Functional analysis of candidate genes in encephalitogenic T cell responses.

Multiple sclerosis (MS) is a chronic degenerative disease in which central nervous system demyelination and white matter inflammation leads to axonal injury and neurological deficit. Canada has one of the highest rates of MS incidence in the world; studying the pathogenesis of MS is of the utmost importance. MS pathology results from myelin-directed autoimmune attack by T cells of the immune system, and the immune components of the pathology can be recapitulated in mice using the experimental autoimmune encephalomyelitis (EAE) model.

We aim to assess the contribution of specific genes (and by extension, specific molecular pathways) to T-cell-driven EAE pathogenesis, exploiting transgenic mouse strains that possess myelin antigen-specific CD4+ and CD8+ T cells. When transferred to naive recipient animals, these cells induce symptoms of EAE characterized by paralysis of the extremities. Transgenic myelin antigen-specific T cells can thus be isolated and manipulated in vitro, before being transferred to naive recipients, to assess the effects of pharmacological or genetic treatments on their pathogenic capacity.

This project will entail the overexpression or knockdown of specific genes in these cells using retrovirally-mediated gene delivery followed by the transfer of the cellsto recipient mice to assess their ability to induce EAE. Our ultimate aim is to identify novel therapeutic targets for the immunomodulatory treatment of MS.

Faculty Supervisor:

Manu Rangachari

Student:

AZUCENA GONZALEZ GOMEZ

Partner:

Discipline:

Medicine

Sector:

University:

Program:

Globalink