Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SIMPHONICS (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and Communication Engineering
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 : 1499395.0 €

Reading biomolecular signatures and understanding their role in health and disease is one of the greatest scientific challenges in genome and proteome biology. Yet, complete protein analysis at the single-molecule level remains an unmet milestone. This pursuit is fundamentally hindered by the huge dynamic range of protein expression in cells and the insufficient spatio-temporal resolution of current analysis methods. Next-generation single-molecule techniques that can precisely manipulate and sequence proteins in space and time are urgently needed to reach this goal. Among these, nanopore platforms are at the forefront, leading in terms of read length, throughput and sensitivity. However, the major challenges associated with translocation speed control and the precise-readout in solid-state nanopore devices, remain prohibitive. In SIMPHONICS, I will resolve these issues by developing the first integrated platform that combines nanopore transport measurements, spatially modulated acoustic wavefields and single-molecule fluorescence time traces to confine, scan and optically fingerprint proteins in a non-invasive and massively parallel manner. The feasibility of this method will be established by attaining three main objectives: 1) Confining and controllably manipulating individual molecules using acoustic nanotweezers; 2) On-demand engineering of 2D material optical emitters as ultrabright fluorescent probes for energy transfer based detection, and 3) Identifying proteins/peptides from their optical signatures in multi-color Förster resonance energy transfer (FRET) during acoustophoresis. With this powerful and unique platform, I will harness the vast potential of acousto-photonic interactions in monolithic nanopore devices. Successful achievement of the project objectives will result in a high-throughput and non-destructive protein fingerprinting platform and signify a considerable leap forward in our quest to unravel the human proteome.

Mots-clés : nanopores,2d material photophysics,biophysics,acoustofluidics,protein fingerprinting,single molecule techniques
Projet ERC : INTERACT (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and Communication Engineering
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 : 1499999.0 €

Thanks to developments in computing, sensing and communication technology, great progress has been made in the control of robots affixed to the factory floor, mobile robots in controlled environments, and self-driving cars in medium-complexity environments. However, mobile robots are not yet capable of seamless interaction in human populated environments, primarily due to the high complexity of modeling and reasoning over the effect that robot actions have on other robots and humans, and the inherent uncertainty. Humans rely on intuition, namely the ability to understand interaction instinctively, without the need for conscious reasoning. However, for control systems it is notoriously difficult to model intuition, and to do so with safety guarantees with respect to physical constraints. My goal is to provide mobile robots with the ability to reason about their coordination with other agents and the associated risks, take appropriate actions and continuously reassess.  I will reach this goal by developing an innovative approach across the boundaries of Motion Planning, Multi-Robot Task Assignment and Machine Learning. In INTERACT I propose a holistic view on the interaction of mobile robots and humans, where I will consider multiple spatio-temporal granularities ranging from individual interactions to the interaction of a robot fleet with humans in a city, and from short term (local) to long term (global) effects of the interaction. Robots will use past experience to learn local and global intuition models of their interaction with the environment. These intuition models will be integrated in novel uncertainty-aware optimization methods to compute safe interaction-aware trajectories, task assignments and routes for mobile robots.  INTERACT will lay the foundation for intuitive multi-robot interaction, make it possible for teams of mobile robots to safely interact in human-centric environments and enable a new level of automation in factories and cities.

Mots-clés : multi robot systems,motion planning,dynamic vehicle routing,intelligent transportation
Projet ERC : AlgaeLeaf (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
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 : 1500000.0 €

