Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MitoGuide (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Lausanne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499990.0 €

Cancer immunotherapies harnessing the tumoricidal activity of tumor-reactive T cells represent a major breakthrough in the current paradigm for treating cancer patents. However, the highly immunosuppressive tumor microenvironments found in solid tumors present challenges by restricting the tumoricidal functions and metabolic fitness of infiltrating tumor-reactive T cells. Given that the activation-induced metabolic switch is tightly intertwined with T cell activities, restoring the metabolic fitness of T cells represents a promising strategy for strengthening anti-tumor immunity. However, the success of this strategy relies on our understanding of the underlying mechanisms utilized by tumor cells to abolish the metabolic fitness of T cells, and of how metabolic programming controls T cell functions. Based on our preliminary results, we postulate that tumor cells disrupt the mitochondrial dynamics of tumor-infiltrating T cells by interrupting mitophagy. This causes a metabolic crisis for the infiltrating T cells in sustaining their metabolic fitness and flexibility. Furthermore, we hypothesize that declined mitochondria-derived retrograde signals resulted from mitochondrial dysfunction may lead to T cell dysfunction/exhaustion and altered immune responses through epigenetic reprogramming and altered proteome-metabolic regulatory circuits. The objectives of this proposal are to delineate how tumor cells influence the mitochondrial dynamics of T cells and define the unexplored immunometabolic regulations of T cell functions that are controlled by mitochondria. Lastly, we aim to new methods to restore missing retrograde signals in T cells, which could allow them to prevent mitochondrial dysfunction-induced epigenetic and transcriptomic changes. This work represents an entirely new perspective on control of T cell functions by the immunosuppressive tumor microenvironment, and it may reveal new dimensions of immunometabolic regulation.

Mots-clés : immunometabolism,mitochondria,epigenome
Projet ERC : MechanoIMM (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
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 : 1499800.0 €

Cancer immunotherapy harnessing the power of a patient’s immune system to fight cancer is transforming the standard-of-care for cancer. Adoptive cell therapy (ACT), a potent immunotherapy that directly infuses a large number of tumour-reactive T cells into patients, has elicited dramatic clinical responses in leukaemia patients recently. However, solid tumour remains a major challenge as tumour employs a number of strategies to prevent effector T cells reaching the tumour sites and attacking cancer by generating a highly immunosuppressive microenvironment. Current strategies are focused on controlling the immune system or the microenvironment using biochemical immunomodulatory reagents to enhance T cell based immunotherapy. Approaches exploiting biophysical and mechanical cues for immunomodulation are largely underappreciated. In this proposal, we aim to exploit mechanical immunoengineering strategies through biophysical cues to develop novel immune related treatments to enhance the efficacy and safety of adoptive T cell therapy for cancer. We will first develop a mechano-training approach to promote the T cell infiltration into tumour tissues using engineered microfluidic system for controlled force application on T cells in a high through-put manner. Second, we will develop a mechano-responsive nanoparticle delivery system to selectively deliver T-cell-supporting drugs in tumour to overcome the immune suppression in the microenvironment and enhance T cell functions for killing cancer. Third, we will develop mechano-inducible cytokine-secreting T cell therapies to augment the efficacy and minimize the toxicity of ACT by exploiting and targeting the difference in tissue stiffness between tumour and healthy tissues. This proposed project will open a new horizon for immunoengineering through biomechanical modulation of immunity for enhanced cancer immunotherapy and provide insight into the fundamentals of mechanotransduction in immune system in health and disease.

