Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet SOPMEN (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Metal nanoparticles (NPs) are intriguing systems due to their efficient interactions with light stemming from localized surface plasmon resonances (LSPRs), a phenomenon which is exploited in many applications in fields ranging from physics to biology and medicine. In particular, anisotropic shapes are interesting because of strong electromagnetic field enhancements at corners and tips. Next to monometallic NPs, bimetallic NPs offer an additional way of tuning the functionality and plasmon resonance and are advantageous for applications such as photocatalysis. Understanding the delicate interplay between particle morphology, composition and optical properties is of utmost importance in optimizing particle design for the desired applications. While optical properties of metal NPs have been related to structure by using surface imaging techniques like scanning electron microscopy (SEM), a complete connection to the atomically resolved 3D structure has never been accomplished. Here, I propose to investigate the correlation of the full atomic morphology (including composition) and optical properties of (bi)metallic NPs by single-particle optical experiments and electron microscopy techniques such as atomically resolved electron tomography. I will furthermore study the correspondence and differences between electronically-excited and optically-excited plasmon modes. The key aspect of the proposed research is that the correlated measurements will be performed, for the first time, on the same particle allowing for a full understanding of how the morphology and composition of a metal NP is related to its optical properties.

Mots clés : anisotropic metal nanoparticles, bimetallic metal nanoparticles, optical properties, atomic resolution electron tomography, eels

Participants :
- University of Antwerp (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160800.0 €
Projet Cdc42Adhere (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Metastasis accounts for 90% of cancer deaths, and it is therefore important and timely to identify new therapeutic targets aimed specifically at metastasis. Cdc42 has recently been implicated in a key step of the metastatic cascade: the extravasation of circulating tumour cells, also termed transendothelial migration (TEM) . This project aims to study how Cdc42 contributes to breast cancer cell TEM in vitro and in vivo. Cdc42 regulates β1‐integrin expression via the transcription factor serum response factor (SRF) and thereby stimulates cancer cell adhesion to endothelial cells (ECs) and TEM. To analyse the molecular basis for this regulation, downstream targets of Cdc42 will be depleted by RNAi in a panel of breast cancer cells to determine which target/s are responsible for altering β1‐integrin expression, adhesion to ECs or TEM. Cancer cells interact with platelets as soon as they enter the bloodstream, and this enhances cancer cell TEM in vivo. It is therefore possible that Cdc42 regulates attachment to platelets as well as ECs. The role of Cdc42 in the interaction between platelets and cancer cells will be tested by adding purified platelets to control or Cdc42‐depleted breast cancer cells in vitro and analysing platelet aggregation around cancer cells by confocal microscopy. The role of Cdc42 in platelet attachment to cancer cells during early lung colonization in vivo will be studied by intravenous injection of fluorescently tagged breast cancer cells in mice. This project will increase our understanding of metastasis. The identification of molecular targets involved in cancer cell extravasation will provide a starting point for the development of new drugs, thus contributing to reduce the mortality of patients with metastasis.

Mots clés : rho gtpases, integrins, cdc42, cell adhesion, endothelial cells, breast cancer, transendothelial migration, cytoeskeleton, platelets

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet INHuMAN (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Metastasis is largely refractory to therapy and, thereby, responsible for 90% of cancer-related deaths. An incomplete view of the mechanisms that drive metastasis has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for metastatic patients. There is increasing evidence that this multi-step process involves reversible non-genetic reprogramming events allowing cancer cells to acquire diverse phenotypic features needed to migrate, invade, intra/extra-vasate and actively adapt to the varying environment (stress) they encounter. Understanding metastasis therefore requires methodologies that capture the magnitude and dynamics of non-genetic reprogramming in 4D (space and time) at the single-cell resolution. The advent of reliable single-cell multi-Omics analytical tools allows the simultaneous profiling of single cell’s genome, epigenome and transcriptome. Integrating single-cell profiling with lineage tracing provides a robust framework for defining cell fate transitions, intermediate states and trajectory inference. The host lab has recently used such a powerful combination of approaches to study the cellular origin of melanoma, the early molecular events associated with initiation of the disease and to portray cell state dynamics during therapy response. I propose to exploit this know-how to perform a longitudinal and exhaustive analysis of the diversity and trajectories of melanoma cell states during metastatic dissemination using a clinically-relevant mouse model of melanoma, a disease with a very high metastatic propensity. The gene regulatory networks underlying the identified metastatic cell states will be deciphered and the data exploited to develop therapeutic modalities targeting (amenable) drivers of state switching that contribute to early key steps of the metastatic process. The project is expected to lead to new avenues for early detection and interception of metastatic melanoma.

