Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ArtifiCell (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 800000.0 €

Imagine being able to design into living cells and organisms de novo vesicle transport mechanisms that do not naturally exist? At one level this is a wild-eyed notion of synthetic biology. But we contend that this vision can be approached even today, focusing first on the process of exocytosis, a fundamental process that impacts almost every area of physiology. Enough has now been learned about the natural core machinery (as recognized by the award of the 2013 Nobel Prize in Physiology or Medicine to the PI and others) to take highly innovative physics/engineering- and DNA-based approaches to design synthetic versions of the secretory apparatus that could someday open new avenues in genetic medicine. The central idea is to introduce DNA-based functional equivalents of the core protein machinery that naturally form (coats), target (tethers), and fuse (SNAREs) vesicles. We have already taken first steps by using DNA origami-based templates to produce synthetic phospholipid vesicles and complementary DNA-based tethers to specifically capture these DNA-templated vesicles on targeted bilayers. Others have linked DNA oligonucleotides to trigger vesicle fusion. The next and much more challenging step is to introduce such processes into living cells. We hope to break this barrier, and in the process start a new field of research into “synthetic exocytosis”, by introducing Peptide-Nucleic Acids (PNAs) of tethers and SNAREs to re-direct naturally-produced secretory vesicles to artificially-programmed targets and provide artificially-programmed regulation. PNAs are chosen mainly because they lack the negatively charged phosphate backbones of DNA, and therefore are more readily delivered into the cell across the plasma membrane. Future steps, would include producing the transport vesicles synthetically within the cell by externally supplied origami-based PNA or similar cages, and - much more speculatively - ultimately using encoded DNA and RNAs to provide these functions.
Projet ERC : BIOELE (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
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 : 1486938.0 €

Imagine in the future, bionic devices that can merge device and biology which can perform molecular sensing, simulate the functions of grown-organs in the lab, or even replace or improve parts of the organ as smart implants? Such bionic devices is set to transform a number of emerging fields, including synthetic biotechnology, regenerative medicine, and human-machine interfaces. Merging biology and man-made devices also mean that materials of vastly different properties need to be seamlessly integrated. One of the promising strategies to manufacture these devices is through 3D printing, which can structure different materials into functional devices, and simultaneously intertwining with biological matters. However, the requirement for biocompatibility, miniaturisation, portability and high performance in bionic devices pushes the current limit for micro- nanoscale 3D printing. This proposal aims to develop a new multi-material, cross-length scale biofabrication platform, with specific focus in making future smart bionic devices. In particular, a new mechanism is proposed to smoothly interface diverse classes of materials, such that an active device component can be ‘shrunk’ into a single small fibre. This mechanism utilises the polymeric materials’ flow property under applied tensile forces, and their abilities to combine with other classes of materials, such as semi-conductors and metals to impart further functionalities. This smart device fibre can be custom-made to perform different tasks, such as light emission or energy harvesting, to bridge 3D bioprinting for the future creation of high performance, compact, and cell-friendly bionic and medical devices.
Projet ERC : InfoMatter (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1249733.75 €

Imagine squeezing a crumpled plastic sheet – what is its response? For complex materials – crumpled sheets, granular media, glassy materials – tiny forces already cause a nonlinear response, associated with hopping in the energy landscape, for which we lack a coherent description. The central tenet of this proposal is that this hopping allows complex materials to process information. I propose to understand and unlock the full potential of such complex materials. Central questions are: - How can we describe their nonlinear response? - What are the computational capabilities of complex matter? - Can we create materials for targeted computations? To answer these questions, I will subject macro-scale complex matter to sequentially and spatially patterned driving forces (information input), and observe the sequential response (information output). The responses to multiple forcings form an intricate web of linked pathways, which can be represented in a graph that I interpret as encoding a sequential computation. This is the central link between driving, pathways and information, which allows me to probe the algorithmic capabilities of complex materials. Recent breakthroughs in my group have brought experimental access, modelling and design of pathways within reach. In this proposal, I will investigate these pathways and will develop strategies to create algorithmic matter, using a combination of disordered – crumpling – sheets and carefully designed mechanical metamaterials; I will develop theoretical models for both. Just like a focus on the architecture of complex matter has revolutionized our view of their linear response and gave birth to mechanical metamaterials, a focus on their pathways will revolutionize our understanding of their nonlinear response and opens the door to new forms of information processing matter.