Mots-clés : immunoengineering,cancer immunotherapy,mechanical modulation,adoptive t cell therapy,responsive biomaterials,force and stiffness responsiveness
Projet ERC : Cancer-Drug-Screen (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Cancer is caused by a series of genetic alterations that confer an advantage to cancer cells, leading to uncontrolled growth. However, each tumor exhibits distinct molecular changes, making each patient’s malignancy unique. Hence, in the personalized medicine era, cancer treatment aims to tailor the most suitable treatment for each patient according to his/her genetic background, tumor acquired mutations and clinical indications. The p53 tumor suppressor is the most frequently mutated gene in human cancers, with thousands of different tumor-associated mutations reported. Many such cancer-associated mutations in p53 lead to loss of its tumor suppressive activity and in some cases, to gain of new oncogenic functions, resulting in tumor recurrence and enhanced patient mortality. Importantly, tumors with different p53 mutations exhibit specific cancerous phenotypes and do not respond to particular treatments. Based on our ERC-funded breakthrough technology, where we made a library of ~10,000 distinct p53 variants, and based on our strong IPR offering and competitive advantages, here we propose to develop three products for determining which treatment (or combination) would be most effective for treating a patient’s tumor according to his specific p53 sequence, reducing excruciating side effects and improving treatment outcomes: 1) Offering patients/physicians a list of treatments ranked by their efficacy in treating cells of similar origin and p53 mutations to those present in the patient’s tumor, allowing them to make more informed treatment decisions. 2) Offering companies in the personalized cancer treatment field access to our existing proprietary data regarding treatment efficacies towards p53 genetic variants. 3) A service to drug developing companies that applies our technology for testing the efficacy of a client-supplied drug of interest over all ~10,000 p53 mutations in our library in a cell-line of choice.

Mots-clés : cancer,personalized medicine,personalized cancer treatment,high throughput
Projet ERC : DeShield (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : University of Freiburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149981.0 €

Cancer is one of the most prominent causes for morbidity and mortality in industrialized countries. The key challenge in drug-based anti-cancer therapy is to efficiently kill the cancer cells while minimizing side-effects on healthy parts of the body. The DeShield project will establish the proof of concept for a novel approach to upgrade existing anti-cancer drugs in a way that the anti-cancer effect will be increased while side-effects will simultaneously minimized. DeShield technology will be used to shield approved anti-cancer drugs while circulating in the body in order to minimize side effects. Once the shielded drug accumulated at the cancer site, an external stimulus will be applied to trigger de-shielding. The drug will then locally and specifically be taken up by the cancer cells to exert its therapeutic effect. We have successfully demonstrated the functionality of the DeShield technology using the clinically approved anti-cancer drug Doxil and human cancer cell lines: when the shield is intact, the drug is not taken up by the cells, only upon inducible un-shielding the drug enters and kills the cells. In the DeShield project we aim at establishing the Proof-of-Concept that this approach is functional in cancer animal models, that it increases the therapeutic effect while minimizing side-effects. To this aim we have assembled a team with high expertise in complementary areas covering the technology itself, the conductance of preclinical animal studies up to clinical trials as well as business expertise. The technical advance obtained in this project together with a comprehensive market research and the development of a business strategy will shape a highly attractive commercial proposition for the successful valorization of our ERC-funded research.

Mots-clés : drug delivery,cancer,side effects
Projet ERC : Precision Motifs (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UZH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Cancer precision medicine aims to bring the right drug (or right drug combination) to the right person. To achieve this, the molecular cause of an individual’s disease must be identified and a treatment chosen that targets that cause to remedy the dysfunction. Tumors are dynamic ecosystems with high heterogeneity in tumor, immune, and stromal cell compartments. This complexity is the main obstacle to implementation of precision medicine. Consequently, approaches that rationalize and use tumor ecosystems for precision medicine are needed. To enable this, I propose to establish the concept of functional tissue motif, a multiscale network representation of multi-cellular assemblies that executes a definable set of anti-tumor or pro-tumor functional outputs. The utility of functional tissue motifs for precision medicine will be demonstrated in the context of metastatic breast cancer, which causes nearly 450,000 cancer-associated deaths each year. We will develop a highly multiplexed 3D tissue imaging approach with unprecedented throughput that provides subcellular resolution to analyze a large cohort of primary and matched metastatic tumors. We will then use viable tumor samples ex vivo to systematically perturb intra-cellular and inter-cellular network wiring using approved drugs, and the drug effects will be measured by highly multiplexed imaging. Functional tissue motifs will be identified using community and geostatistical methods and probabilistic network modeling. Analysis of functional tissue motifs in the light of the clinical data will be used to derive a novel classification system and to identify vulnerabilities in metastatic breast tumors. These vulnerabilities will be validated in follow-up experiments and in a clinical study. Given their focus on functional output, information content and versatility, functional tissue motifs promise to be a powerful concept and should enable to point to appropriate treatments, and inform development of new therapies.