Mots clés : intratumoral heterogeneity, mouse models, melanoma, metastasis, single cell sequencing approaches, plasticity, gene signatures

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 166320.0 €
Projet MultiLQB-PC (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Metastatic prostate cancer (mPC) is a lethal disease. Androgen deprivation therapy is the mainstay of patient care. In addition, DNA repair defects is a novel therapeutic target in mPC. However, resistances invariably arise, triggered most of the times by tumor genomic evolution. Liquid biopsy has emerged as a tool to non-invasively profile tumor genomics over time. Beyond circulating tumor DNA (ctDNA) and circulating tumor cells (CTC), small extracellular vesicles, known as exosomes, have been identified to contain tumor genomic material. Over the last years, I have developed a method to pursue analysis of tumor genomic material from exosomes at a very low cost. The analysis of exoDNA/RNA is a promising tool that represents a new non-invasive, sensitive and very informative new method for PC monitoring. In this project, I aim to integrate the genomic analysis of exoDNA/RNA together with ctDNA and CTCs in advanced PC to:1) Identify prognostic signatures for clinically-relevant patient stratification; 2) Define circulating predictive signatures of drug response/resistance; and 3) Validate biomarkers of therapy response for selection of subsequent lines of treatment. Therefore, this fellowship would allow me to take a significant step towards the implementation of this new technology in the study of mPC genomics and mechanisms of response/resistance to novel targeted drugs. Furthermore, I will be able to integrate my research into clinical trials and, ultimately, impact personalized patient care.

Mots clés : prostate cancer, liquid biopsy, personalized medicine

Participants :
- CERCA Institution (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet MiLC (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Mathematics
Statut du projet : CLOSED

MiLC will develop logical characterisations of monotone complexity classes, yielding languages and systems which are machine-independent and well suited for reasoning over such classes of functions. Monotone Boolean functions abound in the theory of computation, e.g. in sorting algorithms and clique detection in graphs, and nonuniform classes of monotone functions have been well studied in computational complexity under the lens of monotone circuits. From the point of view of computation, monotone functions are computed by algorithms not using negation, and this will lead to several recursion-theoretic characterisations of feasible classes such as monotone P, NCi, ACi and the polynomial hierarchy. The main purpose of MiLC will be to capture these classes proof theoretically, by calibrating each class with the formally representable functions of a certain theory. MiLC will work in the setting of Bounded Arithmetic since its techniques are well suited to handling monotonicity, building on recently discovered correspondences with monotone proof complexity. To this end two avenues for controlling monotonicity will be investigated: (a) restricting negation in proofs, inducing monotone witnessing invariants, and (b) restricting structural rules of the underlying logic to eliminate the nonmonotone cases of witness extraction. The aim is to arrive at modular characterisations, where monotonicity of a represented class is switched on or off by the inclusion or exclusion, respectively, of certain structural rules. Finally MiLC will calibrate these theories with well studied systems in proof complexity, namely monotone, intuitionistic and deep inference systems, under the usual correspondence between theories of Bounded Arithmetic and systems of propositional logic. These tight correspondences ensure that the tools developed in MiLC may be employed to attack certain open problems in the area, reformulating and improving existing bounds.

Mots clés : monotonicity, logic, computational complexity, proof theory, implicit complexity, bounded arithmetic, witnessing, realizability, intuitionistic logic, linear logic, proof complexity, recursion theory

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet LignoPrintCap (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Micro-supercapacitors (MSCs) are efficient power sources for miniaturized wearable/portable gadgets; a projected global market of over € 35 billion by 2025. However, MSCs still suffer from high-cost, low dimensional accuracy, and complexity in the fabrication process. This project aims to develop high performance, low-cost, greener compact MSCs through inkjet printing technology. To this end, we will develop a lignin-derived nitrogen-doped activated carbon ink and print the MSCs on flexible substrates. Subsequently, the compact size of MSCs will enable us to print a high number of MSCs into a small footprint area and connect them in-series/in-parallel. This will assist us to alter the cell voltage and capacitance. In addition, to get new insights into the effect of electrode properties on electrode/electrolyte decomposition and cycle stability, we will investigate the lignin-based carbon properties and electrode/gel electrolyte interface using advanced characterization techniques e.g. XPS, NEXAFS, XANES. The world-leading expertise of Prof. Magda Titirici (host); and the state-of-the-art facilities at Imperial College London, provide the perfect environment to successfully host my project despite its challenging nature.

