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3. Biomedical Sciences Research Center "Alexander Fleming", Athens:
The main objective of the research contacted at the Institute of Immunology at the BSRC Fleming, is to achieve detailed understanding of the molecular and cellular mechanisms underlying immunological disease initiation, progression and chronicity. The goal of our research is: to develop more accurate animal models of mechanisms underlying chronic inflammation and autoimmunity and to disclose new diagnostic markers and therapeutic targets for this class of diseases. We have previously developed and established:
Technologies for permanent or conditional genome the mouse, TNF-driven transgenic or mutant animal models of chronic inflammatory polyarthritis, Crohn's-like inflammodification in matory bowel disease, systemic inflammation and autoimmune demyelination - multiple sclerosis, basic knowledge on mechanisms in immunity, inflammation, tolerance and autoimmunity. In continuation of this previous work, we aim to continuously improve the current state of the art in the understanding of aetiology, pathophysiology, progress and outcome of disease by using: conditional and-or tissue-specific targeted mutagenesis in mice to study the impact of ablating specific cells, genes and pathways in our own animal models developing specific immunological diseases, differential gene expression analysis (DNA microarrays or gene chips) on important pathogenic cell types to discover new genes with putative involvement in disease, sensitized phenotypic screens combined with chemical (ENU) mutagenesis in the mouse to search for novel genes that will neutralize pathology. In brief our objectives aim:
- to identify cells, genes and pathways with dominant contributions to disease initiation, progression and chronicity.
- to develop more accurate animal models for chronic immunopathologies and autoimmunity.
- to discover new genes and pathways in immunity and disease.
- to evaluate the function of newly discovered genes in modeled genomes.
- to disclose new diagnostic markers and therapeutic targets.
With these aims and objectives we hope to maintain and further develop our excellence in biomedical-genomic-biotechnological know-how that will constitute the sole ground for the development of new biological concepts and will lead to the introduction of more rational forms of therapies in the coming decade. Expected achievements and deliverables of the research we undertake in our Institute are likely to also help elucidate mechanisms in immune processes or groups of diseases other than those studied here (e.g. transplantation, cancer, AIDS, neurodegenerative diseases, etc), and will therefore be of broad scientific and socio-economic value.
More specifically and in the context of EURO-RA Research Training Network, the main role of our Institute will be:
- to supply murine animal models of Rheumatoid Arthritis
- to develop transgenic mice with synoviocyte cell-specific Cre or Cre-hormone inducible expression, as well as, to create knock out and-or transgenic mice for novel genes identified as involved in Rheumatoid Arthritis
- to create an expression profile of arthritogenic and normal synovial fibroblasts
- to study genetic and cellular pathways of disease induction and progression
- to explore the role of ATX and LPA signaling in the pathogenesis of Rheumatoid Arthritis
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