Mots-clés : single cell analysis,multiscale network inference,data driven
Projet ERC : CANCERSCREEN (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
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 : 1047674.06 €

Cancer screening and the diagnostics industry: a comparative analysis of the political economy of diagnostic innovation A decade after the Human Genome Project, major public and private investments continue to fuel expectations of a genomic revolution in biomedicine. The freight of expectations surrounding the new “age of diagnostics” is accompanied by much uncertainty about how public policy should steer diagnostic innovation, with much debate about inter alia the harms of creating diagnostic monopolies through gene patenting, and the risks of under- or over-regulation. However, due to the paucity of research on diagnostic innovation, policy deliberation is driven more by anecdote and expert opinion than empirical evidence. With a specific focus on screening/early detection of cancer, this project will map industry dynamics, technological trajectories and regulatory developments in Europe and the USA from 1996 to the present day. Combining quantitative and qualitative methods, the project’s innovative dimensions include a new conceptual model of socio-technical transition in the diagnostics sector, and the first integrative analysis linking scientometric data on the interactions between public and private actors in the diagnostic research domain with comparative transnational analysis of regulatory decision-making. Through a novel integration of conceptual insights from the literature on biomedicalisation and scholarship on socio-technical regime change, this project aims to advance both fields of research by applying a new multi-scale, multi-level model of socio-technical transition. The project will provide unprecedented insight into the factors shaping the development of a new generation of molecular diagnostic tests, and examine how these technologies are reconfiguring disease categories and redrawing the boundaries between health and sickness. We will establish a platform of theory and methods for a broader programme of work on diagnostic innovation.

Mots-clés : biomedicalisation,socio technical transitions,responsible research and innovation,regulation,political economy
Projet ERC : SCoTMOF (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Glasgow — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1493777.0 €

Cancers are the leading cause of death in the developed world, with populations facing a 30% chance of developing the disease by the age of 75. As part of a concerted effort to open up new treatments and improve patients’ experiences with existing ones, the concept of drug delivery – using non-toxic carriers to transport medicines directly to the location of disease – has emerged. Metal-organic frameworks (MOFs), porous materials comprised of organic linkers and metal joints, show considerable promise as drug delivery vectors due to their high storage capacities, amenability to functionalization and the ability to prepare entirely non-toxic nanoparticulate derivatives. This proposal will use the PI’s expertise in advanced MOF synthetic methods to facilitate dramatic technological breakthroughs through unprecedented control of MOF self-assembly and surface chemistry. Management of MOF surface chemistry will allow installation of stimuli responsive release mechanisms and offer control over the trapping and release of cargo within MOFs, ensuring drugs are released only at the site of disease in the body. Surface incorporation of sophisticated biotargeting units such as peptides and aptamers will facilitate selective uptake of the MOFs by diseased tissues only. Rapid clean microwave syntheses will allow metal radionuclides to be incorporated for PET imaging, offering a novel alternative to traditional chelates. Comprehensive in vitro and in vivo testing will ensure that this multidisciplinary streamlining of materials, supramolecular and medicinal chemistries with the biosciences will generate highly efficient theranostic devices, offering more efficient, targeted drug delivery to improve treatment efficiency, mitigate side effects and open up new therapeutic avenues such as siRNA delivery. The fundamental advances required to generate these novel materials will also impact across the many applications of MOFs, from molecular storage and separations to catalysis.
Projet ERC : MUMOTT (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Chalmers University of Technology — Pays : Suède — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 84738.75 €

