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PHENOMIN is an active member of the scientific academic and economic landscapes through its implication in National Infrastructures, LABEX, EQUIPEX and Demonstrators, IDEX, International Infrastructures, Universities, Education and Research programs, International and National fundings and Private partners. PHENOMIN places its knowledge and expertise at the service of global Research programs.
Started in March 2016 and funded by the EU Horizon 2020 program, the European Research Consortium CanPathPro (“Generation of the CanPath prototype - a platform for predictive cancer pathway modelling”) gathers 3 industrial partners and 6 research centers. The consortium takes a unique approach and brings together classic cancer research with omics data and systems biology tools, to develop and validate a new biotechnological application: a combined systems and experimental biology platform for generating and testing cancer signaling hypotheses.
EarlyCause, "Causative mechanisms & integrative models linking early-life-stress to psycho-cardio-metabolic multi-morbiditywill", identify and demonstrate causative mechanisms and molecular pathways linking early life stress (ELS) to depression and two of its main physical comorbidities, namely coronary heart disease and diabetes. The consortium will disentangle the complex biological contributions from four key interconnected domains linked to ELS, namely epigenetics, inflammation, neuroendocrine system, and microbiome. Furthermore, modifying effects of environmental factors such as sex/gender, socioeconomics, lifestyle and behavior will be quantified, thus uncovering potential intervention targets that may reverse the causative mechanisms and reduce the impact of ELS on multi-morbidity development in high-risk individuals.
All the genetic material our body requires to make all its proteins is located on 23 paired chromosomes. They contain the code for all the proteins our body makes. All cells carry the entire code, but specific cells express specific proteins according to their functions. Down's syndrome, also known as trisomy-21, is a genetic disorder in which a person has three copies of chromosome 21 instead of the usual two. It is associated with a high risk of both severe obesity and intellectual disorder. On the hypothesis that the locus may be on chromosome 21, the EU-funded GO-DS21 project is investigating the genetic mechanisms of this comorbidity "Gene overdosage and comorbidities during the early lifetime in Down Syndrome". Outcomes should benefit patients with Down's syndrome and the general population.
This project is lead by the CERBM-GIE, in Strasbourg and PHENOMIN-ICS is invoved as the service's platform of CERBM users is involved in the project.
The Immunological Genome Project is a collaborative group of Immunologists and Computational Biologists who are generating a complete microarray dissection of gene expression and its regulation by the mouse immune system. The cells are analyzed through different states of differentiation and maturation, activation responses, effector stages, tissues localization, age and genetic variations. The project will define regulatory modules, the connectivity between genes in different immune cells, and how the network fluctuates with genetic variations. ImmGen is primarily intended as a public resource and provides open access of its database to research and medical communities worldwide.
Collaborators of Immunological Genome Project
Nat Immunol 2020 Jul;21(7):700-703. doi: 10.1038/s41590-020-0687-4.
Marseille Immunopole brings together a unique continuum of excellence ranging from targets discovery to the clinical development of drug candidates. This cluster is exclusively dedicated to the research and development of the two weapons poised to revolutionize the treatment of cancer and inflammatory diseases: immunotherapy antibodies and cell therapies. More than 2,000 researchers, clinicians, engineers and industrials are working together to accelerate the development of these treatments, facilitate patients’ access to these innovations and position the Marseille metropolis at the heart of global competition. In April 2016, the Marseille Immunopole cluster has signed a partnership with MSDAVENIR to set up major research projects aiming at improving the knowledge of the targets of antibodies used in oncology. The Infrastructure is working for the identification of potential synergies between different T lymphocyte signaling pathways; this major work could enable the setup of drug combinations to improve the clinical impact of new antibodies used in immunotherapy.
The PAIN-NET project, funded under the H2020-MSCA-ITN-2016 call for proposal, gathers 10 partners from 6 countries to decipher the individual susceptibility to pain and analgesics responsiveness. We are involved in the generation and validation of 2 new transgenic mouse models of sodium-channel-related neuropathic pain. We will generate two different knock-in mouse models, each carrying in the corresponding mouse gain-of-function mutation of human alpha subunit of Nav1.7 (mutation p.Arg185His) and 1.8 (mutation p.Gly1662Ser) sodium channel. These mutations have been and profiled by cell electrophysiology as gain-of-function in painful neuropathy patients. Models will be thoroughly characterized for pain thresholds by behavioral measures (gait analysis, tail-flick test, hot plate test, formalin test, von Frey test, Randall-Selitto test). In addition, loss of Nav1.7 function is known to alter odor discrimination in human and mouse, thus we propose to explore anosmia in these 2 new models.
The PATHBIO project and its engaged partners are ideally constituted at the European level to develop a strong educational program for Mouse Precision Pathobiology. Five major European mouse clinics (PHENOMIN-ICS via the CERBM, MRC Harwell, HMGU, IMG, and CNR) equipped with integrated facilities for production and characterization of genetically engineered mouse models are part belonging of the various partners of the consortium. These mouse clinics are developing and using state of art mouse imaging technologies and have long standing expertise in pathology phenotyping along with the data-capture, annotation, and bioinformatic analysis capabilities to interpret the resulting datasets.
The PHENOMIN-Axenis partnership is determinant to conduct extensive preclinical evaluation of new class of therapeutics in infection and cancer in order to select efficiently the most potent candidate treatments for further efficacy studies in translational medicine. The scientific synergy and know-how complementarity of PHENOMIN and Axenis will greatly beneficiate to the broad community of immunologists as it will result in the development of unique investigation capabilities of pre-clinical predictive humanized mice models. This partnership is a great opportunity for both PHENOMIN and Axenis to move forward innovative projects and extend the field of application of humanized mouse models in a cost and time efficient manner. Therefore, the combination of very refined humanized mouse models to standardized multiparametric phenotyping methodologies constitute a unique opportunity to evaluate robustly et extensively the response of the human immune system to innovative therapeutics (new effective vaccination approaches, new therapeutics against pathogens and human tumors resistant to treatments currently available) in a perspective of personalized medicine.
The integrated PHENOMIN-Axenis tool-box gathers the generation of preclinical murine models adapted to inflammation, immunotherapy of tumors and vaccination, their functional exploration in a confined BSL2 / BSL3, their standardized immunophenotyping by high-content flow and mass cytometry as well as data exploration using advanced supervised and unsupervised analysis methodologies.
This exciting partnership with Charles River offers their European clients a complete integrated solution for mouse and rat models, from creation to validation. Our combined in vitro and in vivo expertise shapes a broad portfolio of design (ES cell, CRISPR/Cas9, random DNA insertion), breeding and associated services to create and maintain the most relevant models for your studies. Rely our industry-leading germ line transmission, strict quality controls, fast turnaround and dedicated project managers to help you successfully reach your goals.
Genetic Engineering Design Options
The integrated PHENOMIN-Charles River tool-box gathers the safety and rapid concept and generation of your research rodent models. 3 webinars helded and presented by G. Pavlovic (PHENOMIN-ICS) can be viewed by replay : https://www.criver.com/resources/webinar-series-transgenic-mouse-and-rat-model-creation. Have a look !
The project is funded by the French ARC foundation and managed by the LabEx HepSYS to provide new targets for prevention and treatment of Hepatocellular carcinoma (HCC), relevant biological models of the disease, nanocarriers for personalized treatment and optimized clinical care protocols. PHENOMIN has contributed to develop and improve relevant animal models (Wu et al, 2016; Bou About et al, 2019)