Mots-clés : memory and information,complex matter,mechanical metamaterials
Projet ERC : ULTRAIMAGE (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Pavia — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPV
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1894577.0 €

Imaging charge, spin, and energy flow in functional materials when hit by a light pulse, is a current grand challenge in nanotechnology relevant to a host of systems including photovoltaics, optoelectronic and spin devices. The design of such materials relies critically on the availability of accurate characterisation tools of how light-induced function and performance are related to nano-to-mesoscale electronic and lattice structural properties. To address this challenge, ULTRAIMAGE will introduce ground-breaking capabilities in microscopy of nanomaterials, providing access to their far-from-equilibrium states, with resolution on nanometer-to-Ångstrom length and femtosecond time scales. Key to this advance is the combination of extreme ultraviolet (EUV) to soft X-ray tabletop coherent light sources with a technique for coherent diffractive imaging called ptychography, in which multiple diffraction patterns from overlapping fields of view are processed by iterative algorithms to recover amplitude and phase images of sample and beam, separately. Nanoscale movies of the sample’s impulsive response, irradiated by ultrafast laser pulses, will be obtained with extremely high fidelity and in a non-destructive approach, with sub-20nm transverse resolution, 0.5Å axial precision, and ≈10fs temporal resolution. Each movie frame will be characterized by amplitude and phase images of the sample, with exquisite quantitative contrast to material composition, and to its topography. ULTRAIMAGE will introduce a world-class tabletop facility for ultrafast ptychography with coherent short-wavelength EUV light, which will enable the understanding with unprecedented detail of fundamental nanoscale behaviour, vital to a better design of energy-efficient next generation devices.

Mots-clés : characterisation,nanoparticle,superlattice,femtosecond,coherent diffractive imaging,ultrafast ptychography,euv and soft x ray light,structure property relations,collective modes
Projet ERC : HoloStain (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
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 : 150000.0 €

Imaging flow cytometry (IFC) holds great promise as clinical screening and diagnostics platform, as it can capture, process and analyse a large number of cells in bodily fluids, useful for hematology and hemato-oncology. However, currently IFC captures cell morphology by imaging each fluorescently-stained cell organelle on a different region of the camera sensor, dictating complicated and expensive optics and processing units. Current IFC remains a highly inaccessible technology, due to its very high cost, lack of accuracy, required operator expertise, and lack of objectiveness. The global flow cytometry market is estimated as USD 3.29 Billion in 2017, and projected to reach USD 4.79 Billion by 2022. This rapid growth is due to anticipation of becoming more common in clinical use. In this project, we will develop and commercialize a novel IFC platform. Using an external portable interferometric module and novel analysis methods, we perform quantitative holographic virtual staining (HoloStain) of the multiple cell organelles, simultaneously on a single IFC channel, dramatically simplifying the optics, cameras, and processing. Preliminary results are provided. As HoloStain does not require cell staining for morphological evaluation, it is ideal for real-time sorting or subsequent cell use. Moreover, HoloStain provides multiple virtually stained slices from the same camera frame, earning higher throughput. These unique advantages are expected to revolutionize the IFC market in two possible product-realization pathways: (i) as a more cost-effective stand-alone IFC workstation, and (ii) as an add-on module to an existing IFC workstation, upgrading its capabilities. Both pathways are highly attractive for licensing to existing flow cytometry manufacturers or for founding a startup company. In this project, upon completing marketing requirement and product characterizations, we will build an alpha prototype, and present it to potential strategic partners and investors.