Mots clés : micro supercapacitor, inkjet printing, electrode electrolyte interface, lignin derived carbon

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet miRanDa (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

MicroRNAs (miRNAs) are potential biomarkers for cancer diagnosis, prognosis and treatment monitoring. Specific detection and absolute quantification of miRNAs is of clinical relevance for early cancer detection and monitoring progression. The currently available techniques for miRNA detection based on DNA amplification are limited by lack of absolute quantification, low multiplexing capacity and time consumption. Here, I propose to develop a miRNA assay system based on self-assembled nanoscale DNA origami arrays (miRanDa) for the simultaneous detection of multiple miRNA targets from breast cancer cells and plasma by using DNA-PAINT, state-of-art super resolution technique. The formation of specifically configured finite 2D lattices of self-assembled DNA origami structures based on sticky-end hybridization will further improve the capacity of the detection system beyond the currently available techniques. This assay can be further developed and adapted to the rapid, specific, sensitive and multiple detection of additional nucleic acid species, such as ctDNA, mRNA or lncRNA.

Mots clés : microrna, biomarkers, diagnostics, dna nanotechnology, dna origami, dna paint, super resolution microscopy, breast cancer, self assembly

Participants :
- University of Fribourg (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203149.44 €
Projet MultiMEc (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Microbial communities profoundly influence global biogeochemical cycles and human life. Understanding their wiring is crucial to manage, rationally manipulate, or de novo assemble communities for environmental, industrial or medical applications. However, studying the complex web of microbial interactions and how they are affected by the spatial structure of the community is experimentally challenging. Here, I propose an integrative approach to dissect microbial interactions in a synthetic community consisting of two bacterial species of the human gut microbiota, the commensal Escherichia coli and the probiotic lactic acid bacterium Lactobacillus plantarum. These two species were predicted to engage in exploitative and mutualistic metabolic interactions depending on oxygen availability and provide an experimentally tractable and possibly health-relevant model community. I will employ a combination of highly sensitive quantitative analyses on the molecular level (proteomics, metabolomics, CRISPR/Cas9 genetic perturbations) with quantitative analyses on the individual cell and community level (cellular growth rates and spatial organization) to obtain a comprehensive mechanistic understanding of the interactions between the two species. The multilayered nature of the approach, including the conceptualization of the interactions with a mathematical model, is expected to provide novel insights into the fundamental principles underlying microbial interactions and how they are affected by the environment. Furthermore, a detailed understanding of the molecular interactions of L. plantarum with other gut residents could inform the rational modulation of the gut microbiome to treat diseases associated with dysbiosis. This fellowship would have a major impact on my career by facilitating re-integration into the European research landscape. It would allow me to acquire a unique and competitive scientific profile and to establish my own niche in the field of microbial ecology.

Mots clés : microbial ecology, microbial interactions, microbiome, quantitative single cell biology, microfluidics

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203149.44 €
Projet MIMIC (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Microbiota has a major impact on anti-tumor immune responses and efficacy of anticancer treatments. These effects are thought to be mediated by modulation of tumor-infiltrating myeloid cells. These include immunosuppressive macrophages that differentiate from inflammatory monocytes recruited to the tumor. However, what microbiota-derived products are required for efficient anti-tumoral responses is still unclear. We have recently identified the Aryl Hydrocarbon Receptor (AhR) as a key suppressor of monocyte-to-macrophage differentiation. AhR is a ligand-activated transcription factor sensing metabolites derived mainly from dietary intake and microbiota metabolism. Based on our previous work, we hypothesize that AhR is involved in the modulation of anti-tumoral responses by the microbiota, via the regulation of immune cells differentiation or function. The objective of the project is to address whether AhR ligands mediate the impact of microbiota on anti-tumor responses in anti-checkpoint therapy and to determine the cellular mechanisms involved. To address it, we will analyse anti-tumor immune responses in groups of mice with normal or altered microbiota, treated or not with anticheckpoint therapy, fed with a control diet or supplemented for AhR ligands. We will combine two complimentary approaches, employing antibiotics to deplete the microbiota or using germfree mice. The efficacy of immunotherapies using checkpoint inhibitors is greatly reduced in patients who receive antibiotics. This is a major issue as antibiotics are commonly prescribed to prevent or treat infections in cancer patients, who may be vulnerable. This research project will provide critical novel insight into the complex interplay between microbiota and anti-tumor immune responses. Results from this project will be instrumental in designing novel strategies for improving anti-tumoral immunotherapies.

