc binding to low-affinity promoters during the process of tissue regeneration. Thus, by characterizing the regeneration programme induced by Myc we hope to gain further insight on the therapeutic window of Myc inhibition and assess potential side-effects in a Myc-targeting anticancer therapy. Fourthly, we aim to develop strategies to interfere with the oncogenic functions of Myc by (i) developing a novel class of drugs that reduce Myc’s cellular concentrations, and (ii) by testing the therapeutic potential of Myc target genes by inhibiting their function in tumour models. Taken together, TarMyc takes on the challenge of inhibiting the oncogenic functions of Myc in a highly multidisciplinary approach using state-of-the-art molecular biology, advanced tumour models and new concepts in drug development.

Mots-clés : cancer,therapeutic window,protacs,organoids,transcription factor,gene regulation,chip sequencing,rna sequencing
Projet ERC : TWIST (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 686849.44 €

The translation of chirality from molecular to bulk inorganic systems opens many possibilities for new phenomena. The properties of chiral electronic states are interesting scientifically and attractive for applications. While optoelectronic properties of semiconductors are controlled by charge, magnetic materials function by spin. If a material can combine these functionalities, powerful novel applications and large gains in performance are possible in opto-spintronics. Yet, existing magnetic semiconductors often show lower optoelectronic quality or work at low temperature. Development of new systems is a scientific challenge due to the required coordination of spins and control of physical properties of excited states, while minimizing defects. TWIST will demonstrate novel highly-luminescent semiconductors for spin-control and chiral emission that show combined properties of ferromagnets and excellent semiconductors for efficient spin-LEDs at room temperature. To achieve this, TWIST will develop new approaches to control spin and chirality in doped metal-halide perovskites (MHPs) with magnetic elements and molecules, also in chiral superstructures. In 2014, I reported that MHPs are exceptionally bright emitters, which underpins their tolerance to defects and chemical variation, and which recently enabled remarkable doping with transition-metals. Optical spin-control and chiral emission are possible from spin-orbit coupling and Rashba effects, which will enhance spin-order for Curie temperatures towards room temperature. These exceptional properties of MHPs, which have already produced efficient solar cells and LEDs, provide now a unique opportunity for my project. TWIST will use state-of-the art optical and electronic techniques to unravel the fundamental mechanisms how magnetic moments, light and chiral states order and interact in MHPs. The results of TWIST will instigate opto-spintronic applications with novel functionality and lower energy consumption.

Mots-clés : dilute magnetic semiconductors,sustainable materials,chirality,magnetism,optoelectronics,high resolution ultrafast spectroscopy
Projet ERC : WHOLENICHE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

The tumour microenvironment or niche is the vital non-cancerous compartment of the tumour structure. Thus, targeting its tissue-derived cells represents a promising avenue to better therapeutic interventions. However, knowledge about the tissue cells taking part of the tumour niche during early cancer development and later progression is lagging behind due to the difficulty of analysing and following early tissue changes in the surrounding of cancer cells in vivo. In our research proposal we will use a combination of original tools developed in the lab and state of the art technologies to overcome some of these constraints and expand our understanding of which cells in the niche support early cancer cell growth. We also aim to reveal their mechanism of action and identify approaches to block the niche supportive activity. Our five-year plan has three main objectives (I, II, III), which we will meet using two original strategies. With the first strategy we will visualize the early tumourigenic niche in vivo. This will allow us (I) to identify and characterize novel cellular components during dynamic niche evolution both in the context of metastatic colonization as well as during primary tumour onset. We will also use this original approach (II) to deepen our understanding of neutrophils in cancer, a particularly crucial emerging component of the cancer niche, whose role is still debated. After dissemination, cancer cells may encounter an unfavourable niche, failing to start colonization and remaining dormant within the tissue. However, the quiescent-permissive tissue can change, cancer cells reactivate and form metastases even a long period after tumour resection. Little is known about the changes in the niche of dormant cells capable of triggering their reactivation. With the second strategy we will generate an in vivo a controllable, dormant-permissive tissue (III) to screen for potential signals triggering dormant cells reactivation.

Mots-clés : tumour microenvironment
Projet ERC : e-See (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1923958.0 €

The ultimate goal of device miniaturization is to rely on a single charge provided by a single dopant atom: solotronics. Currently the gate length in a transistor cannot be reduced beyond 10-12 nm, as variability between nominally identical devices reaches unacceptable levels. Elaborate quantum transport experiments can monitor the presence and spin state of a single charge, but do not provide information about location and distribution (wavefunction) of the charge or the local chemical and crystallographic environment. The latter, however, determine why the charge is present at a specific location with a particular distribution. Scanning probe techniques can measure charges but are restricted to the near surface region. In contrast, the phase of an electron in transmission electron microscopy (TEM) can probe the sample volume and is sensitive to charge. The target of the e-See project is the first real time observation of the wavefunction associated to a single electron charge in the volume of a device with atomic resolution. I aim to implement low temperature quantum transport experiments in a TEM to allow simultaneous electrical manipulation of this charge. Combined visualization and manipulation of a single charge trapped by Coulomb blockade in a transistor will (i) identify the origins of device variability, and (ii) show how the local properties of the sample affect localization of a single charge and its wavefunction. The project impact involves understanding of variability, improving device design and creation of a new research field on low temperature electrical in situ TEM experiments. It will provide the tool to visualize a single charge wavefunction in any device, enabling ultimate device engineering: deterministic 3D atomic scale control of the position of charge localization. To this end, I will use electron holography and scanning TEM, develop a low temperature electrical TEM sample holder, and novel sample preparation.

Mots-clés : single charge,transmission electron microscopy  tem,devices