Nature fabricates materials with remarkable properties, having the ability to grow, move and sense their environment. Such dynamic and interactive materials are in strong contrast with man-made synthetic materials. Recent scientific interest has emerged to incorporate living cells into materials to form living materials, using most often muscle cells or bacteria. While underexplored, microalgae-based living materials are highly promising due to the light-driven movement of microalgae. The aim of this ERC project is to develop the first microalgae-based photosynthetic living material with a dynamically light-controllable shape and with locally tuned (mechanical) properties. The fabrication of light-responsive microalgal living materials will be possible through novel fundamental knowledge that we will gain regarding the growth and motion of microalgae within a porous hydrogel. Although this constrained environment mimics one of the microalgae natural habitats (soil), we have limited understanding of the microalgae behaviour within such an environment. We will first investigate how cells move within a porous environment and how they respond to light, with the goal of using light for 3D patterning. We will then explore how the hydrogel-based living material can be locally mechanically reinforced with cell-secreted polymers, and finally how to harness the microalgae light response as a mean to create a soft actuator. My independent research team uniquely combines expertise in microalgae cell biophysics and in engineered living materials, and we are thus ideally positioned to take on the challenge of creating microalgae-based living materials dynamically controlled by light. This ERC project opens up a new class of materials with life-like functionalities such as shape change and light-sensing, which are likely to find wide applications, from soft robots to photosynthetic devices.

Mots-clés : cell materials interactions,light responsive materials,microalgae,hydrogel
Projet ERC : CARDIOCALC (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
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 : 1209375.0 €

With this project I propose to identify fundamental mechanisms of cardiovascular calcification (CVC) and new therapeutic targets using zebrafish as a model system. CVC, characterised by progressive calcification of the soft tissue causing impaired blood circulation, is a frequent form of cardiovascular disease. Because the pathophysiology of CVC is highly heterogeneous, the exact cell types and signalling pathways triggering tissue calcification are still unknown, thus limiting therapy options. Most studies on CVC rely on in vitro systems, which fail to reproduce the multicellular environment, or mammalian in vivo models, limited for live-imaging and high-throughput analyses. By combining my expertise in cardiovascular research and bone biology, I propose to use zebrafish as a model to elucidate the multifactorial mechanisms of CVC, focusing on different developmental stages and cardiovascular tissues. In Aim 1, I will use a broad array of zebrafish genetic models to characterise the cellular dynamics, molecular mechanisms and functional impact of CVC in vivo. I will also study the role of specific cell populations present in regenerating valves and human valve implants with CVC. In Aim 2, I propose to identify new local and systemic therapeutic strategies to block/reverse CVC, taking advantage of the zebrafish amenability for genetic manipulation and high-throughput screening. I will recruit bone-degrading cells to the CVC site and determine their potential to reverse tissue calcification. Moreover, I will select a short list of small molecules identified in a large-scale screen in zebrafish and will test their therapeutic potential in cardiovascular cells derived from hiPSCs of CVC patients. Altogether, with this interdisciplinary approach, I expect to bring a new perspective on the mechanisms and therapeutic targets to block/reverse CVC, which could have a considerable impact on the European population, severely affected by these diseases.

Mots-clés : zebrafish cardiovascular calcification  cardiac valve  outflow tract  valve implant  hipsc  chemical screen  live imaging therapeutics
Projet ERC : MeDiSyn (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
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 : 1490250.0 €

The discoveries of microbial secondary metabolites (SM) led to an incalculable impact on human health and lifespan. A large share of the antibiotics, anticancers and immunosuppressants in use today originate from microorganisms. However, discoveries of SMs of microbial origin through traditional approaches have declined in the past decades, depriving drug pipelines from a key source of bioactive molecules. The consequences are dire, in particular in the case of antibiotics. Encouragingly, the study of the biosynthetic genes responsible for the synthesis of SMs indicates that the natural repertoire remains vastly underexplored, and new ways to access it are enabled by DNA technologies. In particular, untapped biosynthetic genes can be interrogated by transferring them into heterologous hosts. I am developing a method for transfer which fulfils the conditions to unleash theoretically massive economies of scale. Here I propose to multiply the scalability of the current heterologous expression framework and effectively overcome the diminishing returns faced by traditional approaches. In the first axis, I will implement a full-fledged discovery platform, optimized to systematically interrogate novel biosynthetic gene clusters identified bioinformatically from a large collection of soil bacteria. Second, the scale and parallel nature of the heterologous expression setup will be used to better understand the logic of activation of biosynthetic genes, and identify optimal ways to increase activation rates among the large reservoir of conditionally silent biosynthetic genes. Finally, the general strategy will be extended to new fungal and bacterial clades to enable interrogation of their vast potential through scalable heterologous expression. Overall, this proposal aims at developing heterologous expression into a major way to discover microbial secondary metabolites and drug leads.