Mots-clés : imaging cytometry,digital holographic microscopy,quantitative phase imaging
Projet ERC : Crosstag (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Immune therapies are therefore currently being pursued to reinvigorate the immune reaction against tumours. This is not trivial, as the right type of immune cells must be activated against a tumour-specific antigen. One method to achieve this is by targeting tumour antigens to certain cross-presentation-promoting receptors on antigen presenting cells. The most intriguing of these is the mannose receptor (MR) as the method by which it does this is unknown. This glycoprotein-binding receptor appears to have two functions on APCs: general uptake-enhancement and, in certain isolated cases, cross-presentation-enhancment. What ligand parameters are important in causing cross-presentation enhancement is not known. Current tools, such as anti-MR antibodies and randomly glycosylated ligands fail to selectively enhance cross-presentation. The main aim of this proposal is to determine what structural parameters of the glycoprotein antigen result in enhanced cross-presentation upon MR-ligation. I will synthesise a library of biologically traceable single glycoform ligands - with controlled variation in glycan nature, stoichiometry and positioning - for the MR and study differences in uptake, routing and antigen presentation. A 2nd aim is to uncover what happens to the antigen after uptake by the MR. I.e. whether changes in antigen routing and proteolysis are responsible for enhanced cross presentation of different glycoforms. A 3rd aim is to develop a new method to study the kinetics of surface appearance of epitopes without T-cell reagents to quantify differences between glycoforms. With this approach I aim to gain new insight into methods for enhancing cross-presentation resulting in improved immune therapies against cancer. My background in carbohydrate and protein modification chemistry will provide the toolkit to synthesise the relevant reagents and my background in immunology will ensure the successful immunological validation of the synthetic single glycoforms.

Mots-clés : antigen cross presentation,bioorthgonal chemistry,mannose receptor,cancer immunotherapy
Projet ERC : PeptiCHIP (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Helsinki — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Immunotherapeutic strategies have emerged as powerful tools to treat many types of cancers. However, the majority of patients still fails to respond to immunotherapies as targetable tumour characteristics vary from patient to patient. Thus, a greater degree of personalisation is required to fine-tune immunotherapies to the specific vulnerabilities of each patient’s tumour. While therapies that target tumour-specific antigens (neoantigens) invoke a strong and specific anti-tumour immune response, we are currently unable to accurately identify patient-specific neoantigens. Current neoantigen identification and purification methods either require impractically large quantities of tumour material or are laborious, expensive, time-consuming (weeks or months) and inaccurate. As part of ERC project PEPTICRAD (2016-2021), Prof. Vincenzo Cerullo at the University of Helsinki has developed a novel microfluidic chip-based device (PeptiCHIP) which condenses the neoantigen purification steps into a single chip capable of accurately analysing minute quantities of human tumour tissue. PeptiCHIP permits cost-effective, rapid, sample-conserving, user-friendly, accurate and standardised tumour neoantigen identification, thereby unleashing the full potential of personalised anti-tumour immunotherapies. In this ERC PoC project, a team of technological and commercial experts will ascertain the technical and commercial viability of the innovative PeptiCHIP device. We will prepare the first steps toward the start-up of a spin-off by defining the most optimal business strategy and model. Furthermore, we will explore the technical potential of the PeptiCHIP and solidify our IP-position. We will develop a solid business strategy based on the technological aspects, the market needs and trends. Finally, during this project we will gain technical and commercial proof-of-concept, providing the necessary information for potential commercialisation routes.

Mots-clés : immunotherapy,oncoimmunology,tumor antigens,neoantigens,cancer immunotherapy,virotherapy,oncolytic virus
Projet ERC : ImageMelanoma (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1613750.0 €

Immunotherapies targeting immune regulators are revolutionizing cancer treatment, most prominently in melanoma, but only for a subset of patients. While it is known that the immune tumor microenvironment (iTME) plays a vital role in this process, there is limited understanding on how distinct tumor, immune and stroma cells interact as a system to collectively define progression and response to treatment, and there is no biomarker to predict patient response. Tumors are spatially organized ecosystems that are comprised of distinct cell types, each of which can assume a variety of phenotypes defined by coexpression of multiple proteins. To underscore this complexity, and move beyond single cells to multicellular interactions, it is essential to interrogate cellular expression patterns within their native context in the tissue. We have recently pioneered MIBI-TOF (Multiplexed Ion Beam Imaging by Time of Flight), a novel platform that enables simultaneous imaging of forty proteins within intact tissue sections at subcellular resolution. We propose to (1) Use MIBI-TOF to chart the iTME in dozens of clinical samples from melanoma patients and delineate its function in response to different immunotherapies. (2) Profile murine melanoma tumors to elucidate genetic and temporal mechanisms that drive iTME organization in vivo. (3) Develop new experimental tools for tracing and barcoding thousands of cells to decouple the effects of tumor genetics and the immune microenvironment on tumor organization and clonal dynamics. (4) Develop machine-learning-based algorithms to analyze this novel data and facilitate accessibility of the scientific community to high-dimensional imaging to study human malignancies. This proposal applies state-of-the-art imaging technology and computation to unravel design principles of the iTME in melanoma, with a grand goal to reveal basic principles in tumor immunology and improve treatment and diagnostics.

