Institute Curie, French National Center for Scientific Research, French Institute of Health, Medical Research, Assistance Publique Hopitaux De Paris and University of Paris Descartes | Date: 2016-07-29
A composition that can be used as a vaccine containing means for targeting at least one antigen to dendritic cells and as adjuvants a granulocyte macrophage colony stimulating factor and a CpG oligodeoxynucleotide and/or a CpG-like oligodeoxynucleotide. This composition can used to treat cancers, infectious diseases caused by bacterial, viral, fungal, parasitic or protozoan infections, allergies and/or autoimmune diseases.
Dna Therapeutics, Institute Curie and French National Center for Scientific Research | Date: 2017-03-01
The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.
French National Center for Scientific Research and Institute Curie | Date: 2017-01-25
A fluidic device comprising at least:a/ a solid matrix 5,b/ a textile component 4, embedded in said matrix and mechanically cohesive with said matrix,c/ at least one channel 6 embedded in said matrix and entangled with said textile component 4, said channel 6 being at least partly open. A method for making a fluidic device comprising providing a textile component 4 comprising support fibers 1.1, 1.2 and at least a movable fiber 2 entangled with said textile 4, embedding at least part of said textile 4 and part of said movable fiber 2, in a matrix precursor material 5, applying a treatment in order to obtain a solid matrix 5.
French National Center for Scientific Research and Institute Curie | Date: 2017-01-25
A minifluidic device comprising a matrix, an elongated guiding duct 109 embedded at least in part in said matrix, with at least one port to the outside of the matrix, a movable fiber 104 at least partly contained in said guiding duct 109, and able to undergo within said guiding duct 109, and at least along some part of said fiber 104, at least one action selected among a sliding, or a deformation, or a rotation, at least one zone in fluidic connection with said guiding duct 109, said zone being selected from: a fluid drop area, a reservoir, or a chamber 107.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 2.80M | Year: 2016
The cell is the universal unit of living matter, and there cannot be propagation of life without cell division. DivIDe aims to investigate the mechanisms and principles of cell division and to reproduce them in vitro with synthetic approaches. Crucial to cell division is the mitotic spindle, a structure whose main duty is the separation of chromosomes. The spindle is made of microtubules (MT), molecular motors, and MT-binding factors, some of which show astounding complexity. The mitotic spindle is the one of the cellular structures that best represents the ability of biological matter to self-organize though arrays of dynamic protein-protein interactions. It rapidly assembles when cells enter mitosis, and it disassembles, after sister chromatid separation and mitotic exit. The complexity and dynamic behaviour of the mitotic spindle captures the imagination of synthetic biologists and modellers. These molecular engineers try to understand and harness the principles of self-organization to generate new biological structures endowed with the most typical features of biological matter, the ability to harness energy to do mechanical or chemical work. The emerging discipline of synthetic biology aims to bring together modellers, physicists, and chemists, with biochemists, structural biologists and cell biologists. So does DivIDe, which will train a new generation of molecular engineers endowed with a strong basis in quantitative computational and biochemical methods, and therefore capable of addressing cellular and molecular mechanisms. Furthermore, molecular engineering harbours industrial applications, and DivIDe will continuously provide results for potential exploitation by the three SME partners. Training in management skills, conceptual and ethical thinking, communication and networking will complement the scientific offer. In summary, DivIDe will be able to teach an integrated package of skills and will train the molecular biologists of the future.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-02-2015 | Award Amount: 5.70M | Year: 2016
Despite of their great promise, high-throughput technologies in cancer research have often failed to translate to major therapeutic advances in the clinic. One challenge has been tumour heterogeneity, where multiple competing subclones coexist within a single tumour. Genomic heterogeneity renders it difficult to identify all driving molecular alterations, and thus results in therapies that only target subsets of aggressive tumour cells. Another challenge lies in the integration of multiple types of molecular data into mathematical disease models that can make actionable clinical statements. We aim to develop predictive computational technology that can exploit molecular and clinical data to improve our understanding of disease mechanisms and to inform clinicians about optimized strategies for therapeutic intervention. We propose to focus on prostate cancer, a leading cause of cancer death amongst men in Europe, but also prone to over-treatment. Our approach combines the exploitation of genomic, transcriptomic, proteomic, and clinical data in primary and metastatic tumours, prospective cohorts of well characterized prostate cancer patients, drug screenings in cell lines, and the use of the Watson technology, a last generation cognitive computer developed at IBM. The translational objective of this study is to develop technology for identifying disease mechanisms and produce treatment recommendations for individual patients based on a therapeutic biomarker panel. The proposed software framework will be accessible through a graphical interface that will facilitate its dissemination and use by researchers, clinicians, and biomedical industries. The framework will provide intuitive tools to deposit, share, analyze, and visualize molecular and clinical data; as well as to infer prognosis, elucidate implicated mechanisms and recommend therapy accordingly. This software framework will serve as a proof of concept for future development by industrial partners in Europe.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETOPEN-1-2014 | Award Amount: 3.47M | Year: 2016