Mots-clés : natural products,specialized metabolites,drug discovery,antibiotics,sequencing
Projet ERC : UnaWireD (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Azienda Ospedaliero-Universitaria di Modena — Pays : Italie — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 49798.0 €

Why is the diseased human brain able to produce false beliefs that persist despite evidence to the contrary? Unawareness of neurological disturbances (anosognosia) and Delusions are examples of such false beliefs. Both have productive, narrative features. Both have been independently linked to processes involved in self-reflection, metamemory, and error-monitoring. Despite their phenomenological similarities, the research investigating their mechanisms has progressed independently. UnaWireD will provide the first in-depth investigation of anosognosia and delusions in combination to test the hypothesis that they share common brain mechanisms. Although these symptoms impact significantly on a range of brain disorders, the proposal focuses on Alzheimer’s Disease (AD), in which the difference between patients who show the most severe form of these symptoms and patients who never present them is striking yet largely unexplained. In particular, it is not known whether these symptoms represent a response of the spared brain to the damage (depending on pre-existing vulnerability or resilience) or are a consequence of the damage itself (depending on type, localisation and severity of pathology). By combining advanced imaging with experimental paradigms and extended clinical and biomarker characterisation, UnaWireD will: 1. Establish whether anosognosia and delusions define a specific clinical subtype in AD; 2. Determine if they are associated with premorbid personality and cognitive abilities; 3. Identify the brain networks specifically altered in the anosognosia/delusion AD subtype; 4.Test if anosognosia is associated with an imbalance in the brain neurotransmitter dopamine. UnaWireD will deliver a new framework to study the interplay between the spared and damaged brain in the origin of productive symptoms across neurological diseases. By doing so, it will open a window towards a better understanding of the uniquely human abilities of self-reflection and consciousness

Mots-clés : anosognosia,delusions,functional mri,self reflection,cognitive reserve,premorbid personality,alzheimer s disease
Projet ERC : MitoRNA (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : University Medical Center Göttingen — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UMG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499754.0 €

Mitochondria maintain an organellar genome that encodes for subunits of the respiratory chain. Its coordinated expression is essential for eukaryotic life, and defects in this process lead to severe disease in humans. Mitochondrial gene expression is carried out by unique dedicated molecular machineries, but the underlying molecular mechanisms remain poorly characterized. During my previous work as a PhD student and Project Leader, I provided the structural basis of human mitochondrial transcription. At the same time, structural insights on mitochondrial translation were reported. However, our understanding of mitochondrial gene expression remains limited due to two fundamental knowledge gaps. First, we lack a molecular understanding of the complex mitochondrial RNA life cycle that takes place in between transcription and translation. Second, we do not know how the different steps of mitochondrial gene expression are functionally coupled, as they are not separated by membranes. With MitoRNA, we propose to take the next big leap towards a mechanistic understanding of mitochondrial gene expression by addressing these blind spots. Using an innovative integrated structural biology approach, we will define the molecular basis of the human mitochondrial RNA life cycle and how it is embedded in the concert of mitochondrial gene expression. In particular, we will investigate the structural basis of various key steps of mitochondrial RNA metabolism in vitro and in situ, and dissect how they are coupled to each other. This ground-breaking work will open up the next frontier in mitochondrial biology by drawing a molecular picture of human mitochondrial RNA metabolism and providing insights into the functional organization of mitochondrial gene expression. In addition, it will also advance methods to study mitochondrial biology from the atomic to the organellar scale.

Mots-clés : mitochondria,cryo em,structural biology,gene expression rna
Projet ERC : NEURACT (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1900000.0 €