Mots clés : microbiota, immunotherapy, onco immunology, tumor, aryl hydrocarbon receptor

Participants :
- Institut Curie (France) — Coordinator, beneficiary, Recherche, subvention : 184707.84 €
Projet MRI COMIQSUM (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Microbubbles are an established ultrasound contrast agent; detecting them with Magnetic Resonance Imaging (MRI) would open up a wide spectrum of dual-modality applications such as MR-guided focused ultrasound therapies. So far, MRI has been used to qualitatively assess the concentration of microbubbles based on a decrease in the MRI signal magnitude, which is difficult to differentiate from other sources of signal drop-out. In this fellowship, I will exploit quantitative susceptibility mapping (QSM), a novel approach, to detect microbubbles using MRI. QSM uses the phase, instead of the magnitude, of the complex MRI signal, which promises to enhance MRI of microbubbles because phase images have higher contrast-to-noise ratio than standard magnitude images. With the supervision and mentorship of Dr Karin Shmueli, an MRI physicist and internationally recognized expert in QSM, I will investigate the ability of QSM to quantify microbubble concentrations. Collaborating with Prof. Eleanor Stride, a leader in microbubble engineering, I will tailor the susceptibility of microbubbles for different clinical applications so that microbubbles will create bright contrast in susceptibility maps, clearly distinguishable from anatomical structures and image artifacts. This project will enhance the clinical applicability of microbubbles as a dual-modality, MRI and ultrasound, contrast agent. QSM of microbubbles has the potential to improve MRI guidance and monitoring of microbubble-mediated drug, antibody or gene delivery as well as microbubble-enhanced focused ultrasound surgery, which is currently in use for treating uterine fibroids and bone metastases. This fellowship will be a springboard towards widespread diagnostic and therapeutic applications of QSM of microbubbles. The unique training and skills provided by the fellowship will help me to establish my own research group and share the expertise I build in QSM and contrast agents with academic and industrial partners.

Mots clés : quantitative susceptibility mapping, microbubbles, magnetic resonance imaging, contrast agent, superparamagnetic iron oxide nanoparticles

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet THINPAC (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Microelectronic medical implants with superior performance are needed to improve quality of life for patients. For neuroelectronic applications, this will be enabled through miniaturisation of large numbers of high-density electrodes in bio-mimetic packages. The leading solution is to use ultra-thin silicon chips (UTCs) embedded in flexible polymers with small flexible ribbon cables. However, this technology creates a unique challenge of maintaining sufficient hermeticity, biocompatibility and biostability for decades-long implantation without the use of bulky, rigid glass/Ti boxes. The primary aim of THINPAC (Thin Hermetic Implantables using Novel Packaging of Active Chips) is to realize a robust technology platform for ultra-thin flexible hermetic packaging of UTCs using alternating layers of ceramic nanofilms and polyimide. Innovation beyond existing fabrication technology is needed (i.e. bonding for higher yield, thin-film noble metal patterns over chip edge topography, and hermetic connector strategies). THINPAC will aim to develop these technologies by solving remaining fabrication issues and in-depth in vitro evaluation of the developed technology to ensure long term hermeticity, biostability, and flexibility. New testing strategies will be developed towards highly reliable test protocols for real-time and accelerated testing to mimic long term evaluation of implants. Implant development is a highly multidisciplinary activity and in vivo testing in animals is indispensable. Discussion with medical people and initial tests with dummy devices are essential from the start of the project to avoid less suitable medical devices. Finally, functional probes for implantation into peripheral nerves will be fabricated and fully characterized in rats for foreign body reaction and electrophysiology. With this project, we aim to mature a technology platform for advanced implant fabrication and for the first time make it viable for clinical translation into humans.

Mots clés : flexible electronics, hermetic thin film encapsulation, chip in foil packaging, accelerated aging, direct bonding, foreign body reaction, in vivo electrophysiology

Participants :
- IMEC (Belgique) — Coordinator, beneficiary, Recherche, subvention : 178320.0 €