Neurodegenerative diseases, such as Parkinsons disease, are a major public health issue given the aging population in Europe and beyond. While curative pharmacological treatment of these diseases is not in sight, cell replacement therapies (CTs) are considered very promising, in particular with the advent of stem-cell reprogramming technologies. However, a fundamental challenge in the medical application of CTs in the brain of patients lies in the lack of control of cell behaviour at the site of transplantation, and particularly their differentiation and oriented growth. The aim of this project is to introduce a fundamentally new concept for remote control of cellular functions by means of magnetic manipulation. The technology is based on magnetic nanoparticles functionalized with proteins involved in cellular signalling cascades. These biofunctionalized MNPs (bMNPs) will be delivered into target cells, where they act as intracellular signalling platforms activatable in a spatially and temporally controlled manner by external magnetic fields. The project will focus on engineering these tools for the control of neuronal cell programming and fibre outgrowth by hijacking Wnt and neurotrophin signalling, respectively, with the ulti-mate objective of advancing cell replacement therapies for PD using dopaminergic precursor neurons. To achieve this ambitious goal, we have gathered an interdisciplinary consortium interfacing scientists having cutting-edge know-how in bMNP engineering, surface functionalization and cellular nanobiophysics with renowned experts in neuronal cell differentiation, stem-cell reprogramming and regenerative (nano-)medicine. By exploiting this complementary expertise, a novel, versatile technology for magnetic control of intracellular signalling is envis-aged, which will be a breakthrough for remote actuation of cellular functions and its successful implementation in CTs for neurodegenerative diseases and injuries within the following decade.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 7.97M | Year: 2016
Uveal melanoma (UM) is a rare intraocular tumour with an incidence of 5 cases per million individuals per year. Up to 50% of UM patients develop metastases, most often in the liver, and these are invariably fatal. Despite new discoveries in the genetic and molecular background of the primary tumour, little is known about the metastatic disease; furthermore, there is no therapy to either prevent or treat UM metastases. In UM Cure 2020, we aim to identify and validate at the preclinical level novel therapeutic approaches for the treatment of UM metastases. For this purpose, the consortium brings together the major experts of UM in both patient care and basic/translational/clinical research, as well as patient representatives. An ambitious multidisciplinary approach is proposed to move from patient tissue characterisation to preclinical evaluation of single or combinations of drugs. This approach includes the characterisation of the genetic landscape of metastatic UM and its microenvironment, proteomic studies to address signal pathway deregulation and establishment of novel relevant in vitro and in vivo UM models. We also aim to validate accurate surrogate endpoint biomarkers to evaluate therapies and detect metastases as early as possible. Underpinning this will be the UM Cure 2020 virtual biobank registry, linking existing biobanks into a harmonised network, which will prospectively collect primary and metastatic UM samples. Together, our approach will lead to the identification of new therapies, allowing the initiation of UM-dedicated clinical trials sponsored by academia or pharma. Dissemination of results will include the building of a patient network across the countries as part of the consortium as well as a dedicated UM patient and caregivers data portal as part of the UM Cure 2020 website, in order to increase patient information and disease awareness.
Agency: European Commission | Branch: H2020 | Program: MSCA-COFUND-DP | Phase: MSCA-COFUND-2014-DP | Award Amount: 5.49M | Year: 2016
The new IC-3i-PhD program of Institut Curie and its partners will produce top-level scientific knowledge by promoting basic interdisciplinary research that will be translated into novel therapeutic avenues for diagnosis and treatment. The completely re-structured, revitalized, and ambitious international Triple i PhD program is strengthened by trans- and inter-disciplinary and inter-sectorial research projects and will offer 35 international PhD positions. The program will teach PhD/Doctoral Program recipients to be excellent researchers of tomorrow; to perform research but also enhance innovation through research via established working relationships with private industry, and by supporting the creation of Small and Medium-sized Enterprises (SMEs). The objective of the doctoral programme is to offer an international, inter-disciplinary, and inter-sectorial training program for the researchers, including training-through-research (both on site and through secondments) as well as hands-on training in transferable skills. Furthermore, supporting researchers career development via a structured career plan, and a commitment to providing fellows with the transferable skills they need, will change the standard of excellence for PhDs at the institute, and beyond. Training IC-3i-PhDs to the high standard set out in the program will ultimately lead to producing a new generation of researchers and researcher-physicians working side by side on improving health outcomes, reducing health inequalities, and promoting active and healthy ageing. Overall the proposed project will further stimulate the development of European research and human resource capacities, knowledge transfer between academic institutions and industrial stakeholders and thus strengthen the competitiveness and innovation of EU industries.
Agency: European Commission | Branch: H2020 | Program: ERC-ADG | Phase: ERC-ADG-2015 | Award Amount: 2.50M | Year: 2016
A central question in chromatin biology is how to organize the genome and mark specific regions with histone variants. Understanding how to establish and maintain, but also change chromatin states is a fundamental challenge. Histone chaperones, escort factors that regulate the supply, loading, and degradation of histone variants, are key in their placement at specific chromatin landmarks and bridge organization from nucleosomes to higher order structures. A series of studies have underlined chaperone-variant partner selectivity in multicellular organisms, yet recently, dosage imbalances in natural and pathological contexts highlight plasticity in these interactions. Considering known changes in histone dosage during development, one should evaluate chaperone function not as fixed modules, but as a dynamic circuitry that adapts to cellular needs during the cell cycle, replication and repair, differentiation, development and pathology. Here we propose to decipher the mechanisms enabling adaptability to natural and experimentally induced changes in the dosage of histone chaperones and variants over time. To follow new and old proteins, and control dosage, we will engineer cellular and animal models and exploit quantitative readout methods using mass spectrometry, imaging, and single-cell approaches. We will evaluate with an unprecedented level of detail the impact on i) soluble histone complexes and ii) specific chromatin landmarks (centromere, telomeres, heterochromatin and regulatory elements) and their crosstalk. We will apply this to determine the impact of these parameters during distinct developmental transitions, such as ES cell differentiation and T cell commitment in mice. We aim to define general principles for variants in nuclear organization and dynamic changes during the cell cycle/repair and in differentiation and unravel locus specific-roles of chaperones as architects and bricklayers of the genome, in designing and building specific nuclear domains.