A paramount component of intelligence is our ability to extract useful information in the world through our sensory observations. Object recognition is a fundamental problem in visual perception: every day we depend on our ability to identify objects in our visual environment, and our brain is capable of accomplishing it effortlessly and in a fraction of a second, in spite of immense variation in the sensory information that arrives in our retinas. Understanding the algorithm that the brain uses to do this complex task is a decisive conquest in neuroscience but in order to understand ethologically relevant visual processing, we need to understand how it drives behavior. Despite significant progress characterizing visual processing, we do not understand how the visual system solves visual inference problems in natural environments and we are still far from having a complete understanding of how the brain creates untangled transformation-invariant object representations in the perceptual/visual domain, that can subsequently be used to guide behavior. The proposed research effort aims to (i) create a state-of-the-art behavioral virtual navigation system for mice, (ii) combine it with recent advanced functional brain recording techniques and sophisticated neural data analysis to study how objects are represented in the activity of large populations of neurons across the visual hierarchy and beyond and (iii) causally relate these representations to the behavior of the animal. The outcomes of this project will provide significant insights into the computations used by the mouse visual cortex to extract relevant features from the environment, identify how distinct features are represented across the mouse visual areas and how in turn these representations guide the behavior of the animals.

Mots-clés : object recognition,object manifold,mouse model,visual discrimination task,visual processing,conceptual representation,continual learning
Projet ERC : gutTEimpact (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
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 : 1498420.0 €

Life-long tissue homeostasis requires sustained function of differentiated cell types as well as progenitor cells, which ensure tissue self-renewal. Little is known about the role that non-genic repetitive DNA sequences play in the maintenance of cellular homeostasis in divers somatic tissues in vivo. Transposable elements (TEs) are omnipresent, highly repetitive DNA sequences that mobilize and propagate within host genomes. Though previously thought to be fully repressed in the soma, TEs can be actively transcribed and, at least to some extent, mobile in certain somatic tissues. Indeed, somatic TE activity was proposed to contribute to normal development, aging, and pathologic conditions, such as cancer or neurodegeneration, underscoring the potential bearing that these selfish genetic elements could have in the soma. Nevertheless, the dynamics of activity and tissue-specific regulation of TE sequences are poorly understood, as is the impact of TE activity on different somatic cell-types and tissues. We have recently uncovered that prevalent, tissue-specific TE mobility occurs in the Drosophila intestine and can lead to gene inactivation and tumor formation. Here, using this powerful and genetically amenable in vivo model system, I aim to combine genomic techniques with developmental and cell biology approaches to address the intriguing interplay between TEs and somatic tissue function in vivo. I will ask: 1- How TE activity differs between diverse cell types and how it changes in a tissue under normal or pathological conditions, as well as during aging? 2- What processes control TE activity in somatic cells in vivo?; and 3- What are the direct consequences of TE transcriptional activity and mobility on somatic cell function, and the long-term impacts at a tissue and organism level? Ultimately the proposed research program will shed new lights on the importance of mobile DNA sequences in the maintenance of lifelong tissue homeostasis in vivo.

Mots-clés : transposable elements,drosophila,intestinal tissue,adult stem cells,aging
Projet ERC : PLaisTICITY (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1494740.0 €

Neurons have the remarkable ability to continuously integrate and propagate information while maintaining their activity state within physiological range. The axon initial segment (AIS) is the keystone of neuronal excitability and pivotal for the maintenance of network homeostasis. The molecular organization of the AIS dictates the generation of action potentials, and thereby shapes the principal output of neurons. Although the AIS has long been considered as a static and passive structure, recent work from my lab and others demonstrated that network activity induces robust plasticity of the AIS, causing long-lasting changes in excitability. However, how AIS plasticity is regulated to maintain network homeostasis remains elusive.  In this proposal, I aim to resolve, at the molecular level, how the AIS adapts in response to acute and chronic changes in neuronal activity and how maladaptation may lead to disease. To this end, I developed genome editing tools to label and manipulate endogenous AIS components, enabling live and super-resolution imaging of AIS organization. In combination with proteomics, optogenetics and electrophysiology, this project will address the following key objectives: 1. Resolve the nanoscale distribution and dynamics of AIS components 2. Unravel the mechanisms controlling acute and chronic re-distribution of ion channels during AIS plasticity and their consequences for excitability 3. Address the implication of maladaptive AIS plasticity in the pathology of Angelman Syndrome  This project bridges the cell biology of the neuron to its physiology, provides new insights into how AIS plasticity orchestrates network activity and identifies how maladaptation contributes to disease.

Mots-clés : axon initial segment,neuronal cell biology,neuronal plasticity,action potential generation,genome editing,super resolution microscopy