Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system (CNS) that affects more than a million individuals worldwide. The disease develops through the immunologic attack and eventual destruction of the myelin sheath (demyeli nation) that protects neurons of the CNS. The body attempts to repair the ensuing damage through remyelination, which eventually succumbs to the destructive nature of the disease. Our goal is to employ Experimental Autoimmune Encephalomyelitis (EAE), the animal model of MS, to decipher the cellular and molecular events that influence disease processes. Tumour Necrosis Factor (TNF) is one of the immunological components that have proven instrumental for orchestrating the balance of de- and remyelination.
We have developed conditional genetic animal models that differentially express soluble TNF (sTNF) vs. transmembrane TNF (tmTNF) and their receptors, p55TNFR vs. p75TNFR, to be exploited for the study of the evolution of EAE. We will specifically investigate how the cell-specific expression and signalling through TNF components affect cellular processes, including oligodendrocyte physiology and immune functions, as well as molecular events, such as signalling cascades, suspected or known to participate in the evolution of EAE. This study will extend our knowledge of the nature of EAE; it will reveal novel biological markers of disease progression and potential targets for its therapy.
The project will benefit from the applicant's knowledge of autoimmune diseases a s well as her expertise in a variety of in vitro and in vivo imaging modalities, including confocal microscopy and optical imaging, which will be employed to address the proposed scientific questions. The applicant will be trained in using genetic animal models of neurodegenerative diseases, will extend her knowledge of immuno- and neuro-histopathology and benefit from the transgenic and knockout facilities available at the host institute.
Field of science
- /medical and health sciences/basic medicine/immunology/autoimmune diseases
- /natural sciences/physical sciences/optics/microscopy/confocal microscopy
- /medical and health sciences/medical biotechnology/cells technologies/stem cells
- /medical and health sciences/basic medicine/neurology/multiple sclerosis
- /natural sciences/biological sciences/neurobiology
Call for proposal
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