Mots-clés : multiplexed imaging,proteomics,melanoma,immunotherapy
Projet ERC : IT4-TALL (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Fundación Josep Carreras Contra la Leucemia — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Immunotherapy has revolutionized cancer treatment over the last decade. Adoptive cell immunotherapy with T-cells genetically redirected to a tumor-specific antigen using a chimeric antigen receptor (CAR) has achieved impressive response rates in advanced B-cell acute lymphoblastic leukemia (B-ALL). CAR T-cell strategies beyond B-cell tumors are, however, hampered by expected toxicities, owing to the lack of bona fide therapeutic and safe antigens. Indeed, there are no immunotherapeutic therapies (including CAR T-cells) approved for T-cell malignancies (T-ALL or T-cell lymphomas), as the shared expression of target antigens between CAR T-cells and T-blasts induces CAR T-cell fratricide and T-cell aplasia, leading to fatal immunodeficiency. We recently identified the CD1a antigen as a safe target for CD1a+ cortical T-ALL (coT-ALL), a major subgroup of T-ALL, and we have developed a novel CD1a-specific CAR. Results generated from my previous ERC-funded work (INFANTLEUKEMIA nº646903 and IT4-BALL nº811220) have just been protected by a European Patent (EP19382104.8; CARTs for the treatment of CD1a+ cancer). Our intellectual property rights coupled to our internationally-endorsed top-tier scientific publication are a major strength of our proof-of-principle demonstration that CD1a-directed CAR T-cells constitute a unique immunotherapy approach for coT-ALL. We propose to consolidate final technical-biological improvements and GMP-grade manufacturing of our CD1a-directed CAR T-cells in compliance with the requirements of the Spanish Regulatory Agency of Medicines and Medical Devices for advanced adoptive cellular therapies (AEMPS). Data from this project will be added to the final Investigational Medicinal Product Dossier (IMPD) of the CARCD1a T-cells to be submitted to AEMPS for regulatory approval to launch a pan-European open Phase Ib clinical trial for relapse/refractory coT-ALL in early 2022, ensuring social and health value of this innovative immunotherapy.

Mots-clés : acute leukemia,immunotherapy,car t cells,cd1a,clinical trial
Projet ERC : NEURODIAM (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Université Gustave Eiffel — Pays : France — Rôle : PI
Acronyme de l'entité : UGE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499865.0 €

Implantable neuroprosthetic devices offer the promise of restoring neurological functions to disabled individuals. Tests demonstrated that an array of microelectrodes implanted in cortex allows to record activity of the brain and to induce a movement on prosthetic limbs or electrical stimulations restore some visual sensations. For these applications the life time and stability of the electrodes are critical features for the reliable operation of any implantable neuronal device. It’s also necessary to have high density implant with small electrodes to cover a large surface of the cortex to have access of neuronal code. A reliable packaging for long term implantable devices are in titanium or glass but not suitable in the case of ECoG (ElectroCorticoGraphy) implant. Indeed, it is necessary to achieve a polymer implant as a core material, to follow the topology of the brain surface. But in long term the polymer swells and moisture penetrates the implant and degrades its performances therefore reducing the lifetime. The goal of NEURODIAM project is to address two major challenges: - increase the lifetime of implant by a specific packaging, - reduce the size of the electrodes to be equivalent to the neurones size (10 µm) without degradation of noise and consequently increase the electrode density for a fine mapping of the cortex. To avoid performance drift of the implant, a new packaging solution completely hermetic will be developed based on the last developments of micro and nano structuration of diamond layer that combines conductive and intrinsic synthetic diamond. Fast ageing tests will be settled to demonstrate the viability of this diamond technology. In-vitro and in-vivo assessment will be performed to demonstrate the efficiency of these implants for recording and stimulation of neuronal tissue. This project will produce high performance diamond based technology that can be later used for various implants dedicated to fundamental studies in neurosciences.

Mots-clés : micro and nanotechnology,neuroprothesis,electrocorticography  ecog,diamond material