Capture structures without looking at them directly, but rather by probing their interaction with electromagnetic waves - this is the basic principle for the new multi-modal tensor tomography developed in this research programme. It will enable to study the arrangement of nanostructures in macroscopic samples, six orders of magnitude larger than its building blocks, allowing to apprehend the structure of complex hierarchical materials. I will use visible light observing change in their polarization state as well as the scattering of hard X-rays to probe nanostructure. Both modes capture alignment of nanostructure, while complementary in other aspects e.g. high penetration depth of synchrotron radiation and easy accessibility of laboratory polarimetric setups. At the core of MUMOTT lays the development of the methodological framework implemented in an open-source software package allowing for the reconstruction of tensors in each sub-volume or voxel of the three-dimensional tomogram. Whereas in a first step I will work out a general approach, we will incorporate flexible modules to capture details of the different types of interaction. This approach includes method development pushing the boundaries of traditional synchrotron methods to make full use of the high brilliance and coherence of the new generation of synchrotrons coming online as well as the enabling of studies with lab-based equipment. It opens up for addressing new scientific problems by widening the range of materials as well as the user community. Apart from the methodology framework we will implement the different modes to prove their capability to solve critical problems in materials and bio-science; to investigate the structure of light-weight composites based on cellulose nanofibrils, reveal how the arrangement of nanoparticles in a plasmonic composite is connected to its sensing capabilities, as well as shed light on the disruptive collagen network in liver fibrosis.

Mots-clés : small angle x ray scattering,computed tomography,soft matter
Projet ERC : MUMOTT (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Recherche
Financement ERC de l'entité : 1318080.0 €

Capture structures without looking at them directly, but rather by probing their interaction with electromagnetic waves - this is the basic principle for the new multi-modal tensor tomography developed in this research programme. It will enable to study the arrangement of nanostructures in macroscopic samples, six orders of magnitude larger than its building blocks, allowing to apprehend the structure of complex hierarchical materials. I will use visible light observing change in their polarization state as well as the scattering of hard X-rays to probe nanostructure. Both modes capture alignment of nanostructure, while complementary in other aspects e.g. high penetration depth of synchrotron radiation and easy accessibility of laboratory polarimetric setups. At the core of MUMOTT lays the development of the methodological framework implemented in an open-source software package allowing for the reconstruction of tensors in each sub-volume or voxel of the three-dimensional tomogram. Whereas in a first step I will work out a general approach, we will incorporate flexible modules to capture details of the different types of interaction. This approach includes method development pushing the boundaries of traditional synchrotron methods to make full use of the high brilliance and coherence of the new generation of synchrotrons coming online as well as the enabling of studies with lab-based equipment. It opens up for addressing new scientific problems by widening the range of materials as well as the user community. Apart from the methodology framework we will implement the different modes to prove their capability to solve critical problems in materials and bio-science; to investigate the structure of light-weight composites based on cellulose nanofibrils, reveal how the arrangement of nanoparticles in a plasmonic composite is connected to its sensing capabilities, as well as shed light on the disruptive collagen network in liver fibrosis.

Mots-clés : small angle x ray scattering,computed tomography,soft matter
Projet ERC : ARENA (Horizon 2020, appel 2016, Proof of concept grants)
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 : 149963.0 €

Carbon Nanotubes (CNTs) are considered to be one of 21st century’s most promising materials and over the past decade, tremendous scientific advances have been achieved in the synthesis and processing of these materials. However, the uptake of CNTs by high-tech industry is hampered by a lack of high-throughput processes to structure CNTs into aligned and densely packed assemblies. This is key to fabricate next generation CNT devices, and to date, the CNT community is still struggling to achieve this, especially over large areas. As part of the ERC Starting Grant HiENA, we are pioneering a potentially disruptive strategy to control the packing of CNTs and to fabricate large area films of aligned CNT. In this process, we start from newly developed ultra-high density dispersion of CNTs which can form liquid crystal domains. These domains are aligned by controlling shear in a custom designed coating head which then continuously dispenses the CNTs on a roll-to-roll coater which was recently purchased by the host group. To quantify the performance of the proposed technology, the parameter space of the coating process will be mapped out in terms of throughput, film thickness, uniformity, and conductivity. Finally, we devised a two-step commercialisation plan which targets less to more demanding markets including thin film heaters, ultra-lightweight electro-magnetic shields, as well as interconnects and sensors for flexible electronics. We believe this project is timely on the one hand because of the technology push of improved CNT processing and on the other hand by the pull from several new markets including flexible electronics and the rise of the Internet of Things which will require a drastic increase in low cost electronic manufacturing technologies. The ERC Proof of Concept grant ARENA aspires to contribute to this need by taking a leap forward in the large scale processing of next generation CNT devices.

Mots-clés : nanotechnology,carbon nanotubes,roll to roll coating